OPTIMIZATION OF INVENTORY MODEL COST PARAMETERS AS FUZZY NUMBERS

In general, the demand rate and the unit cost of the items remains constant inspite of lot size in inventory models. But in reality, the demand rate and the unit cost of the items are connected together. In this research, demand dependent unit cost inventory model is considered where different cost parameters, maximum inventory and the lot size of the model are taken under fuzzy environment. First an analytic solution of the crisp model is obtained by the method of calculus where the inventory parameters are exact and deterministic. Later, the problem is developed with fuzzy parameters where inaccuracy has been introduced through triangular membership functio

A STUDY ON THE JONES REVOLUTION

In this section we introduce the Jones polynomial a link invariant found by Vaughan Jones in 1984. Later on, Louis Kauffman expanded further Jones study of knot polynomials, allowing for a much simpler presentation of the Jones polynomial

Kalman Filter Algorithm for Mitigation of Power System Harmonics

The maiden application of a variant of Kalman Filter (KF) algorithms known as Local Ensemble Transform Kalman Filter (LET-KF) are used for mitigation and estimation power system harmonics are proposed in this paper. The proposed algorithm is applied for estimating the harmonic parameters of power signal containing harmonics, sub-harmonics and inter-harmonics in presence of random noise. The KF group of algorithms are tested and applied for both stationary as well as dynamic signal containing harmonics. The proposed LET-KF algorithm is compared with conventional KF based algorithms like KF, Ensemble Kalman Filter (En-KF) algorithms for harmonic estimation with the random noise values 0.001, 0.05 and 0.1. Among these three noises, 0.01 random noise results will give better than other two noises. Because the phase deviation and amplitude deviation less in 0.01 random noise. The proposed algorithm gives the better results to improve the efficiency and accuracy in terms of simplicity and computational features. Hence there are less multiplicative operations, which reduce the rounding errors. It is also less expensive as it reduces the requirement of storing large matrices, such as the Kalman gain matrix used in other KF based methods

Design, Synthesis, Characterisation and Biological Evaluation of Some Novel 1, 3, 4-Thiadiazole Derivatives as Anti-Tubercular Agents Targeting Decaprenyl Phosphoryl Beta-D-Ribose 2’ Epimerase-1

