Standardization of Some Commercial Anti-diabetic Herbal Products containing Syzygiumcumini

An isocratic HPLC method was developed for standardization of five commercially available products containing S. cumini seeds (DIABECON, MADHULENE, HYPONIDD, D-FIT and DIABEGON)using methylxanthoxylin (MXX)as marker. The method was validated in accordance with ICH Q2(R1) guidelines. The chromatographic separation of MXX was achieved on a C18 column by mobile phase composed of methanol and water (60:40%v/v) at a flow rate 0.5 mL/min. The eluent was detected at 280 nm.The method was linear over concentration of 1-200 μg/mL with correlation coefficient of 0.9999. The LOD and LOQ were 0.175 and 0.530 µg/mL, respectively. The method was precise (%RSD <0.31), accurate and robust for determination of MXX in herbal extracts. The content of MXX in the seed extract was found to be 0.0433%w/w while it was ranging from 0.026-0.041%w/w in the products. The content of MXX was found to be equivalent to the pure seed extract only in DIABECON tablets and D-FIT soft gelatine capsules while it was found to be significantly less in the other formulations

Active power regulation of hydro dominating energy system using IDD optimized FPA

In this paper an attempt is made to propose the different models of control and design such as integral derivative (ID), proportional integral derivative (PID) and integral double derivative (IDD) effectively optimized through flower pollination algorithm (FPA) for active power regulation of modern energy system having hydro dominating areas. At first, the performance of FPA-ID, FPA-PID and FPA-IDD founded LFC are evaluated for standard load change in one control area and their performance for system model is judged on the basis of inverse time multiplied absolute error (ITAE). The results obtained show the advancement of FPA-IDD over other designs for hydro dominating energy system. The performance of the control lacks in minimizing system overshoot, oscillations and settling time due to large responding time of hydro turbines. Hence, the collective operation of unified power flow control (UPFC) in series with tie-line and active power support from redox flow battery is installed in the hydro dominating energy system. The significant improvement in system results are obtained by installing the UPFC and RFB in system model. Further enhancement in the system results are achieved by recalculating the gains of IDD with the help of FPA with positive support from RFB and UPFC. The application results are obtained for standard load change and results show the effectiveness of the proposed technique for the hydro dominating energy system.10th International Conference on Applied Energy (ICAE2018), 22-25 August 2018, Hong Kong, Chinahttp://www.elsevier.com/locate/procediaam2020Electrical, Electronic and Computer Engineerin

Frequency regulation of wind integrated power system using dual mode fuzzy

Owing to the increase in electrical load demand the dimension of interconnected energy system is increasing day by day and getting more complex with power injection from renewable technologies such as wind energy in order to supply and meet rising energy demands as well as to limit the dependency on conventional sources of power generation. However, the rising trends towards power generation via wind power will cause the challenging task to maintain the equilibrium between the power generation and load demand and hence to keep the power system frequency to standard value. Hence, in this work a new control design based on switching logic having additional fuzzy intelligence is proposed for wind integrated energy system. In addition, it is also tried to reduce the rule base for proposed design and hence to reduce the complexity of fuzzy based design. The proposed design is tested for standard load change and the results are matched with fuzzy PI and with natural response of the system to show the power of the proposed design. Further, it is also shown that doubly fed induction generator (DFIG) wind integrated system with proposed control design have the capability to improve the standard frequency profile in case of sudden change in the power demand of the energy system and hence it helps to deliver the required power to the modern clients.10th International Conference on Applied Energy (ICAE2018), 22-25 August 2018, Honk Kong, Chinahttp://www.elsevier.com/locate/procediaam2020Electrical, Electronic and Computer Engineerin

Imatinib and Thyroid Dysfunction in BCR-ABL Positive CML Patients

Background: Thyroid dysfunction is a known adverse effect of some tyrosine kinase inhibitors like sunitiniband sorafenib while imatinib hasbeen shown to induce hypothyroidism and increased requirement of levothyroxine in thyrectomizedpatients. Very few retrospective studies are available for CML patients treated with imatinib,which havedemonstrated conflicting effects on thyroid function.Experimental design: We have prospectively studied thyroid function at baseline and at 6 months of imatinib treatment in 30 newly diagnosed BCR-ABL positive CML patients.Results: Two (6.7%) patients had subclinical hypothyroidism at diagnosis with the prevalence not being different from general population. Though the TSH levels increased significantly from baseline (3.80±2.00 mIU/L vs. 3.14±1.65 mIU/L, p =0.016) after6 months of treatment, 90% of the patients remained euthyroid. Only 3 patients had subclinical hypothyroidism.Conclusion: Imatinib did not have any significant impact on thyroid function in CML patients but may possibly alter the peripheral metabolism of thyroid hormones

