Inference of distributional parameters from compositional samples containing nondetects

Low concentrations of elements in geochemical analyses have the peculiarity of being compositional data and, for a given level of significance, are likely to be beyond the capabilities of laboratories to distinguish between minute concentrations and complete absence, thus preventing laboratories from reporting extremely low concentrations of the analyte. Instead, what is reported is the detection limit, which is the minimum concentration that conclusively differentiates between presence and absence of the element. A spatially distributed exhaustive sample is employed in this study to generate unbiased sub-samples, which are further censored to observe the effect that different detection limits and sample sizes have on the inference of population distributions starting from geochemical analyses having specimens below detection limit (nondetects). The isometric logratio transformation is used to convert the compositional data in the simplex to samples in real space, thus allowing the practitioner to properly borrow from the large source of statistical techniques valid only in real space. The bootstrap method is used to numerically investigate the reliability of inferring several distributional parameters employing different forms of imputation for the censored data. The case study illustrates that, in general, best results are obtained when imputations are made using the distribution best fitting the readings above detection limit and exposes the problems of other more widely used practices. When the sample is spatially correlated, it is necessary to combine the bootstrap with stochastic simulation

Plan exportador para quesos del Vecchio S.A. en el mercado de Estados Unidos, Ecuador y España

Mediante el uso de distintas metodologías para la elaboración de un plan exportador, se ha elaborado un análisis integral que le permitirá a la empresa Quesos Del Vecchio S.A., tener algunos elementos clave a su disposición en el momento en que deseen aprobar su plan de exportación o elaborar uno propio. Se inicia entonces con un análisis del sector de quesos en Colombia, identificando las empresas que hacen parte del sector y que se destacan por tener ingresos operacionales por encima del nivel de las otras empresas esto por medio del AESE del Profesor Hugo Rivera. Así se encuentra que hay pocas empresas en pocos lugares de Colombia que conservan estas características.. Luego, pasamos a observar la empresa en su totalidad, pasando desde un planteamiento de su estrategia competitiva hasta un análisis financiero, pasando por todas las áreas de la empresa puesto que una exportación, al ser una actividad integral, involucra a la empresa en su totalidad y por esto se debía analizar completamente. El siguiente paso es entonces decidir a qué mercado exportar y las razones por las cuales se le da prioridad a estos destinos por encima de los demás. Se toman tres potenciales mercados y, a través de la calificación y el nivel de hacinamiento encontrado por el AESE se identifica cuál se adapta mejor a las necesidades y capacidades de la empresa. Finalmente se mencionan estrategias claves que pueden ser utilizadas por la empresa para la consecución del plan exportador. Se espera entonces que este ejercicio sea de gran utilidad para la empresa Quesos Del Vecchio S.A. Palabras Clave: Exportación, plan exportador, quesos, estrategia, Ecuador, Estados Unidos, y España.

Influence-matrix diagnostic of a data assimilation system

The influence matrix is used in ordinary least-squares applications for monitoring statistical multiple-regression analyses. Concepts related to the influence matrix provide diagnostics on the influence of individual data on the analysis - the analysis change that would occur by leaving one observation out, and the effective information content (degrees of freedom for signal) in any sub-set of the analysed data. In this paper, the corresponding concepts have been derived in the context of linear statistical data assimilation in numerical weather prediction. An approximate method to compute the diagonal elements of the influence matrix (the self-sensitivities) has been developed for a large-dimension variational data assimilation system (the four-dimensional variational system of the European Centre for Medium-Range Weather Forecasts). Results show that, in the boreal spring 2003 operational system, 15% of the global influence is due to the assimilated observations in any one analysis, and the complementary 85% is the influence of the prior (background) information, a short-range forecast containing information from earlier assimilated observations. About 25% of the observational information is currently provided by surface-based observing systems, and 75% by satellite systems. Low-influence data points usually occur in data-rich areas, while high-influence data points are in data-sparse areas or in dynamically active regions. Background-error correlations also play an important role: high correlation diminishes the observation influence and amplifies the importance of the surrounding real and pseudo observations (prior information in observation space). Incorrect specifications of background and observation-error covariance matrices can be identified, interpreted and better understood by the use of influence-matrix diagnostics for the variety of observation types and observed variables used in the data assimilation system. Copyright © 2004 Royal Meteorological Society

