Development in a Country Cause Significant Damage to the Environment? Essay

In this essay I am going to examine whether development in a country causes significant damage to the environment. Firstly, when a country becomes developed, they have to become industrialised first. This means that the country changes from being mainly an agricultural production and people living in the countryside, to the people flocking to the newly increasing cities, in search of more money and work from the factories that have been put there. With lots of people living in one area, things and places start to become contaminated, such as rivers as many cities are based around them. Fish that would once have lived in the river would be extinct due to the boats driving up the river to take or deliver supplies to the city. This is a serious issue for the world as for humans to wipe out an entire specie can have serious consequences, for example people further up the river might depend on the fish to eat, and just because the city being there, could threaten the existence of the community. Secondly, TNC’s will move their factories to developing countries due to lower tax laws which will boost their overall profits. When they build these factories the amount of pollution that is produced will be incredible that it is visible when you look at them. This causes the air that people breathe when they are at work and for the people are living in the surrounding areas to be very dangerous and contaminated, with some cases of people becoming very ill. In a country such as china for example, lung cancer is more common here than anywhere else in the world; and this is caused by the amount off pollution produced by the factories. Also, whole cities in china have been built in china where practically no one lives in, so people can go and live their to work in the factories, however, as no one lives there the raw materials have been wasted and caused pollution being made, but being useless. Finally, in developing countries, their natural resources are usually drained by western countries or TNC’s who exploit the developing countries for the materials that they desperately need. However when the resources have run out, if the world doesn’t have another energy resource other than oil, then the world will go backwards in time and technology, because we won’t be able to run simple things like radiators for example. In conclusion, I feel TNC’s are a major part to blame in the damage to environments, especially in certain areas like Asia, as they the exploit the easy law on pollution ect. to maximise their profits, but however don’t think of the effects and consequences. Natural resources – going to run out soon – be moving backwards instead of forwards