Robust multi-machine power system stabilizer design using bio-inspired optimization techniques and their comparison

DATA AVAILABILITY : Data will be made available on request.This paper reports a comparative study among four bio-inspired meta-heuristic techniques i.e. Sooty-Tern Optimization (STO), Grey Wolf Optimization (GWO), Genetic Algorithm (GA), and Particle Swarm Optimization (PSO) to tune the robust Power System Stabilizer (PSS) parameters of the multi-machine power system. These approaches are successfully tested on two bench-mark systems: sixteen-machine, sixty-eight-bus New England Extended Power Grid (NEEPG) and three-machine, nine-bus Western System Coordinating Council (WSCC). The efficacy of planned PSS via STO and GWO is validated by extensive non-linear simulations, eigenvalue analysis, and performance indices for numerous operating conditions under decisive perturbations, and outcomes are matched with those of GA and PSO techniques. In addition, the robustness is also tested for these algorithms. The results indicate that the PSS design using STO and GWO improves the small-signal stability and damping performance for mitigating inter-area and local area modes of low-frequency oscillations compared to GA and PSO.https://www.elsevier.com/locate/ijepeshj2024Electrical, Electronic and Computer EngineeringSDG-07:Affordable and clean energ

Ybp2 Associates with the Central Kinetochore of Saccharomyces cerevisiae and Mediates Proper Mitotic Progression

The spindle checkpoint ensures the accurate segregation of chromosomes by monitoring the status of kinetochore attachment to microtubules. Simultaneous mutations in one of several kinetochore and cohesion genes and a spindle checkpoint gene cause a synthetic-lethal or synthetic-sick phenotype. A synthetic genetic array (SGA) analysis using a mad2Δ query mutant strain of yeast identified YBP2, a gene whose product shares sequence similarity with the product of YBP1, which is required for H2O2-induced oxidation of the transcription factor Yap1. ybp2Δ was sensitive to benomyl and accumulated at the mitotic stage of the cell cycle. Ybp2 physically associates with proteins of the COMA complex (Ctf19, Okp1, Mcm21, and Ame1) and 3 components of the Ndc80 complex (Ndc80, Nuf2, and Spc25 but not Spc24) in the central kinetochore and with Cse4 (the centromeric histone and CENP-A homolog). Chromatin-immunoprecipitation analyses revealed that Ybp2 associates specifically with CEN DNA. Furthermore, ybp2Δ showed synthetic-sick interactions with mutants of the genes that encode the COMA complex components. Ybp2 seems to be part of a macromolecular kinetochore complex and appears to contribute to the proper associations among the central kinetochore subcomplexes and the kinetochore-specific nucleosome

Four new degradation products of doxorubicin: An application of forced degradation study and hyphenated chromatographic techniques

Forced degradation study on doxorubicin (DOX) was carried out under hydrolytic condition in acidic, alkaline and neutral media at varied temperatures, as well as under peroxide, thermal and photolytic conditions in accordance with International Conference on Harmonization (ICH) guidelines Q1(R2). It was found extremely unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80 °C, and to oxidation at room temperature. It degraded to four products (O-IâO-IV) in oxidative condition, and to single product (A-I) in acid hydrolytic condition. These products were resolved on a C8 (150 mmÃ4.6 mm, 5 µm) column with isocratic elution using mobile phase consisting of HCOONH4 (10 mM, pH 2.5), acetonitrile and methanol (65:15:20, v/v/v). Liquid chromatographyâphotodiode array (LCâPDA) technique was used to ascertain the purity of the products noted in LCâUV chromatogram. For their characterization, a six stage mass fragmentation (MS6) pattern of DOX was outlined through mass spectral studies in positive mode of electrospray ionization (+ESI) as well as through accurate mass spectral data of DOX and the products generated through liquid chromatographyâtime of flight mass spectrometry (LCâMSâTOF) on degraded drug solutions. Based on it, O-IâO-IV were characterized as 3-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 1-hydroxy-9-desacetyldoxorubicin-9-hydroperoxide, 9-desacetyldoxorubicin-9-hydroperoxide and 9-desacetyldoxorubicin, respectively, whereas A-I was characterized as deglucosaminyl doxorubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of doxorubicin were outlined and discussed. Keywords: Doxorubicin, TOF, Forced degradation, Liquid chromatography, Degradation product, Mass fragmentation patter

