EAPB0503, an Imidazoquinoxaline Derivative Modulates SENP3/ARF Mediated SUMOylation,and Induces NPM1c Degradation in NPM1 Mutant AML

Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML.     

Investigation of fluidized bed behaviour using electrical capacitance tomography

The temporal and cross-sectional distributions of particles in a 127 mm diameter fluidized bed have been obtained using a new generation, high-speed electrical capacitance tomography. Two planes of eight electrodes were used and mounted at 160 and 660 mm from the gas distributor which was a 3 mm thick porous plastic plate (maximum pore size of 50-70 μ m). 3 mm diameter, nearly-spherical polyethylene granules made up the bed. Experiments at sampling frequencies of 200-2000 cross-sections per second and gas superficial velocities from just below the minimum fluidization to 83% above minimum fluidization velocities were used. The time series of the cross-sectional average void fractions have been examined both directly and in amplitude and frequency space. The last two used probability density functions and power spectral densities. The information gathered shows that the fluidized bed was operating in the slugging mode, which is not surprising given the size of the particles. It has been found that an increase in the excess gas velocity above the minimum fluidization velocity resulted in an increase in the mean void fraction, an increase in the length and velocity of the slug bubbles as well as the bed height, and a slight decrease in the slug frequency. The results are presented in a level of detail suitable for comparison with later numerical simulation.     

Surface analysis and adsorption behavior of caffeine as an environmentally friendly corrosion inhibitor at the copper/aqueous chloride solution interface

Abstract

Corrosion inhibitors based on environmentally friendly and harmless products are currently being studied and developed. The corrosion inhibition properties of caffeine (1,3,7-trimethylxanthine) on copper corrosion in aqueous chloride solution (3.5?wt.% NaCl) are analysed here using stationary and transient electrochemical methods, and a theoretical study based on density functional theory is carried out. Caffeine is a very competitive compared to the chemical inhibitors that are often used for copper protection. Electrochemical and impedance experiments reveal that the protective efficiency of caffeine reaches a value of 96% at a concentration of 10^?2?mol L^?1. Based on these results, the Langmuir model appears to be the best representation of the adsorption of caffeine onto the copper surface. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy and X-ray diffraction (XRD) were used to determine the surface morphology and the chemical composition of the copper surface in chloride media, in the absence and presence of caffeine. The results show the development of a mechanism of corrosion inhibition. In order to confirm the correlation between the inhibitory effect and the molecular structure of caffeine, quantum chemical parameters are used to calculate its electronic properties.     

Non-Cytokine Protein Profile of the Mesenchymal Stem Cell Secretome That Regulates the Androgen Production Pathway

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-aged women, and it typically involves elevated androgen levels. Recently, it has been reported that human bone marrow mesenchymal stem cells (hBM-MSCs) can regulate androgen synthesis pathways. However, the details of the mechanism are still unclear. hBM-MSC-derived secreted factors (the secretome) are promising sources of cell-based therapy as they consist of various types of proteins. It is thus important to know which proteins interact with disease-implicated biomolecules. This work aimed to investigate which secretome components contain the key factor that inhibits testosterone synthesis. In this study, we fractionated hBM-MSC-conditioned media into three fractions based on their molecular weights and found that, of the three fractions, one had the ability to inhibit the androgen-producing genes efficiently. We also analyzed the components of this fraction and established a protein profile of the hBM-MSC secretome, which was shown to inhibit androgen synthesis. Our study describes a set of protein components present in the hBM-MSC secretome that can be used therapeutically to treat PCOS by regulating androgen production for the first time.     

Energy efficient fuzzy-based DASH adaptation algorithm

With the expansive demand for video streaming over mobile networks, it is necessary to adopt schemes that balance the need for high video quality with the available network resources when streaming or downloading the video. Several approaches were proposed in the literature, including Dynamic Adaptive Streaming over HTTP (DASH). In this work, we consider an approach in which we place sufficient emphasis on the constrained battery resources in mobile devices when making decisions on the quality (or bitrate) of the video to be requested. This is done by using a fuzzy logic controller that enhances the performance of the Fuzzy-based DASH (FDASH) scheme. Simulation results show that our proposed approach conserves more energy than its predecessor while maintaining similar video quality and avoiding playback interruptions.     

Synthesis,characterization, and gas-sensing performance of macroporous Zn-doped NiO thin films for ammonia gas detection

Journal of Materials Science: Materials in Electronics - Zinc-doped nickel oxide (NiO:Zn) thin films have been synthesized by chemical spray pyrolysis (CSP), then we have studied the structural,...     

A survey of recent interactive image segmentation methods

Computational Visual Media - Image segmentation is one of the most basic tasks in computer vision and remains an initial step of many applications. In this paper, we focus on interactive image...     

An effective weighted rule-based method for entity resolution

Entity resolution is an important task in data cleaning to detect records that belong to the same entity. It has a critical impact on digital libraries where different entities share the same name without any identifier key. Conventional methods adopt similarity measures and clustering techniques to reveal the records of a specific entity. Due to the lack of performance, recent methods build rules on records’ attributes with distinct values for entities to overcome some drawbacks. However, they use inadequate attributes and ignore common and empty attributes values which affect the quality of entity resolution. In this paper, we define a multi-attributes weighted rule system (MAWR) that investigates all values of records’ attributes in order to represent the difficult record-entity mapping. Then, we propose a rule generation algorithm based on this system. We also propose an entity resolution algorithm (MAWR-ER) depending on the generated rules to identify entities. We verify our method on real data, and the experimental results prove the effectiveness and efficiency of our proposed method.     

An algorithm for capturing variables dependences in test suites

The use of dynamic dependence analysis spans several areas of software research including software testing, debugging, fault localization, and security. Many of the techniques devised in these areas require the execution of large test suites in order to generate profiles that capture the dependences that occurred between given types of program elements. When the aim is to capture direct and indirect dependences between finely granular elements, such as statements and variables, this process becomes highly costly due to: (1) the large number of elements, and (2) the transitive nature of the indirect dependence relationship.The focus of this paper is on computing dynamic dependences between variables, i.e., dynamic information flow analysis or DIFA. First, because the problem of tracking dependences between statements, i.e., dynamic slicing, has already been addressed by numerous researchers. Second, because DIFA is a more difficult problem given that the number of variables in a program is unbounded. We present an algorithm that, in the context of test suite execution, leverages the already computed dependences to efficiently compute subsequent dependences within the same or later test runs. To evaluate our proposed algorithm, we conducted an empirical comparative study that contrasted it, with respect to efficiency, to three other algorithms: (1) a naïve basic algorithm, (2) a memoization based algorithm that does not leverage computed dependences from previous test runs, and (3) an algorithm that uses reduced ordered binary decision diagrams (roBDDs) to maintain and manage dependences. The results indicated that our new DIFA algorithm performed considerably better in terms of both runtime and memory consumption.