Case Study Illy Cafe

About Illy Company background and description The history of illycaffe is linked to the lives of the company's founder, Francesco Illy, and his family. Francesco in 1933 set up a business in the cocoa and coffee sector, and then decided to concentrate exclusively on coffee. Nowadays the illy group is made up of several companies located in North America, France, Germany, Spain and Benelux. Product Illy serves coffee to its customers. They insist on the fact that there are not selling basic coffees but the one which is a result of Scientifics’ research.They want to serve the best coffee due to a result of a long experience, knowledge of coffee biology and chemistry, very good skill at roasting, enabling technologies, and also a family’s entrepreneurial passion. They are also selling products which fit to the coffee world like, machines, capsules and also accessories. Revenue In 2007 turnover amounted to $221. 000. 000. In 2011 the turnover was $342. 000. 000. There is a real increase over the years. Customers 70% of its sales circuit cafes, hotels and restaurants, 20% for individuals and 10% in companies, these are illy’s customers.Illy has developed solutions for small restaurants, small hotels, cafes and other places of conviviality where coffee consumption is low but still want a perfect coffee. The company offers machines meeting the needs of its business customers. To match with its image of unique coffee Illy is increasing partnerships with the biggest names in tourism Meridien and Hyatt. The company also Illy customers offices, employees may have during their break espresso from the brand. To do this, Illy provides the I-Espresso and offers a complete range.Also Illy own its own bars called â€Å"Illy bar†, so the customer can go there and have a coffee in the company’s atmosphere. It is also possible to buy coffee brand for personal use at home. The website offers the purchase of cafe, cafe machine but also derivatives (eg cups). Most of its customers are the professionals (served in more than 50,000 public places) but Illy is developing the â€Å"Illy’s bar† to create an atmosphere for the company. Location Illycaffe was founded in Trieste in Italy. Nowadays the Illy group is a multinational organization that operates in more than 140 countries across the 5 continents.The main markets for Illy are US, Europe and Japan. Employees The company has about 700 employees. Industry With a turnover of â‚ ¬ 695 million and a growth of over 30% per year since 2001, the European leader in espresso is Nespresso. The level of competition that Illy faces differs according to the sectors, for example in the Hotel, Restaurant and Cafe sector the main competitors are Starbucks and Lavazza. Whilst in the coffee machines and coffee capsule systems the main competitor is Nespresso from Nestle group. The competition in both sectors is quite intense with Starbucks and Nestle having global reach.The adv antages these companies have over Illy are their vast economies of scale, stronger brands and higher customer reach. Mission and vision The mission: produce and deliver the best coffee that nature can offer for connoisseurs and those who will appreciate it with a special attention to methods of growing and processing the most suitable and sustainable. They want to create an emotional experience through the degustation of their coffee. The vision: being an innovative company, proud of its history rooted in the contemporary and future-oriented.Combine art, science and experience to offer the best products. They have for vision to be recognized as a world reference for coffee culture and excellence, ti be the first choice of professionals. The values: passion for excellence, the pursuit of perfection and ethics, the valuation of individual talent and teamwork. The desire to improve the lives of all those involved in the coffee chain. Attention to people and the environment. Illy Coffee : Alternatives Selection 1)Problem definition – how to become more responsible (=sustainable) coffee producer without losing the revenues/customers/quality.The original goal of Illy was to provide best coffee to customers, but the good quality coffee does not necessarily mean responsibly produced coffee. So many coffee growing countries use unethical growing practices which reduces the price of 1 kg of coffee from the farmer, but jeopardizes the company? s ethical image. Thus now Illy needs to balance three aspects – quality, profitability and ethical aspect, which is a difficult problem, since it involves the whole supply chain and for the company of such scale of operation to solve this problem will be extremely difficult (140 countries on 5 continents).Plus this challenge is also industry driven – all big coffee companies are moving towards sustainability of supply chain, and greater awareness of the customers about these issues nowadays can give a coffee com pany additional competitive advantage. 2)First of all before we outline alternatives and solutions, we need to clarify, what responsible coffee business means. Although â€Å"sustainability† has been defined in a variety of ways over the past several decades, the Brundtland Report (1987) has provided the most widely-accepted and enduring definition at the international level.According to the Brundtland report: â€Å"Sustainable development is development that meets the needs of the present without compromising the ability of future generations to meet their own needs.. In relation to coffee business Acting Responsibly involves a complex activity spread over whole supply chain: -Environmentally related: bear in mind environmental impacts of coffee production (â€Å"technified† or mono-culture growing practices impact, rain forests, pesticides, waste water and etc. -Social aspects: well-being of farmers and their families (minimum fair price limits, no price dumping, ch ild labor prevention) -Business-wise: when all actions and decisions taken are analyzed in terms of long-term goals of the company, current and future benefits for stakeholders and preserving viability of the company. With responsible business and supply chain model in mind a multinational like Illy might choose one of few alternative pathways: – -Marketing based approach – market the idea under a good â€Å"sauce† to your customers.Might involve working with few sustainable/ organic pilot farms and making public aware of this, or introducing your own quality standard, like own CAFE standard of Starbucks. This alternative does not involve additional costs, or reengineering of supply chain, it is more like exploitation of Responsible practices idea. But it might create additional revenues due to the fact that company can sell â€Å"responsible† coffee with even bigger price margin. Time wise this idea might be implemented quite quickly. -Supplier related a pproach.This involves responsible purchasing strategy – control and assessment on the level of bigger supply chain units – cooperatives/processing plants/exporters. Does not require complete reengineering of whole supply chain or additional costs related to separate farmers support/educational programs. More time consuming – selection, assessment of existing and new suppliers might take time. Does not really fit with Illy, since its strategy has always been close work with separate farmers. -From bottom to top strategy – every level of supply chain needs to be re-thought.Company needs to realize the importance of each individual farmer (f. ex through payment of Fair trade or responsible farming bonuses to ensure the sustainable existence of farmer communities), not only use quality control (Illy is already working with ISO quality control standards) but rather keep an eye on whole production and processing process. Moreowever, the efficiency of packing, l ogistics and transportation should be analyzed and improved – which will result in eliminating or reducing the costly, non-environmentally-friendly steps.But doing this Illy might incur additional costs (because now it will have to pay more for raw material), which can however be offset not at the expense of the â€Å"responsible† customer (who is ready to pay more for responsibly produced coffee), but rather through improving the efficiency of the whole supply chain, which will reduce the average COGS. This strategy involves extensive cooperation with all other stakeholders in coffee business – working on and adhering to commonly accepted quality and sustainability standards (like Fair Trade label, Utz coffee, RA and etc. , cooperation with local research institutes to introduce better and more sustainable farming practices for growers, or even bringing together all main players like Sara Lee, Nestle and the European branch of Kraft did in 2002 by creating of t he Common Code for the Coffee Community, a multi-stakeholder initiative aimed at increasing sustainability and responsibility awareness in the coffee sector. 3)While choosing the alternative, we have been guided by Illy? s strategy, code of conduct and long-term benefits of the decision to the company.We do not want any satisficing decision, we want to optimize the whole system – company has a lot of strengths, we can use them to build up more powerful structure. We want our customers to get only the best coffee, but we also want to do it responsibly. If there is any decision to be taken, which will involve not only additional costs or revenue growth, but also extensive long-run improvement of the whole business model, we will chose this decision. Meaning, that we will opt for alternative number 3. 