Reaping the benefits: science and the sustainable intensification of global agriculture

Food security is one of this century’s key global challenges. By 2050 the world will require increased crop production in order to feed its predicted 9 billion people. This must be done in the face of changing consumption patterns, the impacts of climate change and the growing scarcity of water and land. Crop production methods will also have to sustain the environment, preserve natural resources and support livelihoods of farmers and rural populations around the world. There is a pressing need for the ‘sustainable intensifi cation’ of global agriculture in which yields are increased without adverse environmental impact and without the cultivation of more land. Addressing the need to secure a food supply for the whole world requires an urgent international effort with a clear sense of long-term challenges and possibilities. Biological science, especially publicly funded science, must play a vital role in the sustainable intensifi cation of food crop production. The UK has a responsibility and the capacity to take a leading role in providing a range of scientifi c solutions to mitigate potential food shortages. This will require signifi cant funding of cross-disciplinary science for food security. The constraints on food crop production are well understood, but differ widely across regions. The availability of water and good soils are major limiting factors. Signifi cant losses in crop yields occur due to pests, diseases and weed competition. The effects of climate change will further exacerbate the stresses on crop plants, potentially leading to dramatic yield reductions. Maintaining and enhancing the diversity of crop genetic resources is vital to facilitate crop breeding and thereby enhance the resilience of food crop production. Addressing these constraints requires technologies and approaches that are underpinned by good science. Some of these technologies build on existing knowledge, while others are completely radical approaches, drawing on genomics and high-throughput analysis. Novel research methods have the potential to contribute to food crop production through both genetic improvement of crops and new crop and soil management practices. Genetic improvements to crops can occur through breeding or genetic modifi cation to introduce a range of desirable traits. The application of genetic methods has the potential to refi ne existing crops and provide incremental improvements. These methods also have the potential to introduce radical and highly signifi cant improvements to crops by increasing photosynthetic effi ciency, reducing the need for nitrogen or other fertilisers and unlocking some of the unrealised potential of crop genomes. The science of crop management and agricultural practice also needs to be given particular emphasis as part of a food security grand challenge. These approaches can address key constraints in existing crop varieties and can be applied widely. Current approaches to maximising production within agricultural systems are unsustainable; new methodologies that utilise all elements of the agricultural system are needed, including better soil management and enhancement and exploitation of populations of benefi cial soil microbes. Agronomy, soil science and agroecology—the relevant sciences—have been neglected in recent years. Past debates about the use of new technologies for agriculture have tended to adopt an either/or approach, emphasising the merits of particular agricultural systems or technological approaches and the downsides of others. This has been seen most obviously with respect to genetically modifi ed (GM) crops, the use of pesticides and the arguments for and against organic modes of production. These debates have failed to acknowledge that there is no technological panacea for the global challenge of sustainable and secure global food production. There will always be trade-offs and local complexities. This report considers both new crop varieties and appropriate agroecological crop and soil management practices and adopts an inclusive approach. No techniques or technologies should be ruled out. Global agriculture demands a diversity of approaches, specific to crops, localities, cultures and other circumstances. Such diversity demands that the breadth of relevant scientific enquiry is equally diverse, and that science needs to be combined with social, economic and political perspectives. In addition to supporting high-quality science, the UK needs to maintain and build its capacity to innovate, in collaboration with international and national research centres. UK scientists and agronomists have in the past played a leading role in disciplines relevant to agriculture, but training in agricultural sciences and related topics has recently suffered from a lack of policy attention and support. Agricultural extension services, connecting farmers with new innovations, have been similarly neglected in the UK and elsewhere. There is a major need to review the support for and provision of extension services, particularly in developing countries. The governance of innovation for agriculture needs to maximise opportunities for increasing production, while at the same time protecting societies, economies and the environment from negative side effects. Regulatory systems need to improve their assessment of benefits. Horizon scanning will ensure proactive consideration of technological options by governments. Assessment of benefi ts, risks and uncertainties should be seen broadly, and should include the wider impacts of new technologies and practices on economies and societies. Public and stakeholder dialogue—with NGOs, scientists and farmers in particular—needs to be a part of all governance frameworks.

