Lupe e paisagem

Trata-se de um relato pessoal em que o autor rememora sua convivência com Lupe Cotrim, de quem foi aluno na então recém-fundada Escola de Comunicações, no conturbado período da ditadura militar.

A professora-poeta

A evocação da experiência da poeta Lupe Cotrim como professora de Estética nos três primeiros anos da ECA-USP ressalta a sua liderança na criação de um diálogo entre alunos e professores de diferentes setores da Escola; a memória desta experiência luminosa, vivida pelo autor como aluno, dá ensejo a observações sobre o isolamento atual dos vários segmentos das artes e da comunicação na pesquisa e na formação dos alunos, tema que requer uma reflexão mais efetiva.

Apectos conceituais e metodológicos de redes sociais e sua influência no estudo de fluxos de informação

As ligações e interações propiciadas pelas redes sociais permitem compreender como ocorrem os fluxos de informação entre indivíduos e instituições que unem esforços na busca de metas comuns. O artigo apresenta aspectos conceituais sobre redes e redes sociais ressaltando que a estrutura e as relações de interação e intermediação entre os elos da rede impulsionam mudanças nos fluxos de informação. Descreve a metodologia de Análise de Redes Sociais (ARS) sinalizando como esta pode ser utilizada na área da Ciência da Informação para compreender os fluxos de informação que se configuram e re-configuram nas redes sociais a partir da estrutura de relacionamento

Redox Control of 20S Proteasome Gating

The proteasome is the primary contributor in intracellular proteolysis. Oxidized or unstructured proteins can be degraded via a ubiquitin-and ATP-independent process by the free 20S proteasome (20SPT). The mechanism by which these proteins enter the catalytic chamber is not understood thus far, although the 20SPT gating conformation is considered to be an important barrier to allowing proteins free entrance. We have previously shown that S-glutathiolation of the 20SPT is a post-translational modification affecting the proteasomal activities. Aims: The goal of this work was to investigate the mechanism that regulates 20SPT activity, which includes the identification of the Cys residues prone to S-glutathiolation. Results: Modulation of 20SPT activity by proteasome gating is at least partially due to the S-glutathiolation of specific Cys residues. The gate was open when the 20SPT was S-glutathiolated, whereas following treatment with high concentrations of dithiothreitol, the gate was closed. S-glutathiolated 20SPT was more effective at degrading both oxidized and partially unfolded proteins than its reduced form. Only 2 out of 28 Cys were observed to be S-glutathiolated in the proteasomal alpha 5 subunit of yeast cells grown to the stationary phase in glucose-containing medium. Innovation: We demonstrate a redox post-translational regulatory mechanism controlling 20SPT activity. Conclusion: S-glutathiolation is a post-translational modification that triggers gate opening and thereby activates the proteolytic activities of free 20SPT. This process appears to be an important regulatory mechanism to intensify the removal of oxidized or unstructured proteins in stressful situations by a process independent of ubiquitination and ATP consumption. Antioxid. Redox Signal. 16, 1183-1194.

Xylella fastidiosa comparative genomic database is an information resource to explore the annotation, genomic features, and biology of different strains

The Xylella fastidiosa comparative genomic database is a scientific resource with the aim to provide a user-friendly interface for accessing high-quality manually curated genomic annotation and comparative sequence analysis, as well as for identifying and mapping prophage-like elements, a marked feature of Xylella genomes. Here we describe a database and tools for exploring the biology of this important plant pathogen. The hallmarks of this database are the high quality genomic annotation, the functional and comparative genomic analysis and the identification and mapping of prophage-like elements. It is available from web site http://www.xylella.lncc.br.

