La Clemenza di Tito Assignment Example | Topics and Well Written Essays - 1000 words

La Clemenza di Tito - Assignment Example He could read and write music from the age of five and wrote composition by the age of six. He was considered a rare music prodigy. Mozart’s work is a great work of art and is considered epic in each and every aspect. He also composed operas, single pieces for the piano, symphonies, concertos, operas and much more. He had a talent of memorizing and learning what he heard from others. He had incorporated the styles of Haydn and J.C. Bach in his music whereas he also evolved his own style of music. He was also influenced by Beethoven (Pettinger, 2008). Few features of Baroque style of music were also integrated in Mozarts music (Johnson, 2013). The Baroque is the period between 1600-1750. Certain characteristics of the Baroque music is a continuous rhythm, a balance between polyphonic and homophonic textures, instantaneous transformations from loud to soft which is accomplished by the addition or subtraction of instruments. A baroque music can be summarized as one that expressed the moos or expression through a single musical piece (Mostlywind.co.uk, 2011). This style of music can also be observed in Mozart’s ‘Jupiter’ symphony wherein, the double basses play their separate individual parts instead of doubling the cellos, this was the customary style of baroque and classical periods (White, 1994). Another example of this style can be seen in symphony No. 29 in A Major K 201, which utilizes contrapuntal as its central theme (Johnson, 2013). Contrapuntal in other words, may also be referred to as counterpoint which literally means ‘note against note’. This involves the movement of two different lines which move in relation to each other (Feezell, n.d.). This theme can be seen in its first movement and inconsistent length of phrases. There are 1773 finales in few of his quartets that are based on fugal style, which might be influenced by Haydn. The three final finales were

Recovery of Financial Markets and Institutions and Challenges in the Essay

Recovery of Financial Markets and Institutions and Challenges in the Post-Crisis Era - Essay Example According to the World Investment Report 2010 presented by United Nations Conference on Trade and Development, the world economies have recovered from the global financial crisis (UNCTAD, 2010). The aim of this report is to study the recovery of financial markets and institutions and challenges which these institutions are facing in the post-crisis era. In this research essay, the impact of financial crisis on three major stock markets of the world including FTSE-100, NIKKEE and DOW has been studied. Moreover, the underlying factors contributing to the downturn of the stock markets have also been discussed. The report also highlights the recovery process and the performance of the stocks in the post-crisis era. In this report, the prospects of financial regulatory reforms and financial sector and economic growth have been discussed. Finally, the new trends on the financial landscape and changes in institutions have been discussed.... The index started declining around the mid of 2008 and in the first quarter of 2009 the index reached to its lowest level in the history. Figure II: DOW Index Historical Performance of Five Years The following chart shows the NIKKIE 225 Index performance from 2007 to 2011. The table shows that the stock points declined very sharply at the end of year 2008 when stock markets were facing a huge impact of financial crisis. The index started declining around the mid of 2008 and in the first quarter of 2009 the index reached to its lowest level in the history. Figure III: NIKKIE Index Historical Performance of Five Years Underlying Factors Contributed to the Decline of Stock Markets The global financial markets are strongly integrated markets thanks to the rapid process of globalisation. One of the major factors that lead to the current financial crisis is the real estate bubble. Actually 80 percent of the U.S. market is securitised because excess capital globally has been pushed into the U.S. mortgage market (Stock Market Investors). Before the financial crisis, the world was facing the greatest expansion of leveraged debt and greatest explosion in the prices of the equity markets. All kinds of financial markets such as NASDAQ 100, Platinum futures, oil prices or gold stocks, started demonstrating the power of trend-following crows on the up and down sides of the markets and in this way the four-hundred years of market history destructed and with the unwinding of leveraged debt, the prices and confidence of investors destroyed (Wakefield, 2008). The financial crisis penetrated into the world’s stock markets because stock market is one of the major activities in the corporate world. Dash & Mallick explain that the indices of the stock markets

A Synthesis of Sildenafil

A Synthesis of Sildenafil For many reasons, this route was assumed suboptimal as a commercial manufacturing for example; it is linear with nine steps, sulphonyl chloride, which is one of the toxic substances produced from this route is in the final bond-forming reaction. Final material required a lot of recrystallizations to reduce the toxic impurities to appropriately low levels in order to produce the high quality of drug required by pharmaceutical company. Due to competing hydrolysis through the increased quenched times on scale-up chlorosulphonation in chemical development; the difficulties of scaling-up reactions are well-known. In this route, 2-pentanone and diethyl oxalate are condensed to give the diketoester 1. Then, cyclizating the diketoester by hydrazine produces pyrazole 2 which methylated with selective to give pyrazole3. Hydrolysing the reaction generated the acid 4, then convert acid to the amide by nitration to give nitropyrazole 5, which is common intermediate in all synthetic routes. Reduction of 5 with tin (II) chloride dehydrate to give the amine 6 which is by 2-ethoxybenzoyl chloride was acylated to produce diamide 7. The later was cyclized using aqueous sodium hydroxide and hydrogen peroxide to result in 8 pyrazolo[4,3-d]pyrimidin-7-one. Sildenafil was produced by selective chlorosulfonation and reaction with N-methylpiperazine.