Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration.

The cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.

Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease.

BACKGROUND: For free-breathing cardiovascular magnetic resonance (CMR), the self-navigation technique recently emerged, which is expected to deliver high-quality data with a high success rate. The purpose of this study was to test the hypothesis that self-navigated 3D-CMR enables the reliable assessment of cardiovascular anatomy in patients with congenital heart disease (CHD) and to define factors that affect image quality. METHODS: CHD patients ≥2 years-old and referred for CMR for initial assessment or for a follow-up study were included to undergo a free-breathing self-navigated 3D CMR at 1.5T. Performance criteria were: correct description of cardiac segmental anatomy, overall image quality, coronary artery visibility, and reproducibility of great vessels diameter measurements. Factors associated with insufficient image quality were identified using multivariate logistic regression. RESULTS: Self-navigated CMR was performed in 105 patients (55% male, 23 ± 12y). Correct segmental description was achieved in 93% and 96% for observer 1 and 2, respectively. Diagnostic quality was obtained in 90% of examinations, and it increased to 94% if contrast-enhanced. Left anterior descending, circumflex, and right coronary arteries were visualized in 93%, 87% and 98%, respectively. Younger age, higher heart rate, lower ejection fraction, and lack of contrast medium were independently associated with reduced image quality. However, a similar rate of diagnostic image quality was obtained in children and adults. CONCLUSION: In patients with CHD, self-navigated free-breathing CMR provides high-resolution 3D visualization of the heart and great vessels with excellent robustness.

Diapiro de Salinas de AÑana: ¿Un diapiro con un overhang? Modelo 3D gravimetrico

Se presenta el mapa gravimétrico de la Cubeta Alavesa, donde se pueden localizar de forma clara los diapiros salinos aflorantes en la misma, y también otras estructuras también diapíricas situadas a mayor profundidad. Se ha modelizado en 3D, mediante dos técnicas gravimétricas diferentes, el diapiro de Salinas de Añana. El cual presenta una gran extensión en superficie pero que en cambio no se proyecta de la misma manera en profundidad, habiéndose detectado la presencia de una extensión lateral u overghang hacia el SW.

3D-tuoteyhdistelmämallien ja mittakuvien tuottaminen PDM-järjestelmästä

Tämä diplomityö on selvitystyö mittakuvien ja kolmiulotteisten CAD-mallien tuottamisesta. Mittakuvat ja 3D-CAD-mallit halutaan Neles-tuotemerkin omaaville tuotteille. Olennaisena osana työssä on tuotetiedonhallintajärjestelmä AtonPDM, koska mittakuvia ja malleja toivottaisiin hallittavan AtonPDM-järjestelmällä. Työ tehdään Metso Automationin (MA) Flow Control (FC) –liiketoimintalinjalle. Nykyiset mittakuvat aiheuttavat ongelmia sekä MA:ssa että asiakkaille. MA:ssa mittakuvien tekeminen kestää kauemmin kuin asiakas toivoisi. Nykyisen mittakuvaohjelmiston riittämättömät ominaisuudet aiheuttavat lisätyötä mittakuvien valmistuksessa. Asiakkaille mittakuvien viivästyminen on suunnittelua hidastava tekijä. Mittakuvissa olevat virheet ja puutteet vaikeuttavat asiakkaan suunnittelutyötä ja saattavat päästä läpi tarkatuksien myös loppusuunnitelmiin, jolloin seurauksena voi olla rahallisia menetyksiä. Tämän päivän putkistosuunnittelu hoidetaan suurimmaksi osaksi 3D-CADohjelmistoilla. Suunnittelua helpotetaan ja nopeutetaan valmiilla komponenttien 3Dmalleilla, joihin on liitetty tuotetietoa. Työssä on haastateltu MA:n henkilökuntaa, CAD-järjestelmien toimittajia ja asiakkaita. Haastattelut ovat työn tärkein tiedonlähde. Teoriatietoa on selvitetty kirjoista, lehdistä ja internetistä. Teoriaosiossa käydään läpi tuotetiedonhallinta (Product Data Management, PDM), tietokanta ja parametrinen mallintaminen. Työn lopputuloksena on pyritty saamaan kuvaus siitä miten tuotetaan 3D-CAD-mallit ja mittakuvat Neles-tuotteista käyttäen tiedonlähteenä AtonPDM:ää ja millaisia 3Dmallien ja mittakuvien tulee olla. Malleja ja mittakuvia tuottavaan järjestelmään on etsitty ratkaisuja CAD-ohjelmistoista. Ratkaisuja on verrattu keskenään ominaisuuksien, joustavuuden ja AtonPDM yhteensopivuuden perusteella.