RNA extraction from ten year old formalin-fixed paraffin-embedded breast cancer samples: a comparison of column purification and magnetic bead-based technologies

Abstract Background The development of protocols for RNA extraction from paraffin-embedded samples facilitates gene expression studies on archival samples with known clinical outcome. Older samples are particularly valuable because they are associated with longer clinical follow up. RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue is problematic due to chemical modifications and continued degradation over time. We compared quantity and quality of RNA extracted by four different protocols from 14 ten year old and 14 recently archived (three to ten months old) FFPE breast cancer tissues. Using three spin column purification-based protocols and one magnetic bead-based protocol, total RNA was extracted in triplicate, generating 336 RNA extraction experiments. RNA fragment size was assayed by reverse transcription-polymerase chain reaction (RT-PCR) for the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD), testing primer sets designed to target RNA fragment sizes of 67 bp, 151 bp, and 242 bp. Results Biologically useful RNA (minimum RNA integrity number, RIN, 1.4) was extracted in at least one of three attempts of each protocol in 86–100% of older and 100% of recently archived ("months old") samples. Short RNA fragments up to 151 bp were assayable by RT-PCR for G6PD in all ten year old and months old tissues tested, but none of the ten year old and only 43% of months old samples showed amplification if the targeted fragment was 242 bp. Conclusion All protocols extracted RNA from ten year old FFPE samples with a minimum RIN of 1.4. Gene expression of G6PD could be measured in all samples, old and recent, using RT-PCR primers designed for RNA fragments up to 151 bp. RNA quality from ten year old FFPE samples was similar to that extracted from months old samples, but quantity and success rate were generally higher for the months old group. We preferred the magnetic bead-based protocol because of its speed and higher quantity of extracted RNA, although it produced similar quality RNA to other protocols. If a chosen protocol fails to extract biologically useful RNA from a given sample in a first attempt, another attempt and then another protocol should be tried before excluding the case from molecular analysis.

Concentração plasmática de cortisol decorrente do exercício físico em cavalos de enduro

O objetivo deste trabalho foi relacionar a intensidade do exercício físico e as concentrações de cortisol plasmático em cavalos de enduro, uma competição em que somente animais experientes podem competir nas provas mais longas. Foram utilizados 30 equinos Puro Sangue Árabe e mestiços Árabe, machos ou fêmeas participantes de provas de enduro. Foram divididos em três grupos de 10 animais: (G1): percorreram mais de 100km, (G2): percorreram menos de 100km, e (G3): desqualificados por causa metabólica. Foram realizadas dosagens de cortisol plasmático em três momentos diferentes: (t0): dia anterior à competição, (t1): 30 a 60 minutos após o término da prova e, (t2): 90 a 120 minutos após o término da prova. Concluiu-se que o enduro leva ao aumento do cortisol plasmático; animais que percorrem maiores distâncias apresentam menor aumento das concentrações de cortisol; animais desqualificados por causa metabólica, que passam por situações de extremo esforço físico, tendem a valores de cortisol mais elevados e animais menos experientes apresentam valores de cortisol mais elevados mesmo tendo percorrido menores distâncias.

In loving memory: Escritura última y memoria en los cementerios ingleses de Canarias

[ES] El estudio de las inscripciones que se conservan en los tres cementerios ingleses de Canarias, así como de los propios monumentos funerarios en los que estas se inscriben, permite un acercamiento al ars moriendi, pero también a los mecanismos de autorrepresentación de los miembros de la comunidad británica radicada en Canarias cuyos restos reposan en estas necrópolis. El presente estudio pretende analizar estas escrituras últimas en el contexto de una historia social de la cultura escrita en Canarias que cuenta, como elemento de diferenciación con respecto a otras regiones españolas, con una importante presencia británica, evidenciada en la mayor concentración de cementerios protestantes de todo el país.

Aldo Rossi, autobiografia scientifica: scrittura come progetto. Indagine critica tra scrittura e progetto di architettura