4)Implementing the decision.Improve the technology and introduce Integrated Process management to cut production and logistics costs and reduce business complexity to offset the co sts of high quality coffee. The company buys coffee beans directly from farmers that reduce the higher prices in the spot market. The shipping and the supply of coffee beans from farmers to the company is carried out by company under strict supervision and inspections. This shows that the bargaining power of suppliers is low with company’s commitments to provide higher quality coffee to the customers.There is a need to create a strategy for the developing economies especially the BRICs (Brazil, Russia, India and China) which will in future become key markets. A safe bet would be to create an alliance with a local partner who has expertise in the local markets, cultures and politics for example in India and China which are very big geographically, population-wise and culture-wise the local partner will add immense value in launching and growing the Illy products in a way that best suits that particular market. 5)Results Evaluation – might be performed in several steps.O n one hand, we will analyse the actual performance – if the revenue and market share is growing, if COGS are decreasing due to better efficiency, this means the strategy has been chosen and implemented right. On the other hand we need to understand the degree of customer awareness of our strategy – that means answering the question: did all these changes happen because we turned to more responsible business, or it was just due to other favourable factors†¦In this case customer opinion must be collected and analysed.Competitors’ reaction and Illy’s response: What can the competitors do? There is a wide variety of ways – from fair competition by improving the quality or reducing the price to unfair battle, consisting for example of running a systematic smear and defamatory campaign against a competitor, both directly and indirectly (on the internet and through certain machine distributors), designed to put consumers off buying Illy? s coffee.Som e competitors try to do their own investigation to uncover the unsustainable practices within supply chain (sometimes a company itself has no idea what sub-sub-suppliers are doing) and make sure that it leaks to social networks. Illy should in its turn double-check the standards and practices within its supply chain to avoid bad rumor spread, and be proactive – have active campaign in social media to create awareness of its brand and customers’ loyalty. SWOT Tangible Product: The product which is coffee is very fine.So the foundation of the brand which is the basic product is solid Basic Brand: Illy brand is is a red background with white lettering. You will also find Illy in plain bold red lettering. I believe is to attract the attention of the people. This logo has been used since (1980). The core elements for Illy are a strong brand name, high quality, attractive packaging and design The Augmented brand: Illy has added value to their brand by selling fresh beans in sealed cans, also giving the consumer the option to have it grind whether they want it bold, decaffeinated, caffeinated. hey also have tablet which goes inside espresso machines sold in any illy location. . The main factor is that along with high quality the brand is also associated with high price and hence is getting restricted to a niche market only The Potential Brand: When consumers only rely their morning coffee on the Illy brand than Illy has made their mark, even though in many other key markets like Italy it has been a major success, but it still needs to win other important key market like Japan and China.There are in all six products that will be analysed here, premium coffee, coffee pods for machines, ready to drink canned coffee, Agrimontana, the confectionary products, Domori the chocolate business and Dammann Feres the tea brand. Leader: Coffee Try Harder: All the small brands come under this sector but mainly the pods of coffee business Double or Quit: Coke has partn er up with the Illy brand to make up a canned coffee business in which the coffee will be sold to the consumer.Custodial: Is similar to the cash cow concept in BCG, this would be the chocolate business Cash Generator: this is undoubtedly the premium coffee business Phased withdrawal: this is a difficult one to point but it seems the confectionary business is the most likely candidate as it is not generating as much growth or profits as it should Divest: Again a difficult one but once again the wine or confectionary products in the Illy portfolioKey Points Analysis â€Å"Illy has a strong brand and is associated with high quality and premium pricing! † The company has shown impressive growth despite recession The key strategic partnerships like the one with Coca Cola company for canned coffee are proving to be the real winners The group needs to focus its attention on the sister brands and needs to extend the well-established Illy rand image to these sister concerns There is a n urgent need to improve the sales and awareness of the sister companies The company applies to its R, supply chain and marketing expertise to grow its coffee products like coffee pods and machines There is a need to create a strategy for the developing economies especially the BRICs (Brazil, Russia, India and China) which will in future become key markets The company needs to constantly re-invent the ways to sustain customer interest in its brand and its products, just like the Universita del caffe. † Strenghts: Strong retail store operations:50,000+: events in which illy is involved annually worldwide and more than 6 million cups are consumed each day. -Wide geographic presence: 140: countries where illy is available -Top-quality final product: 4: major certifications for quality and sustainability, 4: company-founded research facilities, 4 of 8: major worldwide coffee industry innovations, This is a known and appreciated throughout the world for high quality and unique tast e. The company has followed a strategy, which has a high focus on quality and consistency of their products -Experience: created in 1933 Innovation : The first,pressurized packaging, came in 1934, just one year after the company’s founding. By adding inert nitrogen gas under pressure, an oxygen-free environment forms as illy cans are sealed, preserving essential aromas and promoting mingling of coffee’s naturally occurring oils. Result: coffee that not only stays fresher longer than under any other packaging method, but whose flavor is actually enhanced over time by its surroundings. The second, came just one year later, in 1935: the Illetta, precursor of the modern espresso machine that, for the first time, separated pressure and heating elements.Result: espresso that is consistently round, rich and balanced, not bitter or burnt-tasting. 1974 saw illy’s third revolutionary invention: pre-tamped, pre-dosed, expertly ground espresso in single serve paper pods. Re sult: delightful espresso in reach of anyone, anywhere – at home, at the office, or at a favorite cafe or restaurant. The system, called ESE (Easy Serving Espresso) became an industry standard. – Another strength is the strong supply chain right from the coffee bean farmers to the suppliers, Illy has maintained strict quality control and good relations creating value for everyone involved.Weaknesses: sluggish growth rate / Investments needed (coffee machines that support the proprietary Opportunities: -Business expansions: Gruppo illy includes: †¢Domori – premium chocolate (acquired July 2006) †¢Dammann Freres – the legendary French purveyor of tea (March 2007) †¢Mastrojanni – critically lauded winery in Montalcino, Italy – (September 2008) †¢Agrimontana – high- quality jams and marron glace (stake acquired December, 2005) -Rising hotel and food service industry in Italy : Rising trends in coffee exports : 56%: sha re of illy coffee enjoyed outside of Italy, 200+: espressamente illy coffee bar locations worldwide -10% rate growth market -Been recognized from the market as the dominating market -Scientific research : genetics, agronomy, botany, physics, mathematics, chemistry, biochemistry, biology, engineering, physiology and psychology. All areas explored in the four laboratories illy. -Quality and sustainability : Sustainability has three-fold implicationsat illy: economic, social and environmental. Ready to drink coffee business partnering with Coca Cola will attract global customers and create newer segments for the company's products -There is a need to create a strategy for the developing economies especially the BRICs (Brazil, Russia, India and China) which will in future become key markets. Threats : -Highly competitive market : Key competitors : Caffee Negro Group, Luigi Lavazza, Segafredo Zanetti, Starbucks Corporation -Risk of battle in dominating the market by multinationals : Nesp resso -Economic crisis : Most of the global markets including nearly all the major markets that Illy perates in have suffered from recent credit crisis and economic downturn -While expanding globally the major risk involved is the supply of high quality premium coffee beans -The inconsistency in the growth of the sister brands and their chare in the portfolio creates a real threat of losing these brands at some point if they get totally overshadowed by the coffee business. At this point, Illy needs to consider the growth rate and growing strategies of these newly acquired brands to keep them profitable.

