Changing from Base 10 to Base 2 in Mathematics

Changing from Base 10 to Base 2 in Mathematics Assume we have a number in base 10 and need to discover how to speak to that number in, state, base 2. How would we do this? All things considered, there is a straightforward and simple strategy to follow. Let’s state I need to compose 59 in base 2. My initial step is to locate the biggest intensity of 2 that is under 59.So let’s experience the forces of 2: 1, 2, 4, 8, 16, 32, 64. Alright, 64 is bigger than 59 so we make one stride back and get 32. 32 is the biggest intensity of 2 that is as yet littler than 59. What number of â€Å"whole† (not halfway or partial) times can 32 go into 59? It can go in just once in light of the fact that 2 x 32 64 which is bigger than 59. Along these lines, we record a 1. 1 Presently, we take away 32 from 59: 59 †(1)(32) 27. Furthermore, we move to the following lower intensity of 2. For this situation, that would be 16. What number of full occasions would 16 be able to go into 27? Once. So we record another 1 and rehash the procedure. 1 1 27 †(1)(16) 11. The following most reduced intensity of 2 is 8.How many full occasions would 8 be able to go into 11?Once. So we record another 1. 111 11 11 †(1)(8) 3. The following most minimal intensity of 2 is 4.How many full occasions would 4 be able to go into 3?Zero.So, we record a 0. 1110 3 †(0)(4) 3. The following least intensity of 2 is 2.How many full occasions would 2 be able to go into 3?Once. In this way, we record a 1. 11101 3 †(1)(2) 1. Lastly, the following most reduced intensity of 2 is 1. What number of full occasions would 1 be able to go into 1?Once. In this way, we record a 1. 111011 1 †(1)(1) 0. What's more, presently we stop since our next most minimal intensity of 2 is a fraction.This implies we have completely composed 59 in base 2. Exercise Presently, have a go at changing over the accompanying base 10 numbers into the necessary base 16 into base 416 into base 230 in base 449 in base 230 in base 344 in base 3133 in base 5100 in base 833 in base 219 in base 2 Arrangements 1001000013211000110101122101314410000110011

Outline and explain the religious and secular argu Essay Example For Students

Blueprint and clarify the strict and mainstream argu Essay Mrments encompassing both avoidance and end of pregnancyContraception is the intentional counteraction of pregnancy utilizing a few strategies accessible today. Family arranging is the strategy that alludes to the creation choices about when and what number of kids to have, and picking approach to accomplish this. Catholics accept that sex ought to be procreative, unitive, informative and conscious. They accept that a human’s sexuality is a blessing from God and that it ought to be regarded, they accept that unnatural types of contraception energize ‘casual sex’ with numerous accomplices. ‘Casual sex’ is neither unitive nor informative. Rather than the utilization of unnatural types of contraception, for example, the condom or the utilization of Spermicidal or hormonal contraceptives, they recommend the act of Natural Family Planning. This framework is one whereby the couple controls from sex during the most rich time of a woman’s menstrual cycle. This period ranges from five days before ovulation to two days after ovulation. One method of deciding richness is the basal internal heat level strategy, where a lady takes her temperature simultaneously every morning before getting up. In a great deal of ladies, internal heat level ascents around one degree u pon the arrival of ovulation and remains raised for a few days. This sort of preventative strategy can just is utilized in a steady and progressing relationship, a relationship wherein sexuality is regarded and the relationship is unitive. Individuals regularly rule against this choice since it is just 81 percent compelling. Catholic couples that utilization Natural Family Planning should aside from and think about the kid that my outcome from that 19 percent, this isn't an issue perceived in the Catholic confidence, as sex to them must be procreative. Numerous individuals use contraception with the goal that a relationship can be evaded however this isn't procreative or unitive so again this contention for contraception is excused by the Catholic Church. Non-strict and strict gatherings both help contraception for various valid justifications one of the contentions they use for contraception is that in the USA, around 56 percent of ladies between 16 to 45 years of age practice anti -conception medication. At the point when contraception isn't utilized around 85/86 percent of explicitly dynamic guardians experience a pregnancy. Contraception plainly forestalls undesirable pregnancies, which if the lady has any clinical sicknesses could bring about death of the mother or of the kid or both. It is frequently referenced by individuals other than the catholic’ s that it is up to the particular people included and that they ought to follow their inner voice, this isn't dismissed by the catholic confidence however they contend that if an individual is left to follow their heart they should have an educated still, small voice. Premature birth is the end or consummation of pregnancy before the introduction of a youngster, coming about in, or joined by, the demise of the hatchling (unborn kid). A few premature births happen normally on the grounds that an embryo doesn't grow typically. Premature births are incited, in light of the fact that a pregnancy is undesirable or presents a hazard to a woman’s wellbeing. It was legitimized (fetus removal act) in 1968 in light of the fact that before then there were hundreds passings brought about by back road premature births each year. It was believed that it is smarter to legitimize premature births and make it a protecte d method than to permit additional ladies kick the bucket. Some common social orders contend for premature birth saying that it is a method of maintaining a strategic distance from hereditary deformities, for example, Downs Syndrome. In any case, the Church contends against this idiom that try not to have the option to direct another individuals critical regardless of what circumstance or imperfection, to murder the youngster since it isn't ‘perfect’ according to a â€Å"normal† individual is a ‘throwing away’ of Gods endowment of life to that individual. It says in Genesis 1:26 ‘Then God said â€Å"let us make man in our image.†Ã¢â‚¬â„¢ God didn't require us so we are accordingly a blessing; to slaughter a ‘imperfect child’ is a dismissal of that blessing. God cherishes that individual for what they are and doesn't see the blemishes that others may have. According to God all men/ladies are equivalent in Galatians 3:28 it sa ys: ‘There is neither Jew nor Greek there is neither bond nor free, there is neither male nor female for you are every one of the one in Christ. Another contention for premature birth is that the prematurely ended hatchling isn't an individual †mainstream contention. The congregation juxtaposes this contention and says that we can't make certain of the hour of ensoulment, when an embryo turns into an individual (person), it is smarter to take this point from the soonest time conceivable, this is the snapshot of origination. On the off chance that starting here it is an individual (living being) at that point it is just plain wrong to crush the life of that individual which is a blessing from God on the grounds that in the Ten Commandments it says ‘thou shalt no kill.’ We realize that individuals are a blessing from God on the grounds that in 1 Sam 1:20 it says: ‘in due time Hannah imagined and bore a child. She named him Samuel, for she stated, â€Å"I have solicited him from the Lord†Ã¢â‚¬â„¢ this is a fundamentalist view.At the snapshot of origination, when the male sperm and female ovum intertwine both half cells †23 chromosomes (qualities) in each breaker to make an exceptional individual (human), related yet not totally like it guardians, another individual is made and has in this manner all the privileges of a brought into the world person, hence among others the Catholic Church totally dislikes premature birth, with the exception of in the instances of disease of the belly or an ectopic pregnancy. For the situation if disease, after both chemotherapy and radiotherapy have been attempted and there is no decision premature birth is plausible. On account of an ectopic pregnancy †were the baby starts to create in the fallopian tube, medical procedure to expel the fallopian cylinder may start. For this situation you are acting to constrain insidious, the abhorrence of the demise of the infant is out weighed by t he life of the mother and hence the guideline of Double Effect becomes an integral factor, the passing of the youngster in both of the above cases is inescapable along these lines it is ideal to permit the mother to live. .u5b435b8f7cea7056b51efd9e83409030 , .u5b435b8f7cea7056b51efd9e83409030 .postImageUrl , .u5b435b8f7cea7056b51efd9e83409030 .focused content zone { min-stature: 80px; position: relative; } .u5b435b8f7cea7056b51efd9e83409030 , .u5b435b8f7cea7056b51efd9e83409030:hover , .u5b435b8f7cea7056b51efd9e83409030:visited , .u5b435b8f7cea7056b51efd9e83409030:active { border:0!important; } .u5b435b8f7cea7056b51efd9e83409030 .clearfix:after { content: ; show: table; clear: both; } .u5b435b8f7cea7056b51efd9e83409030 { show: square; progress: foundation shading 250ms; webkit-change: foundation shading 250ms; width: 100%; haziness: 1; progress: darkness 250ms; webkit-change: mistiness 250ms; foundation shading: #95A5A6; } .u5b435b8f7cea7056b51efd9e83409030:active , .u5b435b8f7cea7056b51efd9e83409030:hover { obscurity: 1; progress: murkiness 250ms; webkit-progress: haziness 250ms; foundation shading: #2C3E50; } .u5b435b8f7cea7056b51efd9e83409030 .focused content region { width: 100%; position: relative ; } .u5b435b8f7cea7056b51efd9e83409030 .ctaText { fringe base: 0 strong #fff; shading: #2980B9; text dimension: 16px; textual style weight: striking; edge: 0; cushioning: 0; content design: underline; } .u5b435b8f7cea7056b51efd9e83409030 .postTitle { shading: #FFFFFF; text dimension: 16px; textual style weight: 600; edge: 0; cushioning: 0; width: 100%; } .u5b435b8f7cea7056b51efd9e83409030 .ctaButton { foundation shading: #7F8C8D!important; shading: #2980B9; outskirt: none; outskirt sweep: 3px; box-shadow: none; text dimension: 14px; textual style weight: intense; line-tallness: 26px; moz-outskirt range: 3px; content adjust: focus; content adornment: none; content shadow: none; width: 80px; min-stature: 80px; foundation: url(https://artscolumbia.org/wp-content/modules/intelly-related-posts/resources/pictures/straightforward arrow.png)no-rehash; position: total; right: 0; top: 0; } .u5b435b8f7cea7056b51efd9e83409030:hover .ctaButton { foundation shading: #34495E!important; } .u5b435b8 f7cea7056b51efd9e83409030 .focused content { show: table; stature: 80px; cushioning left: 18px; top: 0; } .u5b435b8f7cea7056b51efd9e83409030-content { show: table-cell; edge: 0; cushioning: 0; cushioning right: 108px; position: relative; vertical-adjust: center; width: 100%; } .u5b435b8f7cea7056b51efd9e83409030:after { content: ; show: square; clear: both; } READ: Fall Of Rome EssayBibliography:My Own Work and Research

