Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging.

AIMS: The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. METHODS AND RESULTS: We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). CONCLUSION: The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

rKv1.2 overexpression in the central medial thalamic area decreases caffeine-induced arousal.

The voltage-gated potassium channel Kv1.2 belongs to the shaker-related family and has recently been implicated in the control of sleep profile on the basis of clinical and experimental evidence in rodents. To further investigate whether increasing Kv1.2 activity would promote sleep occurrence in rats, we developed an adeno-associated viral vector that induces overexpression of rat Kv1.2 protein. The viral vector was first evaluated in vitro for its ability to overexpress rat Kv1.2 protein and to produce functional currents in infected U2OS cells. Next, the adeno-associated Kv1.2 vector was injected stereotaxically into the central medial thalamic area of rats and overexpression of Kv1.2 was showed by in situ hybridization, ex vivo electrophysiology and immunohistochemistry. Finally, the functional effect of Kv1.2 overexpression on sleep facilitation was investigated using telemetry system under normal conditions and following administration of the arousing agent caffeine, during the light phase. While no differences in sleep profile were observed between the control and the treated animals under normal conditions, a decrease in the pro-arousal effect of caffeine was seen only in the animals injected with the adeno-associated virus-Kv1.2 vector. Overall, our data further support a role of the Kv1.2 channel in the control of sleep profile, particularly under conditions of sleep disturbance.

Per "una ricognizione nel retrobottega" : Meneghello alla luce del suo archivio, tra storia delle carte e indagine filologica

Il lungo e complesso itinerario narrativo di Luigi Meneghello è ben rappresentato dalle migliaia di documenti che compongono il suo Archivio, oggi conservati in varie sedi pubbliche: il Centro Manoscritti dell'Università di Pavia (che ha acquisito la parte più abbondante e notevole delle carte, a partire dal 1983 e grazie soprattutto al lungimirante intervento di Maria Corti) la Biblioteca dell'Università di Reading, il Museo Casabianca di Malo e l''Archivio di Scrittori Vicentini della Biblioteca Civica Bertoliana di Vicenza. Il presente lavoro è il frutto di una ricerca che si è sviluppata in due direzioni strettamente interrelate: la prima parte, di taglio storico-archivistico, riguarda il Fondo Meneghello di Pavia, anche in relazione all'intero Archivio dello scrittore; la seconda parte analizza filologicamente e criticamente il caso specifico della genesi di una delle sue opere maggiori, Pomo pero (Rizzoli, 1974), rivelando e indagando una fitta rete di connessioni nell'intera produzione narrativa. Più nel dettaglio, nel primo capitolo del lavoro (L'ARCHIVIO DI LUIGI MENEGHELLO, pp. 1-92) ho cercato di delineare il quadro complessivo dell'Archivio, segnalando i dati dei diversi Fondi sparsi, per poi concentrare l'attenzione sul Fondo pavese. Di questo Fondo ho tracciato brevemente la storia, fornendo un quadro molto dettagliato delle carte conservate, carte che ho provveduto integralmente a catalogare. La schedatura si trova alle pp. 29-92 ed è divisa in due sezioni: la prima è relativa ai materiali donati dall'autore in vita (a partire dal 1983/4 sino al 2001, per un totale di 36000 documenti); la seconda comprende i conferimenti postumi. Alle pp. 29-33 della tesi ho chiarito preliminarmente i criteri di ordinamento adottati, in gran parte dedotti dalle indicazioni e dalle linee guida del progetto Archivi Letterari Lombardi del Novecento, a cura di Simone Albonico. Il secondo capitolo (UN CASO DI FILOLOGIA D'ARCHIVIO: LA GENESI DI POMO PERO, pp. 93-166) si occupa dell'elaborata vicenda compositiva di Pomo pero, terzo romanzo, e altro scomparto dell'epopea maladense che segue al primo Libera nos a malo, ma anche se ne differenzia per tratti e tonalità non irrilevanti (in Appendice si fornisce trascrizione del testo con indici topografici e cronologici). Ho cercato di seguirne per tappe la formazione alla luce delle numerose testimonianze dell'Archivio, partendo dai primi materiali ancora rintracciabili tra le carte di Libera nos a malo, e individuando progressivamente il filo intricato dell'elaborazione testuale, tra frequenti intrecci con le altre opere e continui ripensamenti e rielaborazioni, dunque in un percorso complessivo che dal 1962 (dunque a monte dell'uscita di Libera nos a malo) va sino al 1974, a ridosso della stampa. Sono emersi anche progetti totalmente sconosciuti di testi inediti, collocabili nel fertile periodo della metà degli anni Sessanta, che conducono alla suggestiva ipotesi di un "cantiere unico" di elaborazione testuale (cfr. cap. III «CONCLUSIONI PROVVISORIE». TRA I PROGETTI DEGLI ANNI SESSANTA; L'ESPEDIENTE DEL FRATELLO; L'IPOTESI DEL CANTIERE UNICO, pp. 167-186).