Pharmacophore development for identification of anti-lung cancer drugs Essay

Lung cancer is one particular type of cancer that is more deadly and common than any other. Lung cancer is treated with chemotherapy, radiation therapy and surgery depending on the type of lung cancer and the stage of the disease. Focusing on the drugs used for chemotherapy and their associated side effects, there is a need to design and develop new anti-lung cancer drugs with lesser side effects and improved efficacy. Pharmacophore model proves to be a very helpful tool serving in the designing and development of new lead compounds. In this paper, pharmacophore of 10 novel anti-lung cancer compounds has been identified and validated for the first time. Using LigandScout the pharmacophore features were predicted and 3D pharmacophore have been extracted via VMD software. A training set data was collected from literature and the proposed model was applied to the training set whereby validating and verifying their similar activity as that of the most active compounds. Therefore they could be recommended for further studies. Key words: Pharmacophore, anti-lung cancer drugs, Computer aided drug designing, LigandScout, VMD INTRODUCTION Lung cancer is known to have a high fatality rate among males and females and takes more lives each year as compared to colon, prostate, ovarian and breast cancers (1).Lung cancer is classified into two main types namely Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC) of which NSCLC accounts for about 80% cases and SCLC accounts for 10-15% among all other types of lung cancers (2). Non-small cell lung cancer (NSCLC) is a worldwide leading cause of death (3). The surgical resections are not applicable when first diagnosed as NSCLC is usually in an advanced stage. The patient may have a possibility of prolonging survival with chemotherapy (4). Chemotherapy for advanced NSCLC is often considered excessively toxic. However, meta-analyses have demonstrated that as compared with supportive care, chemotherapy results in a small improvement in survival in patients with advanced NSCLC (5). *Corresponding author. Email:drhamid@jinnah.edu.pk Abbreviations: HBA, hydrogen-bond acceptor, HBD, hydrogen-bond donor, NSCLC, Non-small cell lung cancer, SCLC, Small Cell Lung Cancer, EGFR Epidermal Growth Factor Receptor. Drugs developed for cancer are single agents although for the maximum advantage they need to be used in recipe with other drugs or therapeutic agents. Initial candidate chemicals or â€Å"leads†, are often recognized and tested for single agents that change cancer-cell proliferation or prolong survival. This led to the identification of most of the clinically active cancer drugs used today. Specific leads then must be further optimized and assessed to characterize their pharmacokinetic and pharmacodynamic properties and evident toxic effects. Clinical evaluation is performed by trails in humans to identify a maximum tolerated dose, define severe toxic effects, and estimate bioactivity. These trails are time consuming and expensive (6). Pharmacophore is the initial step towards understanding the interaction between a receptor and a ligand. Pharmacophore was often postulated as the â€Å"essence† of the structure-activity knowledge they had gained(7).Today’s researcher task is to interpret the binding of anatomically varied molecules at a common receptor site. To generate common feature pharmacophore from the set of compounds active for certain receptor, the characteristics necessary for binding receptor in a generalized way(8). The understanding of the common properties of binding group is vital for the determination of the type of inhibitor binding the target. Pharmacophore model is very convenient for attaining this goal. Surface of the cell are the regions where the ligand-receptor and receptor-receptor interaction occur. The process undergo Sequential levels of activity starts initially  from the cell surface and then moves towards the intracellular signaling pathways, then gene transcription which corresponds to cellular responses. Epidermal growth factor receptor (EGFR) was initially identified as an abnormally activated or mutated form which leads to a number of other abnormalities in the signaling pathway and hence leads to the formation of tumor (9). In our research, a 3D pharmacophore model was developed in order to promote the discovery of precise and effective EGFR inhibitor for the treatment of non-small cell lung cancer. The compounds used in this study have been characterized as reported in reference papers. In order to correlate experimental and computational studies we used their bioactivity data. MATERIALS AND METHODS The work was initiated using LigandScout software. LigandScout is a tool for deriving the 3D from structural data of ligand complexes more speedily and evidently in a completely automated and expedient way. It offers flawless workflow both from ligand and structure based pharmacophore modeling (10). LigandScout is thought to be an essential software tool for structure based drug designing, it is not only beneficial for carrying out analysis of binding sites but also for alignment based on pharmacophore and the designing of shared feature pharmacophores. LigandScout runs freely on all common operating systems. Till  date  a  number  of  successful  application  examples  have  been  carried out and standpublished (11). The very important and the very first step in pharmacophore model generation is the selection of data set compounds.  A  number  of  drugs have been reported that are in some way related to, or used in the treatment of Non-Small Cell Lung Cancer which include Platinol(generic name: cisplatin)( 12),carboplatin, Taxotere(generic name: docetaxel), Gemzar(generic name: gemcitabine) ,Taxol(generic name: paclitaxel) , Almita(generic name: pemetrexed), Avastin(generic name: Bevacizumab), Xalkori(generic name: Crizotinib), Navelbine(generic name: vinorelbine , Iressa(generic name: Gefitinib) and Terceva(generic name: Erlotinib) (13)( 14)( 15). The two dimensional (2D) chemical structures of the compounds were drawn using ChemDraw Ultra (8.0) and the structures were saved as .Pdb files. Subsequently the 2D structures as shown below ( Figure 1) in the form of Pdb files were imported into LigandScout and converted into corresponding 3D pharmacophore structures. Cisplatin Pemetrexed Docetaxel Bevacizumab Viblastine Carboplatin Gemcitabine Crizotinib Gefitinib Paclitaxel Vinorelbine Erlotinib Hydrochloride Figure 1. 2D structures of selected data set of anti non small lung cancer The pharmacophoric features include H-bond donor, H-bond acceptor, Hydrophobic, aromatic, positively and negatively ionizable groups (16).The pharmacophore for each compound was generated and the distances among the pharmacophoric features were calculated using VMD software. VMD is designed not only for modeling, visualization, and analysis of biological systems such as proteins, nucleic acids, lipid bilayer assemblies but it may also be used to view more general molecules, as VMD can read standard Protein Data Bank (PDB) files and display the contained structure with their features. A number of application examples have been published to date (17). Once the pharmacophore of all the compounds were identified, the ligand was then super imposed so the pharmacophore elements overlap and a common template i-e the pharmacophore model is identified. The training set consisting of four compounds was collected from literature and it was found that the groups show enhanced and similar activity as that of the most active compounds based on the 3D pharmacophore being generated for non small lung cancer. RESULTS AND DISCUSSION Pharmacophore analysis is considered as an fundamental part of drug design. The pharmacophore