Dont Let Fake Debt Collectors Scam You Out of Money You Dont Owe

Dont Let Fake Debt Collectors Scam You Out of Money You Dont Owe Dont Let Fake Debt Collectors Scam You Out of Money You Dont Owe Dont Let Fake Debt Collectors Scam You Out of Money You Dont OweScammers love to pose as debt collectors and make threatening phone calls demanding payment for debts that never even existed. Dont let them fool you!Almost exactly one year ago, the Federal Trade Commission (FTC) busted a group of fake debt collectors that had been calling people and demanding payment on debts these people didnt owe. Posing as lawyers, members of this group would threaten lawsuits and jail-time if these “debts” weren’t paid back immediately.It would be great if we could tell you that those actions by the FTC put a stop to fake debt collectors scams once and for all, but we both know that isn’t true. Like the many-headed Hydra from Greek mythology, cutting down one debt collection scam only means that two others will rise to take its place.If you’ve ever applied for a personal loanâ€"especially if it was an online loanâ€"then there is a chance your information could be used against you by scamm ers posing as scary debt collectors. Here’s how the scam works, and what you can do in order to keep yourself safe.Records of your loan applications can end up in the wrong hands.  In ye olden days, anyone who wanted to get a loan had to stop by a bank in person. Even folks who wanted a payday loan had to visit their local storefront. But now, in an age where you can order pretty much anything under the sun with a tap of your smartphone, all it takes to apply for a loan is to visit a lender’s website.Here’s where things get tricky. Many websites that you visit to get a loan aren’t actually lenders at all. They’re not anything frighteningâ€"don’t worry. They’re just lead generators. Once you submit your information and hit apply, they send out your info to a bunch of different lenders so that they can process your application and offer you a loan.However, this process means that there are a bunch of lists of customer info floating around out there, lists that can be bou ght. Many times they’ll be bought by legit lenders, but sometimes they’ll be bought by scammers who want just enough info on a person to be able to trick them.Once one of these scammers gets their hands on a list, they start hitting the phones. Using the information from your application, they will call your phone and tell you that such-and-such loan was never paid back. They’ll inform you that they work for a debt collector and that it’s time to pay up.The funny thing about these scams is that many of the loans they are demanding payment for never even existed. (Okay, we lied. It’s not that funny.) All these scammers need is the information that you once applied for a loan in order to gin up a story where you are in deep, deep troubleâ€"even though, in reality, you’re totally fine.They will make big threats to scare people into paying.There are two reasons that these con artists call people over the phone. The first is that they want to leverage the fear and awkwardness they can create by yelling at people. Scammers will make huge, scary-sounding threats. They’ll tell their mark that they could end up in jail or get sued and taken to court if they don’t settle the debt right now.That first part is an outright lie. You can’t get sent to jail for failing to pay a debt collector. And using threats in order to extract payment is illegal. Debt collectors cannot threaten you (especially with jail time), they can’t swear at you, and they cannot threaten to ruin your reputation. Of course, these debt collectors aren’t really debt collectors, so they will do all of these things.The scammer will likely pose as an attorney. They threaten to take you to court and have your wages garnished if you don’t pay them now.  And while a creditor or debt collector can take you to court and get a court order to garnish your wages, they cannot threaten garnishment without the said court order, and they can’t threaten legal action if they don’t intend to follow through.But again, these scammers are not going to follow the rules set down for legitimate debt collectors. Identifying these illegal behaviors is a great way to nail them for what they are: criminals.The second reason that scammers like to call people over the phone is that its much harder to leave a paper trail. Letters or emails will contain information that can be easily traced back to them or help their mark verify that theyre a fake. As well lay out in the following section, getting info on your scammer is the best way to take them down.3 ways to sniff out a fake debt collector.Aside from taking note of their abusive and illegal behavior, here are three ways you can identify whether or not the debt collector on the other end of the phone is really who they say they are. These suggestions come courtesy of the Consumer Financial Protection Bureau (CFPB):Ask them to verify the debt in writing. You have a legal right to something called a “validation notice.” This is a written form that specifies the amount of the debt, the name of the creditor, and certain rights you hold under the Fair Debt Collection Practices Act. Tell the debt collector you refuse to speak with them until you receive such a notice in writing. Legit companies will send you one immediately. Scammers won’tAsk them for their company’s info. A real debt collector will have no trouble providing this info, while a scammer will do everything they can to avoid it. Ask them for their name, their bosss name, the name of their company, and their business address. Also, ask them for their phone number and their business license. If they give you this information, check them out! You can also call your state Attorney General’s office to see if any complaints have been filed against them.Call your original creditor. If this company is a debt collector, then that means that they bought your debt from someone else. If you can’t get them to tell you what lender sold them the debt, the n call that original lender to verify that this debt collector is real. And if you can’t get the debt collector to tell you any of this info, just hang up. They’re trying to scam you.Do not give them any of your personal info over the phone.This is the most important thing you can do when dealing with any debt collector, but especially with one you’re not sure is legitimate. Keep your wits about you and your sensitive info like your bank account, Social Security number, and credit cards away from them.Scammers want to put the screws to you so that youll cough up this information to make them go away. But giving them sensitive personal and financial info doesn’t just mean you’re paying them for a debt you never owed. It means giving them the tools they need to steal your identity, something that could plague your finances for years to come.In the end, keeping yourself safe from these fake debt collections scams is actually pretty easy. Just follow the advice laid out in thi s post and you’ll be fine. Or, if you want to go on the offensive, you can follow the example set by this guy, who got a call from a shady debt collector and proceeded to, well, just read the story and find out for yourself. It’s a trip.Dont let a scammer decimate your savings and leave you relying on no credit check loans, title loans, and cash advances just to get by. Even a safe, affordable bad credit loan pales in comparison to not needing any loans at all. To learn more about how you can keep your finances safe from scammers, check out these related posts and articles from OppLoans:Beware These Scams That Target SeniorsReverse Mortgages: How They Work and How to Shop For One SafelyHow to Avoid Scam Contractors and Fake Charities Post-Natural DisasterHave you ever been contacted by a fake debt collector? We want to hear from you! You can find us  on  Facebook  and  Twitter.

