Analysis and Optimization of Machining Process Parameters Using Design of Experiments

In any machining process, apart from obtaining the accurate dimensions, achieving a good surface quality and maximized metal removal are also of utmost importance. A machining process involves many process parameters which directly or indirectly influence the surface roughness and metal removal rate of the product in common. Surface roughness and metal removal in turning process are varied due to various parameters of which feed, speed, depth of cut are important ones. A precise knowledge of these optimum parameters would facilitate reduce the machining costs and improve product quality. Extensive study has been conducted in the past to optimize the process parameters in any machining process to have the best product. Current investigation on turning process is a Response Surface Methodology applied on the most effective process parameters i.e. feed, cutting speed and depth of cut while machining Aluminium alloy and resin as the two types of work pieces with HSS cutting tool. The main effects (independent parameters), quadratic effects (square of the independent variables), and interaction effects of the variables have been considered separately to build best subset of the model. Three levels of the feed, three levels of speed, three values of the depth of cut, two different types of work materials have been used to generate a total 20 readings in a single set. After having the data from the experiments, the performance measures surface roughness (Ra) of the test samples was taken on a profilometer and MRR is calculated using the existing formulae. To analyze the data set, statistical tool DESIGN EXPERT-8 (Software) has been used to reduce the manipulation and help to arrive at proper improvement plan of the Manufacturing process & Techniques. Hypothesis testing was also done to check the goodness of fit of the data. A comparison between the observed and predicted data was made, which shows a close relationship. Key words: Surface Roughness and Metal Removal Rate, Turning, Response Surface    Methodology, Aluminium Alloy, Resin.

Imidazodiazepine Anticonvulsant, KRM-II-81, Produces Novel, Non-diazepam-like Antiseizure Effects

The need for improved medications for the treatment of epilepsy and chronic pain is essential. Epileptic patients typically take multiple antiseizure drugs without complete seizure freedom, and chronic pain is not fully managed with current medications. A positive allosteric modulator (PAM) of α2/3-containing GABAA receptors (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81 (8) is a lead compound in a series of imidazodiazepines. We previously reported that KRM-II-81 produces broad-based anticonvulsant and antinociceptive efficacy in rodent models and provides a wider margin over motoric side effects than that of other GABAA receptor PAMs. The present series of experiments was designed to fill key missing gaps in prior preclinical studies assessing whether KRM-II-81 could be further differentiated from nonselective GABAA receptor PAMs using the anticonvulsant diazepam (DZP) as a comparator. In multiple chemical seizure provocation models in mice, KRM-II-81 was either equally or more efficacious than DZP. Most strikingly, KRM-II-81 but not DZP blocked the development of seizure sensitivity to the chemoconvulsants cocaine and pentylenetetrazol in seizure kindling models. These and predecessor data have placed KRM-II-81 into consideration for clinical development requiring the manufacture of kilogram amounts of good manufacturing practice material. We describe here a novel synthetic route amenable to kilogram quantity production. The new biological and chemical data provide key steps forward in the development of KRM-II-81 (8) as an improved treatment option for patients suffering from epilepsy

PHARMACOLOGICAL EVALUATION OF ANTIDEPRESSANT ACTIVITY OF AQUEOUS EXTRACT OF ROSA CENTIFOLIA PETALS IN MICE

ABSTRACT To study the antidepressant activity with aqueous extract of Rosa centifolia. The extract was primarily subjected for preliminary phytochemical investigation and for Maximum Tolerance Dose (MTD). Antidepressant activity was evaluated in various animal models like Forced swim test, Tail suspension test, Apomorphine induced hypothermia and 5-HTP potentiation of head twitches in mice. The aqueous extract of Rosa centifolia was positively identified with carbohydrates, tannins, proteins, amino acids, alkaloids, flavonoids, flavanone, glycosides and phenolic compounds. The extract was subjected for maximum tolerance dose upto the dose level of 2000mg/kg has not produced any mortality. The extract of Rosa centifolia showed significant antidepressant activity at high dose (100 mg/kg) in Tail suspension test, Forced swim test and Potentiation of 5-HTP induced head twitches. The extract didn't antagonized the hypothermia induced by apomorphine

Completion of the Total Synthesis of Several Bioactive Sarpagine/Macroline Alkaloids including the Important NF-κB Inhibitor <i>N</i>₄-Methyltalpinine

The unification of the general synthetic strategy regarding the important and emerging group of C-19 methyl-substituted sarpagine/macroline alkaloids has culminated in the completion of the total synthesis of several bioactive alkaloids. Key transformations include an ACE-Cl mediated late-stage N(4)-demethylation and an anhydrous acid-mediated intramolecular quaternary hemiaminal formation between a tertiary amine and an aldehyde function to allow efficient access to several biologically important alkaloids from this group. Herein, the enantiospecific total synthesis of the first known sarpagine/macroline alkaloid with NF-κB inhibitory activity, N(4)-methyltalpinine (as a chloride salt), as well as the anticancer alkaloids talpinine, O-acetyltalpinine, and macrocarpines F–G, are described