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Pyrimidine derivatives are synthesized to possess various pharmacological and biological activities. In the present work, we have synthesized 3-(4-methoxyphenyl)-1-phenyl prop-2-en-1-one (1) (chalcone) by using 4-methoxybenzaldehyde and acetophenone in the presence of alcoholic KOH by Claisen-Schmidt condensation reaction. After purification and characterization by physical and spectral methods, The synthesized chalcone have been converted into 6-(4-methoxyphenyl)-4- phenyl-1,6-dihydropyrimidin-2-amine (2) by treating with guanidine nitrate in the presence of alcoholic KOH. The structure (2) has been characterized by spectral analysis. The synthesized compound (2) is further reacted with ethyl 2-cyano-3, 3-bis (methylthio)acrylate in the presence of catalytic amount of potassium carbonate in DMF under reflux condition to givenovel 2- (4-methoxyphenyl)-8-(methylthio)-6-oxo-4-phenyl-1,6,9,9a-tetrahydro-2H-pyrimido[1,2-a] pyrimidine-7-carbonitrile(3) in good yields. The compound (3) possesses replaceable methylthio (-SCH3) group at 8 position. The compound (3) is further reacted with various nucleophiles like substituted aromatic amines, aromatic phenols, hetryl amines and active methylene compounds to give 2-(4-methoxyphenyl)-8-substituted-6-oxo-4-phenyl-1,6,9,9a-tetrahydro-2H-pyrimido[1,2-a]pyrimidine-7-carbonitrile in good yields.

Background: Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9)-low density lipoprotein receptor interaction with injectable monoclonal antibodies or small interfering RNA lowers plasma low density lipoprotein-cholesterol, but despite nearly 2 decades of effort, an oral inhibitor of PCSK9 is not available. Macrocyclic peptides represent a novel approach to target proteins traditionally considered intractable to small-molecule drug design. Methods: Novel mRNA display screening technology was used to identify lead chemical matter, which was then optimized by applying structure-based drug design enabled by novel synthetic chemistry to identify macrocyclic peptide (MK-0616) with exquisite potency and selectivity for PCSK9. Following completion of nonclinical safety studies, MK-0616 was administered to healthy adult participants in a single rising-dose Phase 1 clinical trial designed to evaluate its safety, pharmacokinetics, and pharmacodynamics. In a multiple-dose trial in participants taking statins, MK-0616 was administered once daily for 14 days to characterize the safety, pharmacokinetics, and pharmacodynamics (low density lipoprotein cholesterol). Results: MK-0616 displayed high affinity ( K i = 5pM) for PCSK9 in vitro and sufficient safety and oral bioavailability preclinically to enable advancement into the clinic. In Phase 1 clinical studies in healthy adults, single oral doses of MK-0616 were associated with >93% geometric mean reduction (95% CI, 84–103) of free, unbound plasma PCSK9; in participants on statin therapy, multiple–oral-dose regimens provided a maximum 61% geometric mean reduction (95% CI, 43–85) in low density lipoprotein cholesterol from baseline after 14 days of once-daily dosing of 20 mg MK-0616. Conclusions: This work validates the use of mRNA display technology for identification of novel oral therapeutic agents, exemplified by the identification of an oral PCSK9 inhibitor, which has the potential to be a highly effective cholesterol lowering therapy for patients in need.