Essay about Coral Divers Resport - 999 Words

Coral Divers Resort Introduction Mr. Jonathan Greywell is contemplating a business decision in which there are four realistic options. He is the owner of Coral Divers Resort, located in the Bahamas on the island of New Providence. He caters to customers looking for a resort package that includes diving. This case discusses a decline in revenues for the three-year period of 2005-2007. His options include: selling the resort, partnering with another business, focusing on higher margin business, or improve his current business to be more competitive. Selling Coral Divers Resort The most significant reason to sell the business is the declining revenues. However, Greywell would need to find another means of income such as another†¦show more content†¦Another factor to consider in making this decision is whether Rascal’s is worth the 30% commission. The fees for families (i.e. more people per room, etc.) when compared to the operation expenses keep the profit margin the same with the added benefit of a unique identity in the market. Higher Margin Adventure Diving Adventure diving generates a higher margin and therefore it is a good idea for Greywell to consider adding it to the mix of dive offerings. However, it cannot be considered without weighing the risks involved. Coral Divers Resort has an excellent reputation and careful consideration should be given as to how to protect this intangible asset. Adventure dives would need specifically trained and experienced dive masters. Simply training existing employees might pose an additional risk since they aren’t too excited about diving with sharks and also lack experience that might be helpful for safety issues. Within an hour’s distance away, competitors are already a part of this market and bringing in $115 per adventure dive which is $50 above the regular dive experience. An additional $600 per week can be earned on two days per week with an average of 6 customers each of those days. Despite hiring or training costs and additional $31,200 in revenue can be generated, after the expenses for shark food and the special dive suit. Perhaps more adventure dive business is possible, yet this

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Fundamentals of a Research Paper Free Essays

In this paper, am going to discuss the different types of research, provide examples f what sort of study is appropriate for each type of research and I will also discuss how these types of research can be used in the human services field. Scientific Research Method What Is the scientific research method? I had to ask myself this question several times before I came to the conclusion of what Is actually Is. There are SIX steps In the scientific research method that will help you get to the bottom of your research with a proven conclusion versus a conclusion that is based solely on a hunch. We will write a custom essay sample on Fundamentals of a Research Paper or any similar topic only for you Order Now According to chapter 1 in our reading, scientific research means to embrace all branches of science; the applications of this approach vary from one research discipline to another. Researchers in disciplines as varied as psychology, biomedicine, business, education, communication, economics, sociology, anthropology, physics, biology, and chemistry all use some variation of this approach. (Orison, 2008, Para. 1) There are six steps to scientific research these include these steps Include (1) stating what the problem is. By discovering what the problem is then you can go to step (2). Gather information, it is very important to gather the appropriate information needed to (3) come to a hypothesis. After you come to a hypothesis then you will need to (4) test your theory. (5) After you are done testing your theory you will need to analyze your data that you have taken. It Is very important to follow these steps otherwise you may come to an Incomplete conclusion In the data you are researching. Quantitative and Qualitative Research Quantitative research is a type of educational research in which the researcher decides what to study; asks specific, narrow questions; collects quantifiable data from participants; analyzes these numbers using statistics; and conducts the inquiry in an unbiased, objective manner. Qualitative research is a type of educational research in which the researcher relies on the views of participants; asks broad, general questions; collects data consisting largely of words (or text) from participants; describes and analyzes these words for themes; and conducts the inquiry in a subjective, biased manner. Quantitative research began in the late 19th century and dominated educational inquiry for most of the 20th century (see De Lancashire, 1988, and Traverse, 1992, for an expanded discussion). It is remarkable how similar quantitative research is today with its beginnings during the late 19th and early 20th centuries. I en Minimal Ideas Tort quantitative research came Trot ten Pensacola silences, such as physics and chemistry. Just as atoms and molecules were subject to predictable laws and axioms, so also were patterns of children’s behaviors in schools. Following this line of logic, early quantitative researchers began identifying educational patterns by assessing or measuring individual abilities, collecting scores (or numbers) from individuals, and employing procedures of psychological experiments and large-scale surveys. In the history of the development of quantitative research, three historical trends are present: statistical procedures, test ND measurement practices, and research designs. Today, qualitative research presents an alternative to the traditional form of quantitative research. However, its historical use in education is more recent than that of quantitative research. The ideas for qualitative research developed in the late sass and early sass in fields other than education. For example, qualitative studies of the poor in Great Britain and Europe, anthropological reports about indigenous cultures, and the fieldwork of sociologists in inner-city Chicago and with immigrants all appear in social science search up through the sass and sass (Bogged ; Bikini, 1998). There are several different ways that both of these research types can be used in human services. The first can be used to track statistics for demographic purposes, this could be helpful if you are writing a grant or applying for some type of business loan. Qualitative research can be used when you are trying to see what kinds of human service needs are necessary in a particular region. Conclusion There are different ways to do research, these include the scientific ways meaning you follow the six steps to come to a conclusion and test your theory to make sure hat it works for you. How to cite Fundamentals of a Research Paper, Essays

Emergency Procedures For Hospitality Organisations †Free Samples

Question: Discuss about the Emergency Procedures For Hospitality Organisations. Answer: The Paris attack occurred on the 13th of November in the year 2015 and the act of terrorism shook France to the core. It occurred in the November 13th. The world almost stopped for France when the city of Paris was attacked as it was the heart of the France. The maximum amount of sufferers of the country was the tourists that stayed in the hotels of Paris. Almost 130 people lost their life on account of the Paris attack (Bbc.com, 2017). This incident brought great changes in the legislation of France. The French parliament has overwhelmingly approved the sweeping new surveillance powers in the wake of the terrorist attacks in Paris. The French president convened the Council of ministers on Saturday during the evening of 13 November. The first and foremost legislative change that occurred soon after the attack was that the state was declared under the emergency situation. The mobilization of police forces, the gendarmerie and soldiers continues to be deployed within three days. The bo rder controls were restored by the president (Iacobucci and Toope 2015). There were some legislative changes that occurred after the attack. This included the warrantless house searches are authorized night and day, unless the house is occupied by a lawyer or a Member of Parliament. This authority was granted by the Home Affairs minister or the Perfect of a region. The law included that the prosecutors will be notified without further delay (Henderson et al. 2010). Soon after the attack the warrantless searches of the electronic devices were authorized. It was designed so that the data can be accessed and copied by the enforcement of the law. The legislative change was brought in the decision of the government who had the right to dissolve groups or associations that actively participates in the execution of the acts that represents a serious infringement to the public order or the activities of whom facilitate or incite the execution of such acts (Ortmeier 2017). The next change that was brought was the law was reinforced where the step was taken to allow the concerned authorities to block the websites that promoted the act of terrorism, without the intervention of a judge. There was an enforcement of anti-terrorism law. The biggest change was brought when the French President announced the proposal to modify the French constitution (Paraskevas 2013). However the incident abused the fundamental rights and there was lot of impacts on the Muslims in France. They are at a high risk of stigmatization and having their social links broken down. The changes claimed the nation to be much more triumph democracy (Nytimes.com, 2017). The changes brought in the democracy made the situations for the tourists much better and they were formed with the aim of improving the condition of the tourists as well as the inhabitants better. The changes were implemented from the January attack itself. The legislative changes in Paris were remarkable and they had a great impact in the running of the government smoothly (Groenenboom and Jones 2003). The aim of the formation of the acts was to bring the nation out of the threat of the future terrorists attacks (Wilks, Stephen and Moore 2013). Annotated bibliography 'Hotel safety and security systems: bridging the gap between managers and guests', International Journal of Hospitality Management, March, no. 32, pp. 202216 Mest, CE (2015) The following journal article includes the matter of safety and security of the guests of any hotel. The safety and security are always considered to be the most important factors for any hotel. The owners of the hotel usually follow the local regulations while designing the safety and security of the hotel. The article includes the fact that the gap between the hotel safety and security`s managers` and hotel guests` perceptions of the relative importance of safety and security facilities. It includes two sets of questionnaires that have been designed for the managers and the guests. The questionnaires are about the attributes that were used to gauge the respondent`s perceptions of different hotel safety and security system installations. The findings revealed that the guests perceive the well-equipped fire prevention systems in accordance with the local regulations. It was referred as an emergency plan. On the contrary the managers of the hotel perceive the close-circuit television systems for the public areas of the hotel. The final results included a fine matching between the two thoughts. However the end of the article concluded with the fact that the managers must understand the expectations of the guests. The gap addition includes the study that discusses the importance of the staff security and security training. It also includes the acceptance of the high-tech safety and security systems and the necessity of female guest floors and provides a huge number of insights to help the hotel managers to better understand the need of the customers which in return allows the mangers to employ measures that are likely to keep the satisfaction of the customers (Woo 2015). According to Chan and Lam (2013), it is the duty of the hotel and hospitality sector to ensure that the people visiting the places are safe from any type of mistreatment. Customers visit these places in order to relax, enjoy and spend quality time trying to understand the place. However, in the modern days, it is seen that the threat of terrorist attacks has dampened the spirits of the people in visiting different places. Terrorist attacks have become a sudden trend in most countries particularly due to the cold war that exists between certain countries over political reasons. Hence, common people find it difficult to lead a healthy life without any fear of terrorist activities. The advent of the Paris attacks in November 2015 has resulted in the rise of such a fear among the people. As such many hotels and restaurants have increased the security level in order to protect the safeguard of the customers. Understanding the source of the attacks is one of the major points that need to be followed. Terrorists may attack from different sources that are unpredictable to the normal people. However, it is not always possible for every person to analyse and improve security in every place. Hence, the basic protocols need to be followed in order to mitigate the threat of the terrorists. As stated by Paraskevas (2013) the Paris attack had a huge negative impact on the hotels of not only in France but also around the world. Following the attack, hotels around Paris had received about 300 cancellations. The effect of the attack lasted for over a year during which many people and sportsmen had refused to travel to Paris due to security concerns. This was a big blow for France as the economic condition of the country also depleted. The hospitality sectors ran at a loss due to lack of customers. It has been seen that some hotels managed to tighten security in order to ensure that customers find it safe to visit the places. A reputed hotel in London, Troxy, increased the number of security by increasing bag searches to feel the guests as safe. Discussions were made with clients and promoters in order to increase the security by arranging hidden cameras within the premises of the hotels. The optimism factor is that despite the international event, UK did not get affected by lack of tourism. Major tournaments or events did not get cancelled due to the effects of the Paris attack. A multi-agency approach can be considered that works with security team as well as the police in safeguarding the interests of the public. However, it is to be kept in mind that due to the excess security concerns, the ethical consent of the people is not compromised. Wilks, Stephen and Moore (2013) were of the opinion that searching people without proper reason can be considered as a breach of ethical condition. Apart from this stereotyping people on the basis of race, colour and ethnic background are also considered non-ethical behaviour. It is not a hidden fact that a certain ethnic group is considered as the creators of any terrorist activity in every part of the world (Enz and Taylor 2002). Hence, it is to be noted that such stereotype may bring about problems in the hotels while attracting customers. Reports have suggested that following the attack organisations in France have led to the sacking of Muslim workers for maintaining the tradition of the religion. This is a breach of ethical code at a workplace as under no such circumstance employees can be laid off. The fact that such ethnic discrimination has not occurred in the hospitality sector with the customers have been a positive factor among the terror of terrorism (Ortmeier 2017). Hence, it can be concluded that international events such as Paris attack by terrorists cause a great deal of imbalance in the daily lives of people. New laws and legislation related to the travelling from one country to another are formed along with the revision of political connection. Business and economic factors get affected due to such events as people fear about a victim to the affairs. Hence, increasing the security keeping in mind the ethical culture of a country or organisation need to be undertaken in order to ensure such activities can be mitigated in the future. References Bbc.com (2017).Paris attacks: Who were the victims?. [online] BBC News. Available at: https://www.bbc.com/news/world-europe-34821813 [Accessed 27 Nov. 2017]. Berezina, K., Cobanoglu, C., Miller, B.L. and Kwansa, F.A., 2012. The impact of information security breach on hotel guest perception of service quality, satisfaction, revisit intentions and word-of-mouth.International journal of contemporary hospitality management,24(7), pp.991-1010. Chan, E.S. and Lam, D., 2013. Hotel safety and security systems: Bridging the gap between managers and guests.International Journal of Hospitality Management,32, pp.202-216. Didier, B. and Guild, E., 2015.The EU Counter-Terrorism Policy Responses to the Attacks in Paris. Towards an EU Security and Liberty Agenda. Brussel: CEPS. Enz, C.A. and Taylor, M.S., 2002. The safety and security of US hotels a post-September-11 report.The Cornell Hotel and Restaurant Administration Quarterly,43(5), pp.119-136. Gravili, S. and Rosato, P., 2017. Italys Image as a Tourism Destination in the Chinese Leisure Traveler Market.International Journal ofMarketing Studies,9(5), p.28. Groenenboom, K. and Jones, P., 2003. Issues of security in hotels.International Journal of Contemporary Hospitality Management,15(1), pp.14-19. Hassanain, M.A., 2009. Approaches to qualitative fire safety risk assessment in hotel facilities.Structural Survey,27(4), pp.287-300.Marketing Henderson, J., Shufen, C., Huifen, L. and Xiang, L.L., 2010. Tourism and terrorism: A hotel industry perspective.Journal of Tourism, Hospitality Culinary Arts,2(1), pp.33-46. Iacobucci, E.M. and Toope, S.J. eds., 2015.After the Paris Attacks: Responses in Canada, Europe, and Around the Globe. University of Toronto Press. Nytimes.com. (2017).Attacks in Paris. [online] Available at: https://www.nytimes.com/news-event/attacks-in-paris [Accessed 27 Nov. 2017]. Ortmeier, P.J., 2017.Introduction to Security. Pearson. Paraskevas, A 2013 Aligning strategy to threat: a baseline anti?terrorism strategy for hotels, International Journal of Contemporary Hospitality Management, vol. 25, no. 1, pp. 140162 Wilks, J., Stephen, J. and Moore, F. eds., 2013.Managing tourist health and safety in the new millennium. Routledge. Woo, G., 2015. Understanding the Principles of Terrorism Risk Modeling from Charlie Hebdo Attack in Paris.Defence Against Terrorism Review,7(1).