generated by LigandScout for the selected data set of anti  non small cell lung cancer showed three main features i-e H-bond acceptor(blue vectors), H-bond donor(blue vectors) and aromatic rings(yellow spheres).The representative pharacophores of each compound are shown in Figures 2,3,4 and 5 Figure 2. A pharmacophore of Pemetrexed (Alimta ®) The pharmacophoric features for each compound on the whole are shown in Table 1.The pharmacophores of all the compounds were then matched and a unique pharmacophore was identified after a detailed analysis. Figure 3 . A pharmacophore of Bevacizumab Figure 4 . A pharmacophore of Gemcitabine (Gemzar ®) On the whole, the representative pharmacophoric features for each compound are shown in Table 2.Resembling features were identified after analyzing the pharmacophore of all compounds generated by LigandScout. Then the similar features of all the compounds were superimposed and merged into single pharmacophore. The uniquely identified pharmacophoric features are shown in Table 3. Figure 5. A pharmacophore of Gefitinib Our common featured pharmacophore predicted for three compound of anti non small lung cancer is based on three HBAs, six HBDs and four aromatic centers. The distance triangle measured between the common pharmacophore features of each compound using VMD is shown in Table 4.The distance ranges from minimum to maximum and have measured between the HBA and HBD,HBA and aromatic ring and HBD and aromatic ring. Table 1. Pharmacophoric features of each compound Compounds H-Bond Donor H-Bond Acceptor Aromatic Centre Paclitaxel + + + Pemetrexed + + + Bevacizumab + + + Carboplatin + + + Crizotinib + + + Erlotinib Hydrocholride + + + Gefitinib + + + Gemcitabine + + + Methotrexate + + + The distances among the common pharmacophoric features between the predicted pharmacophore are shown in Figure 6. The distances between aromatic ring and HBD range from 4.15-4.80, between aromatic rings to HBA range from 7.03-8.66 and between HBA to HBD range from 5.85-6.97. Table 2. Pharmacophoric features of each compound Compound H-Bond Donor H-Bond Acceptor Aromatic Centre Paclitaxel 4 6 2 Pemetrexed 3 6 3 Bevacizumab 2 3 1 Carboplatin 0 3 0 Crizotinib 2 4 3 Erlotinib Hydrocholride 2 6 3 Gefitinib 2 6 4 Gemcitabine 3 7 2 Methotrexate 3 9 3 Table 3. Uniquely identified pharmacophoric features of compounds Compound Bevacizumab Pemetrexed Gefitinib H-Bond Donor 2 3 H-Bond Acceptor 3 6 2 6 Aromatic Centre 1 3 4 A training set of three compounds was collected from literature i-e MethyNonanoate, MMDA, Flavopirido(18).The generated 3D pharmacophore model was applied to the training set whereby validating and verifying their enhanced and similar activity as that of the standard compounds shown in Table 5. This further confirmed our observation and proposals for a pharmacophore model as it corresponds to the predicted pharmacophore. Table 4.Pharmacophoric triangle distances of each uniquely identified compounds Compounds Acceptor ïÆ'  Aromatic Ring Aromatic Ring ïÆ'  Donor Donor ïÆ'  Acceptor Gefitinib 7.10 4.76 6.97 Pemetrexed 7.03 4.15 5.85 Bevacizumab 8.14 4.29 6.36 Figure 6. Distance ranges among pharmacophoric features in predicted pharmacophore To support the suggested pharmacophore model , distance was estimated. The predicted distance of the training set and the standard drugs respectively are shown in Table 6. This table shows the close resemblance of Flavopiridol with that of standard drugs whereby validating that the compound shows high correlation with the predicted pharmacophoric triangle hence having similar activity. Table 5. The distance triangle for compounds of the training set Model Acceptor ïÆ'  Aromatic Ring Aromatic Ring ïÆ'  Donor Donor ïÆ'  Acceptor MMDA 5.99 5.52 5.95 Flavopiridol 7.01 4.04, 4 6.18 MethyNonanoate 4.01 7.60 2.24 Table 6. The 3D pharmacophoric distance triangle of the training set and the standard drugs respectively Model Standard Drugs Training Set Acceptor ïÆ'  Aromatic Ring 7.37-8.84 7.01-8.96 Aromatic Ring ïÆ'  Donor 4.39-4.89 4.04-4.62 Donor ïÆ'  Acceptor 6.18-6.97 6.18-6.64 CONCLUSION The pharmacophore model is a very handy tool for new lead compounds discovery and development. In this study pharmacophore models were built for novel drugs of non small lung cancer, pharmacophoric features were predicted and 3D pharmacophore has been generated for non small lung cancer. A triangle of three different classes has been selected for pharmacophore and Hydrogen bond Acceptor, Hydrogen bond Donor and Hydrophobic character of standard drugs have been filtered out as key pharmacophoric feature. The generated model was applied to the training set and it has been validated and proposed that Flavopiridol shows similar enhanced activity as that of standard drugs, hence could be used for further studies. Moreover Pharmachopore based docking will be used for virtual screening and designing of some novel  drugs  for  non  small  lung  cancer  in  continuation  of  this  work. ACKNOWLEDGEMENTS We owe special thanks to Dr. Hamid Rashid, Ms. Saima Kalsoom , Faculty Mohammad Ali Jinnah University, Islamabad for support and supervision in the research work. REFERENCES 1. Thomas L, Doyle LA, Edelman MJ. Lung cancer in women: emerging differences in epidemiology, biology, and therapy. Chest. 2005;128:370-381. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008; 83(5):584-594. Ginsberg RJ, Vokes EE, Raben A. Non-small cell lung cancer. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia, PA: Lippincott-Raven, 1997:858– 910 Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a metaanalysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995; 311:899– 909 Rapp E, Pater JL, Willan A, et al. Chemotherapy can prolong survival in patients with advanced nonsmall-cell lung cancer — report of a Canadian multicenter randomized trial. J Clin Oncol 1988;6:633-41. Sridhar Ramaswamy, M.D. Rational Design of Cancer-Drug Combinations, 2007. Peter Gund Evolution of the Pharmacophore Concept in Pharmaceutical Research. Pharmacopeia Inc., Princeton, New Jersey. Omoshile O. Clement and Adrea Trope Mehl. HipHop: Pharmacophores based on multiple commonfeature alignments. Molecular Simulation Inc. San Diego, California,2000 Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000; 19: 6550–65. Drc :A Review of LigandScout, 2008 Wolber, G.; Langer, T.; LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters. J. Chem. Inf. Model; 2005; 45(1); 160-169. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Helsing M, Bergman B, Thaning L, Hero U Eur J Cancer. 1998 Jun; 34(7):1036-44. NSCLC Meta-Analyses Collaborative Group (October 2008). â€Å"Chemotherapy in Addition to Supportive Care Improves Survival in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and MetaAnalysis of Individual Patient Data From 16 Randomized Controlled Trials†. J. Clin. Oncol. 26 (28): 4617– 25. doi:10.1200/JCO.2008.17.7162. PMC 2653127. PMID 18678835. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452-60. Lynch TJ, Bell DW, Sordella R. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. May 20 2004;350(21):2129-39. Kapetanoic,I.M., 2008. Computer aided Drug discovery and development: insilico-chemico-biological approach. chem. Biol. Interact. 171, 165-176 Huang, Xiaoqin, Zheng, Guangrong, Zhani, Chang-Guo Microscopic Binding of M5 Muscarinic Acetylcholine Receptor with Antagonists by Homology Modeling, Molecular Docking, and Molecular Dynamics Simulation journal of physical chemistry b, 116:532-541, JAN 12 2012 2012 Bose P, Perkins EB, Honeycut C, Wellons MD, Stefan T, Jacobberger JW, Kontopodis E, Beumer JH, Egorin MJ, Imamura CK, Douglas Figg W Sr, Karp JE, Koc ON, Cooper BW, Luger SM, Colevas AD, Roberts JD, Grant S. Cancer Chemother Pharmacol. 2012 ;69(6):1657-67. doi: 10.1007/s00280-012-18395. Epub 2012 Feb 15.PMID

