Inibidores de tirosina-quinase no tratamento de mastocitomas cutâneos em cães: revisão

The mast cell tumor (MCT) is the second most common type of tumor in dogs. It is characterized by uncontrolled proliferation of mast cells in the skin. Treatment involves surgical resection, chemotherapy and radiotherapy. Recently, new treatment protocols have been developed, such as the use of tyrosine kinase inhibitors. With the increasing knowledge about the genome and the evolution of methods in molecular genetics, drugs with specific molecular targets are surely going to become promising therapeutic modalities in the near future. Besides being involved in the normal cell cycle, some studies suggest that tyrosine kinases have a fundamental role in neoplastic processes. Therefore, some strategies such as the development of antibodies anti-receptors for tyrosine kinases and small-molecule tyrosine kinase receptor inhibitors have been developed in an attempt to inhibit tumor development. The purpose of this review is to describe the use of tyrosine kinase inhibitors in the treatment of mast cell tumors in dogs.

Estudos estruturais de complexos entre fosfolipases A2 homólogas isoladas do veneno de Bothrops moojeni e inibidores da atividade miotóxica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patofisiologia de osteonecrose induzida por bisfosfonatos e inibidores de RANK-L

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vanishing of Ext and Tor over complete intersections

Let (R,m) be a local complete intersection, that is, a local ring whose m-adic completion is the quotient of a complete regular local ring by a regular sequence. Let M and N be finitely generated R-modules. This dissertation concerns the vanishing of Tor(M, N) and Ext(M, N). In this context, M satisfies Serre's condition (S_{n}) if and only if M is an nth syzygy. The complexity of M is the least nonnegative integer r such that the nth Betti number of M is bounded by a polynomial of degree r-1 for all sufficiently large n. We use this notion of Serre's condition and complexity to study the vanishing of Tor_{i}(M, N). In particular, building on results of C. Huneke, D. Jorgensen and R. Wiegand [32], and H. Dao [21], we obtain new results showing that good depth properties on the R-modules M, N and MtensorN force the vanishing of Tor_{i}(M, N) for all i>0. We give examples showing that our results are sharp. We also show that if R is a one-dimensional domain and M and MtensorHom(M,R) are torsion-free, then M is free if and only if M has complexity at most one. If R is a hypersurface and Ext^{i}(M, N) has finite length for all i>>0, then the Herbrand difference [18] is defined as length(Ext^{2n}(M, N))-(Ext^{2n-1}(M, N)) for some (equivalently, every) sufficiently large integer n. In joint work with Hailong Dao, we generalize and study the Herbrand difference. Using the Grothendieck group of finitely generated R-modules, we also examined the number of consecutive vanishing of Ext^{i}(M, N) needed to ensure that Ext^{i}(M, N) = 0 for all i>>0. Our results recover and improve on most of the known bounds in the literature, especially when R has dimension two.

Um novo protocolo in silico para a predição de complexos flexíveis entre proteínas: estudo de caso para inibidores plasmáticos de fosfolipase A2 de serpentes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insulin and TOR pathways regulate cellular and organismal growth through the myc oncogene in Drosophila