«In altri termini mi sfuggiva e ancora oggi mi sfugge gran parte del significato dell’evoluzione del tempo; come se il tempo fosse una materia che osservo dall’esterno. Questa mancanza di evoluzione è fonte di alcune mie sventure ma anche mi appartiene con gioia.» Aldo Rossi, Autobiografia scientifica. The temporal dimension underpinning the draft of Autobiografia scientifica by Aldo Rossi may be referred to what Lucien Lévy-Bruhl, the well-known French anthropologist, defines as “primitive mentality” and “prelogical” conscience : the book of life has lost its page numbers, even punctuation. For Lévy-Bruhl, but certainly for Rossi, life or its summing up becomes a continuous account of ellipses, gaps, repetitions that may be read from left to right or viceversa, from head to foot or viceversa without distinction. Rossi’s autobiographical writing seems to accept and support the confusion with which memories have been collected, recording them after the order memory gives them in the mental distillation or simply according to the chronological order in which they have happened. For Rossi, the confusion reflects the melting of memory elements into a composite image which is the result of a fusion. He is aware that the same sap pervades all memories he is going to put in order: each of them has got a common denominator. Differences have diminished, almost faded; the quick glance is prevalent over the distinction of each episode. Rossi’s writing is beyond the categories dependent on time: past and present, before and now. For Rossi, the only repetition – the repetition the text will make possible for an indefinite number of times – gives peculiarity to the event. As Gilles Deleuze knows, “things” may only last as “singleness”: more frequent the repetition is, more singular is the memory phenomenon that recurs, because only what is singular magnifies itself and happens endlessly forever. Rossi understands that “to raise the first time to nth forever”, repetition becomes glorification . It may be an autobiography that, celebrating the originality, enhances the memory event in the repetition; in fact it greatly differs from the biographical reproduction, in which each repetition is but a weaker echo, a duller copy, provided with a smaller an smaller power in comparison with the original. Paradoxically, for Deleuze the repetition asserts the originality and singularity of what is repeated. Rossi seems to share the thought expressed by Kierkegaard in the essay Repetition: «The hope is a graceful maiden slipping through your fingers; the memory of an elderly woman, indeed pretty, but never satisfactory if necessary; the repetition is a loved friend you are never tired of, as it is only the new to make you bored. The old never bores you and its presence makes you happy [...] life is but a repetition [...] here is the beauty of life» . Rossi knows well that repetition hints at the lasting stability of cosmic time. Kierkegaard goes on: «The world exists, and it exists as a repetition» . Rossi devotes himself, on purpose and in all conscience, to collect, to inventory and «to review life», his own life, according to a recovery not from the past but of the past: a search work, the «recherche du temps perdu», as Proust entitled his masterpiece on memory. If you want the past time to be not wasted, you must give it presence. «Memoria e specifico come caratteristiche per riconoscere se stesso e ciò che è estraneo mi sembravano le più chiare condizioni e spiegazioni della realtà. Non esiste uno specifico senza memoria, e una memoria che non provenga da un momento specifico; e solo questa unione permette la conoscenza della propria individualità e del contrario (self e non-self)» . Rossi wants to understand himself, his own character; it is really his own character that requires to be understood, to increase its own introspective ability and intelligence. «Può sembrare strano che Planck e Dante associno la loro ricerca scientifica e autobiografica con la morte; una morte che è in qualche modo continuazione di energia. In realtà, in ogni artista o tecnico, il principio della continuazione dell’energia si mescola con la ricerca della felicità e della morte» . The eschatological incipit of Rossi’s autobiography refers to Freud’s thought in the exact circularity of Dante’s framework and in as much exact circularity of the statement of the principle of the conservation of energy: in fact it was Freud to connect repetition to death. For Freud, the desire of repetition is an instinct rooted in biology. The primary aim of such an instinct would be to restore a previous condition, so that the repeated history represents a part of the past (even if concealed) and, relieving the removal, reduces anguish and tension. So, Freud ask himself, what is the most remote state to which the instinct, through the repetition, wants to go back? It is a pre-vital condition, inorganic of the pure entropy, a not-to-be condition in which doesn’t exist any tension; in other words, Death. Rossi, with the theme of death, introduces the theme of circularity which further on refers to the sense of continuity in transformation or, in the opposite way, the transformation in continuity. «[...] la descrizione e il rilievo delle forme antiche permettevano