Emily Bront's novel Wuthering Heights Essay Example | Topics and Well Written Essays - 1500 words

Emily Bront's novel Wuthering Heights - Essay Example As such, this paper will analyze the relationship between the wild and the civilized in Emily Bronte’s novel Wuthering Heights. The novel Wuthering Heights uses symbols, themes, imagery, flashbacks, and allegory to portray the different aspects of civilization and wilderness as manifested by the characters and the story setting. Notably, passionate and unrestricted actions characterize wildness while order and modernity characterizes civilization (Rathje, n.y). The most significant element that brings out the aspects of wildness and civilization is the differences between the Thrushcross Grange and the Wuthering Heights farmhouses. We can see cold, muddy, and desolate moors separating the two farmhouses, which stands alone. Indeed, the separation by the moors can only mean that there is an aspect of isolation in the characteristics and meaning of the two houses (Rathje, n.y). This isolation reveals the aspects of wildness and civilization in the setting as the entire novel set ting takes place in Wuthering Heights and Thrushcross Grange. Actually, the appearance and atmosphere of Wuthering Heights differ from that of Thrushcross Grange where Wuthering Heights sits and manifests on a stormy hilltop while Thrushcross Grange sits on calm and protected valley. ... Indeed, violent acts like Heathcliff’s abuse by Hindley and Heathcliff’s mistreatment of Hareton take place in Wuthering Heights. This depicts Wuthering Heights as an aggressive, violent, and wild environment. More so, the weather surrounding Wuthering Heights and its inhabitants is also violent (Bronte, 1858). Indeed, the novel opens with a description that, "Wuthering" is "a significant provincial adjective, descriptive of the atmospheric tumult to which its station is exposed in stormy weather (Bronte, 1858)." On the other hand, the novel describes the life at Thrushcross Grange as one that manifests luxury, cultivation, and propriety. Indeed, the novel quotes that Thrushcross Grange is the house that Catherine aspires to socially, the house that will make her a "lady (Bronte, 1858)." These distinctions portray Thrushcross Grange as a representation of civilization and Wuthering Heights as a representation of wildness. More so, we can also see Catherine boxing Edgar Linton on the ear when Edgar seeks to leave Wuthering Heights (Bronte, 1858). Additionally, there are haunting figures in  Wuthering Heights, which depict wildness. Most assuredly, Thrushcross Grange is more luxurious than Wuthering Heights. The luxury in Thrushcross Grange reflects civilization. On the other hand, order and societal expectations defines life at Thrushcross Grange while nature drives life at Wuthering Heights. For example, we can see a snowstorm forcing Lockwood to stay at Wuthering Heights (Rathje, n.y) where he equally experiencers a hostile dream of a ghost child at the window. Indeed, the ghost child was crying, "let me in! Let me in!"â€Å"; I’ m come home: I'd lost my

Unit 7 mini Coursework Example | Topics and Well Written Essays - 500 words

Unit 7 mini - Coursework Example It is important to note how long the carnival will last for a budget to be set. In this case it commences from the 11th to the 20th of September, 1998. A budget committee should be set for the selection process of any proposal. This helps in determining the amount of funds that will be allocated the carnival. Their work is to come up with a budget for every single detail that will be available. The budget proceedings also includes a charge incurred during the week of the carnival. In this case, the risk to be experienced will be overcharging the citizens since the people of Spokane County will take part in the selection of qualified firms for setting this event. The firm that submits an affordable and a well evaluated budget will stand a chance to secure the available carnival contract. Quality of products is a crucial aspect of getting into a contract with Spokane County. Nobody will want poor quality products of their carnival, it poses a risk not only to the firm but also to all the people attending the carnival. An opportunity in the contract exists where quality services are offered and well trained workers are employed based on the level knowledge and skills (Jaafari, 2001). Services offered have to meet the eye of the consumer. The major risks likely to be encountered with this field will be failure to satisfy consumers’ needs. This may lead to a termination of the contract mainly because it is a long term contract for up to 5years. The Spokane County Carnival is expected to have technical equipment such as carnival rides that are meant to satisfy the residents. The firm that provides these services and state of art equipment at reasonable fees lands the contract. According to Jaafari 2001, innovativeness is also crucial, people are accustomed to change, and hence the firm that comes up with new ideas, new carnival games, and shows have a

