Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation

We recently established that fibroblast growth factor (FGF)-1 promotes adipogenesis of primary human preadipocytes (phPA). In the current report, we have characterized the adipogenic effects of FGF-1 in phPA and also in a human PA strain derived from an individual with Simpson-Golabi-Behmel syndrome (SGBS PA), which exhibit an intrinsic capacity to differentiate with high efficiency. In further studies, we compared these models with the well-characterized murine 3T3-L1 preadipocyte cell line (3T3-L1 PA). FGF-1 up-regulated the adipogenic program in phPA, with increased expression of peroxisome proliferator-activated receptor-gamma in confluent PA prior to induction of differentiation and increased expression of adipocyte markers during differentiation. Moreover, phPA differentiated in the presence of FGF-1 were more insulin responsive and secreted increased levels of adiponectin. FGF-1 treatment of SGBS PA further enhanced differentiation. For the most part, the adipogenic program in phPA paralleled that observed in 3T3-L1 PA; however, we found no evidence of mitotic clonal expansion in the phPA. Finally, we investigated a role for extracellular regulated kinase 1/2 (ERK 1/2) in adipogenesis of phPA. FGF-1 induced robust phosphorylation of ERK1/2 in early differentiation and inhibition of ERK1/2 activity significantly reduced phPA differentiation. These data suggest that FGF-1 treated phPA represent a valuable in vitro model for the study of adipogenesis and insulin action and indicate that ERK1/2 activation is necessary for human adipogenesis in the absence of mitotic clonal expansion.

Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture

1 Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) have structural similarities, interact with each others receptors (calcitonin receptor-like receptor (CLR)/receptor-activity-modifying proteins (RAMPs)) and show overlapping biological activities. AM and CGRP receptors are chiefly coupled to cAMP production. In this study, a method of primary dissociated cell culture was used to investigate the presence of AM and CGRP receptors and their effects on cAMP production in embryonic spinal cord cells. 2 Both neuronal and non-neuronal CLR immunopositive cells were present in our model. 3 High affinity, specific [ 125I]-AM binding sites (K(d) 79±9 pM and B(max) 571±34 fmol mg -1 protein) were more abundant than specific [ 125I]-CGRP binding sites (K(d) 12±0.7 pM and B(max) 32±2 fmol mg -1 protein) in embryonic spinal cord cells. 4 Specific [ 125I]-AM binding was competed by related molecules with a ligand selectivity profile of rAM>hAM(22-52)>rCGRPα>CGRP(8-37) ≫[r-(r*,s*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide (BIBN4096BS). 5 Specific [ 125I]-CGRP binding was competed by rCGRPα>rAM≥ CGRP(8-37)≥BIBN4096BS>hAM(22-52). 6 Cellular levels of cAMP were increased by AM (pEC"5"0 10.2±0.2) and less potently by rCGRPα (pEC"5"0 8.9±0.4). rCGRPα-induced cAMP accumulation was effectively inhibited by CGRP(8-37) (pA"2 7.63±0.44) and hAM(22-52) (pA"2 6.18±0.21) while AM-stimulation of cAMP levels was inhibited by CGRP(8-37) (pA"2 7.41±0.15) and AM(22-52) (pA"2 7.26±0.18). BIBN4096BS only antagonized the effects of CGRP (pA"2 8.40±0.30) on cAMP accumulation. 7 These pharmacological profiles suggest that effects of CGRP are mediated by the CGRP"1 (CLR/RAMP1) receptor in our model while those of AM are related to the activation of the AM"1 (CLR/RAMP2) receptor subtype. © 2006 Nature Publishing Group All rights reserved.

