The nature of ornamental stones is anisotropic. The heterogeneous characteristics of the anisotropic rocks vary with direction. The highest to lowest strength ratio is known as the anisotropy ...strength index (ASI). A thorough investigation of the ASI is necessary to determine the best-directed loads for these rocks. On core specimens that have been bored parallel and perpendicular to the weakness planes, this is estimated using both uniaxial compression and point load testing. For this examination, four different rock types had cores that were drilled conventionally and in line with weakness planes. The research shows that drilling cores to weakness planes at a normal or nearly normal angle (90° to 60°) yields the best, most dependable ASI. According to the current study’s findings, the ASI fluctuates depending on how uniformly the mineral content and texture of rocks are. A suggested way to calculate the ASI and the load point strength is also included. This study reveals that the employment of ornamental stone as is (for example, precipitation position is more robust and reliable than that perpendicular form) is critical in determining the resilience of this type of rock and its spatial implementation (e.g. flooring).
Diclofenac sodium (DS) a non-steroidal anti-inflammatory drug has a bitter taste and is a local stomach irritant. The aim of this study was to formulate taste masked DS orally dispersible tablets ...(ODTs) with targeted drug release in the intestine. Pellets of DS were designed using sugar sphere cores layered with DS followed by an enteric coat of Eudragit L100 and a second coat of Eudragit E100 for taste masking. The produced pellets had a high loading efficiency of 99.52% with diameters ranging from 493.7 to 638.9 µm. The prepared pellets were spherical with smooth surfaces on scanning electron microscopy examination. Pellets with the 12% enteric coat Eudragit L100 followed by 5% Eudragit E 100 resulted in 1.4 ± 0.5% DS release in simulated gastric fluid (SGF) and complete dissolution in simulated intestinal fluid (SIF). The pellets were then used to formulate ODTs. In vitro disintegration time of ODTs ranged from 20 ± 0.26 to 46 ± 0.27 s in simulated saliva fluid (SSF). Dissolution was less than 10% in SGF while complete drug release occurred in SIF. The release rate was higher for the optimized formulation (F12) in SIF than for the marketed product Voltaren® 25 mg tablets. The optimized ODTs formulation had a palatable highly acceptable taste.
Background
The prenatal diagnosis of syndromes caused by chromosomal abnormality is a long-established part of obstetric care. Several DNA-based molecular approaches have provided rapid prenatal ...diagnosis of of cytogenomic abnormalities. MLPA has become available for rapid aneuploidy detection of the most common chromosome abnormalities.
Objectives
The aim of this study is to introduce the MLPA technique as a method for the prenatal detection of aneuploidy in Egypt by its validation compared to the FISH technique.
Methods
Fifty AF samples were collected for this study and were subjected to MLPA and FISH assays to detect the most common prenatal chromosomal abnormality.
Results and conclusions
Our study confirmed previous reports that MLPA is analogous to FISH for detecting common aneuploidies and could be a quick and dependable tool for prenatal diagnosis. Therefore, initial prompt testing of AF samples for the copy number of the most common occurring aneuploidies is recommended.
Using data from more than 10 years of observations with the Akeno Giant Air Shower Array (AGASA), we published a result that the energy spectrum of ultra-high energy cosmic rays extends beyond the ...cutoff energy predicted by Greisen Rhys. Rev. Lett. 16 (1966) 748 and Zatsepin and Kuzmin Zh. Eksp. Teor. Fiz. 4 (1966) 114. In this paper, we reevaluate the energy determination method used for AGASA events with respect to the lateral distribution of shower particles, their attenuation with zenith angle, shower front structure, delayed particles observed far from the core and other factors. The currently assigned energies of AGASA events have an accuracy of ±25% in event-reconstruction resolution and ±18% in systematic errors around 10
20 eV. This systematic uncertainty is independent of primary energy above 10
19 eV. Based on the energy spectrum from 10
14.5 eV to a few times 10
20 eV determined at Akeno, there are surely events above 10
20 eV and the energy spectrum extends up to a few times 10
20 eV without a GZK cutoff.