(6) Optimization of the cyclization reaction to make the pyrimidinone was the key finding during the development of the medicinal chemistry route, which impacted on the programme as a whole. Cyclization of compound 4 was done by sodium hydroxide and hydrogen peroxide, which are an aqueous alcoholic solution and lead to moderate yield (30-70%). The hydrolysis of the carboxamide to give the acid either in the presence or absence of the hydrogen peroxide was the main side product from the medicinal reaction. To avoid the hydrolysis side product, cyclization was conducted under anhydrous conditions, KOtBu/ButOH and the reaction continued in 100% product without detected impurities. By considering reordering the steps, the clean cyclization was the final bond-forming reaction. (1) Modification of the medicinal route: A lot of modifications were applied into medicinal chemistry route, which was used at the beginning of the project to prepare fifty kilograms and support supply for the four years. (6) For early scale-up, the tin (II) chloride reduction was removed. Tin is major environmental polluter and a heavy metal. It was replaced with a catalytic hydrogenation. At the early age of the sildenafil production, a tin chloride reduction was employed because the hydrogenation reduction was not in operation. The reason for inefficient of the hydrogenation was a presence of trace levels of sulfur impurities which poison the hydrogenation reaction. Switching to stoichiometric thionyl chloride is one example that controlled sulfur impurities and allows the reliability of the catalytic hydrogenation reaction. Using a hydrogenation, there are options for solvent and catalyst recovery and water is the only by-product. (5) Hydrogen peroxide was used in cyclization method to convert 7 to 8, but it causes skin burns. Furthermore, in contact with organic materials, it is a fire and transportation hazardous. Then, it was replaced with KOtBu/ButOH. Rather than using oxalyl chloride, thionyl chloride is used to prepare 2-ethoxybenzoyl chloride which eliminates exposure to carbon monoxide emissions by workers. (5) Through formation of pyrazole 3 which is an exothermic reaction, a solvent was introduced. Moreover, for 5 preparations, toluene was introduced as a solvent which reduces the level of thionyl chloride from 1.6 to 1.8 equivalents. (6) Sildenafil Citrate Sildenafil Commercial Route: Selection: The target from Sildenafil citrate was for treatment of angina when entered development. But the clinical results were failed. Pfizer made a trial with 12 patients tolerate from male erectile dysfunction in 1994. The results showed improvements in the problems of 10 patients. As a consequence, sildenafil citrate development became one of the highest priorities in the Pfizer portfolio (6). There are many advantages of commercial route over the optimized medicinal one, for example; The synthesis was redesigned to make convergence. The final bond forming step is the clean cyclisation reaction and at the start of the synthesis, the potentially toxic materials occur. Large volumes of aqueous acidic waste require an increased level of hydrolysis and neutralization through a larger scale is an example of environmental and scale-up issues associated with chlorosulphonation reaction. In order to reduce these issues, they are placed at the start of the synthesis. Hence, low molecular weight and cheaper materials are used. (5). DEVELOPMENT: Sulfonamide preparation: Through pyrazole 5, many routes of synthesis proceeded. Using chlorosulfonic acid, 2-ethoxybenzoic acid is Chlorosulfonated by using 1 mol of thionyl chloride to convert the intermediate sulfonic acid to the sulfonyl chloride. Due to low melting point of 2-ethoxybenzoic acid (19-20 C) mp, low molecular volumes of chlorosulfonic acid and thionyl chloride are used and hence no solubilisation. Initially, the sulfonamide 9 was isolated as unusual double salt 10 which is insoluble and difficult to use. Moreover, in order to obtain the double salt to crystallize, the sulphonyl chloride should be dry which lead to a lot of acidic, corrosive fumes in a pilot plant scale. Then, it was discovered that 9 can be isolated as its highly crystalline zwitterions by treatment the double salt with water to dissociate and produce a new form of free crystalline amino acids 8. For efficiency, the sulfonyl chloride was converted to sulfonamide 9 by resuspended in water and reaction with N-methylpiperazine. At the end of the reaction, by the addition of aqueous sodium hydroxide, the pH was adjusted to the isoelectric point and the precipitated compound 8 collected by filtration. As a result, during sulfonamide preparation, no organic solvents are used. Hydrogenation and coupling reaction: In medicinal chemistry, the tin (II) chloride reduction was replaced by a palladium catalyzed hydrogenation reaction to convert pyrazole 1 into the amide2. Toluene was introduced as a heat solvent which increased the safety of the process and reduced the levels of thionyl chloride to 1.2-1.6 equivalents. To convert the nytropyrazole (2) to the amine (3) heterogeneous hydrogenation in ethyl acetate was used. A number of reagents, including thionyl chloride, oxalyl chloride and N,N-cabonyldiimidazole (CDI) are used to examine the activation of the carboxylic acid. CDI costs around 8$/mol and provide such advantages for instances; high quality product, robust and clean chemistry. Furthermore, it provided a combination of the three reactions (hydrogenation, acid activation and acylation) into a single step, employed the ethyl acetate solvent with a simple recovery process and used low energy. In addition, VOC emissions were avoided such as (EtCl) that generated from the interaction of ethyl chloride with thionyl chloride or oxalyl chloride. Moreover, 90% chemical yield over three chemical reactions is produced and optimized to 96%. Cyclisation Reaction: The resulting product is heated for several hours and cyclised with 1.2 equivalents of potassium t-BuOH and t-BuOK. In order to minimize the environmental wastes, this process is run at high concentration (2.5-3.75L Kg-1). Water is added to dilute the reaction and the pH was adjusted with 4M HCl to the isoelectric point (7.5). Clinical very high quality yield of 95% sildenafil was obtained by filtration. Using 2-butanone citric acid, sildenafil was converted to sildenafil citrate to give a yield of 99 to 100%. Sildenafil History of Sildenafil: Initially Viagra was developed to treat angina (heart disease). In Morriston hospital, the drug was tried on men in 1991-1992. The clinical observation showed that the drug enhance penile erection more than treating angina. Pharmaceutical company, Pfizer commercialized the drug as a treatment for erectile dysfunction. In 1996, the drug was patented and approved on 27 March 1998 by FDA. It was the first approved drug for penile erection in the United States and the sales exceed 1$ billion in 1999-2001. The Pfizers patents on this drug will expire in 2011-2013. Dosage of Viagra: Viagra