una continuità altrimenti irripetibile, permettevano anche una trasformazione, una volta che la vita fosse fermata in forme precise» . Rossi’s attitude seems to hint at the reflection on time and – in a broad sense – at the thought on life and things expressed by T.S. Eliot in Four Quartets: «Time present and time past / Are both perhaps present in time future, / And time future is contained in time past. / I all time is eternally present / All time is unredeemable. / What might have been is an abstraction / Remaining perpetual possibility / Only in a word of speculation. / What might have been and what has been / Point to one end, which is always present. [...]» . Aldo Rossi’s autobiographical story coincides with the description of “things” and the description of himself through the things in the exact parallel with craft or art. He seems to get all things made by man to coincide with the personal or artistic story, with the consequent immediate necessity of formulating a new interpretation: the flow of things has never met a total stop; all that exists nowadays is but a repetition or a variant of something existing some time ago and so on, without any interruption until the early dawnings of human life. Nevertheless, Rossi must operate specific subdivisions inside the continuous connection in time – of his time – even if limited by a present beginning and end of his own existence. This artist, as an “historian” of himself and his own life – as an auto-biographer – enjoys the privilege to be able to decide if and how to operate the cutting in a certain point rather than in another one, without being compelled to justify his choice. In this sense, his story is a matter very ductile and flexible: a good story-teller can choose any moment to start a certain sequence of events. Yet, Rossi is aware that, beyond the mere narration, there is the problem to identify in history - his own personal story – those flakings where a clean cut enables the separation of events of different nature. In order to do it, he has to make not only an inventory of his own “things”, but also to appeal to authority of the Divina Commedia started by Dante when he was 30. «A trent’anni si deve compiere o iniziare qualcosa di definitivo e fare i conti con la propria formazione» . For Rossi, the poet performs his authority not only in the text, but also in his will of setting out on a mystical journey and handing it down through an exact descriptive will. Rossi turns not only to the authority of poetry, but also evokes the authority of science with Max Plank and his Scientific Autobiography, published, in Italian translation, by Einaudi, 1956. Concerning Planck, Rossi resumes an element seemingly secondary in hit account where the German physicist «[...] risale alle scoperte della fisica moderna ritrovando l’impressione che gli fece l’enunciazione del principio di conservazione dell’energia; [...]» . It is again the act of describing that links Rossi to Planck, it is the description of a circularity, the one of conservation of energy, which endorses Rossi’s autobiographical speech looking for both happiness and death. Rossi seems to agree perfectly to the thought of Planck at the opening of his own autobiography: «The decision to devote myself to science was a direct consequence of a discovery which was never ceased to arouse my enthusiasm since my early youth: the laws of human thought coincide with the ones governing the sequences of the impressions we receive from the world surrounding us, so that the mere logic can enable us to penetrate into the latter one’s mechanism. It is essential that the outer world is something independent of man, something absolute. The search of the laws dealing with this absolute seems to me the highest scientific aim in life» . For Rossi the survey of his own life represents a way to change the events into experiences, to concentrate the emotion and group them in meaningful plots: «It seems, as one becomes older. / That the past has another pattern, and ceases to be a mere sequence [...]» Eliot wrote in Four Quartet, which are a meditation on time, old age and memory . And he goes on: «We had the experience but missed the meaning, / And approach to the meaning restores the experience / In a different form, beyond any meaning [...]» . Rossi restores in his autobiography – but not only in it – the most ancient sense of memory, aware that for at least 15 centuries the Latin word memoria was used to show the activity of bringing back images to mind: the psychology of memory, which starts with Aristotele (De Anima), used to consider such a faculty totally essential to mind. Keith Basso writes: «The thought materializes in the form of “images”» . Rossi knows well – as Aristotele said – that if you do not have a collection of mental images to remember – imagination – there is no thought at all. According to this psychological tradition, what today we conventionally call “memory” is but a way of imagining created by time. Rossi, entering consciously this stream of thought, passing through the Renaissance ars memoriae to reach us gives a great importance to the word and assumes it as a real place, much more than a recollection, even more than a production and an emotional elaboration of images.

