Bovine papillomavirus on the scene of crime: is E5 oncogene the only guilty party?

Bovine papillomaviruses (BPVs) induce hyperplastic and tumoral lesions not only in cows but also in other different animal species. The transforming activity of BPVs is due to its major E5 oncogene. Recent studies have highlighted the role of E5 in cancer development but very little is known about E6 and E7 oncogenes. In this letter we argue for the need of investigating E6 as well as E7 to better understand the role of these two oncogenes during carcinogenesis

Metabolic control of tumor growth by mitochondrial A-KINASE anchor protein 1 (AKAP1)

Mitochondria are powerhouses present in all eukaryotic cells that play a fundamental role in energy production, survival and metabolism. In cancer cells, mitochondria provide the building blocks for the biogenesis of cellular organelles, cytoskeleton and membranes, and supply all the metabolic needs for cancer growth and spreading in vivo. AKAP1 is a scaffold protein that integrates and focus cAMP and src signaling on mitochondria, regulating protein synthesis, organelle biogenesis, oxidative metabolism and cell survival. During my thesis, I analyzed the mechanisms controlling the expression of AKAP1 in cancer cells and the role of this anchor protein in the control of metabolic pathways and cancer growth. I found that transcription and accumulation of AKAP1 are induced by the Myc proto-oncogene and by steroid hormones. I detected high levels of AKAP1 in a wide variety of high-grade human cancer tissues and cells, including prostate cancer, breast cancer and glioblastoma (GBM). I demonstrated that AKAP1 is required for mTOR pathway, oxidative metabolism and cancer growth, both in vitro and in vivo. Interestingly, I discovered a link between DNA damage pathways and AKAP1. In particular, I found that, in course of DNA damage, AKAP1 is phosphorylated by ATM/ATR kinase at its PKA binding domain. Phosphorylation of AKAP1 by ATM inhibits PKA targeting to mitochondria and downregulates oxidative metabolism. These data disclose a previously unrecognized role of AKAP1 in mTOR pathway and cancer growth AKAP1 and identify AKAP1 as a novel biologically relevant target of the DNA damage pathways

Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid.

Equine sarcoids are benign fibroblastic skin tumours that are recognized throughout the world. Infection with bovine papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in disease development; however, the cellular mechanisms underlying fibroblast transformation remain poorly defined. The present study further characterizes aspects of the association with BPV in 15 equine sarcoids. BPV DNA was demonstrated in 12/15 tumours collected from different areas of Italy. Nine of these 12 tumours expressed the BPV oncoproteins E5 and E7, but these oncoproteins were not expressed by normal equine cells. The BPV E5 protein is known to bind to the platelet-derived growth factor-b receptor (PDGF-bR) and this molecule was expressed by 11 of the 12 sarcoids in which E5 was demonstrated. These findings add further weight to the theory that BPV and the PDGF-bR may have a role in the pathogenesis of this disease

Unified formulation of a family of iterative solvers for power systems analysis

This paper illustrates the construction of a new class of iterative solvers for power flow calculations based on the method of Alternating Search Directions. This method is fit to the particular algebraic structure of the power flow problem resulting from the combination of a globally linear set of equations and nonlinear local relations imposed by power conversion devices, such as loads and generators. The choice of the search directions is shown to be crucial for improving the overall robustness of the solver. A noteworthy advantage is that constant search directions yield stationary methods that, in contrast with Newton or Quasi-Newton methods, do not require the evaluation of the Jacobian matrix. Such directions can be elected to enforce the convergence to the high voltage operative solution. The method is explained through an intuitive example illustrating how the proposed generalized formulation is able to include other nonlinear solvers that are classically used for power flow analysis, thus offering a unified view on the topic. Numerical experiments are performed on publicly available benchmarks for large distribution and transmission systems.Peer ReviewedPostprint (author's final draft

Socio-Economic Benefits from the Use of Earth Observations

This report summarizes the outcomes of the discussion of the workshop on Socioeconomic Benefit from the use of Earth Observation workshop held at JRC from 11 to 13 July 2011.JRC.H.6-Spatial data infrastructure

Papillomavirus E5: the smallest oncoprotein with many functions

Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent

Fuzzing Symbolic Expressions

Recent years have witnessed a wide array of results in software testing, exploring different approaches and methodologies ranging from fuzzers to symbolic engines, with a full spectrum of instances in between such as concolic execution and hybrid fuzzing. A key ingredient of many of these tools is Satisfiability Modulo Theories (SMT) solvers, which are used to reason over symbolic expressions collected during the analysis. In this paper, we investigate whether techniques borrowed from the fuzzing domain can be applied to check whether symbolic formulas are satisfiable in the context of concolic and hybrid fuzzing engines, providing a viable alternative to classic SMT solving techniques. We devise a new approximate solver, FUZZY-SAT, and show that it is both competitive with and complementary to state-of-the-art solvers such as Z3 with respect to handling queries generated by hybrid fuzzers

SENinja: A symbolic execution plugin for Binary Ninja

Symbolic execution is a program analysis technique that aims to automatically identify interesting inputs for an application, using them to generate program executions covering different parts of the code. It is widely used in the context of vulnerability discovery and reverse engineering. In this paper we present SENINJA, a symbolic execution plugin for the BINARYNINJA disassembler. The tool allows the user to perform symbolic execution analyses directly within the user interface of the disassembler, and can be used to support a variety of reverse engineering tasks