Movies and Movements Essay Example | Topics and Well Written Essays - 1000 words

Movies and Movements - Essay Example Human history is full of moments when collective effort was needed to address public concerns. And the history of films is full of examples when the medium was used to rally collective effort. Such movies never failed to get the attention of people and stir them to action. The ability of movies to influence mass audiences has been made use of for a long time. Since the 30s and the 40s movies were used to glorify western culture, to strengthen religion and faith, to celebrate freedom, to decry communism and collectivism and to extol individual achievement and the American Dream. For many Americans the 1930s was a period of contradiction. What started out as the land of dreams was slowly playing out as a land of nightmares. Democracy, capitalism, individualism and the optimism that was based on them were all proving to be myths. Milk, honey and the good life were all mere dreams; reality was a dire struggle for survival. You simply had to see it to believe that such suffering could have existed in America. (Sutton) In the decades that preceded the 1930s settlers from the North and East flocked to the southern plains lured by the promise of an abundance of fertile soil and a happy life. The first few years looked as if they were on the way to achieving their dream. And then came a period of extended drought, which arguably is the worst drought of America. It was a double whammy of sorts. ... Desperate, many of them had to pack up and leave with their families, in search of work, to provide for their families. "The Dust Bowl was the result of a series of dust storms in the central United States and Canada from 1931 to 1939, caused by decades of inappropriate farming techniques" (Dust Bowl) Although there was both government and private effort to help ease the situation, farming communities were not able to tide things over. "Private charities like the Red Cross also helped, but in general the level of assistance available prior to 1933 was minimal (Gregory 14)". People relocated. Often this relocation was as much a nightmare as their life in the dust bowl. But ultimately true grit and hope in the face of adversity were the qualities helped farmers to weather this period. This is the message that films like "The Grapes of Wrath" carried to the suffering masses. 3 The Grapes of Wrath The film explicitly depicts the socio-economic impact of the Great Depression, and the drought of the 1930s on the thousands of displaced farmers from Oklahoma, Colorado, the Texas Panhandle and Western Kansas farmers in general and one family in particular - the Joads. The opening scene is set in Oklahoma. It shows a figure walking in the distance. The figure is Tom Joad on his way back to his family's sharecropping farm. Tom hitches a ride part of the way and then he encounters Jim Casey on the road sitting under a willow tree. Casey is an ex-preacher and together they head towards Tom's farm. When they reach the decrepit Joad cabin they find nobody there. A few moments later a figure emerges from the shadow. He is Muley Graves one of Tom's neighbors. Muley Graves is an instance of an individual who is so shattered at having lost his land that he is literally

Reading response Essay Example | Topics and Well Written Essays - 500 words - 26

Reading response - Essay Example The meaning, that is used by Shames regarding the American culture, is that having more is and has been an essential idea of the country. From my reading of â€Å"The More Factor†, Shame has the opinion that it is already part of the culture of Americans to desire for more, however, I should say that most people desire for more in their lives and not only Americans. This is true because even me I desired and still desire for more in my life. Most of all, I felt greatly surprised by what Shames described as like Americans have lost focus in what is very important as he says â€Å"Americans have been somewhat backward in adopting values, hopes, ambitions that have to do with things other than moreâ€Å". It surprised me because all, what Americans have done, is to find ways to grow and expand. Shames puts it out clearly that lost focus because they became selfish and greedy since they only bothered to help themselves and not others. In any event in 1800,s the speculators built towns and would pay individuals to move into their town and provide for them a home to live in. The fact of the matter was to build the railroad for a real town to develop. I feel that the idea of "more" is not such a terrible thing. I mean it is useful for individuals to need to have a better life and succeed, to goals and aspirations. However, it is my opinion that everything ought to have a limit, or in any event, we ought to know when to stop and enjoy life. I believe that everybody needs to live a life that is full of commodities. I do so as well. I need to go to visit new places around the globe, have things I didnt have and provided my family a home, as well as a better life. Shames’s idea of the concept of more reminds me of my childhood friend. We used to share a lot, do almost all things together; however, the guy did not accept defeat. He was ever competing and always liked to be in the front line in everything. I used to pity him because no

Executive compensation analysis-Is it Excessive Essay

Executive compensation analysis-Is it Excessive - Essay Example ncial Management of the company is one such domain where the management of the company can maximize the value for its shareholders by adopting various practices and policies which can help achieve them their highest goal. However there are also theoretical frameworks i.e. Agency theory which suggest otherwise that the managers and shareholders can conflict with each other when pursuing their individual goals and that the managers can engage into practices where they may take actions which may not help maximizing the shareholders value and rather work in their own benefits. Executive compensation is one such domain where modern executives are largely being criticized for taking high compensations mostly on the pretext that money spent on their compensation could have been utilized for creating value for the shareholders. This essay will look into how the financial management theories and practice can help managers to maximize the value for the shareholders and how it is achieved in practice besides providing a brief outline of how the managers may not, in practice, do things which can help maximize the value for the shareholders. The issue of executive compensation needs to be viewed in the historical context of the way modern businesses developed. The era during 1990s saw a slow and steady increase in the overall median compensation of the CEOs from 1992 to 2000 increased from USD 2.335(m) to USD 6.549(m)- a general increase of 180%1 suggesting the direction of the overall increase in the executive compensation. (Murphy). Similarly, despite the overall decline in the performance of financial sector due to subprime crisis, Goldman Sachs CEO Lloyd Blankfein has been able to gross up a bonus of $70million which is 30% more than what he got in previous year. The research conducted on the executive compensation subtly points towards the fact the executives exercise substantially degree of power over the board besides showing the attitude of grabbing opportunities at

A scientific report about air pollution due to automotive emissions Lab

A scientific about air pollution due to automotive emissions - Lab Report Example Nevertheless, the increased levels, even in converters that are 10 years old, are still lower than the emissions of engines that do not have converters. The world’s population doubled from 3 billion in 1959 to 6 billion in 1999 (International Data Base, 2008). This rapid rise has led to increased demand and use of modern transportation, majority of which, run on the fossil fuels petroleum and diesel. The burning of fossil fuels to power automotives results in production of compounds that do not burn completely to their elemental forms. These products are carbon monoxide, hydrocarbons, carbon dioxide, and nitrous oxides. Carbon monoxide is toxic even in small amounts. Carbon dioxide is the major greenhouse gas, contributing largely to global warming. Nitrous oxides react with water in the environment and are a major contributor to acid rain and the consequent problems associated with acid rain (Driscoll, 2001). Reducing vehicular emissions can be achieved by the use of a catalytic converter, which first came about in 1975 (Environmental Protection Agency, 1994). This simple device is used to reduce harmful emissions to less harmful forms and amounts. As the name implies, the catalytic converter acts by mediating the conversion of nitrous oxides, carbon monoxide and hydrocarbons to nitrogen gas, oxygen and carbon dioxide. The converter has both reduction and oxidation catalysts consisting of a ceramic structure coated with the metal catalysts (platinum, rhodium and/or palladium, and recently, gold). Gold, aside from being cheaper, increases oxidation by up to 40 percent (Kanellos, 2007). Exhaust coming from the engine passes through the converter and is released after the gases have been transformed to less harmful compounds. The objectives of this experiment were to compare the emission levels of automotive that are run by diesel and petrol without catalytic converters, and to test the effect of converter age and speed of the vehicle

Hiv Ethical Dilemma Essay Example for Free

Hiv Ethical Dilemma Essay Hypothetical HIV case The case related to a diagnosed HIV client who sees a psychologist for psycho-education and psychological support following the diagnosis of his condition. In discussing it becomes apparent that the client is reluctant in telling his partner or practicing protective sex. The client is angry and indicated that he even considers deliberately infecting other potential partners. Dilemma 1) Reluctance to advise partner The organisation reasonably believes that the use or disclosure is necessary to lessen or prevent: (i) a serious and imminent threat to an individual’s life, health or safety; or (ii) a serious threat to public health or public safety; or (f) the organisation has reason to suspect that unlawful activity has been, is being or may be engaged in, and uses or discloses the personal information as a necessary part of its investigation of the matter or in reporting its concerns to relevant persons or authorities; or ACTION Taken: All six points including reporting client to Police for taking further action

