Feature preserving mesh network for semantic segmentation of retinal vasculature to support ophthalmic disease analysis.

Introduction: Ophthalmic diseases are approaching an alarming count across the globe. Typically, ophthalmologists depend on manual methods for the analysis of different ophthalmic diseases such as glaucoma, Sickle cell retinopathy (SCR), diabetic retinopathy, and hypertensive retinopathy. All these manual assessments are not reliable, time-consuming, tedious, and prone to error. Therefore, automatic methods are desirable to replace conventional approaches. The accuracy of this segmentation of these vessels using automated approaches directly depends on the quality of fundus images. Retinal vessels are assumed as a potential biomarker for the diagnosis of many ophthalmic diseases. Mostly newly developed ophthalmic diseases contain minor changes in vasculature which is a critical job for the early detection and analysis of disease. Method: Several artificial intelligence-based methods suggested intelligent solutions for automated retinal vessel detection. However, existing methods exhibited significant limitations in segmentation performance, complexity, and computational efficiency. Specifically, most of the existing methods failed in detecting small vessels owing to vanishing gradient problems. To overcome the stated problems, an intelligence-based automated shallow network with high performance and low cost is designed named Feature Preserving Mesh Network (FPM-Net) for the accurate segmentation of retinal vessels. FPM-Net employs a feature-preserving block that preserves the spatial features and helps in maintaining a better segmentation performance. Similarly, FPM-Net architecture uses a series of feature concatenation that also boosts the overall segmentation performance. Finally, preserved features, low-level input image information, and up-sampled spatial features are aggregated at the final concatenation stage for improved pixel prediction accuracy. The technique is reliable since it performs better on the DRIVE database, CHASE-DB1 database, and STARE dataset. Results and discussion: Experimental outcomes confirm that FPM-Net outperforms state-of-the-art techniques with superior computational efficiency. In addition, presented results are achieved without using any preprocessing or postprocessing scheme. Our proposed method FPM-Net gives improvement results which can be observed with DRIVE datasets, it gives Se, Sp, and Acc as 0.8285, 0.98270, 0.92920, for CHASE-DB1 dataset 0.8219, 0.9840, 0.9728 and STARE datasets it produces 0.8618, 0.9819 and 0.9727 respectively. Which is a remarkable difference and enhancement as compared to the conventional methods using only 2.45 million trainable parameters.

Modification and validation of liquid chromatographic method for the quantification of ciprofloxacin in human plasma and its application to a bioavailability study.

A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.

The flexible N-terminus of BchL autoinhibits activity through interaction with its [4Fe-4S] cluster and released upon ATP binding.

A key step in bacteriochlorophyll biosynthesis is the reduction of protochlorophyllide to chlorophyllide, catalyzed by dark-operative protochlorophyllide oxidoreductase. Dark-operative protochlorophyllide oxidoreductase contains two [4Fe-4S]-containing component proteins (BchL and BchNB) that assemble upon ATP binding to BchL to coordinate electron transfer and protochlorophyllide reduction. But the precise nature of the ATP-induced conformational changes is poorly understood. We present a crystal structure of BchL in the nucleotide-free form where a conserved, flexible region in the N-terminus masks the [4Fe-4S] cluster at the docking interface between BchL and BchNB. Amino acid substitutions in this region produce a hyperactive enzyme complex, suggesting a role for the N-terminus in autoinhibition. Hydrogen-deuterium exchange mass spectrometry shows that ATP binding to BchL produces specific conformational changes leading to release of the flexible N-terminus from the docking interface. The release also promotes changes within the local environment surrounding the [4Fe-4S] cluster and promotes BchL-complex formation with BchNB. A key patch of amino acids, Asp-Phe-Asp (the 'DFD patch'), situated at the mouth of the BchL ATP-binding pocket promotes intersubunit cross stabilization of the two subunits. A linked BchL dimer with one defective ATP-binding site does not support protochlorophyllide reduction, illustrating nucleotide binding to both subunits as a prerequisite for the intersubunit cross stabilization. The masking of the [4Fe-4S] cluster by the flexible N-terminal region and the associated inhibition of the activity is a novel mechanism of regulation in metalloproteins. Such mechanisms are possibly an adaptation to the anaerobic nature of eubacterial cells with poor tolerance for oxygen.

Fabrication of Pressure-Sensitive Multiwalled Carbon Nanotubes-Poly(methyl methacrylate) Nanocomposites for Pressure-Sensing Applications.

In this study, we fabricated novel, pressure-sensitive nanocomposites through two different methods. These materials were thoroughly evaluated and compared with one another. Multiwalled carbon nanotubes (MWCNTs) were added to thermoplastic polyurethane (TPU) by melt mixing and to Poly(methyl methacrylate) (PMMA) beads of different sizes to make the first type of sample. A solution mixing method was used to coat PMMA beads of different sizes with MWCNTs, and then the TPU polymer was added to make another nanocomposite. The effects of different PMMA bead sizes on the pressure-sensing properties of both nanocomposites were studied by applying different external loads. PMMA beads were used to increase the internal volume and achieve a segregated electro-conductive network structure, leading to an early percolation threshold. Scanning electron and Raman microscopy were used to study the morphology of the nanocomposites. The electrical and thermal conductivities of the nanocomposites were also investigated under different applied loads, and the two methods were compared. The electrical responses of the nanocomposites under different applied pressures demonstrated a linear decrease in the electrical resistivity with increasing applied external load, thereby confirming that these novel nanocomposites are suitable for use as pressure-sensing materials; they also show repeatability in their electrical response when an external load was applied repeatedly. These materials represent ideal candidates for use in pressure-sensitive devices.

Inexpensive sol-gel synthesis of multiwalled carbon nanotube-TiO2 hybrids for high performance antibacterial materials.

This study reports an inexpensive sol-gel method to synthesize TiO2-CNT hybrid materials. Synthesized TiO2-CNT materials show strong antibacterial activity in the absence of light. Cheap TiO2 source TiOCl2 is used during synthesis in the absence of high temperatures, high pressures and organic solvents. TiO2-CNT materials with 0, 2, 5, 10, 15 and 20wt% of CNT were synthesized and compared for antibacterial activity, surface area, porosity, crystalline structure, chemical state, and HaCaT cell proliferation. The antibacterial strength of hybrid materials increased significantly with the increase in CNT loading amount, and the TiO2-CNT samples with a CNT loading of 10wt% or more nearly removed all of the E.coli bacteria. HaCaT cell proliferation studies of synthesized hybrid materials illustrated that prepared TiO2-CNT systems exhibit minimum cytotoxicity. The characteristics of prepared materials were analyzed by means of XRD, FTIR, Raman spectroscopy, XPS, TEM, and nitrogen gas physisorption studies, compared and discussed.