could be taken once per day as a dose between 25mg to 100mg between 30 min to 4 hours before sexual intercourse. Three dosages are available in market for this drug (25-50-100) mg with a cost of 10$ per pill for all dosages. http://www.chemistrydaily.com/chemistry/Sildenafil Mode of action: Pharmacodynamics: Effects on Penile Erection: Sildenafil citrate is a selective inhibitor of phosphodiesterase-5 (PDE5) and was used for the treatment of the male erectile dysfunction (known as impotence). It is a wide spread condition that effects around 30 million patients in United States. Nitric oxide is released during sexual stimulation and permeates through corpus cavernosum membranes. Then, the enzyme guanylate cyclase is stimulated to enhance levels of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. cGMP has an effects on smooth muscle relaxation and increases blood flow lead to an erection of the penis. Level of PDE5 is high in the corpus cavernosum which hydrolyzes cGMP and leads to inactive GMP. Levels of cGMP in men with impotence are low and as a consequence PDE5 quickly hydrolyses these levels of cGMP. Now, the sildenafil acts by inhibiting the actions of PDE5 and increases the levels of cGMP which cause the erection. (6) figure involved Erection Nitric Oxide Guanylate Cyclase Sildenafil binds to PDE5 and blocks action GMP cGMP Effects on Visual Function: In patients taking sildenafil, it has been reported such visual abnormalities for example; increased blurred vision and perception of light. These effects usually happened with dose more that 100mg which is correlated to the weaker inhibition effects of sildenafil on PDE6 that regulates signal transduction pathways in the retinal receptors. (2) Cardiovascular Effects: Sidenafil has effects on blood pressures by producing transient reduction in systolic and diastolic at 1 hour after the dose. The clinical tests showed no observed effects on heart rate. Sildenafil effects are not age or dose dependent. (2) Clinical trials: The sildenafil was tested in vitro to study the inhibition of PDE5 in human blood platelets. The results showed the potency of sildenafil and it is a selective inhibitor of both c GMP PDEs. Also, a number of trials were carried on rabbit corpus cavernosum to examine the effect on the muscle. From the results, appear that sildenafil was potent in relaxing the corpus cavernosum. Furthermore, to evaluate smooth muscle relaxation, set of experiments were carried in rabbit isolated aortic rings. Sildenafil showed similar values in both denuded and endothelial intact aortic rings. (28) Side Effects from Clinical studies: Patients receiving Viagra showed similar adverse effects in all trials. Some studies showed more effects with increased dose. There were some adverse events reported when Viagra is taken in flexible dose for example; headache, rash, dizziness, diarrhea, urinary tract infection, flushing, dyspepsia and nasal congestion. http://www.rxlist.com/viagra-drug.htm Pharmacokinetics and Metabolism: The cytochrome P450 3A4 metabolizes sildenafil which changes to an active N-desmethyl metabolite that has the 50% activity of the drug for inhibiting PDE5. This metabolite has 40% plasma concentrations of sildenafil, therefore it possess 20% of the pharmacological effects of sildenafil. Terminal half-lives of sildenafil and its metabolite are 4 hours each. Sildenafil distributed into the tissues with a volume of 105 L and excreted in the feces as metabolites. In patients aged >65 years, plasma levels increased as well in patients suffered from hepatic impairment and renal impairment. (2) Viagra Plant: Pfizer Synthesis Facility, Ringaskiddy, Ireland Sildenafil citrate which is the active pharmaceutical ingredients for Viagra was manufactured by Pfizer at Ringaskiddy and the total output from Viagra sales was account for 15%. The facility covers 200 acres and composed of four production units with 500 people working there. OSP4 is the main plant at Ringaskiddy that increase production by 40% and started in 2001. Construction of the new synthetic plant (OSP4), a finished good building (FGB) and all other services were under responsibility of Project Management and Foster Wheeler. Plant started manufacturing in March 2001. Designing facility enable the OSP4 plant to produce primary bulk, batch pharmaceutical products at a reactor of 150,000 liters and six lines are at full scale. To increase service of OSP4, Pfizer was planning to build a third liquid waste incinerator. At the plant, the manufactured products are either bulk active or drug substances. For the bulk materials, they are sent in order to complete formulation and package for shipping. Production and plant facility: http://resources.schoolscience.co.uk/pfizer/viagra/viagch4pg2.html For all drugs, initially they are produced in small a mounts for the investigation and in vitro analysis. Then, quantities are increased if the carried tests are successful to meet the needs for clinical trials and patients. For the first time, production of one kg of Viagra requires a series of eleven reactions with 23 kg of reagents and 139 liters of organic wastes. All preparations are carried in a microwave designed especially for organic chemistry. For scaling up the process, it has to be more efficient and result in fewer wastes. Currently, in Viagra production only 1.5 kg of reagents are used and release just 10 liters of wastes. The company aim to minimize the waste to 6 L per kilogram produced. Now, every year the demand is 45 tones for good quality Viagra in compared to 1998 where the l kg production was enough for people demands in 10 minutes. To scale up reaction, all starting materials were available commercially and used without purification. Using a microwave oven ETHOS 1600, synthesis was performed. In standard Pyrex glassware, all reactions were carried out with a reflux condenser. The reactions were performed by a program which made up of temperature monitoring and holding steps. Purity of the final product was measured using thin-layer chromatography and molecular weight was recorded by electrospray ionization mass spectrometry. sealed vessels are used which controlled and monitored by computers to make the requir ed quantities of pure drug. Pipes are used to add the reagents into the vessel and the products are harvesting later on. Control panels are applied that allow the operator to make any required adjustments and monitoring the process. A microwave-transparent fluoroptic probe that inserted into the solutions was used to monitor the temperature of the stirred reactions mixture. To produce any pharmaceuticals, highest standards of hygiene are necessary