An incremental space to visualize dynamic data sets

In Information Visualization, adding and removing data elements can strongly impact the underlying visual space. We have developed an inherently incremental technique (incBoard) that maintains a coherent disposition of elements from a dynamic multidimensional data set on a 2D grid as the set changes. Here, we introduce a novel layout that uses pairwise similarity from grid neighbors, as defined in incBoard, to reposition elements on the visual space, free from constraints imposed by the grid. The board continues to be updated and can be displayed alongside the new space. As similar items are placed together, while dissimilar neighbors are moved apart, it supports users in the identification of clusters and subsets of related elements. Densely populated areas identified in the incSpace can be efficiently explored with the corresponding incBoard visualization, which is not susceptible to occlusion. The solution remains inherently incremental and maintains a coherent disposition of elements, even for fully renewed sets. The algorithm considers relative positions for the initial placement of elements, and raw dissimilarity to fine tune the visualization. It has low computational cost, with complexity depending only on the size of the currently viewed subset, V. Thus, a data set of size N can be sequentially displayed in O(N) time, reaching O(N (2)) only if the complete set is simultaneously displayed.

Reutilização de imóveis de interesse patrimonial, voltados para a ahabitação: um estudo de caso na Ribeira-Natal/RN

This work analyzes the reutilization of real estate of patrimonial interest, come back toward habitation. One understands as real estate of patrimonial interest the old ones that present relevant architectural typologies that must be preserved; some buildings that represent characteristic architectural styles of a determined period; some valued real estates for the history of the city (historical, memory and image signification that has of certain places) and buildings with exceptional artistic elements. In short, real estate of patrimonial interest. The place or site to be studied will be the neighborhood of the Ribeira, because is an area that protects a bigger interest for the historic patrimony of the city. The habitation use was thought as a booster element of revitalization processes of degradable historic site, contributing to the preservation of artistic, architectural and historic patrimony, and thus to stimulate the accomplishment of the re-qualification of the neighborhood of the Ribeira. It is intended with the present study to examine alternatives to make possible habitation re (uses) in the historical quarter of the Ribeira in old constructions of patrimonial value

Third-body perturbation in the case of elliptic orbits for the disturbing body

This work presents a semi-analytical and numerical study of the perturbation caused in a spacecraft by a third-body using a double averaged analytical model with the disturbing function expanded in Legendre polynomials up to the second order. The important reason for this procedure is to eliminate terms due to the short periodic motion of the spacecraft and to show smooth curves for the evolution of the mean orbital elements for a long-time period. The aim of this study is to calculate the effect of lunar perturbations on the orbits of spacecrafts that are traveling around the Earth. An analysis of the stability of near-circular orbits is made, and a study to know under which conditions this orbit remains near circular completes this analysis. A study of the equatorial orbits is also performed. Copyright (C) 2008 R. C. Domingos et al.

Interfaces cultural, política e organizacional do projeto caminhos do frio rota cultural no contexto da regionalização do turismo no brejo paraibano

This study is the analysis of cultural, political and organizational interfaces of "Caminhos do Frio Rota Cultural" Project in the context of tourism regionalization in Brejo Paraibano and it presents the characterization, routing and inventory of six municipalities of the Project, as well as the identification of cultural elements used for tourist in the routing of the pond, the investigation of political and organizational articulation and the verification of participation of each producing agent in the development of tourism resulting from the swamp of Paraiba. This is a qualitative descriptive and exploratory study, which makes use of the interpretive paradigm to perform an analysis of the environment where occurs the regionalization of tourism in Brejo of Paraíba and the social actors involved in this process in order to pursue development of the region through culture and tourism, with the collection spot in the six counties of the Project participants collected through interviews with managers, community, government agencies and tourist trade, and the use of the technique of direct observation. This time, with the data analysis it was possible to establish the production situation and its cultural and tourist development in the region of Brejo (PB), where culture has become a developmental tool within the tourism industry due to its innovation potential. It was possible to ratify the undisputed vocation of cultural tourism in the region in question, since other projects being developed with the use of cultural resources with a strong influence on the policies of regional tourism. Thus, the main result was that was seen is that the regional development has triggered a refunctionalisation / reappropriation of space just rebuilding a new territorial organization through the development of a regional autonomy of management, a capacity of collective ownership and the use of economic surplus, a spontaneous process of social inclusion as well as awareness and mobilization tourist (even if initial and shy), an appreciation of natural and cultural assets for all stakeholders and especially identification of the population with its region and its culture, as to achieve regional development is not enough to increase the economic, but above all the promotion of endogenous social factors such as changes in social and cultural values and the integration of social actors in this process. Finally, taking into account the definitions of sustainability, it is considered that cannot be said that the development model seen in the swamp of Paraiba is sustainable, but it is a model of regional development based on the unique characteristics that each municipality has and create a regional identity and have correponded expectations / desired results and therefore the viability of the region through the development of cultural tourism was proven