Process Analysis and Problem Solving

Introduction The level of competition in different industries in which organizations operate today is high and calls for increased competitiveness. In order to improve the competitiveness, firms could engage in different firm activities that may include process improvement.Advertising We will write a custom research paper sample on Process Analysis and Problem Solving specifically for you for only $16.05 $11/page Learn More This may call for analysis of the problem and seeking different ways of solving the issues. In order to improve business processes, an organization needs to have the necessary knowledge and expertise. The business process could be attained through establishment of change such as business process reengineering. In spite of the good intentions of the changes, there is always resistance to change that could lead to project failure as examined in this paper. In addition, this paper examines reengineering as an example of process improveme nt in organizations. History of Process Improvement Change is a constant element in organizations given the dynamic business environment that firms operate in. Organizations operate in many business environments that are characterised by free entry and exit, increasing competition and technological advancement. In order for organizations to maintain their competitiveness, they need to embrace change and improve their manufacturing processes, service delivery and operations. Process improvement has occurred in firms over many years. Over many years, quality improvement in firms was done using regular inspection and changed over time to total quality management and the modern six sigma approach. Process improvement concept was first used by Harrington James in 1991 when he published in his book on process improvement. The method involves redesigning and reengineering business process in order to improve quality of an organization’s output while gaining a competitive edge at the same time.Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Since its introduction, process improvement has been able to be applied in many firms. The application of information technology in the process is a vital ingredient that will revolutionalize the future of process improvement in firms. Process Improvement in Firms The improvement of business processes in an organization has not been smooth for most firms. As the management of an organization introduces change in the company, there is always resistance to change with most employees opting to remain with the current processes of the firm. Reengineering According to Hammer Champy (2000, p. 2), process improvement in organization requires reengineering, which is defined as the ability of an organization to disregards all its assumptions and traditional way of doing business and instead developing and adopting a new process ce ntred business organization. The adopted new process should help an organization improve its performance. In order to achieve the required process reengineering for an organization, an organization needs to adopt a fresh perspective and approach. In order to acquire change through process reengineering, it is necessary that an organization rethink and establish radical redesigning of its processes in order to generate the required dramatic improvements. The process could be well illustrated in the figure below. As indicated in the above diagram, Hammer Champy (2000, p. 3) notes that reengineering requires starting over for an organization. In order for an organization to succeed in the modern environment, there is need for its processes to be fast, of high quality, flexible and of low cost.Advertising We will write a custom research paper sample on Process Analysis and Problem Solving specifically for you for only $16.05 $11/page Learn More The initia l phases of organizational change began long time ago with Adam Smith who proposed labour specialization, followed by establishment of infrastructure, the assembly line and hierarchical structure of the firm. In spite of the importance of these principles, their application in the modern business environment could result in delays, rigidity and high overhead costs in the production process. The first step of reengineering begins with the focus on the fundamentals of the company. The fundamentals of an organization relate to the main activities of the firm, why they are done the way they are and the tacit rules and assumptions of present activities. According to Hammer Champy (2000, p. 4), reengineering concentrates on what ought to be or should be done and ignores what is done. The radical redesign phase is concerned with the reinvention of the organization. This does not involve making of superficial changes or marginal enhancements to the firm but changes and designs that enhance new features of the organization. The potential dramatic result is the phase that the firm realizes the outcome of reengineering. According to Piderit (2000), reengineering leads to quantum leaps in the performance of an organization rather than incremental improvements. Business process orientation involves evolving of the firm around its business processes. The processes undertake inputs in order to generate valuable outputs to the customer. In order for a business process to work, it must produce added value rather than internal activity.Advertising Looking for research paper on business economics? Let's see if we can help you! Get your first paper with 15% OFF Learn More Various organizations could undertake the reengineering process. According to Revilak et al. (2007, p. 56), companies that operate in a competitive industry could undertake reengineering to increase their competitive advantage. Other sets of companies are those whose management could realize approaching issues along their paths of operation. The third sets of organizations are those that have ambitious management teams that perceive reengineering as a means of achieving market dominance and leadership. Process improvement of an organization through reengineering is characterised by various features. To begin with, the processes that an organization uses to perform its operations are simplified with the description of jobs being expanded to become multidimensional. Introduction of change in an organization increases employee autonomy and empowerment with power distance in the organization being reduced. Employees work as teams with group work and cooperation being enhanced. As the ma nagement of the organization adopts a flatter arrangement from a hierarchical structure, professionals within the firm become the key personnel to steer change. Employees are motivated to work for the firm and the measurement for performance of employees moves from activities to outcome of each employee. The managers no longer act as supervisors but coaches that help employees attain their maximum potential. Lastly, the organization and employees do not focus on pleasing the management but the end user of products and services, the customer (Hammer Champy 2000, p. 8). Change in organizations can be in different forms. Incremental or first order changes are minor changes that alter small aspects of the firm while leaving the general business environment the same. Transformational or strategic changes in organizations aim at changing the entire business framework of a firm. Change Management Process In order to apply the required change, an organization needs to identify the problem it is facing in order to find and develop the best solution to the problems. According to Brown Kusiak (2007), lack of proper diagnosis of the problem could lead to implementation of the wrong process in the organization. The outcome could worsen performance rather than improve the performance of the organization. The problem identification process involves various steps as outlined below. Problem Identification Organizations face many issues some of which are complex while others are simple. The identification of problems of the firm needs to be followed by prioritizing the issues so that the company can make decision on which issues to be solved first. Symptoms: the establishing of the issues affecting the organization needs to be followed by diagnosing the features or symptoms of the problem. The symptoms of the problems of the firm should be distinguished from the causes of the problem. According to Brown Kusiak (2007), business analysts usually hear many issues affecting the firm and they give many solutions. It is important that the firm does not ignore any solution given. However, the solution provided should be argued out with the management of an organization in order to establish its effectiveness (Boeker 1997, p. 155). Alternatives: after serious analysis of a given situation in an organization and hearing possible solutions from a business analyst, it is important that the organization develops alternatives for its problems. The approaches that could solve the problem of an organization could come with different consequences and costs that make it necessary for the management to discuss each alternative exclusively. After discussion of each alternative, it is important that the management makes a decision regarding the best solution to fix its issues. The decision should be based on the best approach that solves the problem affecting the firm while leaving it with the least negative effects. The decision made should be followed by implementation and follow up of the effectiveness of the approach. According to Brown Kusiak (2007), follow up is important for organization to ensure that the approach follows the set guidelines and that it has no side effects. In the process of solving an issue affecting an organization and effecting change in the firm, firms do use various methods. Some approaches include cause effect approach and business process reengineering. Unsuccessful Process Improvement Not all initiatives of change in firms end up being successful. Some processes end up failing. According to Pardo del Val Martà ­nez (n.d. p, 3), the failure of change management process for firms is due to the resistance to change within the organization. He further notes that resistance to change in the firm introduces unanticipated delays and many costs in the process of change that the management must now consider in the entire process. In spite of the resistance to change as a cause of failure to change, it has been hailed as a source of important information that could help an organization transform its business framework. The sources of resistance to change are many and while some show up during early stages of planning, others show up in the later stages of implementing the planned changes. As noted by Boeker (1997, p. 153), early sources of resistance could be due to distorted perception of change and misinterpretation of the change to be introduced. The organization could also fail to look ahead in future. Other causes could be denial to introduced changes, perpetuation of ideas and making of implicit assumptions. Ford, Ford D’amelo (2008, p. 5) note that communication barriers in addition to organizational silence could also casus misunderstanding within an organization thereby leading to resistance to change. There is another source of resistance to change. This is noted by some researchers as lack of motivation for change within the firm especially for employees of the organization. The low motivation could be due to low costs, cannibalization costs, cross subsidy comforts and past failures that hinder progress. Lorenzo (2000) argues that resistance to change could also be caused by different interests between employees and the management of an organization. For instance, employees could be for proposed changes while the management could be against change. Pardo del Val Martà ­nez (n.d. p, 367) posits that the third set of resistance to change causes inadequate creative responses. Lack of creativity in an organization could be caused by complexity of the business environment and fast changes that do not allow for environmental scan, reactive mindset that could result to resignation and inadequate strategic vision for the firm. The implementation phase of change is a vital stage that requires total concentration in an organization. However, there is resistance to change during implementation. The resistance could also be caused by various sources such as a poor imple mentation climate in the organization that is brought about by different organizational values and culture. Others are departmental politics and incommensurable beliefs or disagreements. The last set of causes to resistance to change includes inaction of leadership in firm, routines that are embedded in the firm and collective action problems in the organization. Successful Reengineering Process: Ford Motor Corporation Ford Motor Corporation applied the process analysis and problem solving in the 1980s by examining its employee accounts of about 500 employees. After a careful examination of the accounts payables, it was revealed that the company took much of the time in the department to track down discrepancies between orders that were purchased, shipping receipts and invoices. The realization of the problem led to a rethink of possible solutions and reengineering was the only viable solution. The company took various steps as explained below. The management began by establishing an online database mainly for the purchase orders whereby all orders issued by buyers were recorded in the database. Goods were received at the dock while there was an individual to check in the database. The match of the shipment and what is in the database led to the reception of the goods and vice versa. This eliminated possibilities of any discrepancies between orders that were made and what is received. Once the shipment is received, the database is updated immediately to reflect the change. In addition, a check was generated automatically and issued to the vendor in time. The process improvement applied by Ford Motor Corporation was a success. This is because the head count people in the purchasing department reduced drastically from 500 to 125 employees with efficiency in time management being improved dramatically. According to Piderit (2000, p. 785), the reengineering process as applied at Ford Motor Corporation is a lesson to be emulated by many firms wishing to reenginee r their processes. The changes that the company implemented could not have been achieved without the aid of the modern information technology. The process reengineering reflects old processes that have undergone new wrinkles. Another lesson learnt is that reengineering depends on a large scale on information technology. Planning the reengineering process in advance cannot work since what is experienced in the course of the process changes the reengineering plan. Innovation for Organizational Growth Knowledge is an important aspect in every organization. An organization is made of human resources that end up being of great importance since they are involved in the productivity of the products of the organization. The human resources could either be skilled, semi skilled or non-skilled. Skilled employees comprise of employees that and endowed with specific knowledge in a given field or sector in the firm such as management, information technology and manufacturing among many others. S emi skilled employees do posses little knowledge in specific fields. However, they extent of know how is limited. Lastly, non skilled employees do not posses any form of knowledge or expertise in any field in the organization. Most of non skilled employees are usually employed by firms as casuals or non-permanent staff of the firm. Skilled employees are important in an organization. It is important that an organization derives the best ways to manage its knowledgeable employees in order to motivate them and improve their performance and the performance of the organization. Knowledge is important for an organization because it helps an organization undertake research and development that is highly needed for innovation to take place. According to Hansen Birkinshaw (2007, p. 122), knowledge management should be customized for a given set of tasks within an organization. Innovation and value added in the output of a firm is as a result of application of knowledge in order to improve, change or develop a specific task and activities (McDermott, 1999). Therefore, innovation could be termed as the primary purpose of knowledge in an organization. In spite of its importance, innovation could be a complex idea that involves uncertainty and political activities. It might involve people with different experiences and teamwork or group work that is extended over long periods of time. In addition, it requires combination of different knowledge endowments within an organization in order to produce expected results in the form of new products or services produced by a firm. As noted by Hansen Birkinshaw (2007, p. 125), innovation does not only occur through research and development, but also through mainstream work activities within an organization. Innovation is characterised by invention, diffusion and implementation. Therefore, it more than just coming up with a good idea, but is more of putting the ideas into practical use within the organization. The creation of new k nowledge and ideas is an important aspect of innovation. However, they must be accompanied by bringing the ideas and knowledge into widespread use and applying them to solve issues affecting the organization. There is also product and process innovation that is vital for the success of an organization. Product innovation involves the application of new knowledge to the development of tangible products of an organization. On the contrary, process innovation involves the application of new knowledge and ideas to the establishment of new processes within the firm. All these are innovations that utilize knowledge at different levels (Nemeth 1997, p. 63). Based on the above description of innovation, knowledge and knowledge management should be linked to innovation. The innovation process involves different steps that range from formation of an agenda through establishment of a routine to the manufacture of a new product or process. In every step of innovation, there is an emphasis of di fferent aspects of knowledge and management of knowledge. Therefore, it can be concluded that knowledge cannot be separated from innovation as it necessitates the innovative ability of the firm. The firm should always struggle to motivate and maintain its knowledgeable employees in order to maintain its innovative ability and competitiveness in the market. Conclusion Problems analysis and problems solving in an organization is an important aspect of every organization. The modern business environment is dynamic and full of many challenges that organizations needs to develop different mechanisms of solving their issues. The process of solving a problem involves first identifying the issue affecting the corporation and determining possible ways of solving the issues. Out of the many alternatives, the management could choose one. Process improvement and reengineering is one of the many methods of solving issues affecting the firm. The reengineering process is vital since it helps an or ganization develop new processes and frameworks of the firm. One of the successful reengineering was conducted by Ford Motors in the 1980s in which it introduced new process of recording purchases thereby ending up cutting down its costs dramatically. Reengineering process could be accompanied by knowledge and innovation. List of References Boeker, W 1997, ‘Strategic change: The influence of managerial characteristics and organizational growth’, Academy of Management Journal, vol. 40, no. 1, pp. 152-170. Brown D Kusiak, J 2007, ‘Problem Analysis Techniques’, IRM Training white paper, IRM Training Pty Ltd. Ford, J, Ford, L D’amelo, A 2008, ‘Resistance to Change: The rest of the Story’, Academy of Management, vol. 33, no. 2, pp. 362-377. Hammer, M Champy J 2000, ‘Reengineering the Corporation: A manifesto for business revolution’, https://summaries.com/. Hansen, A Birkinshaw, J 2007, ‘The innovation value chainâ€⠄¢, Harvard Business Review, June 2007, pp. 121-130. Lorenzo, J 2000, ‘Barreras en los procesos de cambio en las organizaciones: studio de un caso’, Paper presented at the X Congreso Nacional de ACEDE, Oviedo (Spain). McDermott, R 1999, ‘Why information technology inspired but cannot deliver knowledge management’, California Management Review, vol. 41, pp. 103-117. Nemeth, C 1997, ‘Managing innovation: When less is more’, California Management Review, vol. 40, no. 1, pp. 59-74. Pardo del Val, M Martà ­nez, C n.d., ‘Resistance to change: a literature review and empirical Study’, Universitat de Valà ¨ncia, Spain. Piderit, S 2000, ‘Rethinking resistance and recognizing ambivalence: a multidimensional view of attitudes toward an organizational change’, Academy of Management Review, vol. 25 no. 4, pp. 783-794. Revilak, A et al. 2007, Knowledge management and innovation: an analysis of knowledge factors controlled by gove rnments and their impact on patent creation, George Washington University, Washington. This research paper on Process Analysis and Problem Solving was written and submitted by user Nora Ewing to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Free Essays on Sister Carrie