Scienza, Tecnica, Politica: Il Problema del Metodo nel Pensiero di Jacopo Aconcio

The aim of this PhD thesis is to study accurately and in depth the figure and the literary production of the intellectual Jacopo Aconcio. This minor author of the 16th century has long been considered a sort of “enigmatic character”, a profile which results from the work of those who, for many centuries, have left his writing to its fate: a story of constant re-readings and equally incessant oversights. This is why it is necessary to re-read Aconcio’s production in its entirety and to devote to it a monographic study. Previous scholars’ interpretations will obviously be considered, but at the same time an effort will be made to go beyond them through the analysis of both published and manuscript sources, in the attempt to attain a deeper understanding of the figure of this man, who was a Christian, a military and hydraulic engineer and a political philosopher,. The title of the thesis was chosen to emphasise how, throughout the three years of the doctorate, my research concentrated in equal measure and with the same degree of importance on all the reflections and activities of Jacopo Aconcio. My object, in fact, was to establish how and to what extent the methodological thinking of the intellectual found application in, and at the same time guided, his theoretical and practical production. I did not mention in the title the author’s religious thinking, which has always been considered by everyone the most original and interesting element of his production, because religion, from the Reformation onwards, was primarily a political question and thus it was treated by almost all the authors involved in the Protestant movement - Aconcio in the first place. Even the remarks concerning the private, intimate sphere of faith have therefore been analysed in this light: only by acknowledging the centrality of the “problem of politics” in Aconcio’s theories, in fact, is it possible to interpret them correctly. This approach proves the truth of the theoretical premise to my research, that is to say the unity and orderliness of the author’s thought: in every field of knowledge, Aconcio applies the rules of the methodus resolutiva, as a means to achieve knowledge and elaborate models of pacific cohabitation in society. Aconcio’s continuous references to method can make his writing pedant and rather complex, but at the same time they allow for a consistent and valid analysis of different disciplines. I have not considered the fact that most of his reflections appear to our eyes as strongly conditioned by the time in which he lived as a limit. To see in him, as some have done, the forerunner of Descartes’ methodological discourse or, conversely, to judge his religious theories as not very modern, is to force the thought of an author who was first and foremost a Christian man of his own time. Aconcio repeats this himself several times in his writings: he wants to provide individuals with the necessary tools to reach a full-fledged scientific knowledge in the various fields, and also to enable them to seek truth incessantly in the religious domain, which is the duty of every human being. The will to find rules, instruments, effective solutions characterizes the whole of the author’s corpus: Aconcio feels he must look for truth in all the arts, aware as he is that anything can become science as long as it is analysed with method. Nevertheless, he remains a man of his own time, a Christian convinced of the existence of God, creator and governor of the world, to whom people must account for their own actions. To neglect this fact in order to construct a “character”, a generic forerunner, but not participant, of whatever philosophical current, is a dangerous and sidetracking operation. In this study, I have highlighted how Aconcio’s arguments only reveal their full meaning when read in the context in which they were born, without depriving them of their originality but also without charging them with meanings they do not possess. Through a historical-doctrinal approach, I have tried to analyse the complex web of theories and events which constitute the substratum of Aconcio’s reflection, in order to trace the correct relations between texts and contexts. The thesis is therefore organised in six chapters, dedicated respectively to Aconcio’s biography, to the methodological question, to the author’s engineering activity, to his historical knowledge and to his religious thinking, followed by a last section concerning his fortune throughout the centuries. The above-mentioned complexity is determined by the special historical moment in which the author lived. On the one hand, thanks to the new union between science and technique, the 16th century produces discoveries and inventions which make available a previously unthinkable number of notions and lead to a “revolution” in the way of studying and teaching the different subjects, which, by producing a new form of intellectual, involved in politics but also aware of scientific-technological issues, will contribute to the subsequent birth of modern science. On the other, the 16th century is ravaged by religious conflicts, which shatter the unity of the Christian world and generate theological-political disputes which will inform the history of European states for many decades. My aim is to show how Aconcio’s multifarious activity is the conscious fruit of this historical and religious situation, as well as the attempt of an answer to the request of a new kind of engagement on the intellectual’s behalf. Plunged in the discussions around methodus, employed in the most important European courts, involved in the abrupt acceleration of technical-scientific activities, and especially concerned by the radical religious reformation brought on by the Protestant movement, Jacopo Aconcio reflects this complex conjunction in his writings, without lacking in order and consistency, differently from what many scholars assume. The object of this work, therefore, is to highlight the unity of the author’s thought, in which science, technique, faith and politics are woven into a combination which, although it may appear illogical and confused, is actually tidy and methodical, and therefore in agreement with Aconcio’s own intentions and with the specific characters of European culture in the Renaissance. This theory is confirmed by the reading of the Ars muniendorum oppidorum, Aconcio’s only work which had been up till now unavailable. I am persuaded that only a methodical reading of Aconcio’s works, without forgetting nor glorifying any single one, respects the author’s will. From De methodo (1558) onwards, all his writings are summae, guides for the reader who wishes to approach the study of the various disciplines. Undoubtedly, Satan’s Stratagems (1565) is something more, not only because of its length, but because it deals with the author’s main interest: the celebration of doubt and debate as bases on which to build religious tolerance, which is the best method for pacific cohabitation in society. This, however, does not justify the total centrality which the Stratagems have enjoyed for centuries, at the expense of a proper understanding of the author’s will to offer examples of methodological rigour in all sciences. Maybe it is precisely because of the reforming power of Aconcio’s thought that, albeit often forgotten throughout the centuries, he has never ceased to reappear and continues to draw attention, both as a man and as an author. His ideas never stop stimulating the reader’s curiosity and this may ultimately be the best demonstration of their worth, independently from the historical moment in which they come back to the surface.

