A reappraisal of the Italian record of the Cretaceous pachycormid fish Protosphyraena Leidy, 1857

The genus Protosphyraena is known mainly from partial remains, consisting of isolated blade-like teeth, conical rostra and scythe-like pectoral fins. This paper provides a new insight into partial specimens of the genus Protosphyraena from the Cretaceous of NE Italy, housed in historical collections from local paleontological museums and previously poorly known to the international scientific community. The specimens are referred to the species Protosphyraena ferox, based on the morphology of the pectoral fin. This attribution is consistent with the paleobiogeographic distribution and stratigraphic range of this taxon. The Italian material provides new information about the distribution in time and space of Protosphyraena, which is relatively poorly known despite being an iconic taxon. The Italian remains, although fragmentary, contribute to fill a gap in the central Tethys record of the genus, whose range probably extended worldwide, considering also the genus Australopachycormus and its profound (possibly congeneric) similarities

Reverse Engineering and Testing of Rich Internet Applications

The World Wide Web experiences a continuous and constant evolution, where new initiatives, standards, approaches and technologies are continuously proposed for developing more effective and higher quality Web applications. To satisfy the growing request of the market for Web applications, new technologies, frameworks, tools and environments that allow to develop Web and mobile applications with the least effort and in very short time have been introduced in the last years. These new technologies have made possible the dawn of a new generation of Web applications, named Rich Internet Applications (RIAs), that offer greater usability and interactivity than traditional ones. This evolution has been accompanied by some drawbacks that are mostly due to the lack of applying well-known software engineering practices and approaches. As a consequence, new research questions and challenges have emerged in the field of web and mobile applications maintenance and testing. The research activity described in this thesis has addressed some of these topics with the specific aim of proposing new and effective solutions to the problems of modelling, reverse engineering, comprehending, re-documenting and testing existing RIAs. Due to the growing relevance of mobile applications in the renewed Web scenarios, the problem of testing mobile applications developed for the Android operating system has been addressed too, in an attempt of exploring and proposing new techniques of testing automation for these type of applications

Delivery of human apolipoprotein (apo) E to liver by an [E1(-), E3(-), polymerase(-), pTP(-)] adenovirus vector containing a liver-specific promoter inhibits atherogenesis in immunocompetent apoE-deficient mice

Recombinant adenovirus (rAd)-mediated apoE gene transfer to the liver of apoE(-/-) mice is anti-atherogenic. However, first generation rAd vectors were associated with immune clearance of transduced hepatocytes, while an improved [E1(-), E3(-) polymerase(-)] adenovirus vector that persisted in the liver, had transient effects due to cellular shutdown of the cytomegalovirus (CMV) promoter (Ad-CMV-apoE). Here, we utilise an improved class of rAd vector with multiple deletions in the E1, E3, polymerase and pTP (pre-terminal protein) genes, which contains a modular synthetic liver-specific promoter (LSP) to drive expression of the human apoE cDNA (Ad-LSP-apoE) for hepatic gene transfer. Approximately 1 year old apoE(-/-) mice were injected intravenously with 4x10(10) virus particles of either Ad-LSP-apoE or Ad-CMV-apoE. Animals were monitored for plasma apoE, total plasma cholesterol and plasma lipoprotein distribution. The effect of Ad-LSP-apoE on atheroma progression was assessed in animals killed at 8 and 28 weeks after the injections. Ad-LSP-apoE vector administration gave sustained, though low, levels of plasma apoE throughout the study period without inducing a humoral immune response, but failed to reduce plasma cholesterol or normalize the adverse lipoprotein profile. Animals killed 8 weeks after the injections, demonstrated no significant retardation of atherosclerosis, whereas aortic lesions in those killed at 28 weeks were significantly reduced by 30% ( P< 0.006) compared to untreated animals. In summary, the combination of a multiply deleted rAd vector with a liver-specific promoter provided sustained low levels of plasma apoE, resulting in significant retardation of aortic atherosclerotic lesions

Refurbishment of Exterior Wooden Panels of Simpson Strong Tie Building

This paper outlines the refurbishment of the exterior wood panels located on the Simpson Strong Tie Building on the Cal Poly San Luis Obispo campus. This project focuses on the two large 50 square foot wooden panels that act as an exterior skin for the Simpson Strong Tie Building. This project is an individual project that was broken up into 4 phases. This paper will cover all 4 phases of the refurbishment process. These phases include the removal, sanding, staining and reapplication of wood panels onto the Simpson Strong Tie Building. Furthermore, this paper will go in depth about the building permit process and the struggles experienced communicating with the owner and architect during the preconstruction phase. Many struggles had to be overcome during the refurbishment process such as managing a project on an active campus, as well the refurbishment process itself. There were many unforeseen conditions that were experienced during the construction phase due to inadequate project details from the architect, OMNI Design Group. The purpose of this project is to give back to the Cal Poly San Luis Obispo Construction Management Department by refurbishing the weathered and aesthetically unappealing exterior wooden panels on the Simpson Strong Tie Building