Characterization of tumour necrosis factor alpha release by human granulocytes in response to procainamide challenge

The role of human granulocytes in the promotion of procainamide (PA) toxicity in vitro has been studied and one of the agents responsible for DNA strand scission and cell death in human target cells has been characterized. Crude peripheral blood mononuclear cells (cPBMNs) isolated by density centrifugation, and the lymphocyte cell lines--CCRF-HSB2 and WIL-2NS--were exposed to PA, and DNA strand breaks were quantified by fluorescent analysis of DNA unwinding. Therapeutic plasma concentrations of PA (0-50 microM) caused dose-dependent cytotoxicity, determined by dye exclusion, and strand breaks in cPBMNs incubated for 3 and 1.5 hr at 37 degrees, respectively. Using 50 microM PA a five-fold increase in DNA strand breaks was observed after 1.5 hr, with significant induction of strand breaks also being observed for 10 and 25 microM concentrations. Toxicity was much reduced in lymphocyte cell lines (maximal killing = 3.0% at 50 microM PA compared with 13.2% in cPBMNs). A similar decrease in toxicity was observed where N-acetyl procainamide (NAPA) was substituted for PA (less than 50% of strand breaks at all concentrations). Further investigations showed that the presence of a contaminating granulocyte population in the cPBMN fraction was responsible for the induction of PA toxicity. Incubation of a highly enriched granulocyte population with PA for 1 hr prior to exposure to purified peripheral blood mononuclear cells (pPBMNs) led to the complete restoration of the toxic effects. The resulting cyto- and genotoxicity were not significantly different to levels observed in cPBMNs. Significantly, incubation of granulocytes with NAPA did not induce toxicity in target pPBMNs. Ultrafiltration of granulocyte supernatants led to the identification of two toxic fractions of < 3000 and > 30,000 Da. Temporal studies showed that the toxicity associated with the < 3000 Da fraction appeared during the first 10-15 min incubation with PA whereas the > 30,000 Da fraction did not display significant toxicity until the 40-60 min period. Further assessment of the nature of these agents indicated that the 30,000 Da fraction was a protein. SDS-PAGE analysis showed an inducible 17,800 Da species appearing in granulocyte supernatants after 40 min incubation with PA. Dot blot analysis indicated that tumour necrosis factor alpha (TNF alpha) was present in the > 30,000 Da fraction. Evidence that TNF alpha was the high-molecular weight species responsible for PA-induced toxicity was obtained from neutralization assays employing an anti-TNF alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Processing of Medieval Slavic Sources in the Institute of Literature at BAS Repertorium Project (1994–2004)

Mixed-content miscellanies (very frequent in the Byzantine and mediaeval Slavic written heritage) are usually defined as collections of works with non-occupational, non-liturgical application, and texts in them are selected and arranged according to no identifiable principle. It is a “readable” type of miscellanies which were compiled mainly on the basis of the cognitive interests of compilers and readers. Just like the occupational ones, they also appeared to satisfy public needs but were intended for individual usage. My textological comparison had shown that mixed- content miscellanies often showed evidence of a stable content – some of them include the same constituent works in the same order, regardless that the manuscripts had no obvious genetic relationship. These correspondences were sufficiently numerous and distinctive that they could not be merely fortuitous, and the only sensible interpretation was that even when the operative organizational principle was not based on independently identifiable criteria, such as the church calendar, liturgical function, or thematic considerations, mixed-content miscellanies (or, at least, portions of their contents) nonetheless fell into types. In this respect, the apparent free selection and arrangement of texts in mixed-content miscellanies turns out to be illusory. The problem was – as the corpus of manuscripts that I and my colleagues needed to examine grew – our ability to keep track of the structure of each one, and to identify structural correspondences among manuscripts within the corpus, diminished. So, at the end of 1993 I addressed a letter to Prof. David Birnbaum (University of Pittsburgh, PA) with a request to help me to solve the problem. He and my colleague Andrey Boyadzhiev (Sofia University) pointed out to me that computers are well suited to recording, processing, and analyzing large amounts of data, and to identifying patterns within the data, and their proposal was that we try to develop a computer system for description of manuscripts, for their analysis and of course, for searching the data. Our collaboration in this project is now ten years old, and our talk today presents an overview of that collaboration.

