Mechanism and Optimization of Melphalan

Mechanism and Optimization of Melphalan Melphalan Introduction Cancer in general is referred to body cells that grows rapidly and over the limit of normal cells (Hayflick limit). There’s over 200 different types of cancer, where some cancer cells can spread to other parts of the body leading to further complications. It’s one of the biggest leading cause of death worldwide. Therefore interest in finding treatment and prevention for this disease has been growing. One of the most successful chemotherapy drugs is Melphalan. It’s been over 50 years in use and there’s an increase in research to improve this drug. It’s indicated for different type of cancer: for the analgesic treatment of multiple myeloma (MM) and for the alleviation of unresectable epithelial tumor of the ovary. It has also been used alone or in combination with other chemotherapy drugs for relief treatment of locally repeated or unresectable in-transit metastatic melanoma of the extremities. It’s also used in addition to other drugs or surge ry in breast cancer. Mechanism of action Melphalan belong to a class of chemotherapy drugs called nitrogen mustardalkylating agents. It’s the oldest class of anticancer drugs still frequently used. It’s a bifunctional alkylating agent which means it has two sites where the reactivity occurs. It displaces the chloride ion by amine nitrogen to form a cyclic amine ion (aziridinium ring) by intramolecular nucleophilic attack. Afterwards the DNA nucleophile undergoes a nucleophilic attack and opens the azidrine ring, which leads to the alkylation of DNA. The lone pair of electrons on the nitrogen in the drug will then be regenerated when the azidine ring cleaves. The same reactions happen on the second reactive site of the drug, by displacing the second chloride ion. (picture) This will lead to cross-linked DNA molecules through covalent bonds. The covalent bonds can be made in two different ways: either on the same DNA strand which will alter the shape permanently prevents other enzymes or molecules from binding t o it, or on adjacent strand therefore preventing replication/transcription process. (picture) The reaction happens in the N7-site of guanine, which is the most preferred nuclei acid. However the reaction can also take place at the N3-site of adenine. The alkylation of the nucleotide leads to miscoding of DNA as for example Thymine will bind to guanine instead cytosine. Due to the p-orbital of the benzene ring in melphalan that draws the lone pair electrons from nitrogen, this leads to reduction of reactivity to form the azirdine, hence only strong nucleophiles such as guanine will react with it. This has the benefit of reducing the side reactions with water, tissue and blood, leading to the drug can be given orally. The side chain of Melphalan is L-phenylalanine, meaning it has a component that act as the amino acid phenylalanine. (picture) Consequently the drug is most likely to be recognised as an amino acid, and it will be taken into the cell by transporter protein. This increase s the stability of the drug further. Optimization of Melphalan Despite Melphalan being used as an anticancer drug for over 50 years, it’s associated with many complications including poor solubility in water, variable bioavailability and rapid hydrolysis at physiological pH (11-14) which also increase the bioavailability problem. Another major problem is its rapid clearance from the blood circulation due to its short half-life (90 min). A study conducted in USA to tackle these difficulties by adding a poly ethylene glycol (PEG) to the Mel, in order to enhance the formulation of parental and oral administration. PEG is a synthetic polymer which is water soluble and non-ionic. It is an amphipilic polymer meaning it has an exceptional capacity to be soluble in both aqueous and organic solvents. This property makes it ideal for chemical conjugate of substance that has a biological effect. Another advantage of using PEG is it has exceptionally low level of antigenicity and immunogenicity. The process of conjugation is called PEGylation. Itâ₠¬â„¢s a two-step process where in the first step the activation and derivatization of PEG occurs with appropriate functional groups. In step two the conjugation of the activated PEG with Mel occurs. The NH2 group in melphalan undergoes a nucleophilic reaction with mPEG-succinimidyl propionate (mPEG-SPA) under the presence of DMAP catalyst. This reaction produces an amide bond, which is reasonably stable. The mPEG-SPA gets hydrolysed to mPEG and N-hydroxysuccinimide. Fig x. The study conjugated two molecular weight (MW) PEG: 2000 and 5000 Da. Variable test were conducted to measure the difference between the two different MW PEG conjugates and the parent drug Melphalan. The aqueous solubility of the conjugated Melphalan was measured by dissolution test, the results are shown in table 1. The table shows there is an increase in aqueous solubility of MpPEG-2000 by nearly 80 times reading as 7.2 ±0.12  µg/ml and increased by approximately 123 times for MpPEG-5000 reading as 11.07 ±0.8  µg/ml, compared to the measured solubility of the parental Melphalan of 0.09  µg/ml. This results can be explained due to the PEG chain being attached to the drug. On the other hand the haemolytic activity of melphalan versus its conjugates was also determined by assessing the haemoglobin content. The melphalan haemolytic activity was measured to 100% above the concentration 3.5  µg/ml (table 2). With regards to MpPEG-5000 only 48.8 ±1.5% haemolysis observed at concentration of 32  µg/ml (table 3). In case of MpPEG-2000 the highest percentage of haemolysis of 81.3 ±0.5% was recorded at concentration of 32  µg/ml (table 4). The lower haemolytic activity of the conjugates compared to melphalan might be due to the dominated property of polymeric carrier PEG. These results is an indication that the chain length of PEG plays an important role on the haemolytic activity. The property of delaying haemolysis is better in MpPEG-5000 compared to MpPEG-2000 even at higher concentrations. It also has an effect on the aqueous solubility due to the longer the chain the more hydrophilic backbone of PEG will be present. The percentage cumulative hydrolysis of the conjugates was observed in case of MpPEG-2000 to be 10.11 ±0.68 after 6 hours, whereas for MpPEG-5000 was only 5.21 ±1.2% after the same time (table 5). The low cumulative hydrolysis detected in MpPEG-5000 may be understood due to the ester linkage being protected by the PEG molecule du e to the steric hindrance. Furthermore the amide bond is more protected in MpPEG-5000 compared to MpPEG-2000 due to the shielding effect of the larger chain of PEG. Therefore the MpPEG-5000 can be an ideal candidate to provide a slow release drug formulation. Thus, increase the half-life of the drug and decrease the clearance. Clinical trials Conclusion This drug adds a small group, an alkyl group to the DNA to alter its structure and hence modifies the function. It’s an alkylating agent which means it adds an alkyl group to DNA. The alkyl group may be transferred as an alkylcarbocation, afree radical, acarbanionor acarbene(or their equivalents). Nitrogen mustards (NMs) form cyclic aminium ions (aziridinium rings) by intramolecular displacement of the chloride by the amine nitrogen. This aziridinium group then alkylates DNA once it is attacked by the N-7 nucleophilic center on the guanine base. A second attack after the displacement of the second chlorine forms the second alkylation step that results in the formation of interstrand cross-links (ICLs) as it was shown in the early 1960s. At that time it was proposed that the ICLs were formed between N-7 atom of guanine residue in a 5’-d(GC) sequence.[15][16] These kinds of lesions are effective at forcing the cell to undergo apoptosis via p53, a protein which scans the genome for defects. Note that the alkylating damage itself is not cytotoxic and does not directly cause cell death. For the analgesic treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Has also been used alone or as part of various chemotherapeutic regimens as an addition to surgery in the treatment of breast cancer, alone or in combination regimens for palliative treatment of locally recurrent or unresectable in-transit metastatic melanoma of the extremities, as well as for the treatment of amyloidosis with prednisone. http://www.bloodjournal.org.ezproxy.kingston.ac.uk/content/106/2/698 http://onlinelibrary.wiley.com.ezproxy.kingston.ac.uk/doi/10.1002/cncr.27820/full http://www.bloodjournal.org.ezproxy.kingston.ac.uk/content/117/24/6445 http://www.drugbank.ca/drugs/DB01042 http://cancerres.aacrjournals.org/content/44/7/2773.full.pdf+html http://pubs.acs.org.ezproxy.kingston.ac.uk/doi/full/10.1021/jo300351g http://www.bloodjournal.org.ezproxy.kingston.ac.uk/content/100/1/224 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024156/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286742/ http://ac.els-cdn.com/S0898656813000314/1-s2.0-S0898656813000314-main.pdf?_tid=c3b012a4-c411-11e4-944b-00000aab0f27acdnat=1425654312_d9351a386aa77b225426f1c34e100e88 http://ac.els-cdn.com/S0144861714004196/1-s2.0-S0144861714004196-main.pdf?_tid=00c4f2b8-c412-11e4-aee6-00000aab0f6cacdnat=1425654412_90fa9336c00ccddd1706b13914966246 http://ac.els-cdn.com/S0009279702000145/1-s2.0-S0009279702000145-main.pdf?_tid=458a0f50-c412-11e4-b306-00000aacb360acdnat=1425654528_8adc41f2576ed853db84f0b37d63aba7 http://ac.els-cdn.com/S0014827X03001642/1-s2.0-S0014827X03001642-main.pdf?_tid=8710dca6-c412-11e4-ba2b-00000aab0f02acdnat=1425654638_fb397da0e9304b218456d2a2da0cc6bf http://ac.els-cdn.com/S0144861714012533/1-s2.0-S0144861714012533-main.pdf?_tid=ffa7bf86-c412-11e4-9b6f-00000aacb361acdnat=1425654840_9033413b545510662226d20eec11b255 http://www.drugs.com/mmx/melphalan.html http://cancerres.aacrjournals.org/content/23/8_Part_1/1315.full.pdf http://www.hindawi.com/journals/jna/2010/543531/ https://books.google.co.uk/books?id=Sd6ot9ul-bUCpg=PA1208lpg=PA1208dq=nitrogen+mustard+aziridine+ringsource=blots=TMPCHHeGPrsig=tArK9BCztSsPXxLXMj2ojRGFG2shl=ensa=Xei=FggDVaHxFMatU_6zgfABved=0CD8Q6AEwBg#v=onepageqf=false Bifunctional alkylating agents (e.g., nitrogen mustards (melphalan, chlorambucil, cyclophosphamide, and ifosfamide) and chloroethylnitrosoureas (BCNU and CCNU)) possess two reactive sites. These agents cross-link DNA with proteins or, alternatively, cross-link two DNA bases within the same DNA strand (intrastrand cross-links) or on opposite DNA strands (ICLs). ICLs, which block replication forks, are the most serious cytotoxic lesions produced by most bifunctional drugs. Accordingly, the extent of ICLs correlates well with the cytotoxicity of nitrogen mustard drugs

Role of Financial Institution in Economy

Role of Banks and Financial Institutions in Economy Money lending in one form or the other has evolved along with the history of the mankind. Even in the ancient times there are references to the moneylenders. Shakespeare also referred to ‘Shylocks’ who made unreasonable demands in case the loans were not repaid in time along with interest. Indian history is also replete with the instances referring to indigenous money lenders, Sahukars and Zamindars involved in the business of money lending by mortgaging the landed property of the borrowers.Towards the beginning of the twentieth century, with the onset of modern industry in the country, the need for government regulated banking system was felt. The British government began to pay attention towards the need for an organised banking sector in the country and Reserve Bank of India was set up to regulate the formal banking sector in the country. But the growth of modern banking remained slow mainly due to lack of surplus ca pital in the Indian economic system at that point of time. Modern banking institutions came up only in big cities and industrial centres.The rural areas, representing vast majority of Indian society, remained dependent on the indigenous money lenders for their credit needs. Independence of the country heralded a new era in the growth of modern banking. Many new commercial banks came up in various parts of the country. As the modern banking network grew, the government began to realise that the banking sector was catering only to the needs of the well-to-do and the capitalists. The interests of the poorer sections as well as those of the common man were being ignored. In 1969, Indian government took a historic decision to nationalise 14 biggest private commercial banks.A few more were nationalised after a couple of years. This resulted in transferring the ownership of these banks to the State and the Reserve Bank of India could then issue directions to these banks to fund the nationa l programmes, the rural sector, the plan priorities and the priority sector at differential rate of interest. This resulted in providing fillip the banking facilities to the rural areas, to the under-privileged and the downtrodden. It also resulted in financial inclusion of all categories of people in almost all the regions of the country.However, after almost two decades of bank nationalisation some new issues became contextual. The service standards of the public sector banks began to decline. Their profitability came down and the efficiency of the staff became suspect. Non-performing assets of these banks began to rise. The wheel of time had turned a full circle by early nineties and the government after the introduction of structural and economic reforms in the financial sector, allowed the setting up of new banks in the private sector. The new generation private banks have now established themselves in the system and have set new standards of service and efficiency.These banks have also given tough but healthy competition to the public sector banks. Modern Day Role Banking system and the Financial Institutions play very significant role in the economy. First and foremost is in the form of catering to the need of credit for all the sections of society. The modern economies in the world have developed primarily by making best use of the credit availability in their systems. An efficient banking system must cater to the needs of high end investors by making available high amounts of capital for big projects in the industrial, infrastructure and service sectors.At the same time, the medium and small ventures must also have credit available to them for new investment and expansion of the existing units. Rural sector in a country like India can grow only if cheaper credit is available to the farmers for their short and medium term needs. Credit availability for infrastructure sector is also extremely important. The success of any financial system can be fathome d by finding out the availability of reliable and adequate credit for infrastructure projects.Fortunately, during the past about one decade there has been increased participation of the private sector in infrastructure projects. The banks and the financial institutions also cater to another important need of the society i. e. mopping up small savings at reasonable rates with several options. The common man has the option to park his savings under a few alternatives, including the small savings schemes introduced by the government from time to time and in bank deposits in the form of savings accounts, recurring deposits and time deposits. Another option is to invest in the stocks or mutual funds.In addition to the above traditional role, the banks and the financial institutions also perform certain new-age functions which could not be thought of a couple of decades ago. The facility of internet banking enables a consumer to access and operate his bank account without actually visitin g the bank premises. The facility of ATMs and the credit/debit cards has revolutionised the choices available with the customers. The banks also serve as alternative gateways for making payments on account of income tax and online payment of various bills like the telephone, electricity and tax.The bank customers can also invest their funds in various stocks or mutual funds straight from their bank accounts. In the modern day economy, where people have no time to make these payments by standing in queue, the service provided by the banks is commendable. While the commercial banks cater to the banking needs of the people in the cities and towns, there is another category of banks that looks after the credit and banking needs of the people living in the rural areas, particularly the farmers. Regional Rural Banks (RRBs) have been sponsored by many commercial banks in several States.These banks, along with the cooperative banks, take care of the farmer-specific needs of credit and other banking facilities. Future Till a few years ago, the government largely patro-nized the small savings schemes in which not only the interest rates were higher, but the income tax rebates and incentives were also in plenty. The bank deposits, on the other hand, did not entail such benefits. As a result, the small savings were the first choice of the investors. But for the last few years the trend has been reversed. The small savings, the bank deposits and the mutual funds have een brought at par for the purpose of incentives under the income tax. Moreover, the interest rates in the small savings schemes are no longer higher than those offered by the banks. Banks today are free to determine their interest rates within the given limits prescribed by the RBI. It is now easier for the banks to open new branches. But the banking sector reforms are still not complete. A lot more is required to be done to revamp the public sector banks. Mergers and amalgamation is the next measure on the a genda of the government.The government is also preparing to disinvest some of its equity from the PSU banks. The option of allowing foreign direct investment beyond 50 per cent in the Indian banking sector has also been under consideration. Banks and financial intuitions have played major role in the economic development of the country and most of the credit- related schemes of the government to uplift the poorer and the under-privileged sections have been implemented through the banking sector. The role of the banks has been important, but it is going to be even more important in the future.

Morality and Power Essay

Thucydides’ written history of the Mytilenian Debate and the Melian Dialogue reflects the reality of a period where morality is dependent on the exercise of power and those who possess it. The main theme running through the course of these two debates is that those with the power to act as they wish inherently have the power to dictate morality. The arguments that decide the fate of the Mytilene are made not strictly on the basis of morality but on how their power allows them to exercise the moral course they choose. The Melian dialogue reveals how those in power can dictate morality in terms of self-interest. Both cases also demonstrate how morality is also a function of self-interest. The question of the relationship between power and morality also hinges on the definition of these two vague terms. Morality, in the broader sense of moral order, has been defined as â€Å"a set of rules which define what is right and wrong. † (Outka and Reeder, p. 5) Who decides what is right and wrong often depends, as with Thucydides’ history, on who has the power in a given situation. Power can broadly be defined, as the capacity to achieve what one wants. (Dickerson and Flanagan, p. 24) In the case of these two debates, the Athenians were the party who possessed the power. They had the coercive ability to decide the fates of both the Melians and the Mytilenians. This power was derived strictly from the military might their empire was able to build up. In both cases, power allowed them to dictate morality to the inferior parties. Thucydides’ history of the Mytilenian debate details the discussion of a council deciding on how to punish the citizens of Mytilene for a failed revolt. The two options on the table are to either slaughter all the inhabitants, as had been previously agreed upon, or to leave them without severe punishment. Cleon, the Athenian responsible of initially deciding to slaughter Mytilene, argued that it was necessary to take his brutal course of action for the safety of the empire. He stated succinctly that â€Å"leadership depends on superior strength and not on goodwill. † (Thucydides, p. 213) He believed that killing the Mytilenians was a question of safety for the empire; If you are going to give the same punishment to those who are forced to revolt by your enemies and those who do so of their own accord, can you not see that they will all revolt upon the slightest pretext, when success means freedom and failure brings no very dreadful consequences. (Thucydides, p. 216) In this statement, Cleon argues that Athens has a moral duty to put down this revolt in the harshest way. He makes it a moral argument because it is in the self-interest of Athens, and any state, to protect its citizens. It is their moral duty. The Mytilenians, in their own self-interest, would argue that it is immoral to slaughter a whole population. They are both right. Subsequently, the council decides not to slaughter the inhabitants of Mytilene. They are convinced to â€Å"look for a method by which, employing moderation in our punishments, we can in future secure for ourselves the full use of those cities which bring us important contributions. † (Thucydides, p. 221) They do this not the sake of the Mytilenians, but for one of pure self-interest. Morality, in this situation, is dictated by the party in power. The Melian Dialogue concerns the history of the island of Melos. Melis, a colony of Sparta, had refused to join the Athenian empire and side against Sparta; they instead chose neutrality. Athens had brought a force to the island to take Melos by force. Before the siege, the two sides met to discuss the surrender of the Melians. (Thucydides, p. 401) Athens does not argue the morality of what they intend to do, they say strongly that † the standard of justice depends on the equality of power to compel and that in fact the strong do what they have the power to do and the weak accept what they have to accept. † (Thucydides, p. 402) In this situation, power does not dictate morality; it completely voids it. The Melians ask repeatedly if the Athenians â€Å"would not agree to ? being friends instead of enemies. † The Athenians reply by saying that â€Å"if we were on friendly terms with you, our subjects would regard that as a sign of weakness. † (Thucydides, p. 402) The Melians question the Athenian’s morality by saying that this is not â€Å"fair play† since they have not posed any direct threat to the Empire. Athens responds by saying â€Å"that by conquering you we shall increase not only the size but the security of our empire? this is no fair fight? it is rather a question of saving your lives and not resisting those who are far too strong for you. † (Thucydides, p. 403) In the end, the Melians do not surrender and the Athenian army slaughters them. In Thucydides’ history, those in power decide morality. In both of the aforementioned cases, both sides have had morality on their side. The Mytilenians and Melians believed the moral precept of saving their own lives. The Athenians believed in the morality of preserving their empire. Neither side was right or wrong, neither side acted immorally. They both acted in their own self-interest. What decided the moral outcome was that Athenians had the power to impose their moral right on their powerless, but equally moral opponents. Works Cited Dickerson, Mark and Flanagan, Thomas â€Å"Government and Politics† Scarbourough, Ontario: ITP Nelson, 1998 Outka, Gene and Reeeder, John â€Å"Religion and Morality† New York: Anchor Books ,1973 Thucydides â€Å"History of the Peloponnesian War† Toronto: Penguin Books, 1972Ã'Ž

How to Write a Good Dissertation on Microbiology

How to Write a Good Dissertation on Microbiology This is our final   guide on microbiology that teaches you how you can write a perfect dissertation paper. We have included methodologies, as well as outlines and structures of a formal dissertation paper, which a professor seeks in your composition. Reading this guide, and following everything we have discussed will allow you to write an excellent dissertation on microbiology. But to make the most out of our guide, we recommend you to read all our guides thoroughly. Here is why: Reading our first guide, 10 facts for dissertation on microbiology, fills you with adequate information on microbiology that you can further use in your dissertation paper. Without credible facts, and resources (available in this guide), your dissertation paper wouldn’t weigh as it should and chances are, it would be rejected by your professor or just receive a lower mark. On the other hand, our second guide, 20 microbiology dissertation topics, reveals 20 relevant sub-topics on microbiology. This guide allows you to start composing your dissertation paper quickly. We recommend you to read this one as well. With that being said, let’s talk about how to write a good dissertation on Microbiology: Composing a Dissertation Paper A dissertation is one of the most challenging and rewarding tasks a student ever accomplishes in college/university. That’s because the dissertation requires a thorough research, planning, and understanding of the topic you’re writing on. Unlike other essays and assignments, dissertation allows you to choose your own topic. Normally, the university would give you six eight weeks (sometimes four weeks) to complete the paper, along with some specific guidelines to be followed. But generally speaking, here is how a dissertation is structured: Research Proposal or Introduction Literature Review and Methodologies Results and Discussion/Conclusion Here is how each section of the structure should be written: Research Proposal or Introduction This is one of the most important parts of your dissertation. If you want to impress your professor, you should write an informative introduction/research proposal. In this section, you’ll present how you’re going to explore and define the particular topic you have chosen. It will also contain some information as to why you chose that particular subject, for example, immunobiology and why you think there’s a need to write a paper on this topic. You will also discuss how you have gone through the whole dissertation – similar to giving a tour through your paper. We recommend you to put this part in the end of your dissertation. Literature Review and Methodologies Literature review and methodology are often combined. Writing a literature review is fairly easy. You explain the substantial facts, viewpoints and your understanding on the topic. In simple words, you’re actually giving an analysis of your dissertation to the reader. In methodologies section, youll explain why you’ve chosen quantitative or qualitative methods, or sometimes both. You will also describe the research methods you have chosen and used in your dissertation. Results and Discussions/ Conclusion Here, you will explain the process of the research and experiments you have run, and the results you obtained from your tests. In simple words, you will summarize the whole purpose of writing a dissertation paper on your chosen topic, and what you have obtained from it in the end. Final Thoughts That’s it. Following this short guideline will surely improve your understanding of writing a dissertation paper on microbiology. But to make it even more stellar, we recommend you to proofread and edit your content before submitting it to your professor. Happy writing!

Parental Control essays

Parental Control essays The Internet is probably the best invention in the last twenty years. The Internet has more information than you can find in about a million books. While many people used the Internet for informational things, today in the year 2002, kids are taking over. To this day kids all over the world are more knowledgeable than adults when it comes to using and finding information on the Internet. Numerous parents presume that the Internet is good for their children because of the many acquired facts one can find. Parents also believe that the Internet keeps their children out of the streets where they can easily get into trouble. What many parents do not realize is that the Internet is just as dangerous as the outside world. For one, the Internet does not restrict anything. Moreover, kids today use the Internet so they can communicate electronically with friends. This can be bad because there are a lot of crazy people out there and they wont hesitate to do something to whomever they meet online. Grunwald Associates, a marketing research and consulting firm, announced in June 2000 that Internet use by children ages 2 to 17 has tripled since 1997 (Bushong 12). The use of the Internet has gone up tremendously is because many kids do not have much to do after school. Countless parents actually view this as a good thing because they at least know where their kids are in the afternoon. What they are not aware of is that their children have unlimited access to a lot of corrupt information. For instance, your child might be a fan of the WB networks Charmed, a television show for teenagers about three sisters with magical powers. The teenager might be looking for sights on the show and decides to type the word Charmed on the search engine. Innocently, they could click on one of the sites. Instead of the site being about the show, they come to find out that it is about learning witchcraft or people tr...

Applied Law Essay Example | Topics and Well Written Essays - 250 words

Applied Law - Essay Example It is extravagant to allow the public to acquire entertainment materials in digital forms while compromising the right of writers, artists and musicians. It is challenging to attain the rights of both the public and that of writers and musicians in the debate on whether to allow fair use of copyright materials. To protecting the rights of writers and artists, production of copyrighted materials should be subject to constitutional protection. This includes constitutional protections as that of the copyright clause. The first amendment should apply in an effort to protect writers and artists’ rights. The law should protect encryption codes that are important in ensuring access to materials protected under the copyright act. It is a protection of the rights of writers and artists by disallowing fair use. Protection on the rights of the public is under constitutional provisions on the use of copyright materials. Allowing fair use does not, therefore, entail the protection of public rights. Instead, advocating for fair use of copyrighted materials is tantamount to a violation of the rights of artists. It is, therefore, impossible t o attain the rights of both the public and artists in the debate to allow fair use of copyrighted

World War I Essay Example | Topics and Well Written Essays - 2500 words - 1

World War I - Essay Example Since Germany and Austria wanted a quick attack on Serbia, so that other countries would not get involved, an ultimatum was sent. When the ultimatum was sent to Serbia in July 23, 1914, which demanded Serbia to abolish all 'anti-Austrian activities', and allow Austria to investigate the assassination of Francis Ferdinand. Serbia accepted to the ultimatum, but did not allow Austria to investigate the murder. This caused Austria to declare war on Serbia on July 28. When Austria attacked Serbia, as the German leaders had anticipated, Russia prepared to attack Austria. Germany warned Russia to stop the preparation, but because Russia did not listen, Germany attacked Russia on August 1. Two days later, Germany also declared war against France, which was Russia's ally. Germany planned to invade France through Belgium, but unfortunately, Belgium refused this. On August 3, Germany invaded Belgium. The British then became involved in the war, for they had promised Belgium could be neutral, and not get involved in wars.1 In addition, the British had to join in the war because if they did not, Germany would control the continent of Europe. In less than six weeks, the domino effect had caused Serbia, Russia, France, Belgium and Britain to fight against Germany and Austria-Hungary. The WW1 fi... The WW1 finally broke out in June1914 because of an accident in Bosnia. It was the Sarajevo incident, the immediate cause of WW1. It took place on June 28, 1914. On that day, the Archduke Francis Ferdinand, heir to the Austrian throne, and his wife were shot dead by a young Serbian student at Sarajevo, the Bosnian capital. Austria considered the murder of the heir to the throne an open Serbian attack.2 Austria would be left without an heir. Although she could not find any evidence that the Serbian government was connected with the assassination, Austria still declared war on Serbia. Within two month, the war became a world war. Finally, the war ended in 1918. The Central Power included Germany had lost. The First World War lasted from 1914 to 1918 and was called The Great War or the war to end all wars until World War II started. Some scholars believe that the First World War was simply the first phase of a 30-year-long war that entailed the period of 1914 to 1945. The outbreak of the clash is often ascribed to the European alliances. Germany-Austria-Italy formed an alliance against France-Russia; Britain and Serbia supported France and Russia. In fact, none of the alliances was initiated in the early outbreak, though Russian general mobilization and Germany's declaration of war against France were motivated by fear of the opposing alliance being brought into play. By 1882, Germany was allied with Austra-Hungary and Italy, in an alliance called the Triple Alliance. Then, in 1887, they signed the Reinsurance Treaty with Russia. Thus, Germany was allied with three major European nations and France was left isolated. In 1890, the German Kaiser set out to make Germany a major world power. He aimed to increase the number of Germany's overseas colonies.3 To do