Rockfall susceptibility assessment and remote geological mapping with LiDAR point clouds

Characterizing the geological features and structures in three dimensions over inaccessible rock cliffs is needed to assess natural hazards such as rockfalls and rockslides and also to perform investigations aimed at mapping geological contacts and building stratigraphy and fold models. Indeed, the detailed 3D data, such as LiDAR point clouds, allow to study accurately the hazard processes and the structure of geologic features, in particular in vertical and overhanging rock slopes. Thus, 3D geological models have a great potential of being applied to a wide range of geological investigations both in research and applied geology projects, such as mines, tunnels and reservoirs. Recent development of ground-based remote sensing techniques (LiDAR, photogrammetry and multispectral / hyperspectral images) are revolutionizing the acquisition of morphological and geological information. As a consequence, there is a great potential for improving the modeling of geological bodies as well as failure mechanisms and stability conditions by integrating detailed remote data. During the past ten years several large rockfall events occurred along important transportation corridors where millions of people travel every year (Switzerland: Gotthard motorway and railway; Canada: Sea to sky highway between Vancouver and Whistler). These events show that there is still a lack of knowledge concerning the detection of potential rockfalls, making mountain residential settlements and roads highly risky. It is necessary to understand the main factors that destabilize rocky outcrops even if inventories are lacking and if no clear morphological evidences of rockfall activity are observed. In order to increase the possibilities of forecasting potential future landslides, it is crucial to understand the evolution of rock slope stability. Defining the areas theoretically most prone to rockfalls can be particularly useful to simulate trajectory profiles and to generate hazard maps, which are the basis for land use planning in mountainous regions. The most important questions to address in order to assess rockfall hazard are: Where are the most probable sources for future rockfalls located? What are the frequencies of occurrence of these rockfalls? I characterized the fracturing patterns in the field and with LiDAR point clouds. Afterwards, I developed a model to compute the failure mechanisms on terrestrial point clouds in order to assess the susceptibility to rockfalls at the cliff scale. Similar procedures were already available to evaluate the susceptibility to rockfalls based on aerial digital elevation models. This new model gives the possibility to detect the most susceptible rockfall sources with unprecented detail in the vertical and overhanging areas. The results of the computation of the most probable rockfall source areas in granitic cliffs of Yosemite Valley and Mont-Blanc massif were then compared to the inventoried rockfall events to validate the calculation methods. Yosemite Valley was chosen as a test area because it has a particularly strong rockfall activity (about one rockfall every week) which leads to a high rockfall hazard. The west face of the Dru was also chosen for the relevant rockfall activity and especially because it was affected by some of the largest rockfalls that occurred in the Alps during the last 10 years. Moreover, both areas were suitable because of their huge vertical and overhanging cliffs that are difficult to study with classical methods. Limit equilibrium models have been applied to several case studies to evaluate the effects of different parameters on the stability of rockslope areas. The impact of the degradation of rockbridges on the stability of large compartments in the west face of the Dru was assessed using finite element modeling. In particular I conducted a back-analysis of the large rockfall event of 2005 (265'000 m3) by integrating field observations of joint conditions, characteristics of fracturing pattern and results of geomechanical tests on the intact rock. These analyses improved our understanding of the factors that influence the stability of rock compartments and were used to define the most probable future rockfall volumes at the Dru. Terrestrial laser scanning point clouds were also successfully employed to perform geological mapping in 3D, using the intensity of the backscattered signal. Another technique to obtain vertical geological maps is combining triangulated TLS mesh with 2D geological maps. At El Capitan (Yosemite Valley) we built a georeferenced vertical map of the main plutonio rocks that was used to investigate the reasons for preferential rockwall retreat rate. Additional efforts to characterize the erosion rate were made at Monte Generoso (Ticino, southern Switzerland) where I attempted to improve the estimation of long term erosion by