Update of the BIPM comparison BIPM.RI(II)-K1.Cs-134 of activity measurements of the radionuclide 134Cs to include the 2008 results of the BEV (Austria), the 2009 result of the IRA (Switzerland) and the 2010 results of the NMISA (South Africa)

Purine nucleotide pyrophosphotransferase was purified to apparent homogeneity from a culture filtrate of Streptomyces morookaensis. It is a monomeric protein with a molecular weight of 24 000-25 000, and its isoelectric point is 6.9. The enzyme synthesizes purine nucleoside 5'-phosphate (mono, di, or tri) 3'-diphosphates such as pppApp, ppApp, pApp, pppGpp, ppGpp and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides. The purified enzyme catalysed the formation of 435 mumol of pppApp and 620 mumol of pppGpp from ATP and GTP per min mg protein under the standard conditions. The enzyme requires absolutely a divalent cation for activity, and optimum pH for the enzyme activity lay above 10 for Mg2+, for Co2+ and Zn2+ from 9 to 9.5, and for Fe2+ from 7.5 to 8. The following Michaelis constants were determined: AMP, 2.78 mM; ADP, 3.23 mM; GMP, 0.89 mM; GDP, 0.46 mM and GTP, 1.54 mM, in the case of ATP donor. The enzyme is inhibited by guanine, guanosine, dGDP, dGTP, N-bromosuccinimide, iodacetate, sodium borate and mercuric acetate.

Functional Characterization of a n NTPase Activity of the Hepatitis C Virus Nonstructural Protein 4B

Background: Nonstructural p rotein 4 B (NS4B) i s the m asterorganizer of hepatitis C virus (HCV) replication complexformation. It is a multispanning membrane protein that has beenreported to p ossess NTPase activity. This enzymatic functionhas been poorly studied so far and its role in the HCV life cycleis u nknown. T he present w ork-in-progress a ims at validatingand functionally c haracterizing this a ctivity a nd its r ole in t heviral life cycle.Methods: B ioinformatic analyses were performed to i dentifykey residues for site-directed mutagenesis, both in t he contextof s ubgenomic r eplicons a s well as recombinant v iruses.Mutants were investigated with respect to R NA replication andinfectious particle p roduction. In p arallel, expression andpurification of recombinant wild-type and mutant NS4B proteinsare being pursued to characterize enzymatic activity in vitro.Results: B ioinformatic a nalyses revealed t hat p redictedNTPase features are conserved only in H CV NS4B b ut n ot i nNS4B from other Flaviviridae f amily m embers. A laninesubstitutions were designed to target predicted key Walker A, Band C motifs. These substitutions affected RNA replication andinfectious virus production to v arying degrees. Optimization ofrecombinant protein production is i n progress both in b acterialas well as mammalian expression systems.Conclusions: These studies should yield new insights into thefunctions of this hitherto poorly characterized viral nonstructuralprotein and may reveal novel targets for antiviral intervention inthe future.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study)

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12 questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2–2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26–2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak.

The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. Conclusion: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.

The duration of prograde garnet crystallization in the UHP eclogites at Lago di Cignana, Italy

The distinct core-to-rim zonation of different REEs in garnet in metamorphic rocks, specifically Sm relative to Lu, suggests that Sm-Nd and Lu-Hf isochron ages will record different times along a prograde garnet growth history. Therefore, REE zonations in garnet must be measured in order to correctly interpret the isochron ages in terms of the garnet growth interval, which could span several m.y. New REE profiles, garnet crystal size distributions, and garnet growth modeling, combined with previously published Sm-Nd and Lu-Hf geochronology on a UHP eclogite of the Zermatt-Saas Fee (ZSF) ophiolite, Lago di Cignana (Italy), demonstrate that prograde garnet growth of this sample occurred over a similar to 30 to 40 m.y. interval. Relative to peak metamorphism at 38 to 40 Ma, garnet growth is estimated to have begun at similar to 11 to 14 kbar pressure at similar to 70 to 80 Ma. Although such a protracted garnet growth interval is surprising, this is supported by plate tectonic reconstructions which suggest that subduction of the Liguro-Piemont ocean occurred through slow and oblique convergence. These results demonstrate that REE zonations in garnet, coupled to crystal size distributions, provide a powerful means for understanding prograde metamorphic paths when combined with Sm-Nd and Lu-Hf geochronology. (C) 2009 Elsevier B.V. All rights reserved.

La scena nel testo: Enrico IV di Luigi Pirandello

The starting point is the understanding of the dramatic text as literary text, thus it could be analyzed with methodologies coming from literary studies: the dramatic text is literature, creation of language and it can be read and interpreted as such. Of course I acknowledge the text’s performativity, implicit in its characteristic and functions. The analysis of Enrico IV (1921) constitutes a practical application of the proposal and the opportunity for opening the discussion to new perspectives.

