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Highly concentrated antibody formulations are oftentimes required for subcutaneous, self-administered biologics. Here, we report the development of a unique formulation for our firstin-class FSH-blocking humanized antibody, MS-Hu6, which we propose to move to the clinic for osteoporosis, obesity, and Alzheimer’s disease. The studies were carried out using our Good Laboratory Practice (GLP) platform, compliant with the Code of Federal Regulations (Title 21, Part 58). We first used protein thermal shift, size exclusion chromatography, and dynamic light scattering to examine MS-Hu6 concentrations between 1 and 100 mg/mL. We found that thermal, monomeric, and colloidal stability of formulated MS-Hu6 was maintained at a concentration of 100 mg/mL. The addition of the antioxidant L-methionine and chelating agent disodium EDTA improved the formulation’s long-term colloidal and thermal stability. Thermal stability was further confirmed by Nano differential scanning calorimetry (DSC). Physiochemical properties of formulated MS-Hu6, including viscosity, turbidity, and clarity, confirmed with acceptable industry standards. That the structural integrity of MS-Hu6 in formulation was maintained was proven through Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) Spectroscopy. Three rapid freeze–thaw cycles at –80 °C/25 °C or –80 °C/37 °C further revealed excellent thermal and colloidal stability. Furthermore, formulated MS-Hu6, particularly its Fab domain, displayed thermal and monomeric storage stability for more than 90 days at 4°C and 25°C. Finally, the unfolding temperature (Tm) for formulated MS-Hu6 increased by >4.80 °C upon binding to recombinant FSH, indicating highly specific ligand binding. Overall, we document the feasibility of developing a stable, manufacturable and transportable MS-Hu6 formulation at a ultra-high concentration at industry standards. The study should become a resource for developing biologic formulations in academic medical centers. [ABSTRACT FROM AUTHOR]

Sporulene, a pentacyclic triterpenoid, was discovered in Bacillus subtilis and is associated with bacterial endospores. However, the study was not further extended, leaving a trail of questions. One such question is what diversity of sporulenes exists among spore-forming members? Considering the sporulene biosynthesis pathway as a fundamental tool to survey the distribution of this molecule, a genome mining study was conducted. Mining for genes encoding putative proteins of sporulene biosynthesis pathway among the class Bacilli members revealed the presence of hepS, hepT, ytpB, and sqhC genes in the members of the family Bacillaceae, Caryophanaceae, Paenibacillaceae, and Sporolactobacillaceae. However, these genes were completely absent in the members of Staphylococcaceae, Lactobacillaceae, Aerococcaceae, Carnobacteriaceae, and Leuconostocaceae. Unlike other probable pathway related proteins, a conserved amino acid domain of putative terpenoid cyclase (YtpB) appeared deep-rooted among the genus Bacillus members. In-depth analysis showed the constant gene arrangement of hepS, hepT, ytpB, and sqhC genes in these members, there by demonstrating the conserved nature of sporulene biosynthesis pathway in the members of the genus Bacillus. Our study suggests confinement of the sporulene biosynthesis pathway to spore-forming members of the class Bacilli, majorly to the genus Bacillus. [ABSTRACT FROM AUTHOR]

RFID systems are one of the essential technologies and used many diverse applications. The security and privacy are the primary concern in RFID systems which are overcome by using suitable authentication protocols. In this manuscript, the costeffective RFID-Mutual Authentication (MA) using a lightweight Extended Tiny encryption algorithm (XTEA) is designed to overcome the security and privacy issues on Hardware Platform. The proposed design provides two levels of security, which includes secured Tag identification and mutual authentication. The RFIDMA mainly has Reader and Tag along with the backend Server. It establishes the secured authentication between Tag and Reader using XTEA. The XTEA with Cipher block chaining (CBC) is incorporated in RFID for secured MA purposes. The authentication process completed based on the challenge and response between Reader and Tag using XTEA-CBC. The present work is designed using Verilog-HDL on the Xilinx environment and implemented on Artix-7 FPGA. The simulation and synthesis results discussed with hardware constraints like Area, power, and time. The present work is compared with existing similar approaches with hardware constraints improvements. [ABSTRACT FROM AUTHOR]