taking into account also the volumes of the unstable rock compartments. Eventually, the following points summarize the main out puts of my research: The new model to compute the failure mechanisms and the rockfall susceptibility with 3D point clouds allows to define accurately the most probable rockfall source areas at the cliff scale. The analysis of the rockbridges at the Dru shows the potential of integrating detailed measurements of the fractures in geomechanical models of rockmass stability. The correction of the LiDAR intensity signal gives the possibility to classify a point cloud according to the rock type and then use this information to model complex geologic structures. The integration of these results, on rockmass fracturing and composition, with existing methods can improve rockfall hazard assessments and enhance the interpretation of the evolution of steep rockslopes. -- La caractérisation de la géologie en 3D pour des parois rocheuses inaccessibles est une étape nécessaire pour évaluer les dangers naturels tels que chutes de blocs et glissements rocheux, mais aussi pour réaliser des modèles stratigraphiques ou de structures plissées. Les modèles géologiques 3D ont un grand potentiel pour être appliqués dans une vaste gamme de travaux géologiques dans le domaine de la recherche, mais aussi dans des projets appliqués comme les mines, les tunnels ou les réservoirs. Les développements récents des outils de télédétection terrestre (LiDAR, photogrammétrie et imagerie multispectrale / hyperspectrale) sont en train de révolutionner l'acquisition d'informations géomorphologiques et géologiques. Par conséquence, il y a un grand potentiel d'amélioration pour la modélisation d'objets géologiques, ainsi que des mécanismes de rupture et des conditions de stabilité, en intégrant des données détaillées acquises à distance. Pour augmenter les possibilités de prévoir les éboulements futurs, il est fondamental de comprendre l'évolution actuelle de la stabilité des parois rocheuses. Définir les zones qui sont théoriquement plus propices aux chutes de blocs peut être très utile pour simuler les trajectoires de propagation des blocs et pour réaliser des cartes de danger, qui constituent la base de l'aménagement du territoire dans les régions de montagne. Les questions plus importantes à résoudre pour estimer le danger de chutes de blocs sont : Où se situent les sources plus probables pour les chutes de blocs et éboulement futurs ? Avec quelle fréquence vont se produire ces événements ? Donc, j'ai caractérisé les réseaux de fractures sur le terrain et avec des nuages de points LiDAR. Ensuite, j'ai développé un modèle pour calculer les mécanismes de rupture directement sur les nuages de points pour pouvoir évaluer la susceptibilité au déclenchement de chutes de blocs à l'échelle de la paroi. Les zones sources de chutes de blocs les plus probables dans les parois granitiques de la vallée de Yosemite et du massif du Mont-Blanc ont été calculées et ensuite comparés aux inventaires des événements pour vérifier les méthodes. Des modèles d'équilibre limite ont été appliqués à plusieurs cas d'études pour évaluer les effets de différents paramètres sur la stabilité des parois. L'impact de la dégradation des ponts rocheux sur la stabilité de grands compartiments de roche dans la paroi ouest du Petit Dru a été évalué en utilisant la modélisation par éléments finis. En particulier j'ai analysé le grand éboulement de 2005 (265'000 m3), qui a emporté l'entier du pilier sud-ouest. Dans le modèle j'ai intégré des observations des conditions des joints, les caractéristiques du réseau de fractures et les résultats de tests géoméchaniques sur la roche intacte. Ces analyses ont amélioré l'estimation des paramètres qui influencent la stabilité des compartiments rocheux et ont servi pour définir des volumes probables pour des éboulements futurs. Les nuages de points obtenus avec le scanner laser terrestre ont été utilisés avec succès aussi pour produire des cartes géologiques en 3D, en utilisant l'intensité du signal réfléchi. Une autre technique pour obtenir des cartes géologiques des zones verticales consiste à combiner un maillage LiDAR avec une carte géologique en 2D. A El Capitan (Yosemite Valley) nous avons pu géoréferencer une carte verticale des principales roches plutoniques que j'ai utilisé ensuite pour étudier les raisons d'une érosion préférentielle de certaines zones de la paroi. D'autres efforts pour quantifier le taux d'érosion ont été effectués au Monte Generoso (Ticino, Suisse) où j'ai essayé d'améliorer l'estimation de l'érosion au long terme en prenant en compte les volumes des compartiments rocheux instables. L'intégration de ces résultats, sur la fracturation et la composition de l'amas rocheux, avec les méthodes existantes permet d'améliorer la prise en compte de l'aléa chute de pierres et éboulements et augmente les possibilités d'interprétation de l'évolution des parois rocheuses.

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.

Radioterapia externa conformada 3D para o carcinoma de próstata: experiência do Instituto do Radium de Campinas com 285 pacientes

OBJETIVO: Reportar resultados de tratamentos do câncer de próstata com radioterapia conformada 3D realizados em uma única instituição. MATERIAIS E MÉTODOS: De julho de 1997 a janeiro de 2002, 285 pacientes consecutivos com câncer de próstata foram submetidos a radioterapia conformada 3D com dose mediana de 7.920 cGy na próstata e analisados retrospectivamente. A distribuição segundo o grupo de risco foi a seguinte: baixo risco - 95 (33,7%); risco intermediário - 66 (23,4%); alto risco - 121 (42,9%) pacientes. RESULTADOS: Em seguimento mediano de 53,6 meses (3,6-95,3 meses), sobrevidas atuariais global, causa específica, livre de metástases a distância e livre de recidiva bioquímica em cinco anos foram de 85,1%, 97,0%, 94,2% e 75,8%, respectivamente. Sobrevidas atuariais livre de toxicidade retal e urinária tardias em cinco anos foram de 96,4% e 91,1%, respectivamente. Ressecção transuretral pré-radioterapia conformada 3D e doses > 70 Gy em 30% do volume da bexiga implicaram maior toxicidade urinária tardia grau 2-3 em cinco anos (p = 0,0002 e p = 0,0264, respectivamente). CONCLUSÃO: A primeira experiência relatada de radioterapia conformada 3D no Brasil permitiu altas doses de radiação, com toxicidades retal e urinária aceitáveis. A existência de ressecção transuretral de próstata pré-radioterapia conformada 3D pode sinalizar maior risco de toxicidade urinária tardia grau 2-3 após irradiação. Restrição da dose < 70 Gy em 30% do volume da bexiga à tomografia de planejamento pode reduzir complicações urinárias tardias.

Resultados preliminares en la caracterización geométrica 3D de un litosoma arenoso de progradación deltaica mediante Georadar (GPR) (Fm. Arenisca de Roda, Eoceno, Cuenca de Graus-Tremp).

A set of GPR profiles have been recorded in order to determine the 3D geometry of a prograding delta-front sandbody (Roda sandstone formation, Eocene, Graus-Tremp basin). Common Mid Points (CMP) also have been recorded to obtain the velocity of the electromagnetic wave in ground. In order to build the topsurface of a 3D prism a set of topographic points have been acquired. Most of the GPR profiles are oriented parallel to the progradation direction (NNE-SSW) and show the expected geometries. The 3D prism has been built from the individual profiles, which shows the three dimensional geometry of the sandy lithosome.

An Advocacy for the Use of 3D Stem Cell Culture Systems for the Development of Regenerative Medicine: An Emphasis on Photoreceptor Generation

The availability of stem cells is of great promise to study early developmental stages and to generate adequate cells for cell transfer therapies. Although many researchers using stem cells were successful in dissecting intrinsic and extrinsic mechanisms and in generating specific cell phenotypes, few of the stem cells or the differentiated cells show the capacity to repair a tissue. Advances in cell and stem cell cultivation during the last years made tremendous progress in the generation of bona fide differentiated cells able to integrate into a tissue after transplantation, opening new perspectives for developmental biology studies and for regenerative medicine. In this review, we focus on the main works attempting to create in vitro conditions mimicking the natural environment of CNS structures such as the neural tube and its development in different brain region areas including the optic cup. The use of protocols growing cells in 3D organoids is a key strategy to produce cells resembling endogenous ones. An emphasis on the generation of retina tissue and photoreceptor cells is provided to highlight the promising developments in this field. Other examples are presented and discussed, such as the formation of cortical tissue, the epithelial gut or the kidney organoids. The generation of differentiated tissues and well-defined cell phenotypes from embryonic stem (ES) cells or induced pluripotent cells (iPSCs) opens several new strategies in the field of biology and regenerative medicine. A 3D organ/tissue development in vitro derived from human cells brings a unique tool to study human cell biology and pathophysiology of an organ or a specific cell population. The perspective of tissue repair is discussed as well as the necessity of cell banking to accelerate the progress of this promising field.