Arti decorative: Bologna e Faenza tra Ottocento e Novecento

La ricerca approfondisce gli studi iniziati dalla dott.ssa Baldini in occasione della tesi di laurea e amplia le indagini critiche avviate per la mostra sull’Aemilia Ars (2001). La ricerca si è interessata alle aree di Bologna e di Faenza individuando le connessioni che tra Otto e Novecento intercorrono tra la cultura artistica locale e quella nazionale ed europea. Nasce infatti in questo periodo Aemilia Ars, uno dei più innovativi movimenti del contesto nazionale nel campo delle arti decorative. I membri del gruppo, raccoltisi intorno alla carismatica figura di Alfonso Rubbiani nei primi anni Ottanta, sono attratti da influenze nordeuropee e sin dall’inizio si mostrano orientati a seguire precetti ruskiniani e preraffaelliti. Molto importante in entrambe le città, per l’evoluzione dello scenario artistico e artigianale – in questi anni più che mai unite in un rapporto di strettissima correlazione – è l’apporto e il sostegno offerto dai salotti, dai circoli, dai caffè e dai cenacoli locali. Dal punto di vista dello stile, forme lineari con una marcata tendenza all’astrazione caratterizzano la produzione dei principali interpreti faentini e bolognesi dell’ultimo ventennio dell’Ottocento allineandoli con le ricerche dei loro contemporanei nel resto d’Europa. I settori produttivi che si sono indagati sono quelli della ceramica, dell’ebanisteria, dei ferri battuti, dell’oreficeria, delle arti tessili e dei cuoi. Gran parte di queste lavorazioni – attardatesi nella realizzazione di oggetti dalle forme di ispirazione seicentesca, certamente poco adatte alla produzione industriale – subiscono ora una decisa accelerazione verso forme più svelte che, adeguandosi alla possibilità di riproduzione seriale degli oggetti, si diffonderanno quasi capillarmente tra l’aristocrazia e la borghesia, faticando tuttavia a raggiungere le classi meno abbienti a causa degli elevati costi di produzione. Nell’ultima parte viene tracciato sinteticamente il quadro delle attività artistiche e artigianali faentine del periodo indicato, con una particolare attenzione all’opera delle personalità afferenti al Cenacolo baccariniano.