Neglected Masterpieces of Cinema

This article will acquaint you with ten of the more important leftwing films I have reviewed over the past sixteen years as a member of New York Film Critics Online. You will not see listed familiar works such as “The Battle of Algiers” but instead those that deserve wider attention, the proverbial neglected masterpieces. They originate from different countries and are available through Internet streaming, either freely from Youtube or through Netflix or Amazon rental. In several instances you will be referred to film club websites that like the films under discussion deserve wider attention since they are the counterparts to the small, independent theaters where such films get premiered. The country of origin, date and director will be identified next to the title, followed by a summary of the film, and finally by its availability.

Preliminary results of the roman camp of La Cabeza del Cid (Hinojosa, Guadalajara, Spain)

The recent archaeological works in Hinojosa, allowed us to discover a camp from Roman republic period. It is located in the center of the Celtiberian area and its study could open interesting perspectives to study this historical period. This paper shows the results of its preliminary studies.

What is the Point of Copyright History?:Reflections on Copyright at Common law in 1774 by H. Tomás Gómez-Arostegui

Copyright history has long been a subject of intense and contested enquiry. Historical narratives about the early development of copyright were first prominently mobilised in eighteenth century British legal discourse, during the so-called Battle of the Booksellers between Scottish and London publishers. The two landmark copyright decisions of that time – Millar v. Taylor (1769) and Donaldson v. Becket (1774) – continue to provoke debate today. The orthodox reading of Millar and Donaldson presents copyright as a natural proprietary right at common law inherent in authors. Revisionist accounts dispute that traditional analysis. These conflicting perspectives have, once again, become the subject of critical scrutiny with the publication of Copyright at Common Law in 1774 by Prof Tomas Gomez-Arostegui in 2014, in the Connecticut Law Review ((2014) 47 Conn. L. Rev. 1) and as a CREATe Working Paper (No. 2014/16, 3 November 2014).

Taking Prof Gomez-Arostegui’s extraordinary work in this area as a point of departure, Dr Elena Cooper and Professor Ronan Deazley (then both academics at CREATe) organised an event, held at the University of Glasgow on 26th and 27th March 2015, to consider the interplay between copyright history and contemporary copyright policy. Is Donaldson still relevant, and, if so, why? What justificatory goals are served by historical investigation, and what might be learned from the history of the history of copyright? Does the study of copyright history still have any currency within an evidence-based policy context that is increasingly preoccupied with economic impact analysis?

This paper provides a lasting record of these discussions, including an editorial introduction, written comments by each of the panelists and Prof. Gomez-Arostegui and an edited transcript of the Symposium debate.

Vem ouvir o verso de teu cantador : amos, cantadores e toadas no Boi-Bumbá Caprichoso Belém/PA

This thesis aims to investigating the cantadores and the toadas in the Boi Bumbá, debating questions which put together around the construction and performance of amo s and cantador s role in the Boi Bumbá Caprichoso of Belém-PA city and exploring the extent of toadas its characteristics, functions, the uses that are made of theirs and the relations that establishes between them and the cantadores. The problematic of the research consisted on analysing what the amos, cantadores and toadas represent in the whole context of boi-bumbá plays in Belém, nowadays. Considering this perspective, I tried to identify on Boi Caprichoso the most meaningful expressions which were related to toadas and how the roles of amo and cantador were performed. Participative observation, ethnical research, open and semistructured interviews were used as research methods. The role performances on Boi Caprichoso plays an essential part on the playing realization, highlighting themselves as pivotal characters. These performances, characterized by the vocal presence, also highlighted the size that toadas occupy in the whole play, and pointed the way for an emerging model of presentation, in which both toada and cantador appear as central figures

The prose works of Jonathan Swift /

First published in 1897.

