223 research outputs found
Identification of structural alerts for liver and kidney toxicity using repeated dose toxicity data
No full textBackground: The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure-activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed. Results: We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP). Conclusions: It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances
Gendering the comic body: Physical humour in <i>Shirley</i>
No full textThe mock-battles and slap-stick scenes that arise at pivotal moments in Shirley encourage us to reexamine Brontë’s sense of humour, which is neither as grim, nor as naively crude as critics from George Henry Lewes to Virginia Woolf have deemed it. Drawing on Brontë’s engagement with the theatrical traditions of European Carnival and British pantomime, this chapter demonstrates how physical humour in Shirley satirises the gendered dictates of literary realism that Lewes had laid out for the author in public reviews and private correspondence. By rejecting the witty drawing-room comedy often associated with her predecessor Jane Austen, and adopting the brash language of the body common to both popular performance and the work of her male peers Charles Dickens and William Makepeace Thackeray, Brontë participates in important mid-nineteenth-century debates about gendered authorship and the literary marketplace.<br/
Safety of ethyl lauroyl arginate (E 243) as a food additive in the light of the new information provided and the proposed extension of use
No full textAcknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Eleonora Alquati, Anna Christodoulidou and Fabiola Pizzo
A k-NN algorithm for predicting oral sub-chronic toxicity in the rat
No full textRepeated dose toxicity is of the utmost importance to characterize the toxicological profile of a chemical after repeated administration. Its evaluation refers to the Lowest-Observed-(Adverse)-Effect-Level (LO(A)EL) explicitly requested in several regulatory contexts, such as REACH and EC Regulation 1223/2009 on cosmetic products. So far in vivo tests have been the sole viable option to assess repeated dose toxicity. We report a customized k-nearest neighbors (k-NN) approach for predicting sub-chronic oral toxicity in rats. A training set of 254 chemicals was used to derive models whose robustness was challenged through leave-one-out cross-validation. Their predictive power was evaluated on an external dataset comprising 179 chemicals. Despite the intrinsically heterogeneous nature of the data, our models give promising results, with q2 ≥ 0.632 and external r2 ≥ 0.543. The confidence in prediction was ensured by implementing restrictive user-adjustable rules, excluding suspicious chemicals irrespective of the goodness in their prediction. Comparison with the very few LO(A)EL predictive models in the literature indicates that the results of the present analysis can be valuable in prioritizing the safety assessment of chemicals and thus making safe decisions and justifying waiving animal tests according to current regulations concerning chemical safety
Re-evaluation of Quillaia extract (E 999) as a food additive and safety of the proposed extension of use
No full textAcknowledgements: The Panel wishes to thanks the members of the former Working Group Application of the EFSA Panel on Food Additives and Nutrient Sources for the preparatory work on this scientific output and Fabiola Pizzo for the support provided to this scientific output. The FAF Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output
Transport of Aflatoxin M1 in human intestinal Caco-2/TC7 cells
No full textAflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1). After it is formed, it is secreted in the milk of mammals.Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively.In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10-10,000 ng/kg) for short (40 minutes) and long periods of time (48 hours). The AFM1 influx/efflux transport and effects on tight junctions were evaluated by measuring trans-epithelial electrical resistance and observing tight junction protein (Zonula occludens-1 and occludin) localization.The results showed that: i) when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s x 10-6). ii) The integrity of tight junctions was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either.The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified
Alle radici del dibattito Post-Growth. La lezione di Emilio Sereni
No full textSi evidenzia il contributo seminale di Emilio Sereni al superamento della dicotomia economico/ecologico in una prospettiva di sviluppo fortemente ancorata al territorio e ai luoghi.
Cinquant’anni prima che si iniziasse a discutere di paradigmi post-growth come alternativa a forme di crescita insostenibili, irresponsabili e in realtà senza sviluppo, Sereni aveva proposto di guardare al paesaggio agrario, con l’evidenza delle sue stratificazioni di saperi plurisecolari, come prospettiva ottimale per riflettere sulla crisi che nel 1962 appare pervadere le forme assunte dal boom economico postbellico: quella diffusa devastazione del territorio che ha condotto, da un lato, all’ipertrofia delle rendite urbane speculative, dall’altro all’abbandono di interi comprensori interni con esiti fortemente intrecciati che, di lì a pochi anni, mostreranno il tragico volto delle alluvioni, del dissesto idrogeologico, della marginalizzazione territoriale.
La sua prospettiva ha per noi una valenza non solo analitica, ma anche interpretativa e propositiva, messa in luce già negli anni ’60 da Italo Insolera che, per la recensione della Storia del paesaggio agrario, scriveva sulle colonne di Urbanistica: “Nel processo di integrazione delle nozioni proprie di diverse discipline che caratterizza l’attuale preparazione culturale in funzione della pianificazione territoriale e della programmazione economica, il testo di Sereni ha un posto insostituibile”. Infatti, “l’autore ha raccolto una serie di appunti mirabilmente precisi su come, nelle varie epoche, l’organizzazione della proprietà e della conduzione generasse certi tipi e modi di coltura e come poi questi trasformassero la natura, o l’eredità delle precedenti generazioni agrarie, fino a quello che è oggi il paesaggio caratteristico delle varie regioni della Penisola”; “un compendio di storia rurale” che “qui ci interessa per la grande importanza che riveste per l’urbanistica”, e che si dovrebbe “intitolare “Saper vedere l’agricoltura”.
