Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) in the Human Interleukin 12B Gene: Identification and Structural Characterization

Background: Interleukin -12B (IL12B) polymorphism has been identified as a factor in the development of various Immunological disorders and cancer. The objective of this study was to identify the non-synonymous SNPs (nsSNPs) with the strongest predicted negative impact on the function of the IL12B protein.Methods: We employed a variety of computational methods, including SIFT, PolyPhen2, PROVEAN, SNAP2 to determine the functional impact of nsSNPs. Also, In order to investigate the potential association of nsSNPs in the IL12B gene with disease, a computational analysis was conducted using PhD-SNP, SNP&GO, and Pmut. Additionally, I-mutant and MuPro were employed to predict protein stability, while ConSurf was used to identify functional domains and conserved amino acid residues within the protein. Furthermore, SOPMA was used in combination with Project Hope and MutPred2 to predict the impact of mutations on both the structure and function of proteins. Finally, we used GeneMania to analyze the gene-gene interactions of the IL12B gene with other genes.Results: Our results indicate that nine nsSNPs (G72C, G86C, C90R, C131S, Y136D, P235L, V254G, Y258H and P259S) were found to be potentially deleterious in the IL12B gene.Conclusion: Our study emphasizes the significance of identifying functional and structural polymorphisms in the IL12B gene, as they may reveal potential therapeutic targets and provide insight into the underlying mechanisms of related diseases. Further experimental investigation is necessary to fully explore the role of these nsSNPs in disease pathogenesis.Keywords: Interleukin 12B; deleterious nsSNPs; Polymorphisms.; Computational analysis

Amplitude-preserved processing of the Blackfoot 10 Hz seismic data

The broadband 3C-2D seismic survey was acquired in the Blackfoot Field in southern Alberta. The single-component 10 Hz geophone data were reprocessed to increase vertical resolution and provide a better seismic image of the incised valley channel fill deposits in the Glauconitic Formation. The amplitude-preserved seismic processing of the data was followed by the Kirchhoff prestack time migration. The processing parameters and algorithms used were based on parameter optimization approach. Elevation statics and surface consistent residual statics were utilized to remove near surface delays in the data. Seismic noise, such as ground roll and air blast, were attenuated effectively by various algorithms. Amplitude and phase distortions due to near surface conditions were corrected by processing of the surface consistent deconvolution and amplitude balancing. The Kirchhoff prestack time migration was applied to the data to obtain a migrated section that adequately characterizes the subsurface structure. The final stacked seismic section shows a better image of the incised valley of the Glauconitic Formation than the legacy seismic section. Log data from Well 14-09 were utilized to generate synthetic seismogram, establish seismic-to-well tying, and interpret key seismic horizons --Abstract, page iii

Blind Wavelet-Based Image Watermarking

In this chapter, the watermarking technique is blind; blind watermarking does not need any of the original images or any information about it to recover watermark. In this technique the watermark is inserted into the high frequencies. Three-level wavelet transform is applied to the image, and the size of the watermark is equal to the size of the detailed sub-band. Significant coefficients are used to embed the watermark. The proposed technique depends on quantization. The proposed watermarking technique generates images with less degradation

Procoagulant tumor microvesicles attach to endothelial cells on biochips under microfluidic flow

Tumor patients are at a high risk of venous thromboembolism (VTE), and the mechanism by which this occurs may involve tumor-derived microvesicles (MVs). Previously, it has been shown that tumor MVs become attached to endothelial cells in static conditions. To investigate whether this process occurs under physiologically relevant flow rates, tumor MVs were perfused across a microfluidic device coated with growing human umbilical vein endothelial cells (HUVECs). Cell lines were screened for their ability to form tumor spheroids, and two cell lines, ES-2 and U87, were selected; spheroids formed were transferred to a microfluidic chip, and a second endothelial cell biochip was coated with HUVECs and the two chips were linked. Media flowed through the spheroid chip to the endothelial chip, and procoagulant activity (PCA) of the tumor media was determined by a one-stage prothrombin time assay. Tumor MVs were also quantified by flow cytometry before and after interaction with HUVECs. Confocal images showed that HUVECs acquired fluorescence from MV attachment. Labeled MVs were proportionally lost from MV rich media with time when flowed over HUVECs and were not observed on a control chip. The loss of MV was accompanied by a proportional reduction in PCA. Flow cytometry, confocal microscopy, and live flow imagery captured under pulsatile flow confirmed an association between tumor MVs and HUVECs. Tumor MVs attached to endothelial cells under physiological flow rates, which may be relevant to the VTE pathways in cancer patient

Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices

The majority of cancer patients undergoing chemotherapy have a significantly increased risk of venous thromboembolism via a mechanism not yet fully elucidated but which most probably involves tumour microparticles (MP) combined with damaged/activated endothelium. Tumour cell lines (ES-2 and U87) were cultured as 3D spheroids and transferred to biochips connected through to a second chip precultured with an endothelial cell layer (human umbilical vein endothelial cells [HUVECs]). Media were introduced with and without doxorubicin (DOX) to the spheroids in parallel chips under constant flow conditions. Media samples collected pre- and post-flow through the biochip were analysed for tissue factor microparticles (TFMP) and procoagulant activity (PCA). HUVECs were also harvested and tested for PCA at a constant cell number. TFMP levels in media decreased after passing over HUVECs in both conditions over time and this was accompanied by a reduction in PCA (indicated by a slower coagulation time) of the media. The relationship between PCA and TFMP was correlated (r = −0.85) and consistent across experiments. Harvested HUVECs displayed increased PCA when exposed to tumour spheroid media containing TFMP, which was increased further after the addition of DOX, suggesting that the TFMP in the media had bound to HUVEC cell surfaces. The enhanced PCA of HUVECs associated with the DOX treatment was attributed to a loss of viability of these cells rather than additional MP binding. The data suggest that tumour MP interact with HUVECs through ligand-receptor binding. The model described is a robust and reproducible method to investigate cytotoxic agents on tumour spheroids and subsequent downstream interaction with endothelial cells

A membrane- free cation selective water- gated transistor

Sensors for the detection of waterborne cations are of great practical interest, and chemistry has synthesised a formidable catalogue of cation selective complexation agents (‘ionophores’) as selective sensitisers (e.g. 9-13, 15-19, 28, 29). Current ionophore- based sensors separate the complexation of the cation by the ionophore, and the transduction of complexation into an electrical signal, into separate components. We here unite both functions into a single, sensitised semiconducting layer of a water- gated organic thin film transistor (OTFT). The resulting OTFT transduces waterborne cations into an electrical signal with same selectivity, sensitivity, and limit of detection as established sensors at much simplified preparation and operation. This opens a new route to apply the ‘ionophore’ family of functional organic materials in practical cation sensors

Identifying factors influencing the leadership performance of Saudi's healthcare sector

The purpose of this article is to identify the aspects that relate to performance level; including enablers and inhibitors that influence leadership performance in the healthcare sector of the Kingdom of Saudi Arabia (KSA). A grounded research methodology and an action research approach that was ‘issue focused’ were used to gain the perceptions of the participants from the organisational culture as empirical data. The overall trends observed in the collected data emphasize the important role of culture in shaping performance level. In addition, the domination of factors related to the national culture and Islamic values has appeared the greatest factor affecting leaders' decisions; it also forms their relations with subordinates as well as their commitment to the organization. Viewed through this study, the effect of culture aspects on the performance level in this important sector can be understood and new and integrated solutions to overcome potential negative outcomes. Because of the chosen research approach, the research results may lack generalisability. Therefore, researchers are encouraged to test the proposed propositions further. The paper discusses the implications of the study findings for healthcare sector managers in different levels. This paper fulfils an identified need to study how culture can influence workforce practices in healthcare organizations and to what extent can that affect the quality of services delivered to the patients

Interaction between tin/flouride-containing solutions and artificially created dental pellicles on erosion prevetion in vitro

Indiana University-Purdue University Indianapolis (IUPUI)School of dentistryBACKGROUND: Fluoride and stannous ions have been reported to be relevant for dental erosion prevention. However, their interaction with the acquired dental pellicle (ADP), a clinically relevant erosion protective factor, is not well known and needs to be investigated. OBJECTIVES: To investigate the anti-erosive properties of fluoride-containing solutions and stannous solutions on enamel and dentin surfaces with a previously formed ADP. To characterize the protein profile of the ADP treated with the test solutions. METHODS: Phase I tested four solutions: SnCl2/NaF, NaF, SnCl2 and deionized water (DIW) (as negative control). Forty bovine enamel and dentin specimens 104 (4x4x2 mm3) were prepared and randomly distributed into 4 groups (n = 10). The specimens were incubated in clarified human saliva (CHS) for 24 h for pellicle formation and then they were subjected to a cycling procedure that included a 5-min erosive challenge (0.3-percent citric acid, pH 2.6); a 2-min treatment with the solution (between 1st, 3rd and 6th cycles); a 2-h immersion in CHS, and overnight immersion in CHS. Cycles were repeated 6x/day for 5 days. The outcome measure was surface loss (SL) using profilometry. Phase II: Thirty-two (32) bovine enamel specimens (882 mm3) (n = 8) were similarly prepared and incubated in saliva for 24 h and then treated with the solutions for 2 min followed by CHS immersion for 2 h. This cycle was repeated 3x for one day. The pellicles formed and treated with the test rinse solutions were collected, digested, and analyzed for specific protein content using liquid chromatography electrospray ionization tandem mass spectrometry (LCESI-MS/MS). RESULTS: Phase I: for enamel, SnCl2/NaF, SnCl2, NaF solutions provided 89 percent, 67 percent, and 42 percent SL reduction respectively compared with the control, while in dentin they provided 60 percent, 23 percent, and 36 percent, respectively, all significant at p < 0.05. Phase II: Seventy-two (72) common proteins were identified in all groups, 30 exclusive to DIW, 20 to SnCl2/NaF, 19 to NaF, and 13 to SnCl2. SnCl2/NaF increased the abundance of pellicle proteins than each one alone. CONCLUSION: SnCl2/NaF showed the best anti-erosive effect on both enamel and dentin. The findings suggest that the composition of acquired pellicle changes with different solutions, which may be related to their anti-erosive effect