We report for the first time the green synthesis of carbon nanodots (g-CDs) from the peels of T. cucumerina by simple hydrothermal route. An in-situ liquid phase process was adopted for the design of the monoclinic tungsten trioxide (m-WO3)- based nanostructure with g-CDs to obtain a bi-functional g-CDs/m-WO3 system. Characterization techniques, such as X- Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microcsopy (FESEM), Energy Dispersion X-Ray Analysis (EDX), Fourier Transformed Infra-Red (FTIR), Ultra Violet Defuse Reflectance Spectroscopy (UV-DRS) and Photoluminescence Emission Spectroscopy (PLES) were employed for the morphological, dimensional, chemical and optical analysis. The efficiency in the adsorption of the heavy metal, namely Cd2+ ions of the m-WO3 was found improved in the formated nanocomposite with g-CDs to 81%. The detailed adsorption kinetics study through the adsorption isotherms revealed that the reaction mechanism can be described by the pseudo-second-order kinetic model determined by Freundlich isotherms. Furthermore, the photocatalytic degradation efficiency of the crystal violet dye under the visible light was found significantly enhanced to 95% for the studied composite. The photocatalytic ability of the nanocomposite was found remaining almost intact even after four repeated cycles. A study in the presence of different scavengers suggested that the hydroxyl radicals play a crucial role in determining the photocatalytic activity of the nanocomposite. An improvement in the structural stability and charge carrier separation kinetics was achieved by carefully growing the m-WO3 nanostructures in g-CDs. These resultes have revealed the integrated adsorptive and photocatalytic capabilities of the studied nanocomposites for the waste water treatment. Keywords: Tungsten oxide, Carbon dots, Green synthesis, Cadmium removal, Photocatalysis

Pollen cryopreservation in Bottle gourd for breeding and conservation Laxmi Mastiholi*, Anilkumar G S and Rajasekharan P E Division of Flower and Medicinal Crops, ICAR-IIHR, Bengaluru Abstract Bottle gourd (Lagenaria siceraria (Molina) Standl.) also known as Calabash, is one of the most important cucurbitaceous vegetable in India with more genetic diversity. Which can be used as vegetable, water receptacle, musical instrument or as medicinal plants. As monoecious nature of bottle gourd, male flower grows on long peduncle and female flower on short peduncle however it has an ovary in the shape of the fruit. Anthesis and dehiscence time is moderately influenced by humidity and temperature conditions and also there is seasonal variation in photoperiod insensitive and sensitive genotype. So to avoid this seasonal variation in breeding programme, we have done pollen cryopreservation. At the time of anthesis (4:30 to 7 p.m.) pollen were collected from field and pre storage germination assessment was carried by hanging drop technique using modified Brewbaker and Kwack media containing different concentration of sucrose. After 1 hour desiccation in zeolite beads the pollen were packed in butter paper covers enclosed in sealed aluminium pouches which were rapidly plunged into the cryobiological system containing liquid nitrogen. After cryopreservation the germination test was carried out to know the percentage of germination of cryopreserved pollen. The fresh pollen recorded germination percentage of 97.20 % and it was 96.50 % after one week of cryopreservation in 15% sucrose. The results indicate that, there is no significant decline in viability of cryopreserved pollen. The cryopreservation of bottle gourd pollen helps for production of the cross combination genotypes (Photosensitive and insensitive) with year round supplementary pollination. Cryopreservation of pollen offers a simple and effective method of long-term pollen storage. Pollen stored in liquid nitrogen (LN) for many years without loss of its essential capabilities to pollinate, fertilize, and set normal fruit and seed when used in plant breeding, for controlled pollinations, or for the conservation of plant genetic resources. &nbsp

