E2F1 activates p53 transcription through its distal site and participates in apoptosis induction in HPV-positive cells

AbstractThe p53 tumor suppressor protein, one of the most extensively studied proteins, plays a pivotal role in cellular checkpoints that respond to DNA damage to prevent tumorigenesis. However, the transcriptional control of the p53 gene has not been fully characterized. We report that the transcription factor E2F1 binds only to the E2F1 distal site of the p53 promoter in the human papillomavirus positive carcinoma HeLa cell line. Moreover, we showed that etoposide, a DNA damaging agent, activates p53 transcription through the E2F1 pathway. This increase correlates with apoptosis induction as disruption of this pathway led to reduced apoptosis stimulation by the DNA damaging agent

Probable presence of an ubiquitous cryptic mitochondrial gene on the antisense strand of the cytochrome oxidase I gene

<p>Abstract</p> <p>Background</p> <p>Mitochondria mediate most of the energy production that occurs in the majority of eukaryotic organisms. These subcellular organelles contain a genome that differs from the nuclear genome and is referred to as mitochondrial DNA (mtDNA). Despite a disparity in gene content, all mtDNAs encode at least two components of the mitochondrial electron transport chain, including cytochrome <it>c </it>oxidase I (Cox1).</p> <p>Presentation of the hypothesis</p> <p>A positionally conserved ORF has been found on the complementary strand of the <it>cox1 </it>genes of both eukaryotic mitochondria (protist, plant, fungal and animal) and alpha-proteobacteria. This putative gene has been named <it>gau </it>for gene antisense ubiquitous in mtDNAs. The length of the deduced protein is approximately 100 amino acids. In vertebrates, several stop codons have been found in the mt <it>gau </it>region, and potentially functional <it>gau </it>regions have been found in nuclear genomes. However, a recent bioinformatics study showed that several hypothetical overlapping mt genes could be predicted, including <it>gau; </it>this involves the possible import of the cytosolic AGR tRNA into the mitochondria and/or the expression of mt antisense tRNAs with anticodons recognizing AGR codons according to an alternative genetic code that is induced by the presence of suppressor tRNAs. Despite an evolutionary distance of at least 1.5 to 2.0 billion years, the deduced Gau proteins share some conserved amino acid signatures and structure, which suggests a possible conserved function. Moreover, BLAST analysis identified rare, sense-oriented ESTs with poly(A) tails that include the entire <it>gau </it>region. Immunohistochemical analyses using an anti-Gau monoclonal antibody revealed strict co-localization of Gau proteins and a mitochondrial marker.</p> <p>Testing the hypothesis</p> <p>This hypothesis could be tested by purifying the <it>gau </it>gene product and determining its sequence. Cell biological experiments are needed to determine the physiological role of this protein.</p> <p>Implications of the hypothesis</p> <p>Studies of the <it>gau </it>ORF will shed light on the origin of novel genes and their functions in organelles and could also have medical implications for human diseases that are caused by mitochondrial dysfunction. Moreover, this strengthens evidence for mitochondrial genes coded according to an overlapping genetic code.</p