Ad accomunare i due studiosi, è il ricorso alla storia come chiave di lettura del presente: Sereni nei termini dell’analisi marxista, Insolera come arena privilegiata di ricerca interdisciplinare per individuare, nel complesso delle trasformazioni strutturali, quelle “invarianti” delle pratiche spaziali che ne rappresentano il patrimonio collettivo, e in quanto tali, il perno dell'azione pianificatoria.Aim of this proposal is to highlight the seminal contribution of Emilio Sereni to overcoming the economic/ecological dichotomy in a development perspective strongly anchored to the territory and places.
Fifty years before post-growth paradigms began to be discussed as an alternative to unsustainable, irresponsible forms of growth, Sereni proposed to look at the agricultural landscape, with the evidence of its centuries-old stratifications of knowledge, as an optimal perspective to reflect on the crisis that in 1962 appears to pervade the forms assumed by the post-war economic boom: that widespread devastation of the territory which led, on the one hand, to the hypertrophy of speculative urban rents, on the other to the abandonment of entire internal districts with strongly intertwined results which, within a few years, will show the tragic face of floods, hydrogeological instability, territorial marginalization.
Sereni perspective has for us an analytical value, and an interpretive and propositional value. Indeed, they have been highlighted already in the 60s by Italo Insolera who, in reviewing for Urbanistica his “Storia del Paesaggio Agrario Italiano”, wrote: "In the process of integration of the notions of different disciplines that characterizes the current cultural preparation as a function of territorial planning and economic programming, Sereni's text has an irreplaceable place”. In fact, "the author has collected a series of admirably precise notes on how, throughtout time, the organization of ownership and management generated certain types and methods of cultivation and how these then transformed nature, or the inheritance of the previous generations of farmers, up to what is today the characteristic landscape of the various regions of the Peninsula”; “a compendium of rural history” which “interests us here due to the great importance it has for urban planning”, and which should be “entitled ‘Learning to see agriculture’”.
What joined the two scholars is the use of history as a key to understanding the present: Sereni in terms of Marxist analysis, Insolera as a privileged arena of interdisciplinary research to identify, in the complex of structural transformations, the "invariant" ones of spatial practices that they represent its collective heritage, and as such, the core of planning action
World War I and the People of the Purchase
No full textTitle: World War I and The People of the Purchase
Author: Cari Mikez
Faculty Mentor: Dr. David Pizzo
Department: Murray State History Department
ABSTRACT
The extensive impacts of World War I pervaded society on a global scale during the early twentieth century. The United States officially joined the international conflict in April of 1917 by aligning with the Triple Entente composed of Britain, France and Russia in the fight against the central European powers of Germany, Austro-Hungary, and the Ottoman Empire. In a similar fashion as the other warring nations, the American war effort depended on the development of a national ideology and the mobilization of societal resources to support a newly created armed forces. This research project will explore the significant impacts of the American war effort during World War I on the Jackson Purchase home front in Western Kentucky and will also provide an assessment of rural Western Kentucky societal dynamics through an examination of prewar domestic issues, changes to local economic, political, and social processes, and the responses of western Kentuckians to wartime changes. Research for this project was primarily conducted through local public library and local genealogical repositories, as well as oral histories and other special collection materials housed in Pogue Library at Murray State University. Other areas of interest will include: urban/rural dynamic between Jackson purchase population centers and the surrounding counties, civic organizations, racial issues, prohibition, women’s suffrage, education, health care, and the outbreak of the Spanish flu. This project was inspired by the upcoming Centennial of the World War I Armistice signing on November 11, 2018 and the Bicentennial of the ‘purchase’ of the Jackson Purchase region on October 19, 2018. Many topics and issues covered in the paper are still relevant subjects in the twenty-first century
In Silico Models for Repeated-Dose Toxicity (RDT): Prediction of the No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) for Drugs
No full textReliability, Efficiency and Cost Trade-offs for Medium Voltage Distribution Network Expansion using Refurbished AC-DC Reconfigurable Links
No full textThe role of MVDC links for distribution network expansion is important. The distribution network operators (DNOs) can maximize the power transfer capacity of existing grid infrastructure during (n-1] contingencies using reconfigurable parallel ac-dc architecture. In addition this concept involves a range of efficiency, reliability and economic trade-offs. The object of this paper is to present a discussion on the emerging choices involved in adopting a parallel ac-dc reconfigurable link architecture in designing future and flexible power grids.DC systems, Energy conversion & Storag
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