A large body of literature documents in both mice and Drosophila the involvement of Insulin pathway in growth regulation, probably due to its role in glucose and lipid import, nutrient storage, and translation of RNAs implicated in ribosome biogenesis (Vanhaesebroeck et al. 2001). Moreover several lines of evidence implicate this pathway as a causal factor in cancer (Sale, 2008; Zeng and Yee 2007; Hursting et al., 2007; Chan et al., 2008). With regards to Myc, studies in cell culture have implied this family of transcription factors as regulators of the cell cycle that are rapidly induced in response to growth factors. Myc is a potent oncogene, rearranged and overexpressed in a wide range of human tumors and necessary during development. Its conditional knock-out in mice results in reduction of body weight due to defect in cell proliferation (Trumpp et al. 2001). Evidence from in vivo studies in Drosophila and mammals suggests a critical function for myc in cell growth regulation (Iritani and Eisenman 1999; Johnston et al. 1999; Kim et al. 2000; de Alboran et al. 2001; Douglas et al. 2001). This role is supported by our analysis of Myc target genes in Drosophila, which include genes involved in RNA binding, processing, ribosome biogenesis and nucleolar function (Orain et al 2003, Bellosta et al., 2005, Hulf et al, 2005). The fact that Insulin signaling and Myc have both been associated with growth control suggests that they may interact with each other. However, genetic evidence suggesting that Insulin signaling regulates Myc in vivo is lacking. In this work we were able to show, for the first time, a direct modulation of dMyc in response to Insulin stimulation/silencing both in vitro and in vivo. Our results suggest that dMyc up-regulation in response to DILPs signaling occurs both at the mRNA and potein level. We believe dMyc protein accumulation after Insulin signaling activation is conditioned to AKT-dependent GSK3β/sgg inactivation. In fact, we were able to demonstate that dMyc protein stabilization through phosphorylation is a conserved feature between Drosophila and vertebrates and requires multiple events. The final phosphorylation step, that results in a non-stable form of dMyc protein, ready to be degraded by the proteasome, is performed by GSK3β/sgg kinase (Sears, 2004). At the same time we demonstrated that CKI family of protein kinase are required to prime dMyc phosphorylation. DILPs and TOR/Nutrient signalings are known to communicate at several levels (Neufeld, 2003). For this reason we further investigated TOR contribution to dMyc-dependent growth regulation. dMyc protein accumulates in S2 cells after aminoacid stimulation, while its mRNA does not seem to be affected upon TORC1 inhibition, suggesting that the Nutrient pathway regulates dMyc mostly post-transcriptionally. In support to this hypothesis, we observed a TORC1-dependent GSK3β/sgg inactivation, further confirming a synergic effect of DILPs and Nutrients on dMyc protein stability. On the other hand, our data show that Rheb but not S6K, both downstream of the TOR kinase, contributes to the dMyc-induced growth of the eye tissue, suggesting that Rheb controls growth independently of S6K.. Moreover, Rheb seems to be able to regulate organ size during development inducing cell death, a mechanism no longer occurring in absence of dmyc. These observations suggest that Rheb might control growth through a new pathway independent of TOR/S6K but still dependent on dMyc. In order to dissect the mechanism of dMyc regulation in response to these events, we analyzed the relative contribution of Rheb, TOR and S6K to dMyc expression, biochemically in S2 cells and in vivo in morphogenetic clones and we further confirmed an interplay between Rheb and Myc that seems to be indipendent from TOR. In this work we clarified the mechanisms that stabilize dMyc protein in vitro and in vivo and we observed for the first time dMyc responsiveness to DILPs and TOR. At the same time, we discovered a new branch of the Nutrient pathway that appears to drive growth through dMyc but indipendently from TOR. We believe our work shed light on the mechanisms cells use to grow or restrain growth in presence/absence of growth promoting cues and for this reason it contributes to understand the physiology of growth control.

Molluscs of the marine protected area "Secche di Tor Paterno"

The thesis describes the molluscan biodiversity of the infralittoral off-shore reefs in the "Secche di Tor Paterno" marine protected area lying in the Central Tyrrhenian Sea off the coasts of Lazio south of Roma. Data originate from underwater sampling activities carried out by SCUBA diving in four biocoenoses: Posidonia oceanica leaves and rhizomes, coralligenous concretions and detritic pools. The representativeness of molluscs as descriptors of biocoenoses is evaluated by preliminary comparisons with data about Polychaeta, Pleocyemata (Crustacea) and Brachiopoda obtained in the same survey. The malacocoenoses of the four biocoenoses are treated in detail. Then data are compared with other data sets to assess differences and similarities with other communities. The agreement between death and living assemblages in the reefs is evaluated for the Posidonia oceanica and the coralligenous biocoenosis and was carried out by a set of standard metrics and some benthic ecology methods. Molluscs perform very well as descriptors of biocoenoses, better than the other phyla. The molluscan assemblages of the reefs are very rich in species despite richness is mainly concentrated in the coralligenous and in the rhizomes of Posidonia oceanica. The leaves of Posidonia oceanica host a rather poor assemblage. Detritic pools host a poor but peculiar species assemblage. The dead-live agreement showed that death assemblages are highly representative of sediments of nearby biocoenoses as a result of low bottom transport. Fidelity metrics suggest a good agreement between the living and death assemblages when species richness and taxonomic composition are considered. The study suggests that fidelity is lower when considering the species dominance. These differences could be associated to the trophism of species and possibly to the species life span.