Pollen cryopreservation of bitter gourd (Momordica charantia) – An emerging technology for plant breeding and conservation Anilkumar G S1 and P E Rajasekharan2 1 – Research Fellow, Division of Flower and Medicinal Crops, ICAR - IIHR, Bangalore, India 2 – Principal Scientist, Division of Flower and Medicinal Crops, ICAR - IIHR, Bangalore, India Corresponding author mail – anilkumargs14@gmail.com Abstract: Pollen cryopreservation is an important tool for the maintenance of male gametes and can promote improved efficiency in breeding and germplasm conservation and exchange. Previous studies in Momordica genus reported the threat of genetic erosion to a great extent. Hence, storing pollen for future use is an important tool in this genusin conserving genetic diversity. The success of pollen storage for genetic conservation purposes depends on many factors, and it is essential that the chosen procedure will ensure maintenance of high genetic integrity, vigour and germination profiles. Thus, it is essential to evaluate pollen viability before, during and after long-term conservation. In this context, a study was conducted at Division of Flower and Medicinal crops, ICAR-IIHR, Bengaluru to check the pollen viability and feasibility of cryopreservation in Momordica charantia. The flowers buds are bagged one day prior to opening and collected in the next morning at peak anthesis time (7:00 am). The pollen are extracted using camlin paint brush and collected in butter paper and kept for drying in desiccator to reduce the moisture of pollen. Viability by in-vitro germination assessment was carried by hanging drop technique using Brew-bakers media containing different concentrations (10, 15, 20 and 25 per cent) of sucrose solution. Followed by the fresh pollen were packed in butter paper covers enclosed in sealed aluminum pouches which were rapidly plunged into the cryobiological system containing liquid nitrogen. Post cryopreservation germination test was carried out after one week to check the germination ability of pollen. The fresh pollens recorded maximum germination percentage of 78.25 % and it was 72.50 % after one week of cryopreservation with 10 % of sucrose in Brew-bakers media. The results indicate that, there was a variable response to the germination of cryopreserved pollen and these observations ascertained thatM. charantia pollen can be recovered viably after cryogenic storage in various proportions. It is our understanding that pollen cryopreservation is a safe and practical alternative for conserving nuclear genetic variability that is often neglected by potential users. This technique has the potential to overcome challenges of breeding programs, such as flowering asynchrony between different parent genotypes, and the production of insufficient pollen in nature. It alsofinds its commercial importance in hybrid seed production by providing the viable pollen for primary and supplementary pollination during offseason. Key words: Cryopreservation, In-vitro germination, Momordica charantia, Brew-bakers media

Aims The main purpose of this article is to conduct audit of clinical profile and outcomes of patients presenting with acute variceal bleed in a tertiary care hospital. Methods and Material This was a retrospective study of patients presenting with variceal bleed in a tertiary care center. Data were generated through a computerized electronic record system. Data of patients admitted for acute variceal bleed from August 2018 to December 2018 were collected and considered for analysis. Statistical analysis was done using the software Statistical Package for the Social Sciences (SPSS) 22.0 version. Results Overall, 107 cases were analyzed. In 89.7% (96) cases, cirrhosis of liver was a cause of variceal bleed. Besides, 77.6% (83) patients had large esophageal varices. Five patients (4.7%) required glue injection. Rebleed rate in present study was 0.9%. Mortality due to variceal bleed was 9.3% (10). Acute rebleed (p = 0.002), low mean arterial pressure (MAP; p = 0.001), low platelet count (p = 0.001), high serum creatinine (p = 0.001), high serum total bilirubin (p = 0.001), high international normalized ratio (INR; p = 0.001), and higher model for end stage liver disease (p = 0.001) were associated with increased risk of mortality. Door to endoscopy time ( Conclusion Mortality due to acute variceal bleed can be reduced with timely intervention. Low MAP, low platelet count, higher serum bilirubin and creatinine, and higher INR are predictors of increased mortality due to variceal bleed. Endoscopy done within 12 to 24 hours of presentation did not affect the outcome.

Chetan G K and Dr. Anilkumar G Garag (2017), “An Empirical Analysis of Lead and Lag Relationship between CNX Bank Index and Bank Nifty Futures of Indian Capital Market”, International Conference on Global Healthcare Management and Business Issues, Conducted by: Kirloskar Institute of Advanced Management Studies, Pune, pp223-234. (ISBN:978-93- 86256-31-7)

Phenolic compounds from plant sources have significant health-promoting properties and are known to be an integral part of folk and herbal medicines. Consumption of phenolics is known to alleviate the risk of various lifestyle diseases including cancer, cardiovascular, diabetes, and Alzheimer's. In this context, numerous plant crops have been explored and characterized based on phenolic compounds for their use as supplements, nutraceutical, and pharmaceuticals. The present review highlights some important source of bioactive phenolic compounds and novel technologies for their efficient extraction. These techniques include the use of microwave, ultrasound, and supercritical methods. Besides, the review will also highlight the use of response surface methodology (RSM) as a statistical tool for optimizing the recoveries of the phenolic bioactives from plant-based matrices.

HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination regimen. Herein, we describe the discovery and characterization of silyl proline-containing HCV NS5A inhibitor MK-8325 with good pan-genotype activity and acceptable pharmacokinetic properties.