INTRODUCTION:Tuberculosis [TB] is caused by mycobacterium tuberculosis that most often affect the lungs. Tuberculosis is curable and preventable. In 1882, the German physician Robert Koch isolated the bacterium. Tuberculosis is contagious and airborne disease. In 1944, streptomycin was to treat tuberculosis [TB]. This amino glycoside interferes with protein biosynthesis through an interaction with the small 30s subunit of the ribosome. The discovery of Para amino salicylic acid in 1946 was quickly followed by the important discovery of Isoniazid [INH], as one of the most active anti-TB drugs used today. Inhibition of mycolic acids biosynthesis, one of the essential components of the mycobacterium cell wall was determined as the mechanism of action. Pyrazinamide [PZA] appeared as a potential Anti-TB drug in 1952. The TB treatment in the 1980s was a great success as it allowed to shorten the duration of the therapy from 9 to 6 months. Ethambutol [EMB] and Rifampin [RIF], the two last derivatives used in the TB first-line treatment, were discovered during the 60s. Ethambutol is an ethylenediamine discovered in 1961, which affects the cell wall by specifically targeting the polymerization of arabinogalactan and lipoarabinomannan. Finally, Rifampin appeared as a drug of choice for TB treatment around 1970, by acting on replicating and non-replicating mycobacteria. This derivative belongs to the rifampicin family and inhibits bacterial RNA synthesis by binding to the b-subunit of the DNA-dependent polymerase. AIM: The aim of this project is to design molecules with potential anti-tubercular activity that is capable of inhibiting cell wall synthesis by inhibiting Decaprenylphosphoryl-beta-D-ribose2-epimerase-1. The designed compounds will be synthesized, characterized and evaluated for biological activity and toxicity. OBJECTIVE:The compounds are designed and docked against a specific crucial target, Decaprenylphosphoryl-beta-D-ribose2epimerase-1.This is involved in the cell wall biosynthesis and Lipid metabolism. The synthesized compounds are expected to act on the same.SUMMARY:Decaprenylphosphoryl-beta-D-ribose 2-epimerase a critical enzyme for the growth of Mycobacterium tuberculosis was chosen for our study after review of literature. It belongs to the Oxidoreductase family. A database of 200 molecules with high prospects of inhibiting the target Dpre1 were carefully chosen by making changes to the known hit molecules, here the thiadiazole nucleus was chosen. Selected molecules were designed and docked against Dpre1 using Argus lab® software. Six molecules with good docking score [lower binding energy] and interactions were shortlisted for synthesis. Reaction conditions were optimized. The selected molecules were subjected to toxicity prediction assessment by OSIRIS® property explorer developed by Acetilon Pharmaceuticals limited which is available online. The results are color coded as green color which predicts the drug likeness and possibly better activity. The molecules were labelled as SDK1, SDK2, SDK3, SDK5, PAA, HA, and were synthesized with satisfactory yield. The purity of the synthesized compounds was ensured by repeated recrystallization. Further the compounds were evaluated by TLC and Melting point determination. The characterization of the synthesized compounds was done using Infra-red, Nuclear Magnetic Resonance [H1 NMR] and Mass spectrometric methods [LC-MS, GC-MS]. All the Synthesized compounds exhibited molecular ion peak (M+) of varying intensities. The final pure compounds were screened for Anti-mycobacterial activity by in vitro method called Micro plate Alamar Blue Assay [MABA]. The synthesized compounds showed sensitivity [Minimum inhibitory concentration] at 3.12mcg/ml. The standard drugs Pyrazinamide, Streptomycin, Ciprofloxacin exhibited anti mycobacterial activity at 3.125mcg/ml, 6.25mcg/ml, and 3.125mcg/ml concentrations respectively. This indicates that the synthesized compounds are as Potent as the standard drugs.CONCLUSION:All the compounds gave Docking score between -8.73 to 11.37 kcal/mol Pyrazinamide gave docking score 11.55kcal/mol for 4P8Y, Streptomycin gave docking score of 10.87kcal/mol for 4P8Y and Ciprofloxacin gave docking score of 11.25kcal/mol for 4P8Y. There is a correlation between the score and activities of all the compounds which were tested and compared with the standard drugs. This goes to prove that Decaprenyl phosphoryl beta-D-ribose 2’ epimerase-1’ (PDBID: 4P8Y) is a critical enzyme for anti-mycobacterial activity. So the fine tuning the structures of these compounds will yield molecules with better anti mycobacterial activity. Further structural modifications of the synthesized compounds will aid in the development of potential molecules against the tuberculosis pathogen

Iodine and Copper Catalyzed Oxidative Cross Coupling Reactions : Design and Development of Carbon-Carbon and Carbon-Heteroatom Bond Forming Reactions