Cassius Dio's speeches and the collapse of the Roman Republic

This thesis argues that Cassius Dio used his speeches of his Late Republican and Augustan narratives as a means of historical explanation. I suggest that the interpretative framework which the historian applied to the causes and success of constitutional change can be most clearly identified in the speeches. The discussion is divided into eight chapters over two sections. Chapter 1 (Introduction) sets out the historical, paideutic, and compositional issues which have traditionally served as a basis for rejecting the explanatory and interpretative value of the speeches in Dio’s work and for criticising his Roman History more generally. Section 1 consists of three methodological chapters which respond to these issues. In Chapter 2 (Speeches and Sources) I argue that Dio’s prosopopoeiai approximate more closely with the political oratory of that period than has traditionally been recognised. Chapter 3 (Dio and the Sophistic) argues that Cassius Dio viewed the artifice of rhetoric as a particular danger in his own time. I demonstrate that this preoccupation informed, credibly, his presentation of political oratory in the Late Republic and of its destructive consequences. Chapter 4 (Dio and the Progymnasmata) argues that although the texts of the progymnasmata in which Dio will have been educated clearly encouraged invention with a strongly moralising focus, it is precisely his reliance on these aspects of rhetorical education which would have rendered his interpretations persuasive to a contemporary audience. Section 2 is formed of three case-studies. In Chapter 5 (The Defence of the Republic) I explore how Dio placed speeches-in-character at three Republican constitutional crises to set out an imagined case for the preservation of that system. This case, I argue, is deliberately unconvincing: the historian uses these to elaborate the problems of the distribution of power and the noxious influence of φθόνος and φιλοτιμία. Chapter 6 (The Enemies of the Republic) examines the explanatory role of Dio’s speeches from the opposite perspective. It investigates Dio’s placement of dishonest speech into the mouths of military figures to make his own distinctive argument about the role of imperialism in the fragmentation of the res publica. Chapter 7 (Speech after the Settlement) argues that Cassius Dio used his three speeches of the Augustan age to demonstrate how a distinctive combination of Augustan virtues directly counteracted the negative aspects of Republican political and rhetorical culture which the previous two case-studies had explored. Indeed, in Dio’s account of Augustus the failures of the res publica are reinvented as positive forces which work in concert with Augustan ἀρετή to secure beneficial constitutional change.

Politics and protestant Lordship in North East Scotland during the reign of James VI: The life of George Keith, fourth Earl Marischal, 1554-1623

George Keith, fourth Earl Marischal is a case study of long-term, quietly successful and stable lordship through the reign of James VI. Marischal’s life provides a wholly underrepresented perspective on this era, where the study of rebellious and notorious characters has dominated. He is also a counter-example to the notion of a general crisis among the European nobility, at least in the Scottish context, as well as to the notion of a ‘conservative’ or ‘Catholic’ north east. In 1580 George inherited the richest earldom in Scotland, with a geographical extent stretching along the east coast from Caithness to East Lothian. His family came to be this wealthy as a long term consequence of the Battle of Flodden (1513) where a branch of the family, the Inverugie Keiths had been killed. The heiress of this branch was married to the third earl and this had concentrated a large number of lands, and consequently wealth, in the hands of the earls. This had, however, also significantly decreased the number of members and hence power of the Keith kindred. The third earl’s conversion to Protestantism in 1544 and later his adherence to the King’s Party during the Marian Civil War forced the Keiths into direct confrontation with their neighbours in the north east, the Gordons (led by the Earls of Huntly), a Catholic family and supporters of the Queen’s Party. Although this feud was settled for a time at the end of the war, the political turmoil caused by a succession of short-lived factional regimes in the early part of the personal reign of James VI (c.1578-1585) led the new (fourth) Earl Marischal into direct confrontation with the new (sixth) Earl of Huntly. Marischal was outclassed, outmanoeuvred and outgunned at both court and in the locality in this feud, suffering considerably. However, Huntly’s over-ambition in wider court politics meant that Marischal was able to join various coalitions against his rival, until Huntly was exiled in 1595. Marischal also came into conflict briefly with Chancellor John Maitland of Thirlestane as a consequence of Marischal’s diplomatic mission to Denmark in 1589-1590, but was again outmatched politically and briefly imprisoned. Both of these feuds reveal Marischal to be relatively cautious and reactionary, and both reveal the limitations of his power. Elsewhere, the study of Marischal’s activities in the centre of Scottish politics reveal him to be unambitious. He was ready to serve King James, the two men having a healthy working relationship, but Marischal showed no ambition as a courtier, to woo the king’s favour or patronage, instead delegating interaction with the monarch to his kinsmen. Likewise, in government, Marischal rarely attended any of the committees he was entitled to attend, such as the Privy Council, although he did keep a keen eye on the land market and the business conducted under the Great Seal. Although personally devout and a committed Protestant, the study of Marischal’s interaction with the national Kirk and the parishes of which he was patron reveal that he was at times a negligent patron and exercised his right of ministerial presentation as lordly, not godly patronage. The notion of a ‘conservative North East’ is, however, rejected. Where Marischal was politically weak at court and weak in terms of force in the locality, we see him pursuing sideways approaches to dealing with this. Thus he was keen to build up his general influence in the north and in particular with the burgh of Aberdeen (one result of this being the creation of Marischal College in 1593), pursued disputes through increasing use of legal methods rather than bloodfeud (thus exploiting his wealth and compensating for his relative lack of force) and developed a sophisticated system of maritime infrastructure, ultimately expressed through the creating of the burghs of Peterhead and Stonehaven. Although his close family caused him a number of problems over his lifetime, he was able to pass on a stable and enlarged lordship to his son in 1623.