Toward Reverse Engineering of VBA Based Excel Spreadsheet Applications

Modern spreadsheet systems can be used to implement complex spreadsheet applications including data sheets, customized user forms and executable procedures written in a scripting language. These applications are often developed by practitioners that do not follow any software engineering practice and do not produce any design documentation. Thus, spreadsheet applications may be very difficult to be maintained or restructured. In this position paper we present in a nutshell two reverse engineering techniques and a tool that we are currently realizing for the abstraction of conceptual data models and business logic models.Comment: In Proceedings of the 2nd Workshop on Software Engineering Methods in Spreadsheets (http://spreadsheetlab.org/sems15/

The ECJ’s Approach to Dual Preliminarity 5 Years after the ItCC’s Judgment No. 269/2017

This article examines the European Court of Justice (ECJ)’s perspective on dual preliminarity (doppia pregiudizialità) five years after the notorious obiter dictum of the Italian Constitutional Court (ItCC) in its judgment No. 269/2017. More precisely, the article aims at unravelling the essential requirements that any such “triangular” relation (between ordinary national courts, national Constitutional Courts, and the Kirchberg Court) shall satisfy to comply with European Union (EU) law. This analysis builds both on the “classics” and on the recent cases involving (blatant or disguised) restrictions on Hungarian and Romanian judges to refer to the ECJ or apply EU law. Against this backdrop, the compatibility of the current configuration of dual preliminarity in Italy with EU law will be assessed. Although a specific assessment in this regard has not been carried out by the ECJ (yet?), we contend that the refinements and adjustments in the more recent ItCC’s case law have remedied the main issues envisaged in the obiter dictum. Therefore, the current configuration seems to pose no serious threats to the EU systemic principles involved nor to EU law’s uniformity, coherence, and effectiveness. Indeed, provided that national judges continue to enjoy the actual power to refer freely to the ECJ and immediately set aside national law provisions incompatible with EU law rules, the ECJ has adopted a “secularist” approach and respects the Member States’ constitutional models. This article also argues that the early-stage involvement of ItCC’s (“first word”) in the dialogue with the ECJ may well serve the interests of a composite and pluralist system of fundamental rights protection in the EU. We will offer as an example the recent case on the Italian rules on childbirth and maternity allowances, which marks a step down the path of a “cooperative” dialogue between the two courts and shows the potentialities (and the little drawbacks) of such an early involvement

Retardation of atherosclerosis in immunocompetent apolipoprotein (apo) E-deficient mice followingliver-directed administration of a [E1-, E3-,polymerase-] adenovirus vector containing the elongation factor-1a promoter driving expression of human apoE cDNA

Although gene transfer of human apolipoprotein E (apoE), a 34-kDa circulating glycoprotein, to the liver of apoEdeficient(apoE-/-) mice using recombinant adenoviral vectors (rAd) is antiatherogenic, its full therapeutic potentialhas yet to be realized. First generation vectors led to immune clearance of transduced hepatocytes, while animproved vector with adenovirus regions E1, E3 and DNA polymerase deleted also had transient effects due tocellular shutdown of the cytomegalovirus (CMV) promoter. Here, we have studied an alternative promoter from thecellular elongation factor 1a (EF-1a) gene, injecting 6-8 week old apoE-/- mice intravenously with 2x1010 virusparticles (vp) of the [E1-, E3-, polymerase-] rAd vector Ad-EF1·-apoE. Plasma apoE levels were low (18-55 ng/ml)and failed to reduce plasma cholesterol or normalize the adverse lipoprotein profile. By contrast, thehyperlipidaemic phenotype of apoE-/- mice treated with Ad-CMV-apoE (2x1010 vp) was transiently normalized.Nevertheless, at termination (265 days) the aortic lesion areas in animals given Ad-EF1·-apoE were significantlyreduced by 15% (P<0.05) compared to untreated animals, a decrease approaching that in Ad-CMV-apoE-treatedmice (23%; P<0.02). Importantly, the attenuation of apoE transgene expression noted with the CMV promoter wasabsent with the EF-1a promoter, which gave relatively sustained, albeit low, levels of plasma apoE throughout thestudy period

Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion

Adenovirus (Ad) based gene transfer vectors continue to be the platform of choice for an increasing number of clinical trials worldwide. In fact, within the last five years, the number of clinical trials that utilize Ad based vectors has doubled, indicating growing enthusiasm for the numerous positive characteristics of this gene transfer platform. For example, Ad vectors can be easily and relatively inexpensively produced to high titers in a cGMP compliant manner, can be stably stored and transported, and have a broad applicability for a wide range of clinical conditions, including both gene therapy and vaccine applications. Ad vector based gene transfer will become more useful as strategies to counteract innate and/or pre-existing adaptive immune responses to Ads are developed and confirmed to be efficacious. The approaches attempting to overcome these limitations can be divided into two broad categories: pre-emptive immune modulation of the host, and selective modification of the Ad vector itself. The first category of methods includes the use of immunosuppressive drugs or specific compounds to block important immune pathways, which are known to be induced by Ads. The second category comprises several innovative strategies inclusive of: (1) Ad-capsid-display of specific inhibitors or ligands; (2) covalent modifications of the entire Ad vector capsid moiety; (3) the use of tissue specific promoters and local administration routes; (4) the use of genome modified Ads; and (5) the development of chimeric or alternative serotype Ads. This review article will focus on both the promise and the limitations of each of these immune evasion strategies, and in the process delineate future directions in developing safer and more efficacious Ad-based gene transfer strategies

Infantile Pompe Disease and Enzyme Replacement Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141565/1/jpc13733.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141565/2/jpc13733_am.pd

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