and Laboratory should be clean and tidy. Misuse of Viagra in Asia: http://www.ergogenics.org/138.html (faked drug) According to World Health Organization (WHO), one of the most counterfeited drugs in Asia is Viagra which make a big business. Tourists in Thailand use fake Viagra which is bought over numerous pharmacies. Therefore serious health risks affected those tourists. Counterfeited medicines can impose the correct ingredients but fake package, or without active ingredients, wrong ingredients or with insufficient active ingredients. Fake Viagra made up of ingredients that enhance the bodys insulin production which can cause a danger drop in the concentrations of blood glucose. As a result lead to starving the energy of brain which in known as insulin shock syndrome. There is a widespread smuggling of fake and genuine Viagra in Thailand according to A Thai Food and Drug Administration (FDA). Unsurprisingly, Thailand is a centre for fake Viagra. Among young night-clubbers, Viagra is mixing with other party drug to increase the sexual desire. Viagra competitors: There were alternative medications prescribed for erectile dysfunction prior to the introduction of Viagra. Most of them are non-oral treatments. For example; the primary alternatives in the United States were vacuum constriction devices, penile injection therapy, penile prostheses, professional counseling and transurethral. Traditional remedies were used in other countries such as yohimbine. (4) Viagra Sales around the world: Firstly, after FDA granted approval of Viagra, it was sold in the United States. Nowadays more than fifty countries are selling Viagra in their pharmacies. On the U.S. market, one month after launch, the worth of sales was 400$ million which result from 300,000 Viagra prescriptions. Since then, 7$ per tablet was maintained by Pfizer. The average wholesale price is 8.75$ per pill in compare with other treatments such as; Caverject and Muse which priced at 20-30$ per pill. Furthermore, sales in most European countries began shortly in September 1998 after European Medicines Evaluation Agency (EMEA) granted European countries the registration for Viagra uses. In the United Kingdom, Sweden and republic of Ireland, the government Health System covers the purchases of Viagra for limited uses. Public awareness have been increased and focused on the safety issues in men taking Viagra and lead to limit the use of Viagra after reports over deaths and adverse effects that were sent to the FDA. U.S. and most other countries experienced prescription leveling off after information gained by people used the drug. Most of them were not actually suffer from erectile dysfunction. After drugs approval in the United States, Latin America launched the drug. Then, Viagra was available in a number of Asian countries, New Zealand, Australia and Canada. In 1999, Japan approved drugs uses after it accepted from other countries the clinical trials data for the first time. (4) Environmental Performance: In the medicinal route, there are a number of organic solvents included in the production of 1000 kg of drug substance and the volume of these solvents equal to 125,000 liters. These solvents are reduced to 13,500 liters in the commercial route. The solvents required in both routes are illustrated in figure 1. Organic wastes from medicinal route Organic wastes from commercial route For environmental assessment, the reduction of some solvents for example; chlorinated solvents and highly volatile solvents such as; methyl chloride, methanol, acetone and diethyl ether. Elimination of these solvents results in elimination of atmospheric emissions. T-butanol that has been used in the commercial route is completely water soluble and is difficult for reuse. In order to improve environmental performance, t-buanol is replaced by another solvent to facilitate recovery. The optimized process was developed in Ringaskiddy and will be used in the production plant which will give 4 l kg-1 of the final optimized solvent usage. (5) http://en.wikipedia.org/wiki/Atom_economy Atom economy is the efficiency of conversion all reactants in a chemical process in a way of all atoms involved and no atoms are wasted. All starting materials equal to generated process, this represent an important concept in green chemistry. Reaction mass efficiency is a measure for the effect of yield and an increase of used reagents. Between 1994 and 1997 where the new commercial route was introduced, there was an improvement in the reaction mass efficiency and chemical yields. In contrast, the atom economy remained constants over time. Comparisons of these parameters between 1994 and 1997 is shown in figure Fig. Atom economy, chemical yield and RME at 1994, 1997 and the future target in the sildenafil citrate process. The aqueous and organic wastes are actually measured and from modeling process the atmospheric emissions are estimated. There was a large reduction in the aqueous waste when the commercial route was introduced into the production. Moreover, upon introduction of the commercial route, again there was a noticeable reduction in the organic wastes between 1994 and 1997. Due to the impact of introducing solvent recovery operations and reuse in the manufacturing process, a further large reduction occurred after 1997. These decreasing reflect the importance of eliminating wastes and controlling route selection. For the vapor emissions, there have been smaller diminish in the released amount. In addition, it was found there was 35% decrease in the estimated energy used between 1994 and 1997. There are two reasons behind smaller reduction in the vapor emissions and the used energy; firstly, in order to maximize the yield, there is a significant level of solvents stripping performed in the comm ercial process. Secondary, the chemistry team actively managed and followed such parameters for instance; organic, aqueous wastes and yield. On the other hand, they calculated retrospectively the emissions and energy. (5) Figure shows the comparisons between these wastes at various times. The E-factor is the total kilos of wastes per kilogram of product. In commercial route of Viagra production, the E-factor is 6 kg kg-1 which is less than the industry standard of (25-100) (6) Low volumes of the complicated chemical products and the E-factor of the commercial route for Viagra production generate fewer wastes per year. For all of the environmental awareness taken by Pfizer for the sildenafil citrate process, UK Award was granted to this company in 2003. (2) Patents: According to the U.S. Patent and Trademark Office, patent for Viagra by Pfizer will expire on March 27, 2012. Then, a