N-myc controls proliferation, morphogenesis, and patterning of the inner ear

Myc family members play crucial roles in regulating cell proliferation, size, and differentiation during organogenesis. Both N-myc and c-myc are expressed throughout inner ear development. To address their function in the mouse inner ear, we generated mice with conditional deletions in either N-myc or c-myc. Loss of c-myc in the inner ear causes no apparent defects, whereas inactivation of N-myc results in reduced growth caused by a lack of proliferation. Reciprocally, the misexpression of N-myc in the inner ear increases proliferation. Morphogenesis of the inner ear in N-myc mouse mutants is severely disturbed, including loss of the lateral canal, fusion of the cochlea with the sacculus and utriculus, and stunted outgrowth of the cochlea. Mutant cochleas are characterized by an increased number of cells exiting the cell cycle that express the cyclin-dependent kinase inhibitor p27Kip1 and lack cyclin D1, both of which control the postmitotic state of hair cells. Analysis of different molecular markers in N-myc mutant ears reveals the development of a rudimentary organ of Corti containing hair cells and the underlying supporting cells. Differentiated cells, however, fail to form the highly ordered structure characteristic for the organ of Corti but appear as rows or clusters with an excess number of hair cells. The Kölliker's organ, a transient structure neighboring the organ of Corti and a potential source of ectopic hair cells, is absent in the mutant ears. Collectively, our data suggest that N-myc regulates growth, morphogenesis, and pattern formation during the development of the inner ear.

A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss.

Hearing loss can be caused by a variety of insults, including acoustic trauma and exposure to ototoxins, that principally effect the viability of sensory hair cells via the MAP kinase (MAPK) cell death signaling pathway that incorporates c-Jun N-terminal kinase (JNK). We evaluated the otoprotective efficacy of D-JNKI-1, a cell permeable peptide that blocks the MAPK-JNK signal pathway. The experimental studies included organ cultures of neonatal mouse cochlea exposed to an ototoxic drug and cochleae of adult guinea pigs that were exposed to either an ototoxic drug or acoustic trauma. Results obtained from the organ of Corti explants demonstrated that the MAPK-JNK signal pathway is associated with injury and that blocking of this signal pathway prevented apoptosis in areas of aminoglycoside damage. Treatment of the neomycin-exposed organ of Corti explants with D-JNKI-1 completely prevented hair cell death initiated by this ototoxin. Results from in vivo studies showed that direct application of D-JNKI-1 into the scala tympani of the guinea pig cochlea prevented nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. Local delivery of D-JNKI-1 also prevented acoustic trauma-induced permanent hearing loss in a dose-dependent manner. These results indicate that the MAPK-JNK signal pathway is involved in both ototoxicity and acoustic trauma-induced hair cell loss and permanent hearing loss. Blocking this signal pathway with D-JNKI-1 is of potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.

Intracellular trafficking of interleukin-1 receptor I requires Tollip.

Interleukin-1 receptor (IL-1RI) is a master regulator of inflammation and innate immunity. When triggered by IL-1beta, IL-1RI aggregates with IL-1R-associated protein (IL-1RAcP) and forms a membrane proximal signalosome that potently activates downstream signaling cascades. IL-1beta also rapidly triggers endocytosis of IL-1RI. Although internalization of IL-1RI significantly impacts signaling, very little is known about trafficking of IL-1RI and therefore about precisely how endocytosis modulates the overall cellular response to IL-1beta. Upon internalization, activated receptors are often sorted through endosomes and delivered to lysosomes for degradation. This is a highly regulated process that requires ubiquitination of cargo proteins as well as protein-sorting complexes that specifically recognize ubiquitinated cargo. Here, we show that IL-1beta induces ubiquitination of IL-1RI and that via these attached ubiquitin groups, IL-1RI interacts with the ubiquitin-binding protein Tollip. By using an assay to follow trafficking of IL-1RI from the cell surface to late endosomes and lysosomes, we demonstrate that Tollip is required for sorting of IL-1RI at late endosomes. In Tollip-deficient cells and cells expressing only mutated Tollip (incapable of binding IL-1RI and ubiquitin), IL-1RI accumulates on late endosomes and is not efficiently degraded. Furthermore, we show that IL-1RI interacts with Tom1, an ubiquitin-, clathrin-, and Tollip-binding protein, and that Tom1 knockdown also results in the accumulation of IL-1RI at late endosomes. Our findings suggest that Tollip functions as an endosomal adaptor linking IL-1RI, via Tom1, to the endosomal degradation machinery.

Diseño de la instalación de calefacción y ACS, mediante energía solar térmica, en un polideportivo de Fraga

Estudio y diseño de la colocación de un sistema de enregía solar térmica en un polideportivo de Fraga para abastecer al edificio de la energía suficiente para calefacción y agua caliente sanitaria, además de un estudio de viabilidad de la nueva instalación.

Courts and Courtly Cultures in Early Modern Italy and Europe: Models and Languages

This volume deals with the forms of propaganda and self-representation, through words and images, during the rise of the 'civiltà delle corti' and through processes typical of the time, such as confrontation, adaptation, competition and rivalry. This period, which marked the passage of Italian and European culture from the Middle Ages to the Renaissance, is fundamental in the development of Modern Europe, and it lasted up to the XVIII century and beyond. At the heart of many matters debated here lies the relationship between culture and politics. The formation of a 'Lombard identity', central to the Sinergia project which was the frame of the whole research and its conferences, is closely linked to this broad general context. It places the so called 'questione milanese' - above the traditional hierarchies 'Toscana oriented' - at the centre of many questions regarding Northern Italy as a whole, starting from the dissolution of the Medieval communes, through to the rise of the signorie, from the end of the XIII century and the beginning of the XIV century up to the early XVI century.

ReShare and ReCollect: EPrints data repository solutions developed at the UK Data Archive

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Maximilien et Charlotte du Mexique : 1865-1867

UANL

Análisis de iniciativas de memoria colectiva de víctimas del conflicto armado en Colombia a través de expresiones artísticas musicales en Bogotá. Periodo 1991−2010

Dentro del conflicto armado en Colombia, algunas expresiones artísticas musicales se han convertido en mecanismos alternativos de construcción de memoria colectiva, al rescatar y hacer público memorias de individuos y hechos violentos que los relatos oficiales de poder pretenden olvidar.