Sorafenib is one of the clinically used anticancer agents that inhibits several kinases. In this study, novel indole-based rigid analogues of sorafenib were designed and synthesized in order to enhance kinase selectivity and hence minimize the side effects associated with its use. They were tested against Hep3B, Huh7, and Hep-G2 hepatocellular carcinoma (HCC) cell lines to study their potency. Among all the tested target derivatives, compound 1h exerted superior antiproliferative potency against all the three tested HCC cell lines compared to sorafenib. Compound 1h exerted superior kinase selectivity than sorafenib. It is selective for VEGFR2 and VEGFR3 angiogenesis-related kinases, while sorafenib is a multi-kinase inhibitor. Superior kinase selectivity of compound 1h to sorafenib can be attributed to its conformationally-restricted indole nucleus and the bulky N-methylpiperazinyl moiety.
EBERs, the most abundant genes expressed in all forms of EBV infections, are associated with promoting proliferation and resisting apoptosis in EBV-infected cells, thus, contributing significantly to EBV-associated tumorigenesis. About 90% of EBV-associated malignancies are of epithelial origin. In this study, we investigated the proliferative potentials of EBER1 in HEK293T cell line as an epithelial cell model. Our data indicated no significant difference in the growth rate of EBER1 transfected cells compared to the negative control cells. Furthermore, no significant difference was observed in the expression of genes associated with licensing or progression of cell cycle. As a result, we concluded that EBER1 alone, at least in vitro, may not be sufficient to boost proliferation.
Breast cancer (BC) is a highly heterogeneous disease by which different breast cancer subtypes acquire distinct metabolic profiles. Pyruvate dehydrogenase E1A (PDH-E1A) is one of the key regulators of metabolic pathways. Assessing PDH-E1A and Phosphorylated PDH-E1A expressions among BC subtypes would help to stratify BC patients to determine their susceptibility to metabolism targeting treatments. The expression of PDH-E1A and its inactive form (P-PDH-E1A) was investigated in BC cell lines, 115 breast cancer tissues, transcriptomics publicly available data of 1084 breast cancer patients. Multivariant analysis revealed the significant association between PDH-E1A/P-PDH-E1A expressions and the molecular class, histological type, tumor size of BC tissues and hormonal receptor status. Additionally, low PDH-E1A expression in BC patients revealed a better overall survival compared to high PDHA1 expression. This study revealed the differential expression of PDH-E1A and P-PDH-E1A among BC subtypes and suggested that high PDH-E1A expression is a prognostic factor for worse overall survival.
There is an increase in thyroid cancer cases worldwide. Recent studies show that the analysis of genotype and allele frequencies of the genetic polymorphisms aid in understanding the epidemiology of thyroid cancer. The oncogenic variants that lead to thyroid cancer development exhibit inter-ethnic variability which is reflected in the distribution of genotype and allele frequencies across populations. This study aimed to establish the genotype and allele frequencies of 25 single nucleotide polymorphisms (SNPs) implicated in thyroid cancer among the Emirati population and to compare their distribution with other ethnic groups.
Objectives: Our aim was to identify the pathogen that caused stem canker on royal poinciana and evaluate the efficacy of antagonistic Actinomycetes in vitro, in vivo under greenhouse and naturally infested plants. Methodology: DNA isolation, PCR, Phylogenetic analysis, Disease assays and Pathogenicity tests. Results: The fungus DSM 109897, was recovered from tissues, this was confirmed by our laboratory studies. Phylogenetic analyses of the translation elongation factor 1-a (TEF1-?) of N. dimidiatum from the UAE with reference specimens of Botryosphaeriaceae family validated the identity of the pathogen. Three isolates, Streptomyces rochei UAE2, S. coelicoflavus UAE1 and S. antibioticus UAE1, significantly inhibited N. dimidiatum in vitro. "apple bioassay" is useful when performing biocontrol treatment studies. Under field conditions, S. antibioticus proved to be the most effective against N. dimidiatum. Conclusion: Our data suggest that the causal agent of canker on royal poinciana in the UAE is N. dimidiatum.
