Targeted Deletion of Multiple CTCF-Binding Elements in the Human C-MYC Gene Reveals a Requirement for CTCF in C-MYC Expression

BACKGROUND:Insulators and domain boundaries both shield genes from adjacent enhancers and inhibit intrusion of heterochromatin into transgenes. Previous studies examined the functional mechanism of the MYC insulator element MINE and its CTCF binding sites in the context of transgenes that were randomly inserted into the genome by transfection. However, the contribution of CTCF binding sites to both gene regulation and maintenance of chromatin has not been tested at the endogenous MYC gene. METHODOLOGY/PRINCIPAL FINDINGS:To determine the impact of CTCF binding on MYC expression, a series of mutant human chromosomal alleles was prepared in homologous recombination-efficient DT40 cells and individually transferred by microcell fusion into murine cells. Functional tests reported here reveal that deletion of CTCF binding elements within the MINE does not impact the capacity of this locus to correctly organize an 'accessible' open chromatin domain, suggesting that these sites are not essential for the formation of a competent, transcriptionally active locus. Moreover, deletion of the CTCF site at the MYC P2 promoter reduces transcription but does not affect promoter acetylation or serum-inducible transcription. Importantly, removal of either CTCF site leads to DNA methylation of flanking sequences, thereby contributing to progressive loss of transcriptional activity. CONCLUSIONS:These findings collectively demonstrate that CTCF-binding at the human MYC locus does not repress transcriptional activity but is required for protection from DNA methylation

Privacy Architectures: Reasoning About Data Minimisation and Integrity

Privacy by design will become a legal obligation in the European Community if the Data Protection Regulation eventually gets adopted. However, taking into account privacy requirements in the design of a system is a challenging task. We propose an approach based on the specification of privacy architectures and focus on a key aspect of privacy, data minimisation, and its tension with integrity requirements. We illustrate our formal framework through a smart metering case study.Comment: appears in STM - 10th International Workshop on Security and Trust Management 8743 (2014

Comment on opinion paper: Forest management and biodiversity : The role of protected areas is greater than the sum of its number of species

No abstract available

Human-to-Human Interaction: the Killer Application of Ubiquitous Computing

Twenty-five years past the Weiser\u2019s vision of Ubiquitous Computing, and there is not a clear understanding of what is or is not a pervasive system. Due to the loose boundaries of such paradigm, almost any kind of remotely ac-cessible networked system is classified as a pervasive system. We think that that is mainly due to the lack of killer applications that could make this vi-sion clearer. Actually, we think that the most promising killer application is already here, but we are so used to it that we do not see it, as a perfect fitting of the Weiser\u2019s vision: the Human-to-Human Interaction mediated by com-puters

FACT -- the First Cherenkov Telescope using a G-APD Camera for TeV Gamma-ray Astronomy (HEAD 2010)

Geiger-mode Avalanche Photodiodes (G-APD) bear the potential to significantly improve the sensitivity of Imaging Air Cherenkov Telescopes (IACT). We are currently building the First G-APD Cherenkov Telescope (FACT) by refurbishing an old IACT with a mirror area of 9.5 square meters and construct a new, fine pixelized camera using novel G-APDs. The main goal is to evaluate the performance of a complete system by observing very high energy gamma-rays from the Crab Nebula. This is an important field test to check the feasibility of G-APD-based cameras to replace at some time the PMT-based cameras of planned future IACTs like AGIS and CTA. In this article, we present the basic design of such a camera as well as some important details to be taken into account.Comment: Poster shown at HEAD 2010, Big Island, Hawaii, March 1-4, 201

FACT -- The G-APD revolution in Cherenkov astronomy

Since two years, the FACT telescope is operating on the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD), equipped with solid light guides to increase the effective light collection area of each sensor. Since no sense-line is available, a special challenge is to keep the applied voltage stable although the current drawn by the G-APD depends on the flux of night-sky background photons significantly varying with ambient light conditions. Methods have been developed to keep the temperature and voltage dependent response of the G-APDs stable during operation. As a cross-check, dark count spectra with high statistics have been taken under different environmental conditions. In this presentation, the project, the developed methods and the experience from two years of operation of the first G-APD based camera in Cherenkov astronomy under changing environmental conditions will be presented.Comment: Proceedings of the Nuclear Science Symposium and Medical Imaging Conference (IEEE-NSS/MIC), 201

FACT - The First G-APD Cherenkov Telescope: Status and Results

The First G-APD Cherenkov telescope (FACT) is the first telescope using silicon photon detectors (G-APD aka. SiPM). It is built on the mount of the HEGRA CT3 telescope, still located at the Observatorio del Roque de los Muchachos, and it is successfully in operation since Oct. 2011. The use of Silicon devices promises a higher photon detection efficiency, more robustness and higher precision than photo-multiplier tubes. The FACT collaboration is investigating with which precision these devices can be operated on the long-term. Currently, the telescope is successfully operated from remote and robotic operation is under development. During the past months of operation, the foreseen monitoring program of the brightest known TeV blazars has been carried out, and first physics results have been obtained including a strong flare of Mrk501. An instantaneous flare alert system is already in a testing phase. This presentation will give an overview of the project and summarize its goals, status and first results