Third-body perturbation in the case of elliptic orbits for the disturbing body

In the present work it is presented a semi-analytical and a numerical study of the perturbation caused in a spacecraft by a third body using a double averaged analytical model with the disturbing function expanded in Legendre polynomials up to the second-order. The important reason for this procedure is to eliminate the terms due to the short time periodic motion of the spacecraft and to show smooth curves for the evolution of the mean orbital elements for a long time period. The aim of this study is to calculate the effect of lunar perturbations on the orbits of spacecrafts that are traveling around the Earth. It is presented an analysis of the stability of a near-circular orbit and a study to know under which conditions this orbit remains near-circular. A study of the equatorial orbits is also performed.

An analysis of the Hygiea asteroid family orbital region

(10) Hygiea is the fourth largest asteroid of the main belt, by volume and mass, and it is the largest member of its family, that is made mostly by low-albedo, C-type asteroids, typical of the outer main belt. Like many other large families, it is associated with a 'halo' of objects, that extends far beyond the boundary of the core family, as detected by traditional hierarchical clustering methods (HCM) in proper element domains. Numerical simulations of the orbital evolution of family members may help in estimating the family and halo family age, and the original ejection velocity field. But, in order to minimize the errors associated with including too many interlopers, it is important to have good estimates of family membership that include available data on local asteroid taxonomy, geometrical albedo and local dynamics. For this purpose, we obtained synthetic proper elements and frequencies of asteroids in the Hygiea orbital region, with their errors. We revised the current knowledge on asteroid taxonomy, including Sloan Digital Sky Survey-Moving Object Catalog 4th release (SDSS-MOC 4) data, and geometric albedo data from Wide-field Infrared Survey Explorer (WISE) and Near-Earth Object WISE (NEOWISE). We identified asteroid family members using HCM in the domain of proper elements (a, e, sin (i)) and in the domains of proper frequencies most appropriate to study diffusion in the local web of secular resonances, and eliminated possible interlopers based on taxonomic and geometrical albedo considerations. To identify the family halo, we devised a new hierarchical clustering method in an extended domain that includes proper elements, principal components PC1, PC2 obtained based on SDSS photometric data and, for the first time, WISE and NEOWISE geometric albedo. Data on asteroid size distribution, light curves and rotations were also revised for the Hygiea family. The Hygiea family is the largest group in its region, with two smaller families in proper element domain and 18 families in various frequencies domains identified in this work for the first time. Frequency groups tend to extend vertically in the (a, sin (i)) plane and cross not only the Hygiea family but also the near C-type families of Themis and Veritas, causing a mixture of objects all of relatively low albedo in the Hygiea family area. A few high-albedo asteroids, most likely associated with the Eos family, are also present in the region. Finally, the new multidomains hierarchical clustering method allowed us to obtain a good and robust estimate of the membership of the Hygiea family halo, quite separated from other asteroids families halo in the region, and with a very limited (about 3 per cent) presence of likely interlopers. © 2013 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

Estudo do uso de lodo de estações de tratamento de água e de esgoto urbano nas propriedades químicas do solo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Modelagem numérica de dados MCSEM 3D usando computação paralela