Design and Development of Carbon-Carbon and Carbon-Heteroatom Bond Forming Reactions” is divided into two sections. Section-A, contains two chapters, describes the catalytic ability of iodine for cross coupling reactions. Section-B, divided into three chapters, presents the azidation of organic scaffolds under oxidative conditions. Section A Chapter 1 presents a C-H functionalization of tetrahydroisoquinolines using iodine as a catalyst under aerobic conditions.1 This methodology employs Cross Dehydrogenative Coupling (CDC) strategy as a key step, which is highly atom economical as it doesn’t require pre-functionalized starting materials.2 Owing to the importance of tetrahydroisoquinoline moiety which is present in the umpteen natural products, considerable attention has been put up to functionalize tetrahydroisoquinoline scaffold.3 Iodine a non-metal which is non-toxic was found to catalyze the C-H functionalization of tetrahydroisoquinolines with a variety of nucleophiles such as coumarin, alkyl phosphite, phenols, indoles, acetone and dialkyl malonoates were coupled to it. Significant mechanistic study has been carried out to find the possible intermediate and support the mechanistic proposal. A few representative examples are highlighted in Scheme 1.1 Synopsis Scheme 1: A CDC coupling of tetrahydroisoquinoline with variety of nucleophiles Chapter 2 describes the Cross Hetero Dehydrogenative Coupling (CHDC) reactions of amines, alcohols and sulfoximines with various phosphites.4 Phosphoramidates and phosphate esters are structural scaffolds that are present in a variety of biologically active molecules.5 The conventional methods for synthesizing phosphoramidates/phosphate esters largely involve treating alcohol/amine with appropriate phosphorus halides which generates stoichiometric amount of halogen waste.6 Due to the usage of stoichiometric reagents and difficulties associated with the reported methods, there is a need for developing a protocol which is catalytic and mild. Therefore, we developed a method which employs catalytic amount of iodine and aq. H2O2 as a sole oxidant under milder conditions. Using this methodology, variety of phosphoramidates, phosphorous triesters and sulfoximine derived Synopsis Scheme 2: Phosphorylation of amines, alcohols and sulfoximines phosphoramidates have been synthesized with great efficiency and environmentally benign conditions. A few representative examples are highlighted in Scheme 2.4 Section B Chapter 1 of Section B demonstrates a mild way of synthesizing quaternary azides from α-substituted active methylene compounds which will serve as surrogates for several unnatural amino acid derivatives.7 Azidation has emerged as one of the efficient methods to introduce nitrogen atom in to the organic molecules.8 Azides are versatile functional groups which can be converted to amine, amide, and nitro compounds by simple modification. Moreover, azides are potential handle for “click” chemistry and provide late stage modifications in drug candidates, biomolecules and polymers, etc.9 Azidation of 1,3-dicarbonyl compounds is challenging, as both azides and 1,3-dicarbonyl compounds are nucleophilic in nature. In this section of the thesis, azidation of 1,3-dicarbonyl compounds has been carried out using tetrabutyl ammonium iodide (TBAI) as a catalyst, aq. TBHP as an oxidant and TMSN3 as a azide source. This method uses water as a solvent under mild reaction conditions to generate Synopsis quaternary azides in good to excellent yields. This operationally simple, practical, mild and green method provides an opportunity for synthesizing a variety of azidated β-keto esters, amides and ketones in good yields, Scheme 3.7 The application of this methodology has been demonstrated by synthesising a few triazole and pyrazolone derivatives. Scheme 3: Azidation of 1,3-dicarbonyl compounds Chapter 2 of Section B comprises the azidation and peroxidation of β-napthol derivatives using dearomatization strategy. Azidation and peroxidation are efficient ways to introduce nitrogen and oxygen into organic molecules, which serve as surrogates for amines and alcohol functional groups. In the present study, the azidative or peroxidative dearomatization of naphthol derivatives have been described. The azidation of β-napthol derivatives has been achieved by using CuBr (5 mol %) as a catalyst, TMSN3 as an azide source and aq. TBHP as an oxidant. Whereas, the peroxidation β-napthol derivatives has been accomplished using CuBr (5 mol %) in the presence of aq. TBHP at ambient reaction conditions.10 The products obtained are naphthalenone derivatives, which serve as valuable Synopsis synthetic intermediates and has potential handle for further functionalization.11 Several α-amino or α-peroxy naphthalenones are synthesized using this method in good yields. The usefulness of the methodology has been illustrated by synthesizing a few chiral azides and peroxides in good yields and with moderate enantioselectivity Scheme 4.10 Scheme 4: Dearomatizative azidation and peroxidation of 2-naphthols Chapter 3 reveals the azidation of indole at C-2 position by employing CuBr (10 mol %) as a catalyst and aq. TBHP as an oxidant in acetonitrile under reflux conditions (Scheme 5).12 The C-H functionalization of indole at C-2 position is one of pivotal methods, since it paves a way for synthesizing a variety of indolo-alkaloids.13 Azide is a versatile functionality which can be converted to several other nitrogen containing functional groups such as Synopsis Scheme 5: Azidation of indoles amine, amide, triazole, etc.9 A variety of functional groups were tolerated under the reaction conditions, and furnished the azidated product in good to excellent yields. Through radical inhibition study, we presume that the reaction may be proceeding through radical mechanism. In Scheme 5, a few representative examples are depicted