Theodore Dreiser’s Sister Carrie is a simple tale of a young, pretty eighteen year old girl Caroline Meeber also know as Carrie. When Carrie got on the train from Columbia City to Chicago she had only few cheap items in her trunk and her sister’s address on a piece of paper. Being only eighteen she was still "full of the illusions of ignorance and youth"(Dreiser, 7). She was both afraid of the things to come and exited by the countless possibilities offered by one of the largest cities of the late 19th century – Chicago. As soon as Carrie arrives in Chicago various obstacles face her. She has no experience at working outside home, which makes finding any work very difficult. She does not like the simple, and in her view, boring way of life her sister and brother in law live. Being this young and curious woman she yearns for more than what is around her. She has no education, no wealth to fall on and as we read the novel we also discover she has no morals. Even th ough at some point Dreiser claims that Carrie is "the victim of the city’s hypnotic influence"(Dreiser, 79) it becomes clear that in fact she is not a helpless victim by any means – she just simply goes along with anything and anyone who comes along. Tired and disappointed with her early days at a low paying hard work Carrie chooses to leave her sister – the only real family she has in the city – and goes off with a Drouet, a man she just recently met on the train. Carrie knew nothing about Drouet except that he seemed to like her and appeared to have more money than she could ever got her hands on. When she goes off with him there is no conflict within her, no regrets, no second thoughts. As soon as an opportunity to leave her boring life arrived Carrie took it and never looked back. All she cared about was the fact that now she no longer needed to work long hours for little pay. By becoming Drouet’s kept woman she no longer had to worry about get ting comfortabl... Free Essays on Sister Carrie Free Essays on Sister Carrie Theodore Dreiser’s Sister Carrie is a simple tale of a young, pretty eighteen year old girl Caroline Meeber also know as Carrie. When Carrie got on the train from Columbia City to Chicago she had only few cheap items in her trunk and her sister’s address on a piece of paper. Being only eighteen she was still "full of the illusions of ignorance and youth"(Dreiser, 7). She was both afraid of the things to come and exited by the countless possibilities offered by one of the largest cities of the late 19th century – Chicago. As soon as Carrie arrives in Chicago various obstacles face her. She has no experience at working outside home, which makes finding any work very difficult. She does not like the simple, and in her view, boring way of life her sister and brother in law live. Being this young and curious woman she yearns for more than what is around her. She has no education, no wealth to fall on and as we read the novel we also discover she has no morals. Even th ough at some point Dreiser claims that Carrie is "the victim of the city’s hypnotic influence"(Dreiser, 79) it becomes clear that in fact she is not a helpless victim by any means – she just simply goes along with anything and anyone who comes along. Tired and disappointed with her early days at a low paying hard work Carrie chooses to leave her sister – the only real family she has in the city – and goes off with a Drouet, a man she just recently met on the train. Carrie knew nothing about Drouet except that he seemed to like her and appeared to have more money than she could ever got her hands on. When she goes off with him there is no conflict within her, no regrets, no second thoughts. As soon as an opportunity to leave her boring life arrived Carrie took it and never looked back. All she cared about was the fact that now she no longer needed to work long hours for little pay. By becoming Drouet’s kept woman she no longer had to worry about get ting comfortabl...

Critically compare and contrast the methods and aims of Husserls epoch Essay

Critically compare and contrast the methods and aims of Husserls epoch with Descartes method of doubt - Essay Example Anything that surpasses this method is considered as certain by Descartes. For him, the universe fails to survive this method at this juncture. Rather, the only thing that seems to survive according to Descartes is a pure individuality of his cogitations. It is mainly for this that he has perceived as a form of unconditionally unquestionable survival (Taylor, 2009). Descartes perceives this as indubitable since in phrases such as â€Å"I think† or â€Å"I doubt† there exists a being that performs the act of thinking or doubting. In this regard, it would be contradictory for one to doubt of their existence since one must first exists in order to doubt. It is through this ego, as well as its guiding tenets that an objective universe can be deduced. In contrast, Husserl queries whether Descartes’ postulations are worth an investigation because they may not augur well with the current time. Indeed, Husserl acknowledges that those sciences that ought to be grounded in absolute certainty by Descartes have accorded little attention to them. It is notable that in the recent times, the sciences have become faced with several obscurities of their very foundation. By regressing back to concepts of pure ego, Descartes had developed a new form of philosophy that tends to strive towards a situation where true self may be demonstrated in a genuine science. According to Husserl, the failure by Descartes to unify philosophy as a science can be discerned in the modern-day philosophies. Rather than a unitary philosophy, there is a philosophical literature that has superseded all boundaries without coherence. One notable difference in Husserl’s epoch is that as a philosophizing ego, he does not regard the world or other objects as existing. Instead, he only accepts them as mere phenomena. Because these objects are not apodictic, he resorts to parenthesizing of putting them aside in order to perceive what can be left.

Answer quesiton Essay Example | Topics and Well Written Essays - 750 words

Answer quesiton - Essay Example By providing a large number of provincial and local executive offices, the mestizos stamped their mark of authority and control over the bicameral form of government in nearly all aspects of the sociological and political history of the Philippines. Further, they consolidated their rights and power by giving administrative rights and powers in the hands of their blood relatives and friends. Their brothers, sisters and other close members were given senior positions in the power blocs, and sons and nephews were vested with junior authority levels. The idea was to ensure total domination of the country in the hands of the mestizos. Thus they avoided democratic forms of sharing power with the elected representatives of the people. The origin of political dynasty rule was enunciated by the earlier Aquinos and Cojuangcos and has since, through the process of descent, passed onto the hands of the present ruler, Corazon Aquino. The absence of democratic process and the rule of dynasties has been one aspect by which the Filipino political scenario differs significantly from that of other South East Asian nations. Yet another aspect is that, unlike other SE Asian nations, which boast of massive bureaucratic style of governing, in Philippines the mestizos are under the administrative control of the Americans, to whom they have pledged support, in return for a bargain to remain in power. There is a minimum number of positions for civil servants and the entire power sharing lies in the hands of the mestizos. There were massive conversions into Christianity and today, nearly 90% of the population is of Christian faith. These conversions were carried out, not through use of the medium of the Spanish language, but by use of a host of other languages. Although Philippines was ruled by the Spaniards for a considerable length of time, Spanish has not become the common language of the local people of the island