Desenvolvemos a modelagem numérica de dados sintéticos Marine Controlled Source Electromagnetic (MCSEM) usada na exploração de hidrocarbonetos para simples modelos tridimensionais usando computação paralela. Os modelos são constituidos de duas camadas estrati cadas: o mar e o sedimentos encaixantes de um delgado reservatório tridimensional, sobrepostas pelo semi-espaço correspondente ao ar. Neste Trabalho apresentamos uma abordagem tridimensional da técnica dos elementos nitos aplicada ao método MCSEM, usando a formulação da decomposição primária e secundária dos potenciais acoplados magnético e elétrico. Num pós-processamento, os campos eletromagnéticos são calculados a partir dos potenciais espalhados via diferenciação numérica. Exploramos o paralelismo dos dados MCSEM 3D em um levantamento multitransmissor, em que para cada posição do transmissor temos o mesmo processo de cálculos com dados diferentes. Para isso, usamos a biblioteca Message Passing Interface (MPI) e o modelo servidor cliente, onde o processador administrador envia os dados de entradas para os processadores clientes computar a modelagem. Os dados de entrada são formados pelos parâmetros da malha de elementos nitos, dos transmissores e do modelo geoelétrico do reservatório. Esse possui geometria prismática que representa lentes de reservatórios de hidrocarbonetos em águas profundas. Observamos que quando a largura e o comprimento horizontais desses reservatório têm a mesma ordem de grandeza, as resposta in-line são muito semelhantes e conseqüentemente o efeito tridimensional não é detectado. Por sua vez, quando a diferença nos tamanhos da largura e do comprimento do reservatório é signi cativa o efeito 3D é facilmente detectado em medidas in-line na maior dimensão horizontal do reservatório. Para medidas na menor dimensão esse efeito não é detectável, pois, nesse caso o modelo 3D se aproxima de um modelo bidimensional. O paralelismo dos dados é de rápida implementação e processamento. O tempo de execução para a modelagem multitransmissor em ambiente paralelo é equivalente ao tempo de processamento da modelagem para um único transmissor em uma máquina seqüêncial, com o acréscimo do tempo de latência na transmissão de dados entre os nós do cluster, o que justi ca o uso desta metodologia na modelagem e interpretação de dados MCSEM. Devido a reduzida memória (2 Gbytes) em cada processador do cluster do departamento de geofísica da UFPA, apenas modelos muito simples foram executados.

Characterization of Soil Surface Roughness Effects on Runoff and Soil Erosion Rates under Simulated Rainfall

This study aims at identifying the influence of soil surface roughness from small to large aggregates (random roughness) on runoff and soil loss and to investigate the interaction with soil surface seal formation. Bulk samples of a silty clay loam soil were sieved to four aggregate-size classes of 3 to 12, 12 to 20, 20 to 45, 45 to 100 mm, and packed in soil trays set at a 5% slope. Rainfall simulations using an oscillating nozzle simulator were conducted for 90 min at an average rainfall intensity of 50.2 mm h(-1). Soil surface roughness was measured using an instantaneous profile laser scanner and surface sealing was studied by macroscopic analysis of epoxy impregnated soil samples. The rainfall simulations revealed longer times to initiate runoff with increasing soil surface roughness. For random roughness levels up to 6 mm, a decrease in final runoff rate with increasing roughness was observed. This can be attributed to a decreased breakdown of the larger roughness elements on rougher surfaces, thus keeping infiltration rate high. For a random roughness larger than 6 mm, a greater final runoff rate was observed. This was caused by the creation of a thick depositional seal in the concentrated flow areas, thus lowering the infiltration rates. Analysis of impregnated soil sample blocks confirmed the formation of a structural surface seal on smooth surfaces, whereas thick depositional seals were visible in the depressional areas of rougher surfaces. Therefore, from our observations it can be learned that soil surface roughness as formed by the presence of different aggregate sizes reduces runoff but that its effect diminishes due to aggregate breakdown and the formation of thick depositional seals in the case of rough soil surfaces. Sediment concentration increased with increasing soil surface roughness, due to runoff concentration in flow paths. Nevertheless, final soil loss rates were comparable for all soil roughness categories, indicating that random roughness is only important in influencing runoff rates and the time to initiate runoff, but not in influencing sediment export through soil loss rates.

Augmented reality in sport scenarios using cameras mounted on a tripod

[ES] In this paper we address the problem of inserting virtual content in a video sequence. The method we propose uses just image information. We perform primitive tracking, camera calibration, real and virtual camera synchronisation and finally rendering to insert the virtual content in the real video sequence. To simplify the calibration step we assume that cameras are mounted on a tripod (which is a common situation in practise). The primitive tracking procedure, which uses lines and circles as primitives, is performed by means of a CART (Classification and Regression Tree). Finally, the virtual and real camera synchronisation and rendering is performed using functions of OpenGL (Open Graphic Library). We have applied the method proposed to sport event scenarios, specifically, soccer matches. In order to illustrate its performance, it has been applied to real HD (High Definition) video sequences. The quality of the proposed method is validated by inserting virtual elements in such HD video sequence.