cheap generic version of the blockbuster erectile dysfunction drug will be sold by any drug company. This will allow more competition between Pfizers Viagra and the new generic versions and more options with cheaper prices for patients. Pfizer has three options to stay in the Viagras market. Firstly, it can market itself as the main company for selling Viagra, taking into account there are over 25 million men used its version and they donà ¢Ã¢â€š ¬Ã¢â€ž ¢t like to change. Secondary, it can apply for Viagra with FDA for OTC (over-the-counter). Finally, while producing an upgraded version of Viagra which will continue holding value of the patented product, it can license the original recipe to Viagra to other companies. http://www.accessrx.com/research/viagra-patent-expires.htm Alternative Routes to Sildenafil: There are more than 15 different routes have been reported in the chemical and patent literature to sildenafil. Pfizer examined two main alternatives during the development process either by synthesis sildenafil through the aldehyde 11 to produce dihydrosildenafil 12 then oxidize the product or by the halo derivatives for example 13 or 14. 52 % of sildenafil yielded from condensation between aldehyde and aminopyrazole to give dihydrosildenafil by adding an azeotropic distillation to remove the water by product. The yield can be increased to 95% as shown by some workers. (PATENT 22918) Aldehyde Amine Dihydrosildenafil Sildenafil Oxidation of dihydrosildenafil either by using sodium hydrogen sulphite (NaHSO3) or using small quantity of trifluoroacetic acid and Pd/C at high temperature generated a good yield of drug (patent WO 01-98303). Dihydrosildenafil Sildenafil Combination between a nucleophilic displacement reaction that uses ethanol as a solvent and a hindered alkoxide (KOBU) or ethoxide (EtOH) as a base and the cyclization reaction which uses a compound like halo derivatives is another potential synthesis for sildenafil. The combination reaction works for both cyclisation compounds, but by using a compound where (x= F) the yield from combination is 100%. The use of the chloro-series compound (x=cl) in the cyclisation reaction is better because of 2-chlorobenzoic acid is cheaper than 2-ethoxybenzoic acid. (Patent number EP 0994 115) Figure (13, 14, synthesis) Halo Derivatives X= Cl X= Fe, yield= 100% In the end, all of these alternative routes were put on hold due to the high efficiency of the commercial route and the time pressures of the development program. (6) (3) In the WO Patent (98284), amidine 10 or iminoether 11 can be used in order to build pyrimidine ring (sildenafil). By a Pinner reaction, the iminoether is made from the nitrile. Amidine is made by reaction of the nitrile with chloromethylaluminium amide which is synthesized from trimethyl aluminium (Me3Al) and ammonium chloride (NH4Cl) Nitrile Amidine Iminoether Sildenafil Intermediate 14 was prepared from reaction of the acid intermediate 13 with thionyl chloride (SOCl2) to give the lactone which then can be reacted with ammonia (NH3) and (EtOH) to produce the pyrazolopyrimidinone which is away to make sildenafil. Acid intermediate Lactone Sildenafil (Patent EP 1 002 798) sildenafil synthesis from intermediate (6), can be done by chlorosulphonate the intermediate 16 and before cyclisation the intermediate convert to the sulphonamide6. Sildenafil There are many patents activities in producing nonconvergent synthesis of sildinafil. Workers at the Torcan Company reduced Carbamate by (LiALH4) to sildenafil in ayield of 61%. ( Patent 2 235 642). Carbamate Sildenafil Also, sildenafil was synthesized from pyrazolopyrimidinone and the sulphamoyl chlorid (which is prepared by SO2Cl2 and N-methylpiperazine reaction) using Friedel-Craft reaction which requires ALCl3 by workers at the India Orchid company. (Patent EP 1 077 214) Pyrazolopyrimidine and sulphamoyl chloride Sildenafil Furthermore, workers in Cipla Company have synthesized sildenafil by double methylation of this intermediate by using formic acid and formaldehyde (CH2O) and (HCO2H) as the final step. (Patent WO Patent 01/ 19827) Sildenafil

Microsoft Vs Consumers :: essays papers

Microsoft Vs Consumers Antitrust law protects the public from companies that attain an undue domination of the marketplace via mergers, tying 1 product to another, vertical integration, and other practices tending to eliminate competition or bar entry into the market to newcomers. In the early 1980s, Microsoft was a much smaller company than it is today. However, it had already established a reputation of being a predator, a greedy predator. They were known to terminate licenses mercilessly once they figured out a way to clone the given technology, regardless of whether it was legal or not. Back then, Microsoft had some enthusiastic competition. The biggest of which were Borland (programming), Ashton-Tate (databases), Visicalc and Lotus (spreadsheets), as well as Wordstar and WordPerfect (word processors). All of these companies have now either merged out of existence or are completely defunct, with the exceptions of Borland and Lotus (which are barely afloat). Microsoft now has the leading product in each sector of the market once occupied by these firms. The company was responsible for ridding itself of these early competitors by either buying them out or simply driving them into the ground. This early disregard set the tone for how Microsoft does business even today. Microsoft’s advantage comes from their domination of operating systems. â€Å"By definition, if the OS maker creates applications, they will run better with the OS than a third party’s, and the OS owner can, over time, create modifications that will make this even more so,† (Rapacious 1). Microsoft has the power to leverage their dominance in operating systems to gain a large market share in the various application sectors. They have always been able to do this and as a result have been able to get, or achieve, whatever it is that they have wanted. This is the vertical integration that the antitrust laws talk about. In a July 1994, settlement, the Justice Department came to an agreement with the software giant over the antitrust charges it had filed against the company. The charges were brought after the department found out that Microsoft was giving personal computer manufacturers a discount on their OS when the PC manufacturer would pay the company a royalty for each computer sold, including those that without MS-DOS or Windows software. â€Å"The practice gave PC makers little incentive to install competing programs since they would have had to pay a royalty to both the competitor and Microsoft,† (Ramstad 1).