Analisi del protocollo Tor e del simulatore Shadow

L’obiettivo che si pone questa tesi è quello di analizzare alcune soluzioni esistenti riguardo i problemi riguardanti privacy e sicurezza informatica. Nello specifico sarà illustrato il programma Tor, un sistema di comunicazione grazie al quale si garantisce l’anonimato in Internet. Sponsorizzato inizialmente dall’US Naval Research Laboratory, all’origine veniva utilizzato per poter effettuare comunicazioni militari criptate; è stato successivamente un progetto della Electronic Frontier Foundation ed ora è gestito da The Tor Project, un’associazione senza scopo di lucro che si occupa del relativo sviluppo. Le ricerche e gli sviluppi riguardanti questa tecnologia vengono tuttavia resi difficili da problemi di scalabilità e dalla difficoltà di riprodurre risultati affidabili. Nel corso della tesi saranno illustrati gli studi riguardanti il simulatore Shadow, un progetto Open Source gestito da The Tor Project, che permette la simulazione del protocollo Tor. I risultati ottenuti dai test effettuati sul simulatore, possono essere riapplicati in seguito alla rete reale Tor, poiché grazie a Shadow è possibile testare ed ottenere risultati attendibili circa il comportamento e la corretta esecuzione del software Tor.

Tor network forensics and hidden service deanonymization

The cybernetics revolution of the last years improved a lot our lives, having an immediate access to services and a huge amount of information over the Internet. Nowadays the user is increasingly asked to insert his sensitive information on the Internet, leaving its traces everywhere. But there are some categories of people that cannot risk to reveal their identities on the Internet. Even if born to protect U.S. intelligence communications online, nowadays Tor is the most famous low-latency network, that guarantees both anonymity and privacy of its users. The aim of this thesis project is to well understand how the Tor protocol works, not only studying its theory, but also implementing those concepts in practice, having a particular attention for security topics. In order to run a Tor private network, that emulates the real one, a virtual testing environment has been configured. This behavior allows to conduct experiments without putting at risk anonymity and privacy of real users. We used a Tor patch, that stores TLS and circuit keys, to be given as inputs to a Tor dissector for Wireshark, in order to obtain decrypted and decoded traffic. Observing clear traffic allowed us to well check the protocol outline and to have a proof of the format of each cell. Besides, these tools allowed to identify a traffic pattern, used to conduct a traffic correlation attack to passively deanonymize hidden service clients. The attacker, controlling two nodes of the Tor network, is able to link a request for a given hidden server to the client who did it, deanonymizing him. The robustness of the traffic pattern and the statistics, such as the true positive rate, and the false positive rate, of the attack are object of a potential future work.

Geschichte der Juden in Stadt und Synagogenbezirk Essen von der Einverleibung in Preussen (1802) bis zur Errichtung der Synagoge am Steeler Tor (1913) : Festschrift zur Weihe der Synagoge im Auftr. d. Gemeindevertretung quellenmäßig bearb.

von S. Samuel. Mit e. Farbenzeichn. von Fritz Lewy u. 2 Bildn.

Tor Ester : Mittel gegen die falschen Blutbeschuldigungen

von M. Duschak

"Am Tor des Abends"

Arno Nadel