A Clinical study on Prevalence of Hypothyroidism in Diagnosed Cases of Gall Stones

INTRODUCTION: The explanations for possible relationship between hypothyroidism and gall stones are. 1. Disturbance of lipid metabolism in hypothyroidism causes increase in serum cholesterol level which leads to supersaturation of bile with cholesterol. 2. Low bile flow in hypothyroid patients. 3. Sphincter of oddi has thyroxine receptors and thyroxine has direct prorelaxing effect on sphincter of oddi. 4. In hypothyroidism, the effect of UDP glucuronyl transferase get decreased. So increase in unconjugated bilirubin result in formation of pigment stones. 5. In animal model (Rabbits), thyroxine usage dissolves the fatty diet induced gall stones. AIMS OF THE STUDY: 1. To study the prevalence of hypothyroidism in patients diagnosed with cholelithiasis/ choledocholithiasis. 2. To assess if thyroid profile is warranted in patients with biliary stone disease. MATERIALS AND METHODS: This is a cross sectional study conducted in Tirunelveli medical college. 100 patients with USG evidence of cholelithiasis/ choledocholithiasis were evaluated with basic investigations and additionally thyroid function test and USG thyroid were done. Prevalence of clinical/subclinical hypothyroidism in biliary stone patients were studied. RESULTS: Among 100 patients, 27% were males; 73% were females. Most of the Gall stone patients were in the age group of 40-49 years. Male to female ratio: 1 : 2.7. Females were the predominant group. In 100 gall stone patients, 21 patients were found to be hypothyroid (21%), 79 patients (79%) found to be Euthyroid. Among 21 hypothyroid patients, 4 patients (19.1%) were males and 17 patients (80.9%) were females. Most of gall stone patients with hypothyroidism were found to be in the age group of 40-49 years of age. 18 patients (18%) had subclinical Hypothyroidism and gall stones. 3 patients (3%) had clinical Hypothyroidism). CONCLUSION: Hypothyroidism is one of the probable risk factor for developing biliary stones. Screening of biliary stone patient with TFT will help to detect undiagnosed hypothyroidism

Performance analysis of PV powered multilevel inverter

This article deals with the PV based DC/DC boost chopper integrated nine level inverter. This topology requires 7 switches in minimum to obtain a nine level stepped wave output. So the main objective of this paper is to develop a 9 level AC output using PV based DC/DC boost chopper. In the case of conventional multi-level inverter, 16 switches were utilized and the number of sources needed was also more. Here the proposed system comprises of single PV panel and the switches used are also less. Also PV is integrated with DC/DC boost chopper is used to increase the source input level of the inverter. Using MATLAB platform, the proposed system is simulated with a resistive and inductive load. The similar results are obtained in prototype which validates the designed converter

Site-Selective Dehydroxy-Chlorination of Secondary Alcohols in Unprotected Glycosides

To circumvent protecting groups, the site-selective modification of unprotected glycosides is intensively studied. We show that site-selective oxidation, followed by treatment of the corresponding trityl hydrazone with tert-butyl hypochlorite and a H atom donor provides an effective way to introduce a chloride substituent in a variety of mono- and disaccharides. The stereoselectivity can be steered, and a new geminal dichlorination reaction is described as well. This strategy challenges existing methods that lead to overchlorination

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis

In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters ("cord factor") form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn-methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material