Modern World History Essay

The children had very different reactions to the policy of evacuation. They all had a lot of different experiences. Some liked it and felt as if it was an adventure for them, everything was new to them so they enjoyed it especially the ones who lived with wealthy hosts, some did not want to leave. It was like a holiday. But for these children some felt scared and didn’t like the change, for example this is Source I, taken from the Modern World History Heinemann textbook page 138, ‘Everything was so clean in the room. We were given face flannels and tooth brushes. We’d never cleaned out teeth until then. And hot water came from the tap. And there was a lavatory upstairs. And carpets. And clean sheets. This was all very odd. I didn’t like it. It was scary. ‘ This shows hard and weird it must have been for the children, all the changes would be very confusing. It was even worse though for the children who were mistreated, here is Source M from the same book and page. ‘Clarence and I used to sleep together and poor Clarence used to wet the bed because he was a very nervous kid. She (the foster mother) could never tell who’d done it so she used to bash the daylights out of both of us. So, of course, the more Clarence got hit the more he wet the bed. It was then we started to get locked in the cupboard. ‘ This source tells us how hard it must have been for children like Clarence. First of all they leave their family behind, leave the city they grow up in and don’t know what to expect just that it would be safer than the cities. Then they end up getting beaten by the foster parents. They would feel terrified and would probably wish they had never moved. It would also be very hard for children as they would miss their family and for little kids of about 5 and 6 it would be even harder. They would feel lost and not know what to do. For the mothers and fathers it would be probably be a sad experience letting your children go and live with strangers. You only knew that your children would be safer than in the city and hopefully wouldn’t be killed. You yourself wouldn’t know what to expect and would probably fear the worst. All you knew was that you had a job to do in the war and had to work hard. You didn’t know who you children were staying with or what they were like so it would be a traumatic experience for the parents as well as the kids. Only mums with babies were allowed to evacuate out of the cities with them otherwise they had to work. But at least you knew you were doing your bit and hopefully the hard work would take your mind off things and stop you from worrying. The parents knew the policy was a good idea but probably still had their doubts about it. Another reaction was from the emergency services. They seemed to like it. It gave them a lot more time to concentrate on the war and big things rather than having little kids causing trouble. They liked the situation and it helped them out a lot which was another reason why the evacuation itself took place. There was a lot less people in the cities, less crimes, fires etc. which made their job a lot easier which I’m sure they appreciated. They definitely liked the policy. So this shows the different reactions about the policy. There were a lot of mixed opinions on whether it was good or not. Some liked it some didn’t, but in my opinion it was a good thing but maybe if I was there I might have a different reaction to it.