Cationic Antimicrobial Peptides in Humans

Cationic Antimicrobial Peptides in Humans Antimicrobial peptides Introduction Cationic antimicrobial peptides (AMPs) are gene-encoded peptides of the host defence system made up of 12-50 amino acids, with at least 2 positive charges conferred by lysine and arginine residues and about 50% hydrophobic amino acids (Hancock and Scott 2000). They are produced from gene transcription and ribosomal translation and often, further proteolytically processed (Zhoa 2003). The peptides are folded so that non-polar amino acid side-chains form a hydrophobic face and polar, positively charged residues form a hydrophilic face (Robert and Hancock 1997). Expression of antimicrobial peptides can be constitutive or inducible by infectious or inflammatory stimuli like cytokines, bacteria and lipopolysaccharides (LPS) (Cunliffe and Mahida 2004). They have diverse structures to effectively kill a wide range of microbes at prone sites e. g the skin and lungs, and in secretions such as sweat and saliva (Yeaman and Yount 2004; Santamaria 2005). Many mammalian antimicrobial peptides rous e the hosts innate immune system (Jenssen et al 2006) instead of directly killing the host. Peptides which are found in living organisms from bacteria to plants, insects, fish, amphibians to mammals including humans (Kamysz 2005) are recorded in numerous existing databases e. g. AMSDb (Eukaryotic peptides) (Tossi and Sandri 2002), BAPDb (bacterial peptides), ANTIMIC (natural antimicrobial peptides) (Brahmachary et al 2004) and APPDb. Currently, 1831 peptides are hosted by the Antimicrobial peptide database with 99 antiviral, 453 antifungal, 100 anticancer and 1179 antibacterial peptides (The Antimicrobial Peptide database 2010). In humans, antimicrobial peptides are produced by granulocytes, macrophages and most epithelial and endothelial cells. They boost the immune system, have anti-neoplastic properties and help in regulating cell signalling and multiplication. Amphibian AMPs have been discovered from the skin of frogs from families ranging from Iomedusa, Pipidae, Hyperoliidae, Ranidae, Hylidae, Discoglossidae, Agalychnis and Litoria. The structure of these peptides as unravelled by CD spectroscopy, NMR spectroscopy and molecular modeling (Suh et al 1996) have been found to be generally 10-46 amino acid residues long (Rollins-Smith et al 2005), mostly linear and simple-structured, (Conlon et al 2004) the majority being hydrophobic, cationic and possessing an amphipathic a-helix in nature. Following production, they are stored in the granular glands (poison glands) of skin dermal layer to be secreted in response to injury (Bovbjerg 1963), or as defence against pathogenic bacteria, fungi, viruses and parasites. Biologically active molecules including antimicrobial peptides are produced as large proteins harbouring a signal and an acidic propiece which get cut off to give an active peptide prior to or at secretion from the poison glands (Amich e et al 1999). Cationic peptides are also expressed in the gastric mucosa cells and in the intestinal tract (Kamysz 2005). The best-known peptides isolated from frogs are caeruleins, tachykinins, bradykinins, thyrotropin- releasing hormone (Barra and Simmaco 1995), brevinins, esculentins, magainins, ranatuerins and temporins (Conlon et al 2004). In the past, peptides were extracted using solvents like methanol or acid from the skins of amphibians after sun-drying but with concomitant dwindling of many frog species, other alternative techniques have emerged, one of which comprises stimulating the frog using mild electricity and collecting the skin secretion; 2-4 weeks after, the secretion can be re-collected after replenishment of the glands (Barra and Simmaco 1995). Large amounts of small peptides and their analogues which are resistant to protease cleavage and contain D-amino acids can be chemically synthesised while larger peptides can be expressed in a prokaryotic host from cloned cDNAs coding for a fusion protein (Piers et al 1993). An efficient means of producing therapeutic peptides in transgenic mice red blood cells has been explained by Sharma et al (1994) whereby the required peptide is collected from proteolytic cleavage from the fusion protein where the peptide is at the C-terminal end of human a-globin. Structure of antimicrobials In spite of sharing similar features, sequence homology between antimicrobial peptides is low and secondary structure diversity is wide (Jenssen 2006). Secondary structures based on sequence homologies, 3-dimensional structures and functions can be grouped into 5 classes: Linear, mostly a-helical peptides lacking cysteine, with or without a hinge region (cecropins, magainins). Antimicrobial peptides with one disulphide bond that form a loop structure with a tail (bactenecins, esculentins). Antimicrobial peptides with at least two disulfide bonds yielding primarily or solely a Î’-sheet structure (defensins, protegrins). Linear peptides comprising an unusual composition of regular amino acids with the absence of cysteine (histatins, indolicidin, temporins). Antimicrobial peptides derived from larger peptides or proteins with other known functions (lactoferricins, MUC7, Casocidin1). Mode of action of peptides Unlike numerous antibiotics or secondary metabolites that halt microorganisms over a number of days by hindering the action of key enzymes, most of the vertebrate antimicrobial peptides neutralise microbes quickly by disrupting the membrane or permeating it and targeting anabolic reactions (Barra and Simmaco 1995). The antimicrobial properties of most peptides rely on the formation of a-helical (Oren et al 2002) or Î’-sheet-like tubular (Fernandez-Lopez 2001) structures when interacting with negative charges on cell surfaces or when forming a-helical bundles following self-association in solution (Avrahami and Shai 2002). The mechanism of action of antibacterial peptides is thus twofold: membrane acting (membrane permeabilisation) or non-membrane acting (affect vital intracellular processes) as depicted in Figure 3. Different models of membrane permeabilisation exist; in one model, peptides reorient to cross the phospholipid bilayer of the membrane as a cluster without assuming any particular direction, resulting in a micelle-like complex of peptides and lipids. The toroidal pore model suggests that peptides enter the bilayer at 90 degrees to it, the hydrophilic regions interacting with phospholipid head groups and the hydrophobic regions interacting with the lipid core. Additionally, the membrane curves inward so that the bilayer lines the pore too. The barrel-stave model involves insertion of peptides perpendicularly to the bilayer, forming the staves in a barrel-shaped cluster, such that hydrophilic regions of the peptides project into the pore lumen and the hydrophobic regions contact the lipid po rtion of the bilayer membrane. According to the carpet model, peptides group together parallel to the lipid bilayer and local areas are coated like a carpet (Lai and Gallo 2003). Buforin II in frogs crosses the bacterial membrane without causing permeabilisation and binds DNA and RNA in the cytoplasm of E. coli (Park et al 1998). Antifungal peptides have been found to function in different ways one of which is fungal cell lysis e. g. frog Magainin targeting C. albicans (Tytler et al 1995; Zasloff et al 1987) and frog Brevinin-1 acting on Batrachochytrium dendrobatidis as described by Rollins-Smith et al (2002). Defensin from mammals permeabilises the membrane of C. albicans (Lehrer et al 1985; Patterson-Delafield 1980); bovine Indolicidin has been found to act similarly on T. beigelii (Lee et al 2003). Another strategy of antifungal peptides is the disruption of synthesis of fungal cell wall (De Lucca and Walsh 1999). Cecropin from insects as studied by De Lucca et al (1998) binds to membrane cholesterol or ergosterol and affects the fungus Aspergillus fumigates. Bovine lactoferricin and the hybrid peptide of Helicobacter pylori ribosomal protein L1 and magainin-2, HP(2-9)-MA(1-12), have been shown by Bellamy et al (1993) to cause extensive damage to the ultra structure of the cell wall of C. albicans . Yet a nother mode of action has been documented which involves depolymerisation of the actin cytoskeleton illustrated by Pn-AMP 1 from plants which attacks S. Cerevisiae and C. albicans actin. In contrast, as reported by Helmerhorst et al (1999) and Kavanagh and Dowd (2004), Histatin from human primates acts on mitochondria in C. albicans. Rollins-Smith et al (2002b) found that the peptides magainin I and II, PGLa, and X. Laevis CPF, Phyllomedusa sauvagii dermaseptin and R. catesbeiana ranalexin were more potent at the zoospore transmission period of the chytrid fungus life cycle than against mature stages. It has been found that peptides with primarily antifungal activity particularly abound in polar and neutral amino acids, pointing to a structure-activity link (Lustig et al 1996). Numerous studies point to different modes of action of antiviral peptides which interfere with adsorption, entry of the virus into the cell (Belaid et al 2002) or act on the viral envelope (Robinson et al 1998). Targeted viruses are notably enveloped RNA and DNA viruses except non-enveloped adenoviruses (Bastian and Schafer 2001), echovirus 6 (Pietrantoni et al 2006) and feline. Sinha et al (2003) found that rabbit a-defensin NP-1 acts by inhibiting HSV movement from cell to cell. By interacting with the CXCR4 chemokine receptor functional as a coreceptor for HIV-1 entry into T cells (Murakami et al 1991), a polyphemusin analogue, T22 reportedly inhibits the HIV strains using that chemokine receptor (Tamamura et al 1999). Antivirals can also hamper viral entry through interaction with viral glycoproteins as in the case of ?