Objectives: Our aim in this study was to identify the pathogen and evaluate the efficacy of fungicides in vitro and in vivo under greenhouse and naturally infested plants. Methodology: DNA isolation, PCR, Phylogenetic analysis, Disease assays and Pathogenicity test. Results: The fungus DSM 109897, was recovered from tissues; this was confirmed by studies. Phylogenetic analyses of the translation elongation factor 1-a (TEF1-α) of N. dimidiatum from the UAE with reference specimens of Botryosphaeriaceae family validated the identity of the pathogen. The chemical fungicides Protifert®, Cidely® Top and Amistrar® Top significantly inhibited mycelial growth and reduced conidial numbers of N. dimidiatum. "apple bioassay" is useful when performing fungicide treatment studies. Under field conditions, Cidely® Top proved to be the most effective fungicide against N. dimidiatum. Conclusion: Our data suggest that the causal agent of canker on royal poinciana in the UAE is N. dimidiatum.
The main objective of this work was to isolate halophilic actinobacteria from rhizospheric soils of S. bigelovii and to analyse the plant growth promoting (PGP) capabilities by considering these actinobacteria as biological inoculants on seawater-irrigated S. bigelovii plants. Streptomyces chartreusis (Sc), S. tritolerans (St) and S. rochei(Sr) are the three isolates used to determine the effects on S. bigelovii in the greenhouse. The experiments conducted with the three isolates individualy and in combination to apply on S. bigelovii. Plants treated with Sc, St and Sr resulted in 46.1%, 60.0% and 69.1% increase in seed yield, respectively, when compared to control plants. The results also showed a significant (P<0.05) increases in the levels of photosynthetic pigments, endogenous auxins but a reduction in the levels of ACC in tissues of plants inoculated with Sc/St/Sr. Final results showed that the consortium of isolates was the most effective treatment on S. bigelovii growth.
Citrullus colocynthis, a native plant to the Arabian deserts, has several medicinal and economic benefits that enable it to be a potential cash crop. This importance of the species necessitates understanding the dormancy and environmental factors that control germination processes. In the UAE, we noticed big variations in fruit and seed size and morphology between individuals of the same population. Here, we assessed the impacts of seed collection time, the temperature of incubation on salinity tolerance during the seed germination stage of individuals (hereafter referred to as accession) growing in the botanical garden of the University of Sharjah. Results showed significant effects of all factors (accession, collection time, temperature, and salinity) and their interactions on germination percentage. Summer seeds germinated significantly greater and tolerated higher salinity than winter seeds. No germination occurred at lower temperatures, but seeds germinated more than 96% at moderate and higher temperatures.
This paper presents two candidate optimal controllers based on deep learning (DL) technique for physical safety purpose of autonomous cars. The two DL controller's frameworks are based on a Greedy layer-wise (GLW) and a Long Short-Term Memory (LSTM) neural network (NN) algorithms and are utilized to control an active suspension system (ASS). The DL controllers are trained with the dataset generated, at a selected worst-case road profile, from an optimal LQR controller. The applied training methodology allows to develop an effective DL- NN structure capable of providing control that tackles the various operating conditions during handling manoeuvres and isolate/protect the passengers, payload, and expensive sensors from road disturbances. Both trained networks were tested under parameters uncertainties of a real internal road profile. The results have proved that the developed DL based controllers, LSTM and GLW models, outperform the optimal LQR controller in term of minimizing the sprung mass acceleration.
This paper proposes a new two-link compliant manipulator design for safe human-robot interaction. The manipulator consists of two compliant joints, where each joint is basically a discrete variable stiffness actuator (DVSA). The DVSA offers four different stiffness levels (i.e., 6, 50, 100, and 180 [N-m/rad]) for the joint and can shift to any of the given stiffness values instantly (i.e., in 0.048 s), during operation, upon a change in the end-effector's load. First, the 3D model of this manipulator is developed. Then, a prototype of the two-link manipulator with compliant DVSA-joints is developed.