We report the first systematic study to identify and characterize a sample of classical Ae stars in the Galaxy. The spectra of these stars were retrieved from the A-star catalogue using the Large sky Area Multi-Object fibre Spectroscopic Telescope (LAMOST) survey. We identified the emission-line stars in this catalogue from which 159 are confirmed as classical Ae stars. This increases the sample of known classical Ae stars by about nine times from the previously identified 21 stars. The evolutionary phase of classical Ae stars in this study is confirmed from the relatively small mid- and far-infrared excess and from their location in the optical colour–magnitude diagram. We estimated the spectral type using MILES spectral templates and identified classical Ae stars beyond A3, for the first time. The prominent emission lines in the spectra within the wavelength range 3700–9000 Å are identified and compared with the features present in classical Be stars. The H α emission strength of the stars in our sample show a steady decrease from late-B type to Ae stars, suggesting that the disc size may be dependent on the spectral type. Interestingly, we noticed emission lines of Fe  ii , O  i , and Paschen series in the spectrum of some classical Ae stars. These lines are supposed to fade out by late B-type and should not be present in Ae stars. Further studies, including spectra with better resolution, is needed to correlate these results with the rotation rates of classical Ae stars. [ABSTRACT FROM AUTHOR]

Plants are widely used in foodstuff, medicines and industry and it's also essential for environmental protection. However, it's a crucial task to recognizes plant species on earth. Plants are depreciated due to pollution, diseased or nutrient deficiency. The current way of identification and determination of the type of medicinal leaves is still being done manually and prone to human errors. Misclassification of plant species results in huge loss on the production of crops and economical value of market. Plant recognition requires huge amount of labor, knowledge about the plants and also requires more time interval. Image processing is the method of study and manipulation of digitalized images especially to enhance the quality of the images. During image acquisition there is a chance of corruption due to noise images are corrupted by the noise that are applied on medicinal leaves. Filtering and smoothing of images are the important task to scale back or remove the effect of noise. This paper represents analysis of various image preprocessing techniques that are applied on medicinal leaf images. These techniques are used to remove the noise based on their potential. Image preprocessing is a main step for noise removal and for enhancing the standard of an original images. The quality of images is analyzed in support with PSNR (peek signal to noise ratio) values that are applied on various filtering and smoothening methods to get the better-quality images. Further these preprocessing methods are very useful for the segmentation process. [ABSTRACT FROM AUTHOR]

Background and Aim: In recent times, nonopioid analgesics such as gabapentin and pregabalin are being used in preoperative setting for anxiolysis and attenuation of pressor response to endotracheal intubation and laryngoscopy but with conflicting results. Hence, we intended to evaluate and compare the efficacy of pregabalin as premedication alone and in combination with intravenous fentanyl in elective surgeries. Methods: A total of 60 patients aged 18-50 years, with ASA status I and II, and scheduled for laparoscopic surgeries were randomly allocated to Group P (n=30) and Group PF (n=30) by sealed envelope comprising coded study drugs. Group P received oral pregabalin 150 mg an hour before induction of general anesthesia, whereas Group PF received oral pregabalin 150 mg and intravenous fentanyl 2 µg/kg five minutes before induction. Hemodynamic parameters, analgesia (by Visual Analogue Scale), and sedation scores (by Ramsey Sedation scale) were compared between the two groups. Software R version 3.6.0. was employed to analyze the data. Results: The mean heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure were significantly higher in Group P immediately after laryngoscopy and intubation and 1 min after intubation (P<0.0001). No significant difference was observed between the two groups with respect to requirement of intraoperative and postoperative analgesia (P=0.061 and P=0.56, respectively). None of the patients in either group experienced postoperative nausea, vomiting, or intraoperative shivering. Conclusions: Combination of pregabalin and intravenous fentanyl was more effective in attenuating pressor response to laryngoscopy and endotracheal intubation compared to pregabalin alone. [ABSTRACT FROM AUTHOR]