Sugarcane Bagasse Characterization

Sugarcane Bagasse Characterization The major composition of a lignocellulosic biomass is lignin, cellulose and hemicellulose, which is responsible for the structure and rigidity of plant. These components has been reported to have high potential energy and are been widely used as fuel in automobile and industries. The components of the bagasse were chemically characterized by measuring their dry weight. Table # represents the composition of dry sugarcane bagasse analysed in the present study compared with data collected from other research articles. The dissimilarities in composition of lignin and cellulose might be due to genetics variations, growing location, methods of harvesting, growing conditions and analytical procedures. Table 1. Major component of sugarcane bagasse Cellulose (%) Lignin (%) References 46 19.6 Present Study 40.57 25.93 (Zeng, Tong, Wang, Zhu, Ingram, 2014) 25 16.2 (Dhabhai, Jain, Chaurasia, 2012) 40 23 (Irfan, Gulsher, Abbas, Syed, Nadeem, 2011) 45.4 23.4 (Pereira, Jacobus, Cioffi, Mulinari, Luz, 2011) As per the generated data, cellulose content in the bagasse was 46%, which was further reformed into accessible form for the saccharification enzyme. While the lignin constituted 19.6%, thus removal of lignin was carried out by the pre-treatment of bagasse for an efficient enzymatic hydrolysis. Cellulose Unit Activity The AumEnzymes, India generously donated two commercial cellulases, Acid Cellulase and Neutral cellulase. The cellulase activity of Aspergillus terreus, acid cellulase, and neutral cellulase were compared in order to proceed for the optimization of saccharification phase. The International Unit for enzyme activities (IU) of all the three cellulases were based on the total cellulase activity and endoglucanase activity, determined by the CMCase assay and FPU assay respectively. Table# represents the FPU and CMCase activity presented by all the three enzymes. The data in the table# clearly concluded that all the three cellulase have negligible total cellulase activity, while they have a high amount of endoglucanase activity. Table 2. Comparison of Cellulase Activity Cellulase CMCase Activity (IU) FPU Activity (IU) Aspergillus terreus 0.273 0.045 Acid 0.966 0.028 Neutral 0.223 0.000 Which might indicate that all the cellulases has endoglucanase activity but, the negligible exoglucanases activity resulted in considerable reduction in total cellulase activity. Since the Acid cellulase had relatively higher enzyme activity, it was further used as the saccharifying enzyme. The protein content in the Acid cellulose was found using the protein assay and it was found to be 67.67 ÃŽ ¼g/mg of Acid cellulase powder. The specific activity was 14.11 IU/mg of Acid cellulase, indicating that 14.11 ÃŽ ¼mol of sugar is released by 1 mg of Acid cellulase (protein) in one unit. Optimization of alkaline The statistical design used for the microwave assisted alkaline pre-treatment is a four factors (weight of bagasse, power of microwave in wattage, NaOH concentration and the exposure time period) system, the response of the pre-treatment was based on the cellulose composition and reduced lignin after the pre-treatment. The design summary is shown in the Table #. Table 3. Design Summary Study Type: Response Surface Runs: 21 Initial Design: Central Composite Design Model: Quadratic Factor Name Units Low Actual High Actual Low Coded High Coded Mean A Bagasse g% 2.5 10 -1 1 6.25 B Microwave W 100 600 -1 1 350 C NaOH g% 1 5 -1 1 3 D Time minutes 5 10 -1 1 7.5 Response Name Units Analysis Minimum Maximum C.V % R2 Y1 Cellulose g% Polynomial 0 81.2 9.3 0.9679 Y2 Lignin Removal g% Polynomial 0 67.25 8.54 0.9735 The design was a set of 21 runs, combinations of four factor experimental design, based on the RSM and CCD (Tabel#). The RSM is mathematical based system to study the interactions between the factors, while the CCD enables us to deduce an optimal condition for the pre-treatment. Table 4. Test design and results of response surface analysis Factor 1 Factor 2 Factor 3 Factor 4 Response 1 Response 2 Std Run A:Substrate B:Microwave C:NaOH D:Time Cellulose Lignin Removal g W g% minutes g% g% 16 1 6.25 350 3.0 11.7 76.8 48.14 15 2 6.25 350 3.0 3.3 59.2 42.7 6 3 2.50 100 5.0 5.0 55 44.35 21 4 6.25 350 3.0 7.5 72.3 46.7 8 5 2.50 100 1.0 5.0 48.5 35.38 10 6 12.56 350 3.0 7.5 74.6 42.7 13 7 6.25 350 -0.4 7.5 48.25 40 5 8 10.00 100 1.0 10.0 50.6 38.4 9 9 -0.06 350 3.0 7.5 0 0 19 10 6.25 350 3.0 7.5 71.2 46.8 20 11 6.25 350 3.0 7.5 79.5 50.3 2 12 10.00 600 1.0 5.0 56.2 42.7 4 13 2.50 600 1.0 10.0 59.98 48.25 3 14 10.00 100 5.0 10.0 60.6 52.1 11 15 6.25 -70 3.0 7.5 61 48.53 18 16 6.25 350 3.0 7.5 77.1 44.23 7 17 2.50 600 5.0 10.0 75.6 62.5 12 18 6.25 770 3.0 7.5 76.3 67.25 17 19 6.25 350 3.0 7.5 69.7 48.9 1 20 10.00 600 5.0 5.0 71.85 57.23 14 21 6.25 350 6.4 7.5 81.2 60.56 According to the table#, runs #17, #18 and # 21 had maximum lignin removals while the #1, #1 and#21 showed maximum retained cellulose. The quadratic polynomial equations describes the correlation between the significant coefficients i.e. p-value (Prob>F) less than 0.05 and is used to obtain the regression values of coefficients where only significant coefficients are considered. But since this model supports hierarchy, the insignificant coefficients were not omitted. This equation was used to derive the predicted responses for cellulose (equation 1) and lignin removal (equation 2) Equation1 Equation 2 The adequacy of the quadratic model for the experimental responses (cellulose Y1 and lignin removal Y2) was checked using the Analysis of Variance (ANOVA), which was verified using the Fisher’s statistical model (F-value). The table# shows the ANOVA for Y2 response. Table 5. ANOVA result of quadratic regression model for lignin removal Source Sum of Squares Mean squares F-value p-value (Prob > F) Model 3411.23 14 243.66 15.74 0.0014 significant A-Bagasse 911.65 1 911.65 58.88 0.0003 B-Microwave 175.22 1 175.22 11.32 0.0152 C-NaOH 541.91 1 541.91 35.00 0.001 D-Time 14.80 1 14.80 0.96 0.366 AB 3.88 1 3.88 0.25 0.6347 AC 3.14 1 3.14 0.20 0.6684 AD 0.86 1 0.86 0.06 0.8216 BC 4.67 1 4.67 0.30 0.6028 BD 534.56 1 534.56 34.52 0.0011 CD 2.48 1 2.48 0.16 0.7031 A2 955.51 1 955.51 61.71 0.0002 B2 362.14 1 362.14 23.39 0.0029 C2 74.46 1 74.46 4.81 0.0708 D2 3.95 1 3.95 0.25 0.6317 Residual 92.90 6 15.48 Lack of Fit 71.34 2 35.67 6.62 0.0539 not significant Pure Error 21.56 4 5.39 Cor Total 3504.13 20 ANOVA of the regression model for lignin removal had 15.74 â€Å"F-value† which described that the model is significant and also defined that there is only 0.14% chance that a â€Å"Model F-value† this large could arise due to noise. Since the â€Å"p-value† 0.0014, lesser than 0.005, it indicates that the lignin removal is sensitive to the coefficients/factors in the model. In other words weight of bagasse (A), microwave exposure (B), NaOH (C), BD, A2 and B2 have strong influence on the lignin removal. The p-value 0.0011 for BD (B-coded for microwave, D-coded for time), indicates the strong mutual interaction between B and D in removal of lignin. The â€Å"Lack of Fit F-value† of 6.62 justifies that there are 5.39% chances that such large values of â€Å"Lack of Fit F-value† might occur due to noise, where lack of fit is an error that would occur when one of the factor is omitted from the process model. Another statistical measurement that is a sig nal to noise is the ‘‘Adequate precision’’. The desirable ratio is greater than 4, as such the Adeq Precision value is 20.22, this model can be used to navigate design space and further optimization. â€Å"Multiple correlation corfficient or R2† value denotes the correlation between observed and predicted values, i.e. if the value is closer to 1, it means better correlation. In this case the R2 value is 0.9735, indicating better agreement between experimental values and predicted values. The â€Å"coefficient of variation (CV)† indicates the degree of precision to which the experiments are compared. The lower reliability of the experiment is usually indicated by a high value of CV. In the present case the CV value is low (8.5%) indicates a good precision and reliability of the experiment. At the same time, Adjusted determination coefficient (Adj R2)† was high specifies improved precision and reliability of the conducted experiments. The 3D surface plot illustrated below (Figure#) shows co-operative effect of microwaves and NaOH on the removal of lignin. From the plot, it can be predicted that with rise the concentration of NaOH and high powered microwaves exposure a increased degradation of lignin was observed, maximum lignin removal is observed with 5% NaOH concentration and microwave irradiation with power of 600W. But the low power microwaves and NaOH concentrations had no substantial removal of lignin. Figure 1. Co-operative effect of Microwaves and NaOH on lignin removal The second response considered in the pre-treatment was the amount of cellulose retained (Y1) after the process. The ANOVA of quadratic regression model for cellulose retained after pre-treatment illustrated in Table # is a significant model as evident from the Fishers F-test value (12.91) with a very low probability value [(Prob > F) = 0.0165]. This also indicates that there is only 0.24% chance that the F-value occurs due to errors during the experiments. Among model terms A, C, BD and A2 are also significant with probability of 99%. The interaction between B and D significant effect on increase in cellulose retaining response. The goodness of fit of the model was checked by determination coefficient (R2). In this case, the value of the R2 (0.9676) indicates that only 3.24% of the total variation between experimental values and predicted values are not explained by the model. The value of the adjusted determination coefficient (Adj. R2=0.8929) was also high, at the same time a rela tively lower value of the coefficient of variation (C.V. = 9.3%) which indicates model is significant and the conducted experiment is consistent and has a good precision. The level of noise that affected the model is also very low, i.e. 11.16% determined using the Lack of Fit F-value (3.99). The Adequate Precision (15.608) for this model is greater than 4, this suggests the model can be used for navigating the design space and optimizing the experiment. Table 6. ANOVA result of quadratic regression model for cellulose concentration after pre-treatment Source Sum of Squares df Mean Squares F-value p-value (Prob > F) Model 6226.99 14 444.79 12.91 0.0024 significant A-Bagasse 2782.58 1 2782.58 80.76 0.0001 B-Microwave 117.05 1 117.05 3.40 0.1149 C-NaOH 779.62 1 779.62 22.63 0.0031 D-Time 154.88 1 154.88 4.49 0.0783 AB 36.72 1 36.72 1.07 0.3417 AC 1.56 1 1.56 0.05 0.8387 AD 8.14 1 8.14 0.24 0.6441 BC 27.27 1 27.27 0.79 0.4079 BD 1626.88 1 1626.88 47.21 0.0005 CD 1.51 1 1.51 0.04 0.8414 A^2 2013.06 1 2013.06 58.42 0.0003 B^2 4.08 1 4.08 0.12 0.7426 C^2 54.52 1 54.52 1.58 0.2552 D^2 8.46 1 8.46 0.25 0.6379 Residual 206.74 6 34.46 Lack of Fit 137.67 2 68.83 3.99 0.1116 not significant Pure Error 69.07 4 17.27 Cor Total 6433.73 20 Figure # is a 3D response surface plot generated for 6.25 g of bagasse and 7.5 minutes of treatment by the regression mode, illustrates the effect of microwave irradiation (B) and NaOH (C) variables and the interactive effects of each on the cellulose concentration. It can be observed that by increasing both factors B and C results in increased cellulose concentration. The shading on the graph indicates the NaOH concentration from 3% to 5% is adequate for increasing the cellulose concentration to 75% and above along with the microwave irradiation within range of 350 W to 600W. Which indicates that higher microwave irradiation favours lignin removal. This results in high power consumptions and charring of cellulose. To avoid the destruction of cellulose to an inaccessible substance, the treatment can be carried at lower power microwave irradiations under high pressures. The two response models of microwave assisted alkaline pre-treatment have shown positive influence on the removal of lignin and increased cellulose in bagasse. Thus the statistical analysis is reliable to generate the optimal conditions required for pre-treatment, the optimum condition was predicted using numerical optimization. The optimal values selected were, 6.37 g of bagasse irradiated at 350 W in 5% NaOH solution for 8.87 minutes. The predicted cellulose concentration was 81.94% and 56.6% lignin removal. The figure # represents the graph obtained using the numerical optimization methods. Figure 2. Co-operative effect of Microwave and NaOH on cellulose concentration Figure 3. Counter plot for predicted values of Lignin removal and cellulose concentration at optimized condition There was 48% loss in dry weight of the bagasse after pre-treatment at optimized conditions, which might be either due to removal of lignin or lost during the washing process after pre-treatment bagasse. The result was similar to the work done by (Farid, Noor El-Deen, Shata, 2014). Optimization of Saccharification The pre-treated bagasse was washed and further used for saccharification using the Acid cellulase. The efficiency of saccharification is evaluated by the saccharification%, it is the ratio of sugar released and the amount of polysaccharide present in the bagasse. Thus the saccharification% was used as the response factor for the statistical design used to optimize saccharification. The saccharification% response was assessed as a function of pre-treated bagasse loading (A), Acid cellulase loading (B) and time of incubation (C). The design developed using RSM and CCD is summarized in the Table # below. Table 7. Design Summary Study Type: Response Surface Runs: 20 Initial Design: Central Composite Design Model: Quadratic Factor Name Units Low Actual High Actual Low Coded High