Mechanism of resistance to tyrosine kinase inhibitors in philadelphia-positive acute lymphblastic leukaemia (all): from genetic alterations to impaired RNA editing

The Ph chromosome is the most frequent cytogenetic aberration associated with adult ALL and it represents the single most significant adverse prognostic marker. Despite imatinib has led to significant improvements in the treatment of patients with Ph+ ALL, in the majority of cases resistance developed quickly and disease progressed. Some mechanisms of resistance have been widely described but the full knowledge of contributing factors, driving both the disease and resistance, remains to be defined. The observation of rapid development of lymphoblastic leukemia in mice expressing altered Ikaros (Ik) isoforms represented the background of this study. Ikaros is a zinc finger transcription factor required for normal hemopoietic differentiation and proliferation, particularly in the lymphoid lineages. By means of alternative splicing, Ikaros encodes several proteins that differ in their abilities to bind to a consensus DNA-binding site. Shorter, DNA nonbinding isoforms exert a dominant negative effect, inhibiting the ability of longer heterodimer partners to bind DNA. The differential expression pattern of Ik isoforms in Ph+ ALL patients was analyzed in order to determine if molecular abnormalities involving the Ik gene could associate with resistance to imatinib and dasatinib. Bone marrow and peripheral blood samples from 46 adult patients (median age 55 yrs, 18-76) with Ph+ ALL at diagnosis and during treatment with imatinib (16 pts) or dasatinib (30 pts) were collected. We set up a fast, high-throughput method based on capillary electrophoresis technology to detect and quantify splice variants. 41% Ph+ ALL patients expressed high levels of the non DNA-binding dominant negative Ik6 isoform lacking critical N-terminal zinc-fingers which display abnormal subcellular compartmentalization pattern. Nuclear extracts from patients expressed Ik6 failed to bind DNA in mobility shift assay using a DNA probe containing an Ikaros-specific DNA binding sequence. In 59% Ph+ ALL patients there was the coexistence in the same PCR sample and at the same time of many splice variants corresponded to Ik1, Ik2, Ik4, Ik4A, Ik5A, Ik6, Ik6 and Ik8 isoforms. In these patients aberrant full-length Ikaros isoforms in Ph+ ALL characterized by a 60-bp insertion immediately downstream of exon 3 and a recurring 30-bp in-frame deletion at the end of exon 7 involving most frequently the Ik2, Ik4 isoforms were also identified. Both the insertion and deletion were due to the selection of alternative splice donor and acceptor sites. The molecular monitoring of minimal residual disease showed for the first time in vivo that the Ik6 expression strongly correlated with the BCR-ABL transcript levels suggesting that this alteration could depend on the Bcr-Abl activity. Patient-derived leukaemia cells expressed dominant-negative Ik6 at diagnosis and at the time of relapse, but never during remission. In order to mechanistically demonstrated whether in vitro the overexpression of Ik6 impairs the response to tyrosine kinase inhibitors (TKIs) and contributes to resistance, an imatinib-sensitive Ik6-negative Ph+ ALL cell line (SUP-B15) was transfected with the complete Ik6 DNA coding sequence. The expression of Ik6 strongly increased proliferation and inhibited apoptosis in TKI sensitive cells establishing a previously unknown link between specific molecular defects that involve the Ikaros gene and the resistance to TKIs in Ph+ ALL patients. Amplification and genomic sequence analysis of the exon splice junction regions showed the presence of 2 single nucleotide polymorphisms (SNPs): rs10251980 [A/G] in the exon2/3 splice junction and of rs10262731 [A/G] in the exon 7/8 splice junction in 50% and 36% of patients, respectively. A variant of the rs11329346 [-/C], in 16% of patients was also found. Other two different single nucleotide substitutions not recognized as SNP were observed. Some mutations were predicted by computational analyses (RESCUE approach) to alter cis-splicing elements. In conclusion, these findings demonstrated that the post-transcriptional regulation of alternative splicing of Ikaros gene is defective in the majority of Ph+ ALL patients treated with TKIs. The overexpression of Ik6 blocking B-cell differentiation could contribute to resistance opening a time frame, during which leukaemia cells acquire secondary transforming events that confer definitive resistance to imatinib and dasatinib.