Culture Convergence

Introduction In recent times, the globalization topic is one of the most discussed issue across the world. With globalization, countries has started to build stronger economic ties and be increasingly reliant on each other as it has never be. Some researchers argue of cultural convergence; that is, as two countries become closer with each other, they will be more likely to influence each other's culture, thereby bringing the two different cultures to be more similar.For example, the popular culture, which originates from Western European and America, is often to be said to influence the developing Asian countries' culture, and is often dubbed as Westernization (Leung et al, 2008). Conversely, there are many that argue also of cultural divergence; which is the belief that each nation's culture are deeply rooted in the countries' history, so that even if outside culture try to influence the belief and attitude of the people, the difference between cultures can still be maintained, and can even increase over time (Axelrod, 1997; Turnbull & Sheehan, 2012).Hofstede (1980) defined four dimensions of culture that describes the fundamental similarities and differences of human behavior and decision making process that forms part of culture. These dimensions will be valuable for measuring cultural convergence or divergence. They consist of masculinity/femininity, power distance, individualism/collectivism and uncertainty avoidance. Power distance is the dimension of which inequality of power is expected and accepted as normal by the less powerful members of organization and society.Masculinity/ Femininity is the measure of which society is oriented towards ‘masculine' value : competitiveness, assertion, success , good performance, etc. instead of ‘feminine' value: kindness, caring, empathy, etc. Individualism/Collectivism measures to what extent society lets each individual care for their own: more individualism means that the ties between individuals in the society is more loose. Uncertainty Avoidance is the measure as to how much the members of the society avoid risky behaviors and stay the conservative way.This essay will try to discuss whether countries has experienced cultural convergence or divergence, by first looking to the cultural divergence phenomenon, and then the cultural convergence phenomenon, and finally comparing both and giving recommendation as to how the risks of the phenomenon observed can be mitigated. Discussion Cultural Divergence Axelrod (1997) argued in his model that local convergence may cause global polarization. He contends that the convergence in society will stay in local area only, as the culture converge in a region that have nothing in common with neighboring regions.This causes local regions to have culture convergence, but in the bigger area, the difference between cultures remain stable, thus increasing polarization or cultural divergence. Axelrod (1997) also argues that polarization level gets hig her if there are a few dimensions of the culture, many alternative traits on each dimensions, and if the size of the region is large enough to allow for many cultures, but small enough for the change process to finish before all cultural boundaries are dissolved by the spread of cultural traits. Further, Klemm et al. (2003) argued that the level of perturbation to a culture influences how the culture drifts.They argued that perturbation, up to a level, will bring a culture to converge together, but when the perturbation or influence is high enough, the culture will split into several sub-culture, meaning the culture has been polarized or diverged. This phenomenon can be attributed to several reasons, such as preference for more extreme views, geographical isolation, social differentiation (tendency for groups to differentiate themselves compared to other groups), drift, the in and out of fads and fashions, specialization and changing environment or technology (Axelrod, 1997).There a re some examples of this phenomenon in the real life. For one, Turnbull & Sheehan(2012) argued that due to historical and cultural differences, the chain fast food company McDonald have to alter their strategy and brand imaging in Canada and Japan. This happens even though they are a company that is trying to build a similar image in every country they are established in. Furthermore, they also found that some of Australia's public relations policy clearly rejects that their culture has been assimilated to the US culture.Another example is given by Darling-Wolf (2004) interview with Japanese women about foreigners, in which he found that Japanese women are still viewing Western women as shallow, vain and selfish. Martin (2010) also found that Japanese people found foreign actors and actresses to be more likeable if they exhibit some Japanese characteristics. This indicates that Japanese women still hold their cultural values highly, and not influenced by the Westernization that may happen as a result of the strong ties between Japan and America. Finally, Anderson et al. 2000) found that there are significant differences between Indian and American aerospace scientists and engineers, especially in the power distance, individualism and uncertainty avoidance dimension, indicating cultures still at the very least maintain their differences, if not diverging from each other. Cultural Convergence The theory behind cultural convergence notion is that a nation's culture is viewed as a subsystem of a global culture, and that culture is an open system that can exchange input and outputs with other cultures.Given this, to avoid entropy a system needs to reach an equilibrium, which is the state where all cultures are assimilated, and hence forming a culture convergence. This theory proposes that if two cultures interact frequently, they will most likely be converged together(Bergiel, 2011). One example that comes to mind when discussing convergence is Westernization, whic h is the phenomena where non-Western (typically Asian) culture are often changed and influenced with Western cultures through the exposure by media such as TV and Internet, as well as from various other interaction between the two cultures.The ever increasing global marketing, as well as the increasing number of businesses that expands their business to foreign countries, only serve as a vehicle for cultural assimilation to happen, as the two cultures will mesh together and form a stable equilibrium according to this notion. This notion of cultural convergence also gain some support from researchers.As an example, Bergiel (2011) found in his study about Japanese and US culture that in regards of individualism, masculinity and power distance the trend of convergence has been found to be very extreme, as the role of the two country reverses in between the two decades since Hofstede released his study in 1980. In 1980, the US society were said to be holding up the value of individualis m, have low power distance and masculinity, while in this study it was found that now Japan culture has now moved from collectivism to individualism, surpassing the US score in the dimension, have lower power distance compared to the US, and is more masculine.However, this may be also influenced by the politic-economic factors in the two country, and not solely by the fact that the two culture interacted with each other. Also, in the long-term orientation it has been found that the two cultures converge, sporting similar score in that dimension. Further, Nieves et al. (2006) also found from their study that Mexican and American engineers has converged their culture in the individualism dimension, compared to when Hofstede did his research in 1980.Convergence Vs. Divergence Hence, while cultural convergence theory contends that over time and different cultures that interacts with each other will form a stable equilibrium eventually, the cultural divergence theory contends that cultur es will maintain its own unique identity, as culture needs big enough perturbation to have a lasting change, and they typically maintain their difference despite the influence from foreign cultures/countries.Some researchers argue that globalization will make cultures to converge, as globalization means that information is very easily accessible, and cultures are exposed to other cultures constantly, so that in cultural convergence theory this will cause those cultures to form an equilibrium, and that the world is converging into a ‘global village'. (Inglehart & Welzel, 2005). However, some researchers also argue that globalization may not necessarily cause convergence. Inglehart & Norris (2009) argued that the globalization may even cause polarization of the cultures.They argued that the values that the rich country's public hold usually changes rapidly, while poorer countries generally are slower in adapting change in culture. This opens up a gap in culture difference betwee n rich societies and poor societies. Further, they also found that richer countries also differ in culture in religiosity to poor societies. Richer countries are becoming more and more secular in these days, while poorer countries are typically more traditional and religious.Similarly, richer countries are also moving towards gender equality, while many poorer societies still hold patriarchal values highly (Inglehart ; Norris, 2009). Further, this can also apply not to nation's cultures, but also its subcultures. Typically, the richer societies in the urban area adopt new values more rapidly, and rural society sticks with their traditional culture and adopt changes slowly. Finally, convergence theory is argued to be exaggerating the level of consensus of core value between US and other countries, thereby reducing the actual level of assimilation barrier that exists in the real world.Hence, it is most likely that cultural divergence and polarization is what actually happens in the wo rld. Organizations should take note of this divergence phenomenon in order to successfully conduct a global or multinational operation. Some researchers argue that the national cultural difference may bring problems in an organization in the integration process and consequently knowledge transfer (Vaara, 2003). The reason this happens is cultural difference is often thought to impede cooperation between the members.Further, Hogg & Terry (2000) argued that similarity are often a factor in deciding attractiveness and trustworthiness, and having different culture makes an individual automatically less attractive and trustworthy compared to someone from the same culture. However, Sarala & Vaara (2009) argued that with different culture, organization may benefit from having different knowledge and repertoire that could be shared around. Hence, with cultural difference, knowledge transfer can potentially be more effective as there are more knowledge to go around.Although the knowledge pot ential is great, what is more important is to actually manage to spread it around the organization and make sure that individuals from different cultures are comfortable with each other. Sarala & Vaara (2009) argued that the way for organization to do this is through facilitated communication, in order to reduce uncertainty and increase trust between the members of the organization. Also equally important is that the organization management practice must be aligned with the nation's culture that they are in, in order to operate smoothly in the face of cultural difference (Nieves et al, 2006).Hence, to be successful, an organization must proactively try to make the members of the organization increase their trust with each other, as well as changing their managing practices, depending on the culture that they are currently residing in. Conclusion In conclusion, cultural convergence is the theory that different cultures that interact in a regular basis will influence each other and fo rm a stable equilibrium, thus converging the two cultures, while cultural divergence is the theory that states that cultural differences will be maintained, and even grow apart from each other even though they interact in a regular basis.The basis of cultural convergence theory is that the member of society will try to imitate and assimilate the new foreign culture, while the cultural divergence theory contends that group tends to stay within themselves and differentiate themselves from other groups. In real life, it seems likely that the cultural divergence theory is correct, as even if a culture is experiencing change from foreign culture, the rate of change in the different part of society may be different, thus creating a gap as well.For example, richer societies tend to adopt new values quickly, while poorer societies might hold to their traditional value, hence creating a cultural divergence overall. To overcome this issue, organization needs to actively try to facilitate comm unication between the members of their organization if they have different cultures, as well as altering their management practice to fit the culture of the society that they are currently residing in. Reference Anderson, C. J. , Glassman, M. , ; Pinelli, T. (2000).A Comparison of Communications Practices Among Indian and US Scientists and Engineers. Journal of East-West Business,  6(1), 81-108. Axelrod, R. (1997). The Dissemination of Culture A Model with Local Convergence and Global Polarization. Journal of conflict resolution,  41(2), 203-226. Bergiel, E. B. , Bergiel, B. J. , ; Upson, J. W. (2012). Revisiting Hofstede’s Dimensions: Examining the Cultural Convergence of the United States and Japan. American Journal of Management,  12(1), 69-79. Bredillet, C. , Yatim, F. , ; Ruiz, P. (2010).Project management deployment: The role of cultural factors. International Journal of Project Management,  28(2), 183-193. Darling-Wolf, F. (2004). Women and new men: Negotiating masculinity in the Japanese media. The Communication Review,  7(3), 285-303. Hofstede, G. (1980). Culture's consequences: International differences in work-related values  (Vol. 5). Sage Publications, Incorporated. Hogg, M. A. , & Terry, D. J. (2000). Social identity and self-categorization processes in organizational contexts. Academy of management review, 121-140. Inglehart, R. & Welzel, C. (2005). Modernization, cultural change, and democracy: The human development sequence. Cambridge University Press. Klemm, K. , Eguiluz, V. M. , Toral, R. & San Miguel, M. 2003. Global culture: A noise induced transition in finite systems. Physical Review E 67, 045101(R). Leung, K. , Bhagat, R. S. , Buchan, N. R. , Erez, M. , & Gibson, C. B. (2005). Culture and international business: recent advances and their implications for future research. Journal of International Business Studies,  36(4), 357-378. Martin, D. (2012).Foreign women in Japanese television advertising: Content analyses of a cultural convergence paradigm. European Journal of Marketing,46(1/2), 157-176. Nieves, R. , Mujtaba, B. G. , Pellet, P. F. , & Cavico, F. (2011). Culture And Universal Professional Values In Global Organizations: Is There A Divergence Or Convergence Of Cultural Values?. Journal of Diversity Management (JDM),1(1), 31-38. Norris, P. , & Inglehart, R. (2009). Is national diversity under threat? Cosmopolitan communications and cultural convergence. Cosmopolitan Communications and Cultural Convergence Sarala, R.M. , & Vaara, E. (2009). Cultural differences, convergence, and crossvergence as explanations of knowledge transfer in international acquisitions. Journal of International Business Studies,  41(8), 1365-1390. Turnbull, N. , & Sheehan, M. (2012, November). The impact of divergent historical and cultural factors on convergence in global communication practice. In  WORLD PUBLIC RELATIONS FORUM 2012  (p. 128). Vaara, E. (2003). Post? acquisition Integration as Sensemaking: Gl impses of Ambiguity, Confusion, Hypocrisy, and Politicization. Journal of Management Studies,  40(4), 859-894.