Plan of the siege of Plattsburg and capture of the British fleet on Lake Champlain the 11th Sptr. 1814 : to accompany B. Tanner's print of Macdonough's victory.

Relief shown by hachures.

Map of Elizabeth Town, N.J. at the time of the Revolutionary War, 1775-1783. Showing that part of the free borough and town of Elizabeth, which is now the site of the city of Elizabeth.

Scale ca. 1:7,300.

Vem ouvir o verso de teu cantador : amos, cantadores e toadas no Boi-Bumbá Caprichoso Belém/PA

This thesis aims to investigating the cantadores and the toadas in the Boi Bumbá, debating questions which put together around the construction and performance of amo s and cantador s role in the Boi Bumbá Caprichoso of Belém-PA city and exploring the extent of toadas its characteristics, functions, the uses that are made of theirs and the relations that establishes between them and the cantadores. The problematic of the research consisted on analysing what the amos, cantadores and toadas represent in the whole context of boi-bumbá plays in Belém, nowadays. Considering this perspective, I tried to identify on Boi Caprichoso the most meaningful expressions which were related to toadas and how the roles of amo and cantador were performed. Participative observation, ethnical research, open and semistructured interviews were used as research methods. The role performances on Boi Caprichoso plays an essential part on the playing realization, highlighting themselves as pivotal characters. These performances, characterized by the vocal presence, also highlighted the size that toadas occupy in the whole play, and pointed the way for an emerging model of presentation, in which both toada and cantador appear as central figures

Removal of paracetamol on biomass-derived activated carbon: Modeling the fixed bed breakthrough curves using batch adsorption experiments

The remediation of paracetamol (PA), an emerging contaminant frequently found in wastewater treatment plants, has been studied in the low concentration range (0.3–10 mg L−1) using as adsorbent a biomass-derived activated carbon. PA uptake of up to 100 mg g−1 over the activated carbon has been obtained, with the adsorption isotherms being fairly explained by the Langmuir model. The application of Reichemberg and the Vermeulen equations to the batch kinetics experiments allowed estimating homogeneous and heterogeneous diffusion coefficients, reflecting the dependence of diffusion with the surface coverage of PA. A series of rapid small-scale column tests were carried out to determine the breakthrough curves under different operational conditions (temperature, PA concentration, flow rate, bed length). The suitability of the proposed adsorbent for the remediation of PA in fixed-bed adsorption was proven by the high PA adsorption capacity along with the fast adsorption and the reduced height of the mass transfer zone of the columns. We have demonstrated that, thanks to the use of the heterogeneous diffusion coefficient, the proposed mathematical approach for the numerical solution to the mass balance of the column provides a reliable description of the breakthrough profiles and the design parameters, being much more accurate than models based in the classical linear driving force.