Effetti della somministrazione di Testosterone in donne

Come noto, il testosterone (T) gioca un ruolo importante in differenti funzioni fisiologiche. Il ruolo del T nelle donne è tuttavia largamente sconosciuto. Recenti studi riportano un ruolo del T nella modulazione della funzionalità sessuale femminile. SCOPO: Indagare gli effetti del T nelle donne, su parametri metabolici, ossei e composizione corporea e studiare gli effetti del T sulla proliferazione e innervazione della vagina. METODI: 16 soggetti FtM ovariectomizzati sono stati sottoposti a terapia con TU 1000 mg im + placebo o dutasteride. Alla settimana 0 e 54 sono stati valutati: parametri metabolici e composizione corporea. 16 campioni di tessuto vaginale ottenuti da soggetti FtM trattati con T, 16 donne PrM e 16 donne M sono stati analizzati. Sono stati valutati: morfologia, contenuto di glicogeno, espressione del Ki-67, recettori per estrogeni e androgeni ed innervazione. RISULTATI: La somministrazione di T in soggetti FtM determina aumento del colesterolo LDL e riduzione delle HDL. L’HOMA si riduce significativamente nel gruppo TU e tende ad aumentare nel gruppo TU+D. L’ematocrito aumenta. BMI, WHR e grasso tendono a ridursi, la massa magra ad aumentare. Non riportiamo cambiamenti del metabolismo osseo. Nel tessuto vaginale di FtM osserviamo perdita della normale architettura dell’epitelio. La somministrazione di T determina riduzione della proliferazione cellulare. I recettori per E e il PGP 9.5 sono significativamente ridotti nei FtM. La presenza di recettori per A è dimostrata nello stroma e nell’epitelio. L’espressione di AR si riduce con l’età e non cambia con la terapia con T nella mucosa, mentre aumenta nello stroma dopo somministrazione di T. CONCLUSIONI: Non riportiamo effetti avversi maggiori dopo somministrazione di T. La terapia con T determina ridotta proliferazione dell’epitelio vaginale. I recettori per AR sono presenti sia nello stroma che nell’epitelio. T aumenta l’espressione di AR nello stroma.

Design and synthesis of multipotent drugs: application to Alzheimer's disease and benign prostatic hyperplasia

The aim of this thesis was to synthesize multipotent drugs for the treatment of Alzheimer’s disease (AD) and for benign prostatic hyperplasia (BPH), two diseases that affect the elderly. AD is a neurodegenerative disorder that is characterized, among other factors, by loss of cholinergic neurons. Selective activation of M1 receptors through an allosteric site could restore the cholinergic hypofunction, improving the cognition in AD patients. We describe here the discovery and SAR of a novel series of quinone derivatives. Among them, 1 was the most interesting, being a high M1 selective positive allosteric modulator. At 100 nM, 1 triplicated the production of cAMP induced by oxotremorine. Moreover, it inhibited AChE and it displayed antioxidant properties. Site-directed mutagenesis experiments indicated that 1 acts at an allosteric site involving residue F77. Thus, 1 is a promising drug because the M1 activation may offer disease-modifying properties that could address and reduce most of AD hallmarks. BPH is an enlargement of the prostate caused by increased cellular growth. Blockade of α1-ARs is the predominant form of medical therapy for the treatment of the symptoms associated with BPH. α1-ARs are classified into three subtypes. The α1A- and α1D-AR subtypes are predominant in the prostate, while α1B-ARs regulate the blood pressure. Herein, we report the synthesis of quinazoline-derivatives obtained replacing the piperazine ring of doxazosin and prazosin with (S)- or (R)-3-aminopiperidine. The presence of a chiral center in the 3-C position of the piperidine ring allowed us to exploit the importance of stereochemistry in the binding at α1-ARs. It turned out that the S configuration at the 3-C position of the piperidine increases the affinity of the compounds at all three α1-AR subtypes, whereas the configuration at the benzodioxole ring of doxazosin derivatives is not critical for the interaction with α1-ARs.

Stima dell'assetto di un UAV

Lo scopo del lavoro è simulare il comportamento di un sistema di misura dell'assetto detto ARS (Attitude Reference System), dove sostanzialmente le misure fornite da giroscopi ed accelerometri, quindi accelerazioni e velocità angolari, vengono elaborate da un filtro osservatore dello stato che permette di ricavare la stima dell'angolo di elevazione Q e dell'angolo di inclinazione f, non misurabili direttamente, e quindi dell'orientamento del sistema rispetto al piano orizzontale.