Disegni come documento e disegni come monumento : Giovanni Ciampini, Sebastiano Resta e la fortuna del Medioevo artistico nella Roma di Bellori

La tesi di Dottorato, condotta in accordo di colutela tra l'Università di Roma Tor Vergata e l'UNIL di Losanna, ha affrontato l'analisi di un gruppo di undici disegni custodia presso la National Gallery of Scotland di Edimburgo, copie di alcuni dei più significativi mosaici medioevali delle chiese di Roma, ricostruendone la genesi, quindi le vicende legate alla committenza, e il percorso collezionistico. I disegni scozzesi, oggetto di un importante articolo di Julian Gardner pubblicato sul Burlington Magatine nel 1973, furono commissionati intorno agli anni Settanta del XVII secolo dall'antiquario romano Giovanni Giustino Ciampini (1633-1698) in connessione alla stesura della sua opera di erudizione più avvertita e famosa: i Vetera Mommenta in' quibus praecipue Musiva Opera, sacrarum, profanan,mque, Aedìum structura, ac nonnulli antiqui ritus dissertationibus iconìbusque illustrantur. La composizione dei Vetera Mommenta - un'opera riccamente illustrata che nasce per rispondere alle esigenze della ideologia della Chiesa di Roma in un momento di rinnovata crisi del sistema - impone a Ciampini di porsi da un lato nella prospettiva della più alta tradizione antiquaria cinque e seicentesca, di cui recupera i metodi di lettura e di analisi applicati allo studio delle monete e dei monumenti antichi interpretati quali prove per la ricostruzione storica, e dall'altra, come è emerso dalle mie ricerche, lo pone immediatamente in contatto con gli avamposti del più moderno metodo di indagine storica e filologica applicato alle fonti e ai documenti della storia ecclesiastica, inaugurato dall'ambiente bollandista e inaurino. I monumenti paleocristiani e medioevali assumono in quest'ottica lo status di 'fatti incontestabili', le fonti primarie attraverso le quali Ciampini ricuce le tappe salienti della storia della Chiesa, da Costantino fino al XV secolo. Nel 1700 le copie di Edimburgo arrivano nelle mani del mercante e connoisseur milanese il padre oratoriano Sebastiano Resta (1635-1714), di stanza a Roma presso la Chiesa Nuova della Vallicella dal 1660, che decide di rilegarle tutte insieme in un volume da donare al suo maggiore acquirente e patrono, il vescovo di Arezzo Giovanni Matteo Marchetti. Come spiega Resta in alcune sue lettere, il presente avrebbe dovuto costituire insieme una curiosità ed offrire un confronto: infatti «le copie delli mosaici di Roma che erano di Monsignor Ciampini» - afferma Resta - avrebbero mostrato al Marchetti «le maniere di que' tempi gottici, barbari e divoti de cristiani e [fatto] spiccare i secoli seguenti». Questa indagine infatti ha fatto riemergere aspetti della precoce attenzione di Sebastiano Resta per l'arte dei "secoli bassi", mai debitamente affrontata dagli studi. E' infatti sulla scorta di una profonda conoscenza dei testi della letteratura artistica, e in connessione alla esplosione vivacissima della controversia Malvasia/Baldinucci sul primato del risorgere delle arti in Toscana, che Sebastiano a partire dagli anni Ottanta del Seicento comincia a meditare sul Medioevo artistico con il fine di spiegare l'evoluzione del linguaggio tecnico e formale che ha condotto alla perfezione dell'atte moderna. In questa prospettiva ι disegni del XIV e XV secolo che egli riuscì ad intercettare sul mercato valgono quali testimonianze delle maniere degli artefici più antichi e sono imbastiti nei molteplici album che Resta compone nel rispetto della successione cronologica dei presunti autori, e ordinati in base alle scuole pittoriche di pertinenza. La tesi permette perciò di descrivere nelle loro diverse specificità: da un lato il modo dei conoscitori come Resta, interessati nell'opera al dato stilistico, con immediate e sensibili ricadute sul mercato, e disposti anche con passione a ricercare i documenti relativi all'opera in quanto pressati dall'urgenza di collocarla nella sequenza cronologica dello sviluppo del linguaggio formale e tecnico; dall'altro gli antiquari come Ciampini e come Bianchini, per i quali le opere del passato valgono come prove irrefutabili della ricostruzione storica, e divengono quindi esse stesse, anche nel loro statuto di copia, documento della stona. Sono due approcci che si manifestano nel Seicento, e talvolta in una medesima persona, come mostra il caso anche per questo cruciale di Giovati Pietro Bellori, ma che hanno radici cinquecentesche, di cui i protagonisti di queste vicende sono ben consapevoli: e se dietro Resta c'è palesemente Vasari, dietro Ciampini e soprattutto Bianchini c'è la più alta tradizione antiquaria del XVI secolo, da Antonio Augustin a Fulvio Orsini.

Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.