The role of self-assessment in workplace-based assessment remains contested. However, anaesthesia trainees need to learn to judge the quality of their own work. Entrustment scales have facilitated a shared understanding of performance standards among supervisors by aligning assessment ratings with everyday clinical supervisory decisions. We hypothesised that if the entrustment scale similarly helped trainees in their self-assessment, there would be substantial agreement between supervisor and trainee ratings. We collected separate mini-clinical evaluation exercises forms from 113 anaesthesia trainee-supervisor pairs from three hospitals in Australia and New Zealand. We calculated the agreement between trainee and supervisor ratings using Pearson and intraclass correlation coefficients. We also tested for associations with demographic variables and examined narrative comments for factors influencing rating. We found ratings agreed in 32% of cases, with 66% of trainee ratings within one point of the supervisor rating on a nine-point scale. The correlation between trainee and supervisor ratings was 0.71, and the degree of agreement measured by the intraclass correlation coefficient was 0.67. With higher supervisor ratings, trainee ratings better correlated with supervisor ratings. We found no strong association with demographic variables. Possible explanations of divergent ratings included one party being unaware of a vital aspect of the performance and different interpretations of the prospective nature of the scale. The substantial concordance between trainee and supervisor ratings supports the contention that the entrustment scale helped produce a shared understanding of the desired performance standard. Discussion between trainees and supervisors on the reasoning underlying their respective judgements would provide further opportunities to enhance this shared understanding. [ABSTRACT FROM AUTHOR]

Ginger exosome-like nanoparticles (GELNs) have been extensively implicated in alleviating inflammation, maintaining intestinal microbiome and are considered competent drug delivery vehicles. Despite this, the current knowledge of the GELN interaction with cancer cells is limited. Triple-negative breast cancer (TNBC), an aggressive variant lacking efficient therapeutics, necessitates novel natural counterparts with minimal side effects. This study investigates the action of GELNs isolated from ginger rhizomes against TNBC cells. GELNs were isolated by ultracentrifugation and characterized physicochemically. The interaction of GELNs with TNBC cells (MDA-MB-231) was studied in detail. The GELNs induced a concentration-dependent decrease in cell viability in MDA-MB-231 cells without affecting the normal cell lines tested. GELNs induced apoptosis as indicated by morphological changes, nuclear fragmentation, membrane damage, phosphatidyl serine translocation, ROS generation, drop in mitochondrial membrane potential, expression of apoptotic specific proteins, and increased caspase activity. GELNs also instigated cell cycle arrest, retarded cell migration and colony formation in TNBC cells. These findings report a novel action of GELNs against TNBC cells and a closer look at the underlying molecular mechanism of this interspecies communication. This opens newer prospects for using dietary ELNs to target therapeutically challenging cancers. Dietary exosome-like nanoparticles are a vital part of nutrition with multiple health benefits. In this study, ginger exosome-like nanoparticles (GELNs) were isolated from ginger rhizomes. The GELNs were similar to mammalian exosomes in size and morphology. GELNs not only induced apoptosis but also inhibited cell migration and colony formation in triple negative breast cancer MDA-MB 231 cells. Hence, in future, it can be developed as a new pharmacological agent against triple negative breast cancer. [Display omitted] • First report on the effect of GELNs against TNBC cells. • GELNs specifically induced apoptosis in TNBC cells. • It increased ROS generation and G2/M cell cycle arrest. • Also, it inhibited the migration and colony formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • The presence of SPR peak in absorption spectrum at 440 nm confirms the formation of AR-AgNPs. • Serum renal marker levels were significantly reverted near control in AR-AgNPs treated mice. • The AR-AgNPs protected kidney tissue against gentamicin induced oxidative damage. • Oral administration of AR-AgNPs to gentamicin induced mice restored the GSH level to normal level. A study on green synthesized silver nanoparticles (AgNPs) using aqueous extract of Actiniopteris radiata and investigated the effect of A. radiata biosynthesized silver nanoparticles (AR-AgNPs) against gentamicin induced nephrotoxicity. The surface plasmon resonance (SPR) peak at 440 nm in UV–visible absorbance spectrum reveals the presence of AgNPs. DLS analysis shows that the distribution of size is normal and the average size of AgNPs converges about 100 nm. SEM revealed the consistent shape, uniform distribution, and closely packed characteristics of NPs whereas EDX confirms the presence of metallic silver with a strong peak at 3 keV. The N–H and O–H stretching vibrations are observed in the FTIR spectrum around 3450 and 3423 cm−1. Gentamicin induced changes in serum parameters resulted in a significant increase in the level of serum urea, creatinine, bilurubin and uric acids. AgNPs even at modest doses (250 mg/kg), significantly reverted the level of serum markers. The gentamicin-induced AR-AgNP in mice with the levels of CAT, GPx, SOD and TBARS ensured the protection against the oxidative damage in mice which clearly implies that enhancing the antioxidant defense mechanism. Nephrotoxicity of gentamicin induced mice were demonstrated by significantly elevated levels of blood urea, serum creatinine, bilirubin, and uric acids. The exposure of AR-Ag nanoparticles leads to a substantial decrease in blood urea and serum creatinine levels and enhanced the antioxidant and anti-nephrotoxic activity. [ABSTRACT FROM AUTHOR]