The antimicrobial activity of tilapia piscidin 3 (TP3) was determined in vitro against a locally isolated Aeromonas hydrophila. A 388 bp fragment was amplified from the TP3 cDNA and sequenced. The ...coding sequence (CDS) of TP3 was estimated to be 231 bp codes for 76 amino acids long and stop codon. In silico analysis was performed to detect both the signal peptide and the prodomain cleavage sites to follow the amino acids number 22 and 70, respectively. Based on this, a peptide 23 amino acids long with a remarkably high computed antimicrobial probability was synthesized and used in the subsequent experiments. The antimicrobial activity of TP3 was determined with minimum inhibitory concentration (MIC) and minim um bactericidal concentration (MBC) methods. TP3 exhibited relatively weak antimicrobial activities against the tested bacteria. A challenge experiment was then performed in Nile tilapia with low and high doses of A. hydrophila, followed by timely recognition; after 3, 6, 24 h, and 7 days of the specific TP3 gene expression, immunohistochemical localization was also performed. Histopathological examination revealed provoked inflammatory responses and congestion in the same organs of TP3 expression. Immunohistochemical localization showed that A. hydrophila induced tilapia fish to express TP3 after 24 h within the gills, intestine, hepatopancreas, spleen, and posterior kidney. In quantitative real time (RT)‐polymerase chain reaction analysis, the high dose showed higher mRNA expression levels than the low dose, and its expression levels increased in the A. hydrophila‐infected fish. It was therefore concluded that TP3 plays an essential role in fish immunity.
Tilapia piscidin 3 is significantly expressed due to A. hydrophila infection.
The highest gene expression level of TP3 in A. hydrophila‐infected Nile tilapia was detected after 24 h after infection.
The immunostaining of TP3 was detected within gills, intestine, hepatopancreas, spleen, and posterior kidney 24 h postinfection.
Digital transformation (DT) is defined as a strategy for boosting mining assets by attempting significant changes to of own properties through the integration of communication, data computing, and ...property technologies. Making large-scale changes will be difficult with digital technology, especially if the business is not well-positioned to do so. Increasing cybersecurity protection levels is the most effective way to ensure the success of the transformation. When making significant changes, a clear digital vision should be outlined and implemented with strong leadership. However, the majority of digital transformation initiatives fail before they are completed. The problem does not just affect the mining industry. The purpose of this paper is to investigate the major challenges encountered in digital transformation projects and to propose a strategic solution for implementing and scaling digital initiatives.
Cadmium (Cd) is an important inorganic toxicant widely distributed in the environment because of its various industrial uses. The aims of the current study were to investigate the efficacy of ...purified Egyptian and Tunisian montmorillonite clays (EMC and TMC) to inhibit genotoxicity and histological alterations induced by cadmium chloride (CdCl2) utilizing the Nile tilapia fish as an in vivo model. Chromosomal aberrations (CAs), micronucleus (MN) frequencies and DNA fingerprinting profile were genotoxic end points and histopathological changes that were used in this investigation. Six groups of fish were treated for 2 weeks and included control group, CdCl2-treated group and groups treated with EMC or TMC alone or in combination with CdCl2.
The present results revealed that, treatment of fish with CdCl2 exhibited significant increased in the number of micronucleated erythrocytes (MnRBCs), frequency of CAs and instability of genomic DNA. Treatment of EMC and TMC in combination with CdCl2 significantly reduced the frequency of MnRBCs by the percentage of 53.28% and 60.77% and the frequency of CAs by 43.91% and 52.17% respectively. As well as, normalized DNA fingerprinting profile and significantly improved histopathological picture induced by Cadmium treatment. It is worth mention that both clays have the ability to tightly bind CdCl2 and decreased its cytotoxicity and genotoxicity; however, Tunisian clay was more efficient in binding with the CdCl2 than Egyptian clay.