Miniaturisation d'antennes en bande VHF pour applications spatiales

Le développement de l électronique embarquée et miniaturisée est pleinement d actualité de nos jours, dans les domaines tels que l armement, la médecine, et les télécommunications. La miniaturisation des antennes large-bande, opérationnelles sur plus d une décade, présentent un défi particulier. Ces travaux de thèse proposent de travailler sur la miniaturisation d une antenne spirale, afin d en réduire l encombrement, à savoir son diamètre, tout en conservant au mieux ses caractéristiques de rayonnement et polarisation intrinsèques. Cette recherche sera appliquée à la bande des Très hautes Fréquence (Very High Frequencies VHF), allant de 30MHz à 300MHz La géométrie inédite proposée consiste à associer à une antenne spirale un ensemble d anneaux résonnants, dont le diamètre n excède pas celui de la spirale, et permettant de diminuer la fréquence basse de fonctionnement. Pour un ensemble de cinq anneaux associé à la spirale, la réduction de la fréquence basse de fonctionnement est de plus de 30%. Pour deux antennes spirales de même fréquence basse de fonctionnement, l antenne miniaturisée a donc un diamètre réduit de 30%, soit une surface réduite de 50%. Les performances de l état de l art d après lesquelles les réductions sur le diamètre des antennes spirales n excèdent pas 15% sont donc dépassées. De plus, d après cet état de l art, les méthodes de réduction appliquées aux antennes large bande dégradent en général le gain et l axial ratio dans les bandes basses de fréquences de fonctionnement. La méthode proposée permet de conserver l efficacité de l antenne, voire de l augmenter, dans les fréquences proches de la fréquence basse de fonctionnement. Le rayonnement de l antenne spirale miniaturisée dans la bande passante de l antenne sans anneaux n est pour autant pas modifiée. Ces résultats très encourageant ont été confirmés par la mesure d antennes spirales miniaturisées, réalisées pour un diamètre de 8cm et de 1m : une réduction de 30% du diamètre sans dégradation du rayonnement a été observée. Les mesures ont par ailleurs donné lieu à l étude de la réalisation d une antenne en bande VHF, avec pour implication les problématiques de réalisation (masse, encombrement, résistance mécanique) et de mesure (isolation, effets parasites en VHF avec une longueur d onde de 4m).Miniaturizing electronic devices is a great challenge in crucial research domain such as defense, medicine, and telecommunications. Wideband antenna miniaturization operating on more than a decade is a particular issue. This thesis presents an original method for miniaturizing a spiral antenna, reducing its diameter while keeping its bandwidth, its radiating performances and its axial ratio characteristics. This method is applied to UHF spiral antenna (from 750MHz) and VHF antenna (from 75MHz). The new geometry adds stacked resonant rings to an Archimedean spiral antenna. Their diameter are the same, hence no rise of the antenna diameter. For a 5-ring spiral antenna, the lowest operating frequency reduction is higher than 30%. That is equivalent to a 30% reduction of the diameter for two antennas sharing the same lowest operating frequency, hence a 50% reduction of the area of the antenna. These reduction factors surpass the reduction factors of the state of art of 15%. Besides, according to the state of art, the miniaturizing techniques imply some degradation of the gain and axial ratio performances at the lowest operating frequencies. The new method improves on the other hand these characteristics at these frequencies. At higher frequencies, the rings do not interfere with the matching of neither the spiral antenna nor its radiation characteristics. These results were validated by fabricated antenna measurements. A 30% reduction of the diameter was obtained on a 5-ring-8cm-large antenna as well as on a 5-ring-1m-large antenna. No impairment was noticed on the radiation of the antennas, even at the lowest operating frequencies. The thesis also discusses the difficulties which came in addition for the fabrication (mass, size and mechanical resistance) and measurement (radiation interferences and measurement isolation the wavelength being 4m) of the VHF antenna.TOULOUSE-INP (315552154) / SudocSudocFranceF

Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries

One root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. A rapid, performance friendly and low cost method to detect rabies virus (RABV) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries.; We evaluated a rapid immunodiagnostic test (RIDT) in comparison with the standard fluorescent antibody test (FAT) and confirmed the detection of the viral RNA by real time reverse transcription polymerase chain reaction (RT-qPCR). Our analysis is a multicentre approach to validate the performance of the RIDT in both a field laboratory (N'Djamena, Chad) and an international reference laboratory (Institut Pasteur, Paris, France). In the field laboratory, 48 samples from dogs were tested and in the reference laboratory setting, a total of 73 samples was tested, representing a wide diversity of RABV in terms of animal species tested (13 different species), geographical origin of isolates with special emphasis on Africa, and different phylogenetic clades. Under reference laboratory conditions, specificity was 93.3% and sensitivity was 95.3% compared to the gold standard FAT test. Under field laboratory conditions, the RIDT yielded a higher reliability than the FAT test particularly on fresh and decomposed samples. Viral RNA was later extracted directly from the test filter paper and further used successfully for sequencing and genotyping.; The RIDT shows excellent performance qualities both in regard to user friendliness and reliability of the result. In addition, the test cassettes can be used as a vehicle to ship viral RNA to reference laboratories for further laboratory confirmation of the diagnosis and for epidemiological investigations using nucleotide sequencing. The potential for satisfactory use in remote locations is therefore very high to improve the global knowledge of rabies epidemiology. However, we suggest some changes to the protocol, as well as careful further validation, before promotion and wider use