Degradation Study on Sulfasalazine and a Validated HPLC-UV Method for its Stability Testing

Sulfasalazine (SSZ) was subjected to degradation under the conditions of hydrolysis (acid, alkali, and water), oxidation (30% H2O2), dry heat, and photo-lysis (UV-VIS light) in accordance with the ICH guidelines. An RP-HPLC method was developed to study the degradation behavior. No degradation was noted under any condition except alkaline hydrolysis where SSZ was degraded to a single minor product. SSZ was optimally resolved from this product on an XTerra® RP18 column with a mobile phase composed of methanol and an ammonium acetate buffer (10 mM, pH 7.0) (48:52, v/v) delivered at a rate of 0.8 mL/min in an isocratic mode. The method was validated and found to be linear (r2=0.99945), precise (%RSD <2), robust, and accurate (94–102%) in the concentration range of 0.5–50 μg/mL of SSZ. The PDA analysis of the degraded sample revealed the SSZ peak purity to be 998.99 and the drug peak eluted with a resolution factor of >2 from the nearest resolving peak, indicating the method to be selectively stability-indicating for the drug analysis. The method was applied successfully for the stability testing of the commercially available SSZ tablets that were under varied ICH-prescribed conditions. An explanation for the unusual stability of the drug when exposed to acidic hydrolysis, despite the presence of the sulfonamide linkage, is also discussed

Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLCâUV method for their quantification

Leflunomide (LLM) is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A(R2). In total, four degradation products (IâIV) were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions. LLM and all degradation products were optimally resolved by gradient elution over a C18 column. The major degradation product (IV) formed in hydrolytic alkaline conditions was isolated through column chromatography. Based on its 1H NMR, IR and mass spectral data, it was characterized as a British Pharmacopoeial impurity B. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged and robust for quantification of LLM as well as product IV. Finally, the method was applied to stability testing of the commercially available LLM tablets. Keywords: Leflunomide, Characterization, Forced degradation, Degradation product, HPLCâU

Chromone hybrids as interleukin-6 and acetylcholinesterase inhibitor for treatment of Alzheimer's disease: Design, docking, synthesis and evaluation

The course of Alzheimer's disease (AD) is largely influenced by interleukin-6 (IL-6) and acetylcholinesterase (AChE). Therefore, concurrent suppression of these two targets is a rational approach for the development of anti-AD molecules. The study is aimed to design a molecule with pharmacophore capable of inhibiting both the targets. Four series are designed by coupling a chromone moiety (a pharmacophore that inhibits IL-6) with a N,N-disubstituted amine (that inhibits AChE) through a linker (1–4 carbon chain). The in silico studies on the designed compounds led to the identification of 16 best-fit compounds having good oral bioavailability and blood brain barrier permeability. All 16 compounds were synthesized and evaluated for anti-AChE activity. Six compounds showing >45 % inhibition of AChE at 1 μM concentration are further evaluated for BuChE (butyrylcholinesterase) and IL-6 inhibitory activities. Compound YS3g is the most potent inhibitor of EeAChE (IC50 = 0.45 μM) and of IL-6 (IC50 = 0.46 μM). Subsequently, it is found to show dose-dependent effects in STZ (streptozotocin)-induced memory deficit model at three doses (0.2, 0.4 and 0.8 mg/kg). At higher dose (0.8 mg/kg), it reverses the deficit as also supported by histopathological studies. The findings reveal that a chromone nucleus coupled with a piperazine via a three-carbon linker may be a useful template for developing novel moieties against AD