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•Tunisian and Egyptian clays prevent the genotoxicity and cytotoxicity of cadmium.•They normalized DNA profile and significantly improved histopathological picture.•Absorbability of different clay differs according to their specific surface area.•So, Tunisian clay was more efficient in binding with the CdCl2 than Egyptian clay.
Bacterial histidine kinases (HKs) are considered attractive drug targets because of their ability to govern adaptive responses coupled with their ubiquity. There are several classes of HK inhibitors; ...however, they suffer from drug resistance, poor bioavailability, and a lack of selectivity. The 3D structure of Staphylococcus aureus HK was not isolated in high-resolution coordinates, precluding further disclosure of structure-dependent binding to the specific antibiotics. To elucidate structure-dependent binding, the 3D structure of the catalytic domain WalK of S. aureus HK was constructed using homology modeling to investigate the WalK-ligand binding mechanisms through molecular docking studies and molecular dynamics simulations. The binding free energies of the waldiomycin and its methyl ester analog were calculated using molecular mechanics/generalized born surface area scoring. The key residues for protein-ligand binding were postulated. The structural divergence responsible for the 7.4-fold higher potency of waldiomycin than that of its ester analog was clearly observed. The optimized 3D macromolecule-ligand binding modes shed light on the S. aureus HK/WalK-ligand interactions that afford a means to assess binding affinity to design new HK/WalK inhibitors.
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•Design and synthesis of a novel series of nitric oxide donating Cucurbitacin Inspired Estrone Analogs (NO-CIEAs).•Binding affinity of NO-CIEA 17 and 20a towards EGFR and ERK was ...suggested by docking study.•Anti-proliferative activity was examined against HepG2 and Erlotinib-resistant HepG2 cell lines.•Intracellular NO release was examined using NO-sensitive fluorophore DAF-FM DA.•Flow cytometric studies showed that both 17 and 20a mainly arrested the HepG2 cells in the G0/G1 phase.•ICW assay revealed the dual inhibitory activity of NO-CIEA 17 towards EGFR and ERK in a dose dependent manner.•The significant impact on the chemotherapeutic resistance was confirmed by inhibition of MRP2 in a dose dependent manner by NO-CIEA 17.
Development of hybrid drug candidates is well known strategy for designing antitumor agents. Herein, a novel class of nitric oxide donating cucurbitacin inspired estrone analogs (NO-CIEAs) were designed and synthesized as multitarget agents. Synthesized analogs were initially evaluated for their anti-hepatocellular carcinoma activities. Among the tested analogs, NO-CIEAs 17 and 20a exhibited more potent activity against HepG2 cells (IC50 = 4.69 and 12.5 µM, respectively) than the reference drug Erlotinib (IC50 = 25 µM). Interestingly, NO-CIEA 17 exerted also a high potent activity against Erlotinib-resistant HepG2 cell line (HepG2-R) (IC50 = 8.21 µM) giving insight about its importance in drug resistance therapy. Intracellular measurements of NO revealed that NO-CIEAs 17 and 20a showed a significant increase in NO production in tumor cells after 1 h of incubation comparable to the reference prodrug JS-K. Flow cytometric analysis showed that both NO-CIEAs 17 and 20a mainly arrested the HepG2 cells in the G0/G1 phase. Also, In-Cell Based ELISA screening showed that NO-CIEA 17 resulted in a potential inhibitory activity towards the EGFR and MAPK (25% and 29% inhibition compared to untreated control cells, respectively). This data suggests the binding ability of NO-CIEA 17 to the EGFR and ERK to be well correlated along with the docking and cellular studies. Also, treatment of HepG2-R cells with NO-CIEA 17 showed a potential reduction of MRP2 expression in a dose dependent manner providing a significant impact on the chemotherapeutic resistance. Overall, the current study provides a potential new approach for the discovery of a novel antitumor agent against HCC.
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