The Pointing System of the Herschel Space Observatory. Description, Calibration, Performance and Improvements

We present the activities carried out to calibrate and characterise the performance of the elements of attitude control and measurement on board the Herschel spacecraft. The main calibration parameters and the evolution of the indicators of the pointing performance are described, from the initial values derived from the observations carried out in the performance verification phase to those attained in the last year and half of mission, an absolute pointing error around or even below 1 arcsec, a spatial relative pointing error of some 1 arcsec and a pointing stability below 0.2 arsec. The actions carried out at the ground segment to improve the spacecraft pointing measurements are outlined. On-going and future developments towards a final refinement of the Herschel astrometry are also summarised. A brief description of the different components of the attitude control and measurement system (both in the space and in the ground segments) is also given for reference. We stress the importance of the cooperation between the different actors (scientists, flight dynamics and systems engineers, attitude control and measurement hardware designers, star-tracker manufacturers, etc.) to attain the final level of performance.Comment: 28 pages, 8 figures, accepted for publication in Experimental Astronom

Le Produit Concept Virtuel pour l'évaluation de produit: Le cas ROSSIGNOL SA

Cette étude est le fruit de notre collaboration avec l'entreprise ROSSIGNOL SA, spécialisée dans les collecteurs de déchets. L'objectif était d'évaluer les apports de la réalité virtuelle, dans les phases préliminaires du processus de conception. Pour cela, nous avons défini une nouvelle représentation intermédiaire virtuelle, le Produit Concept Virtuel (PCV). Plus qu'une maquette virtuelle, le PCV permet de mettre en situation un produit et d'évaluer ses fonctionnalités. Nous avons tenté de mettre en évidence les avantages de cette nouvelle représentation virtuelle. Le projet sur lequel s'est basée notre collaboration était la réalisation d'un PCV de collecteur de déchets innovant. Les résultats ont montré que le PCV a permis d'amélioré la compréhension du produit concept, facilitant ainsi les prises de décisions qui orientent les choix de conception. De plus, le PCV a permis d'augmenter le nombre de cycles d'évaluations

Inference of Wi-Fi Busy Time Fraction based on Markov Chains

IEEE 802.11 has emerged as a vital wireless network access technology for mobile devices. By providing the potential for high connectivity speeds, this technology has led to a huge rise in the number of access points (APs). In such environments, mobile devices have the choice to join several Wi-Fi networks. Despite its importance to user Quality of Experience (QoE), the AP selection is still trivial since it focuses at best on the received signal strength if not only the user's history. Crucial metrics that capture the overall dynamics of the AP load condition, such as the network load, are not taken into account. In this paper, we propose to use the Busy Time Fraction (BTF) as a metric to choose the best AP to attach to. The BTF level of a given channel is inferred based on the frame aggregation scheme proposed since the 802.11n standard. In this regard, we build a proof of concept system, FAM (Frame Aggregation based method) that leverages the theoretical frame aggregation levels of a probe traffic returned by two analytical Markovian models and the measured ones in order to estimate not only the BTF but also the nature of the traffic. We validate the accuracy of our proposed approach against ns-3 simulations under several scenarios

Renewed global partnerships and redesigned roadmaps for rabies prevention and control

Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this "incurable wound" persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination