This study investigates the influence of wall roughness on large-scale structures within turbulent boundary layers, using wall-parallel stereoscopic Particle Image Velocimetry (PIV) at a Reynolds number of 1.3 × 106m−1. The data was collected at a distance of = 2.8 from the wall under adverse = 0.98, small = −0.04, and favorable = −0.60 pressure conditions. It was observed that coherent structures larger than the field of view (FOV) modify their length scales, streamwise orientation and spanwise distribution in response to changes in surface roughness and pressure gradients. The study also examines implications wall similarity hypothesis by comparing the development of these large-scale structures over smooth and rough wall flows under small pressure gradient and identical test conditions. Notably, the results reveal that existing models may not accurately capture the observed dynamics, as evidenced by discrepancies with previous studies, thereby enhancing our understanding of turbulent flow dynamics in non-equilibrium conditions. / Master of Science / Understanding the behavior of turbulent air and water flows around objects is crucial for improving engineering designs and various environmental applications. This study investigates how surface roughness, such as on ship hulls or aircraft wings, affects the movement of large-scale structures in turbulent flows. Advanced flow visualization techniques were employed to observe these turbulent structures in detail over homogeneous roughness and varying pressure gradients. The findings demonstrate that rough surfaces significantly alter the movement and interaction of these large-scale turbulent structures. Specifically, favorable pressure gradients result in organized flow structures, whereas adverse pressure gradients cause reorganization, altering the size and distribution of these structures within the flow. By comparing smooth and rough surfaces under identical conditions, the study aims to evaluate how well existing hypotheses predict these changes. The results highlight that rough surfaces and pressure variations critically impact turbulent flow characteristics, emphasizing the need for more sophisticated criteria to improve predictions and designs in real-world applications. This research provides valuable insights into the dynamics of turbulent flows over rough surfaces and stresses the importance of refining current models for better accuracy in practical engineering applications.

Brown marmorated stink bug, Halyomorpha halys (Stål), is a crossover pest impacting agriculture and invading urban environments. Studies were conducted to better understand the management of the bug through its physiology, behavior and susceptibility to insecticidal intervention. Halyomopha halys exhibit great variability in overwintering site selection with choices including manmade structures and tree bark. Because of these diverse sites, the bug must have the ability to withstand varying conditions throughout the overwintering cycle. We were able to determine that H. halys is chill intolerant and capable of adapting its tolerance to temperatures by season, sex, and location of acclimation. The mean supercooling point (± SEM) in the winter in Minnesota was -17.06°C ± 0.13° and in Virginia was -13.90°C ± 0.09°. Laboratory experiments conducted in Blacksburg, VA were able to determine baseline lethal high temperatures over time against H. halys adults. To achieve 100% mortality, temperatures fell between 45°C and 50°C, 40°C and 45°C, and 42°C and 45°C, over 15-min, 1-h, and 4-h, respectively. Moving forward, we were able to utilize this information to develop heat treatment guidelines for export shipping cargo infested with overwintering H. halys. In a controlled field experiment, we determined that exposing the coldest areas of an infested vehicle to temperatures greater than 50°C for a minimum of 15 minutes resulted in 100% mortality of overwintering BMSB adults. In 2012 and 2013, citizen scientists were recruited through Virginia Cooperative Extension to assist in evaluating several in home light traps designed to help eradicate overwintering H. halys adults in homes. Over the course of the two year study, fourteen houses participated in the study with 72% of those houses having stink bug activity. It was found that the most effective trap was an aluminum foil pan trap. In 2013, the trap was 19 times more effective at catching stink bug adults than any other trap tested. In September of 2014, a near-field experiment was conducted to determine the residual efficacy of several recommended and labeled insecticides for treatment of homes against invading H. halys adults. This study used constructed window screen bags that were dipped in insecticide solution. After the initial treatment, bugs were exposed to the bags for 24h weekly, up to 54 days after treatment (DAT). It was determined that 2 DAT all insecticides had activity except for indoxacarb. All insecticides lost efficacy after 29 DAT except for lambda-cyhalothrin, beta-cyfluthrin, beta-cyfluthrin + imidacloprid, lambda-cyhalothrin + thiamethoxam, and dinotefuran, which had some measureable activity even after 40 DAT. Each of these insecticides contained a pyrethroid alone or in combination with a neonicotinoid. Laboratory bioassays were conducted to determine the LC50 values of clothianidin, dinotefuran, imidacloprid, and thiamethoxam against H. halys nymphs using a systemic application method. Those LC50 values were found to be 0.077, 0.013, 0.068, and 0.018 ppm, respectively. Field experiments conducted in Virginia in 2012 and 2013 showed a significant reduction of stink bug damage using two soil applications of neonicotinoid insecticides in pepper and tomato. In North Carolina, a single drip irrigation application significantly reduced stink bug damage in 2012 and 2014 using dinotefuran or imidacloprid. / Ph. D.

Pulse63 is a live streaming and projection mapping installation at architectural scale developed for Moogfest 2018, in Durham, NC. The project explores the relationship between telepresence and "superarchitecture". This paper will consider the artistic aspects of these terms through the work of Eduardo Kac, Pipilotti Rist, Doug Aitken, and others. The intent is to create a visual installation at Moogfest that works as a monolithic visual signifier by applying artistically mediated telepresence and "superarchitecture." / Master of Fine Arts / Pulse63 is an outdoor art installation at Moogfest 2018 in Durham, NC. It uses live concert videos as source material for projection onto a 10 storey building in downtown Durham, NC. The intent of the installation is to create an artistic interpretation of what is happening now from multiple venues within the city and the festival as a singular public art installation.

The first focus of this thesis is a basic scientific research in the field of super-regenerative receivers (SRRs) and, in particular, super-regenerative oscillators (SROs). In chapter 3, a theoretical analysis of SROs is performed and its nonlinear behavior is studied in both time and frequency domains. The cross-coupled architecture is studied as a special case, however, widely used topology in the SRO design. The start-up and decay envelopes of the oscillator output are studied in relation to the input. The SRO start-up time and the maximal achievable quenching frequency are investigated. For phase modulation purposes, the relation between the initial phases of the input and output signals is investigated. In addition, a frequency-domain analysis is performed to ease the characterization of test circuits at high frequencies where time-domain measurements are not possible. The analytical results are verified by circuit-level simulations and measurements of a 2.4-GHz SRO. This study provides design guidelines for the design of SROs and helps in determining the optimal system parameters when targeting both amplitude and phase modulations. The SRO concept and its phase sampling capability are further studied in chapter 4. For this purpose, two SRO circuits operating around 60GHz are investigated, designed − in both CMOS and SiGe BiCMOS technologies − and characterized. Different circuit techniques are studied in order to improve the energy efficiency and maximize the switching speed. For instance, a novel quenching technique to maximize the power efficiency is presented. This circuit approach includes a pulse generator, which generates the quench signal allowing to switch the SRO with a minimum duty cycle. In fact, the SRO input is sampled at the onset of oscillation and, therefore, it is unnecessary for the oscillator to run for a long time in its steady state. This allows to minimize the on-time of the SRO and to considerably reduce its power consumption. Compared to the state of the art, the circuit achieves by far the highest power efficiency of 21.7%. In addition, a novel switching scheme is presented in order to maximize the quenching speed. This approach enables to greatly reduce the switching time constant, allowing to improve the SRO quench rate by approximately a factor of 3 compared to the state of the art. A record switching frequency of up to 10GHz is achieved. The second focus of this thesis is the investigation of on-off-keying (OOK) receivers operating at a carrier frequency of 60GHz. OOK modulation schemes have the advantage of low circuit complexity and, therefore, low power consumption and small chip area. The drawback of low spectral efficiency can be mitigated by the large bandwidth at mm-wave frequencies, in particular, at the 60-GHz ISM band, 9GHz from 57 to 66GHz, which allows to achieve high data rates. The goals of this study are enhancing the speed, maximizing the energy efficiency and improving the sensitivity. For this purpose, several circuit approaches are studied. A highly efficient envelope detector and a novel limiting amplifier architecture with simultaneously large bandwidth and high gain ensure high-speed low-power operation. A high-gain low noise amplifier is employed to increase the sensitivity. A feedforward dc-offset cancellation technique is used to ensure the proper operation of the receiver. As a proof of concept, the chips are implemented in a 130-nm SiGe BiCMOS technology. The OOK receiver achieves a record data rate of up to 20Gb/s at a bit-error-rate less than 10^(-12). The low power consumption and the ultra high speed capability allow a highly energy-efficient operation of only 2.2pJ/bit. Finally, this thesis studies the design of 60-GHz amplifiers. In fact, one of the main challenges of transmitting data at mm-wave frequencies is the high free-space path loss, which limits the transmission range. To alleviate this issue, amplifiers with high output power at the transmitter side and with low noise figure and high gain at the receiver side are required. Chapter 6 investigates the design of a low noise amplifier (LNA), with the study focus being achieving simultaneously large bandwidth, high gain, low noise figure and low power consumption in order to enable a high-speed receiver with high power efficiency and high range. The LNA achieves a bandwidth of 23GHz, a gain of 23.8dB and an average noise figure of 3.2dB and consumes only 8mW, remarkably improving the state of the art. In addition, this chapter presents the investigation and design of a 60-GHz power amplifier with an output power of up to 14.7dBm and a small chip area to ensure a sufficient communication range at the transmitter side.

Yes / As a type of excellent reinforcing filler, super-fine stainless wire (SSW) can form widely distributed network in reactive powder concrete (RPC) to transfer crack tip stresses as well as inhibit the initiation and propagation of cracks, leading to significant improvement of flexural toughness of RPC. In this paper, the flexural toughness of RPC beams and plates reinforced with 1% and 1.5% by vol. of SSWs was investigated, and its calculation model was established according to the composite material theory. Experimental results showed that the flexural toughness of unnotched beams fabricated with RPC containing 1.5% SSWs is 146.5% higher than that of control RPC without SSWs according to load-deflection relationships. The equivalent flexural strength of notched RPC beams is enhanced by 80.0% as SSW content increases from 1% to 1.5%. The limitation ability of SSWs on crack mouth opening can be used to evaluate the flexural toughness of composites. An addition of 1.5% SSWs leads to 201.9% increase of flexural toughness of RPC plates in accordance with load-deflection relationships. The calculation model based on the composite material theory can accurately describe the toughening effect of SSWs on RPC beams and plates. The enhancement of flexural toughness of RPC caused by SSWs is beneficial for improving the safety of structures as well as broadening the engineering applications of composites. / National Key Research and Development Program of China (2018YFC0705601) and China Postdoctoral Science Fundation (2019M651116).

Yes / Super-fine stainless wires (SSWs) with micron diameter and large specific surface area can simultaneously strengthen and toughen reactive powder concrete (RPC) at low volume fraction, so SSW reinforced RPC composites have potential for developing infrastructures bearing fatigue load or with aseismic requirements. In this paper, the uniaxial compressive fatigue characteristics of such composites under high stress levels were investigated, and the modification mechanisms of SSWs to RPC were revealed through failure state and microstructure analyses. The results showed that incorporating only 0.5 vol.% SSWs into RPC enables the fatigue life and energy dissipation capacity to increase by 252.0% and 262.3%, meanwhile, the fatigue limit strength of composites at the failure probability of 50% reaches up to 76.6% of static uniaxial compressive strength, due to the improvement effect on microstructure compactness, inhibiting effect on flaw initiation, and the ability to convert single main crack into radial multiple micro cracks centered on SSWs. Furthermore, the average maximum fatigue strain and residual strain of composites are improved by 73.7% and 87.2%, respectively, which can be ascribed to the bridging, debonding and being pulled-off effect of SSWs. It can be therefore concluded that the incorporation of SSWs endows RPC with excellent fatigue performance, thus further enlarging the application of composites. / The authors would like to thank the National Science Foundation of China (51908103 and 51978127), and the China Postdoctoral Science Foundation (2019M651116) for providing funding to carry out this investigation.

I denna mastersuppsats undersöker författaren det möjliga värdet av karriärteorier. Värdet är empiriskt undersökt med utgångspunkt I tio fallstudier av intervjutyp. Författaren kommer till slutsatsen att kunskap om karriärteorier möjliggör en bättre förståelse av hur individer fattar karriär- och utbildningsbeslut. Författaren argumenterar för att kunskap om karriärteorier är, och bör vara relevant för vägledarnas profession och yrkesroll. / In this master thesis the author investigates the potential value of career theories. The potential value is empirically investigated on the basis of ten interviewee case studies. The author reaches the conclusion that career theories does enable a better understanding of how individuals make career- and educational choices and argues that knowledge of career theories is, and should be relevant for the guidance counsellors professional role.

Les carcinomes de la corticosurrénale (CC) sont des tumeurs malignes rares dont le pronostic est globalement sombre et les thérapeutiques encore limitées, la chirurgie étant le seul traitement efficace. Il est donc important de comprendre les mécanismes impliqués dans le développement et l'agressivité des CC. L’activation constitutive de la voie de signalisation Wnt/b-caténine est fréquente dans les CC (40%) et est associée à un caractère agressif. L’objectif de mon projet de thèse était d’étudier l’implication de la voie Wnt/β-caténine dans la tumorigenèse corticosurrénalienne. La lignée cellulaire humaine H295R, issue d’un CC présente une activation de la voie Wnt/β-caténine qui a pour origine une mutation activatrice de la β-caténine. Nous avons montré que l'invalidation de la β-caténine dans les cellules H295R inhibe l'activité transcriptionnelle de la voie Wnt/β-caténine, diminue la prolifération, augmente l'apoptose et bloque la progression du cycle cellulaire. De plus, nous avons montré que la voie Wnt/b-caténine est essentielle au développement tumoral de xénogreffes de ces cellules chez la souris. L’activation de la voie Wnt/b-caténine participe à la tumorigenèse de nombreux organes en régulant l’expression de gènes impliqués par exemple dans la prolifération, la survie cellulaire ou l'adhésion. Afin de mieux comprendre comment la voie Wnt/β-caténine participe à la tumorigenèse corticosurrénalienne, nous avons cherché à identifier les gènes cibles de cette voie dans les CC. L’analyse des transcriptomes de deux cohortes indépendantes de CC et des cellules H295R avec ou sans invalidation de la β-caténine a permis d’identifier des gènes dont l'expression est corrélée à l'activation de la voie Wnt/b-caténine. Nous avons montré que parmi ces gènes, AFF3 est essentiel pour transmettre les effets de l'activation de la voie Wnt/b-caténine dans les carcinomes de la corticosurrénale. En effet, AFF3 est un gène cible direct de la voie Wnt/b-caténine et son invalidation dans les cellules corticosurrénaliennes H295R diminue la prolifération cellulaire et déclenche l'apoptose à l'image de l'invalidation de la b-caténine. AFF3 est une protéine nucléaire, localisée au niveau des speckles qui sont impliqués dans l'épissage des ARNm. De plus, AFF3 interagit avec le P-TEFb (CDK9/CyclineT1/2) au sein du Super elongation complex (SEC) nécessaire à l’élongation de la transcription des ARNm par l'ARN polymérase II. Nous avons ainsi montré dans les cellules corticosurrénaliennes H295R, que la surexpression d'AFF3 altère l’organisation des speckles et la localisation de CDK9 et Cycline T1. En conclusion, ce travail a permis d'identifier une nouvelle cible transcriptionnelle de la voie de signalisation Wnt/b-caténine, AFF3, qui code pour un médiateur important des effets de l'activation de cette voie dans la tumorigenèse corticosurrénalienne. AFF3 agirait notamment en altérant la structure des speckles et en interagissant avec le P-TEFb qui sont importants respectivement pour l'épissage des ARNm et la transcription. Ces résultats conduisent à une meilleure compréhension de la tumorigenèse corticosurrénalienne et permettent d'envisager le P-TEFb et le SEC comme de nouvelles cibles thérapeutiques pour le traitement des CC. / Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic option. Currently, surgical resection is considered the only effective treatment. It is therefore essential to understand the molecular mechanisms involved in ACC development in order to improve their clinical management. Activation of the Wnt/b-catenin signaling pathway is frequent (40%) in ACC and is associated with poor prognosis. The aim of my thesis was to study the involvement of the Wnt/b-catenin signaling pathway in adrenocortical tumorigenesis. The human cell line H295R, derived from an ACC, carries the S45P β-catenin mutation which leads to constitutive β-catenin/TCF transcriptional activity. In the ACC cell line H295R we show that β-catenin silencing resulted in a decreased transcriptional activity of the Wnt/b-catenin signaling, cell cycle alterations, a decreased cell proliferation and an increased apoptosis. Moreover we show that β-catenin silencing abolish xenograft development of H295R adrenocortical cells. Aberrant activation of the Wnt/b-catenin signaling promotes tumorigenesis of several organs by enhancing expression of genes involved in proliferation, cell survival or cell adhesion. To better understand the role of the Wnt/b-catenin signaling in adrenocortical tumorigenesis, we wanted to identify target genes of this pathway in ACC. Combined transcriptomic analysis on two independent cohorts of ACC and on H295R adrenocortical cells with or without β-catenin silencing allow us to identify alterations of gene expression due to aberrant Wnt/βcatenin pathway activation. Among these genes, we show that AFF3 is essential to mediate the effect of the activation of the Wnt/β-catenin signaling pathway in adrenocortical cancer. Indeed, AFF3 is a direct target gene of the Wnt/b-catenin and its silencing in H295R adrenocortical cells induces a decreased cell proliferation and an increased apoptosis similar to that induced by b-catenin silencing. AFF3 is a nuclear protein located in nuclear speckles, which serve as a reservoir of factors participating in mRNA splicing. Moreover, AFF3 interacts with P-TEFb (CDK9/CyclinT1/2) in the Super elongation complex (SEC) required for transcriptional elongation of mRNA by RNA polymerase II. In H295R adrenocortical cells, we show that strong overproduction of AFF3 altered the structural organization of nuclear speckles and the localization of CDK9 and Cycline T1. In conclusion, this study has identified a new transcriptional target of the Wnt/β-catenin signaling pathway, AFF3, which encodes an important mediator of this pathway in adrenocortical tumorigenesis. AFF3 might especially act by affecting the structural organization of speckles and interacting with the P-TEFb, which are respectively involved in mRNA splicing and transcription. These results provide a better understanding of the biological process involved in ACC development and suggest that P-TEFb and SEC could be new therapeutic targets for the treatment of ACC.

Les transferts horizontaux de gènes (THG) ont été démontrés pour jouer un rôle important dans l'évolution des procaryotes. Leur impact a été le sujet de débats intenses, ceux-ci allant même jusqu'à l'abandon de l'arbre des espèces. Selon certaines études, un signal historique dominant est présent chez les procaryotes, puisque les transmissions horizontales stables et fonctionnelles semblent beaucoup plus rares que les transmissions verticales (des dizaines contre des milliards). Cependant, l'effet cumulatif des THG est non-négligeable et peut potentiellement affecter l'inférence phylogénétique. Conséquemment, la plupart des chercheurs basent leurs inférences phylogénétiques sur un faible nombre de gènes rarement transférés, comme les protéines ribosomales. Ceux-ci n'accordent cependant pas autant d'importance au modèle d'évolution utilisé, même s'il a été démontré que celui-ci est important lorsqu'il est question de résoudre certaines divergences entre ancêtres d'espèces, comme pour les animaux par exemple. Dans ce mémoire, nous avons utilisé des simulations et analyser des jeux de données d'Archées afin d'étudier l'impact relatif des THG ainsi que l'impact des modèles d'évolution sur la précision phylogénétique. Nos simulations prouvent que (1) les THG ont un impact limité sur les phylogénies, considérant un taux de transferts réaliste et que (2) l'approche super-matrice est plus précise que l'approche super-arbre. Nous avons également observé que les modèles complexes expliquent non seulement mieux les données que les modèles standards, mais peuvent avoir un impact direct sur différents groupes phylogénétiques et sur la robustesse de l'arbre obtenu. Nos résultats contredisent une publication récente proposant que les Thaumarchaeota apparaissent à la base de l'arbre des Archées. / Horizontal gene transfer (HGT) had been demonstrated to play an important role in the evolution of prokaryotes. Their impact on phylogeny was the subject of a heated debate, with some proposing that the concept of a species tree should be abandoned. The phylogeny of prokaryotes does contain a major part of the historical signal, because stable and functional horizontal transmissions appear to be by far rarer than vertical transmissions (tens versus billions). However, the cumulative effect of HGT is non-negligible and can potentially affect phylogenetic inference. Therefore, most researchers base their phylogenetic inference on a low number of rarely transferred genes such as ribosomal proteins, but they assume the selection of the model of evolution as less important, this despite the fact that it has been shown of prime importance for much less deep divergences, e.g. like animals. Here, we used a combination of simulations and of real data from Archaea to study the relative impact of HGT and of the inference methods on the phylogenetic accuracy. Our simulations prove that (1) HGTs have a limited impact on phylogeny, assuming a realistic rate and (2) the supermatrix is much more accurate than the supertree approach. We also observed that more complex models of evolution not only have a better fit to the data, but can also have a direct impact on different phylogenetic groups and on the robustness of the tree. Our results are in contradiction to a recent publication proposing that the Thaumarchaeota are at the base of the Archaeal tree.

Les carcinomes de la corticosurrénale (CC) sont des tumeurs malignes rares dont le pronostic est globalement sombre et les thérapeutiques encore limitées, la chirurgie étant le seul traitement efficace. Il est donc important de comprendre les mécanismes impliqués dans le développement et l'agressivité des CC. L’activation constitutive de la voie de signalisation Wnt/b-caténine est fréquente dans les CC (40%) et est associée à un caractère agressif. L’objectif de mon projet de thèse était d’étudier l’implication de la voie Wnt/β-caténine dans la tumorigenèse corticosurrénalienne. La lignée cellulaire humaine H295R, issue d’un CC présente une activation de la voie Wnt/β-caténine qui a pour origine une mutation activatrice de la β-caténine. Nous avons montré que l'invalidation de la β-caténine dans les cellules H295R inhibe l'activité transcriptionnelle de la voie Wnt/β-caténine, diminue la prolifération, augmente l'apoptose et bloque la progression du cycle cellulaire. De plus, nous avons montré que la voie Wnt/b-caténine est essentielle au développement tumoral de xénogreffes de ces cellules chez la souris. L’activation de la voie Wnt/b-caténine participe à la tumorigenèse de nombreux organes en régulant l’expression de gènes impliqués par exemple dans la prolifération, la survie cellulaire ou l'adhésion. Afin de mieux comprendre comment la voie Wnt/β-caténine participe à la tumorigenèse corticosurrénalienne, nous avons cherché à identifier les gènes cibles de cette voie dans les CC. L’analyse des transcriptomes de deux cohortes indépendantes de CC et des cellules H295R avec ou sans invalidation de la β-caténine a permis d’identifier des gènes dont l'expression est corrélée à l'activation de la voie Wnt/b-caténine. Nous avons montré que parmi ces gènes, AFF3 est essentiel pour transmettre les effets de l'activation de la voie Wnt/b-caténine dans les carcinomes de la corticosurrénale. En effet, AFF3 est un gène cible direct de la voie Wnt/b-caténine et son invalidation dans les cellules corticosurrénaliennes H295R diminue la prolifération cellulaire et déclenche l'apoptose à l'image de l'invalidation de la b-caténine. AFF3 est une protéine nucléaire, localisée au niveau des speckles qui sont impliqués dans l'épissage des ARNm. De plus, AFF3 interagit avec le P-TEFb (CDK9/CyclineT1/2) au sein du Super elongation complex (SEC) nécessaire à l’élongation de la transcription des ARNm par l'ARN polymérase II. Nous avons ainsi montré dans les cellules corticosurrénaliennes H295R, que la surexpression d'AFF3 altère l’organisation des speckles et la localisation de CDK9 et Cycline T1. En conclusion, ce travail a permis d'identifier une nouvelle cible transcriptionnelle de la voie de signalisation Wnt/b-caténine, AFF3, qui code pour un médiateur important des effets de l'activation de cette voie dans la tumorigenèse corticosurrénalienne. AFF3 agirait notamment en altérant la structure des speckles et en interagissant avec le P-TEFb qui sont importants respectivement pour l'épissage des ARNm et la transcription. Ces résultats conduisent à une meilleure compréhension de la tumorigenèse corticosurrénalienne et permettent d'envisager le P-TEFb et le SEC comme de nouvelles cibles thérapeutiques pour le traitement des CC. / Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic option. Currently, surgical resection is considered the only effective treatment. It is therefore essential to understand the molecular mechanisms involved in ACC development in order to improve their clinical management. Activation of the Wnt/b-catenin signaling pathway is frequent (40%) in ACC and is associated with poor prognosis. The aim of my thesis was to study the involvement of the Wnt/b-catenin signaling pathway in adrenocortical tumorigenesis. The human cell line H295R, derived from an ACC, carries the S45P β-catenin mutation which leads to constitutive β-catenin/TCF transcriptional activity. In the ACC cell line H295R we show that β-catenin silencing resulted in a decreased transcriptional activity of the Wnt/b-catenin signaling, cell cycle alterations, a decreased cell proliferation and an increased apoptosis. Moreover we show that β-catenin silencing abolish xenograft development of H295R adrenocortical cells. Aberrant activation of the Wnt/b-catenin signaling promotes tumorigenesis of several organs by enhancing expression of genes involved in proliferation, cell survival or cell adhesion. To better understand the role of the Wnt/b-catenin signaling in adrenocortical tumorigenesis, we wanted to identify target genes of this pathway in ACC. Combined transcriptomic analysis on two independent cohorts of ACC and on H295R adrenocortical cells with or without β-catenin silencing allow us to identify alterations of gene expression due to aberrant Wnt/βcatenin pathway activation. Among these genes, we show that AFF3 is essential to mediate the effect of the activation of the Wnt/β-catenin signaling pathway in adrenocortical cancer. Indeed, AFF3 is a direct target gene of the Wnt/b-catenin and its silencing in H295R adrenocortical cells induces a decreased cell proliferation and an increased apoptosis similar to that induced by b-catenin silencing. AFF3 is a nuclear protein located in nuclear speckles, which serve as a reservoir of factors participating in mRNA splicing. Moreover, AFF3 interacts with P-TEFb (CDK9/CyclinT1/2) in the Super elongation complex (SEC) required for transcriptional elongation of mRNA by RNA polymerase II. In H295R adrenocortical cells, we show that strong overproduction of AFF3 altered the structural organization of nuclear speckles and the localization of CDK9 and Cycline T1. In conclusion, this study has identified a new transcriptional target of the Wnt/β-catenin signaling pathway, AFF3, which encodes an important mediator of this pathway in adrenocortical tumorigenesis. AFF3 might especially act by affecting the structural organization of speckles and interacting with the P-TEFb, which are respectively involved in mRNA splicing and transcription. These results provide a better understanding of the biological process involved in ACC development and suggest that P-TEFb and SEC could be new therapeutic targets for the treatment of ACC.