Exosome-like nanoparticles (ELNs) are a class of nanosized extracellular vesicles from plants that can deliver drugs, siRNA, DNA, and proteins to various types of cells. Purification of ELNs from plants are tricky when compared to that from body fluids or cell culture medium because the initial suspension of the former contains high amounts of sugar, fiber, fat, etc. In this study, we have optimized the different steps for the isolation of ELNs from grapes. After preparing the juice, the bulk density was measured by Brix analysis and followed the same bulk density whenever doing the isolation. Differential centrifugation at various speeds and times and membrane filtration using different pore-size membranes were also optimized before the final step of ELN separation by ultracentrifugation. The size, zeta potential, and PDI value of the isolated ELNs were measured using a Malvern Zeta Sizer. SEM analysis showed that the grape ELN has an average size of 140.8 ± 10.75 nm. The results indicated that filtration and centrifugation at different levels are essential before the ultracentrifugation for isolating homogenous grape ELNs with desired size, zeta potential and PDI value. From the optimized method, we have obtained 4.8 ± 0.509 mg protein equivalents of ELNs from 100 g of grapes. [ABSTRACT FROM AUTHOR]

AryabhaTa's and kaTapayAdi systems of encoding numbers in Sanskrit words have been in vogue since antiquity in Indian science. The process of decryption and decoding such numbers from the verses has been achieved only manually hitherto. Automating this process has been the focus of this communication. The process of decryption was achieved using a code written in LabVIEW platform of programing. [ABSTRACT FROM AUTHOR]

The steady increase in world cheese demand keeps the search for appropriate coagulating enzymes as rennet substitutes in the scientific focus. This work reports the milk-clotting activities of aqueous crude enzyme (CE) from different parts of Calotropis gigantea using skim milk as substrate. CE from latex exhibited high caseinolytic (86.445 ± 1.055 U/ml) as well as milk-clotting activity (450 U/ml) when compared to other parts. Significant milk clotting index (MCI) was presented by crude enzyme of latex followed by stem, flower and leaf in the decreasing order ( p < 0.05). CE from all parts showed an optimum activity at 37 °C, pH 5.5 and 10 mM calcium chloride concentration with excellent pH (4.5-6.5) and thermal stability (30-60 °C). Hydrolysis pattern of casein components by CE during 1 h incubation, as assessed by Tricine-SDS-PAGE, and subsequent peak analysis revealed CE from stem to be closely similar to that of rennin. However, extensive casein hydrolysis was observed when incubated with crude latex enzyme. Casein bands of CE and rennin tended to disappear as incubation progressed to 24 h. Proteolytic degradation was found to be advanced and resulted in complete breakdown of casein fractions unravelling the importance of incubation time as a possible essential requisite for controlled and appropriate casein hydrolysis. The study provides evidence of rennin-like activity associated with C. gigantea plant parts which may serve as a promising source of vegetable milk coagulant. [ABSTRACT FROM AUTHOR]