-Defensin (retrocyclin 2) claimed by Yasin et al (2004) to protect cells from HSV-2 infection by acting on HSV-2 glycoprotein B. Viral antimicrobial peptides can a ct in the cell as well, stimulating genes or proteins, thereby affecting host cell antiviral mechanisms (Bowdish et al 2004);viral gene and protein expression (Wachinger et al 1998) can be hampered too. Antimicrobial activity of peptides Features of antimicrobial peptides The emergence of resistant bacterial strains worldwide necessitates (Bonomo 2000) development of new families of antibiotics. Antimicrobial peptides have properties which render them attractive for development of new antimicrobial therapies. Antibiotic-resistant bacteria are often vulnerable to antimicrobial peptides (Jacob and Zasloff 1994; Tencza et al 1997); minimum inhibitory concentrations (MIC) of 1-8 Â µg/mL competitive with the most powerful antibiotics against resistant organisms have been recorded with peptides (Isogai et al 2009). Lui et al (2009) observed strong effectiveness of peptide nanoparticles against bacteria, Streptococcus haemolyticus (gram-positive bacteria), Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis and also against drug-resistant bacteria methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, yeast tropicalis and fungi, Candida albicans, Cryptococcus neoformans and Stachybotrys chartarum. Antimicrobial pe ptides not only eradicate bacteria rapidly and neutralize endotoxins but are synergistic with antibiotics and active in animal models (Hancock and Scott 2000). Furthermore, they exhibit a broad spectrum of activity by virtue of their relatively non-specific mode of action. In addition, mutations leading to classical antibiotic resistance do not affect them and they do not easily select antibiotic resistant variants (Shai 2002; Huang 2000). However, peptides have drawbacks limiting their use e. g. they are cleaved by proteases notably trypsin-like proteases and researchers still need to probe further into uptake mechanisms into different tissues (Boman 1995). Activity of Frog peptides Numerous studies aimed at understanding further antimicrobial expression of antimicrobial peptides have been conducted. In line with a first line of defence to the frog, release of antimicrobial peptides are stimulated in response to an environment conducive to microbial proliferation; it has been observed that while the freeze-tolerant wood frog, Rana sylvatica, shows no signs of any antimicrobial peptide activity in winter, it produces and secretes an active peptide upon exposure to warmer conditions (Matutte et al 2000). Rollins-Smith et al (2002a) found that effectiveness is enhanced when mixtures of peptides rather than single ones are released; magainin II and PGLa, synergistically hamper growth of B. dendrobatidis and B. ranarum on the skin of X. Laevis. Frog peptides are seen as interesting and potentially useful molecules that could be effective against a range of human pathogens (VanCompernolle et al 2005), viral, bacterial or fungal. In the 1960s, a 24 amino acids long antibiotic peptide bombinin secreted from the skin of the frog Bombina variegata was isolated but discouraging high haemolytic activity restricted applicability (Csordas and Michl 1970). Since then, large numbers of various peptides have been discovered with antimicrobial potential; Gaegurin, for instance, from a Korean frog is described as having a considerable spectrum of activity with mild haemolytic activity, rendering it a potential antibiotic (Suh et al 1996). Recently, high amounts of peptides were discovered in Litoria chloris, the Australian red-eyed tree frog which blocked HIV without harming T cells; the peptides appeared to target the HIV virus probably by insertion into its outer membrane envelope and punching holes in it (VanCompernolle et al 2005). S ome frog peptides have aroused interest as potential agents for treatment of Type 2 diabetes as exemplified by a peptide isolated from the skin secretions from the leaf frog, Hylomantis lemur with the ability to release insulin from the rat BRIN-BD11 clonal B cell line; A synthetic version of the peptide, phylloseptin-L2 was remarkably good at that. Other peptides from phyllomedusid frogs are a 13 amino-acid-residue peptide from Agalychnis calcarifer (Abdel-Wahab et al 2005) and peptides from Agalychnis litodryas (Marenah et al 2004a) and Phyllomedusa trinatis (Marenah et al 2004b) with a structure similar to dermaseptins. Therapeutic applications Antimicrobial peptides are appealing for therapeutics since they are rapidly produced at low metabolic expenses, stored easily in abundance and readily available shortly following an infection, to rapidly counteract a wide range of microbes (Zhoa 2003). The 20 existing amino acids confer tremendous diversity in sequence and structure of peptides, presenting opportunities in creating a whole range of novel drugs (Hancock and Scott 2000) Peptides can be used for battling antibiotic-resistant bacterial infections or septic shock (Finlay and Hancock 2004). Other potential applications include topical applications for preventing sexually transmitted diseases (Rana et al 2006) including HIV/HSV (Reddy et al 2004), Meningococcal meningitis, diabetic wounds e. g. foot ulcers, gastric helicobacter infections, impetigo (Gunaratna et al 2002; Reddy et al 2004), treating eye infections (Migenix 1998). Creams with snails mucin containing antimicrobial peptides are currently marketed for topical applications treating skin infections and acne inflammation (Cottage 2007). Efforts have also been directed at developing magainin analogs into anticancer drugs (Boman 1995). Furthermore, as attempts persevere to alter the immune system of the vectors or their symbionts to confer to the vectors the ability to eradicate the parasites (Ham et al 1994; Gwadz et al 1989), peptide antibiotics are seen as a potential weapon in fighting insect- borne diseases like malaria, trypanosomiasis, and filariasis. Besides using AMP as proteins, genes encoding AMP can be delivered as gene therapy. Genetically altered bacteria making the antimicrobial in situ can be used for targeting pathogens, which is particularly relevant to the treatment of dental caries, Crohn disease, and other disorders in which disturbances in natural microflora play a role and host-microbe balance must be preserved (Palffy 2009). Peptides are also used for food preservation as exemplified by Nisin, produced by certain strains of Lactococcus lactis subsp. Lactis (Joerger 2003). Engineering peptides for enhanced activity Natural peptides do not always possess all the features required to make them suitable therapeutics, validating the need to engineer their primary structure to confer those properties to them (Sarah et al 1999) e. g. stability, reduced toxicity (Won and Ianoul 2009); existing desirable properties e. g. potency, selectivity or specificity of antimicrobial activity can also be strengthened. In cationic AMPs, antimicrobial activity has been ascribed to the net positive charge since the outermost portion of bacterial membranes is negatively charged by virtue of the negatively charged phospholipids (Brogden 2005). Substitution of acidic residues with basic ones, reportedly boosted the potency of LLP1 against S. aureus from the increase in net charge of the peptide (Robert and Hancock 1997). Hydrophobicity (aiding in membrane insertion) and flexibility, driving the peptides change in conformation to allow interaction with the membrane, have also been identified as important (Jenssen 2006). Antibacterial activity of peptides can be enhanced by altering their flexible secondary structures; altering the membrane-associated conformation of indolicidin to bring the N and C termini closer together increased activity against gram-negative bacteria (Ianoul 2010). Oren and Shai (2000) claim that a successful designing strategy in the synthesis of antimicrobial peptides is the incorp oration of non-natural amino acids (such as Ornithine) and the utilization of D-Amino acids with the aim to sustain natural activity and confer resistance against proteases. It has been found that, often, modest alterations to ineffective antimicrobial peptides successfully confer antifungal properties as evidenced by the resulting potent action of magainin analogues coupled with undecanoic acid or palmitic acid in contrast to the native peptide, against yeast and opportunistic fungal infections (Avrahami and Shai 2003) However, often, one roadblock in peptide production is that expression of antibacterial proteins in bacteria may be suicidal to the cells; this could be circumvented by making a fusion protein which is made to accumulate in inclusion bodies at a later stage in growth (Boman 1995). A report of this technique applied on four fusion proteins was recently published (Piers et al 1993). Use of expression vectors in hosts that are insensitive to the peptide antibiotic is also proposed as a solution that has met with success in producing an insect defensin in yeast (Reichchart et al 1992). There are reports of the baculovirus system being used to express a fusion protein cecropin A although with rather low yields, in an insect cell line (Andersons et al 1991). Using the same virus vector in live insects, expression of cecropin about 60 times higher was recorded in the hemolymph. Pseudin antimicrobial peptides Introduction Pseudin-1, Pseudin-2, Pseudin-3 and Pseudin-4 are antimicrobial peptides with structural similarity, which are secreted from the skin of the bright green and pink paradoxical frog from the Pseudidae family, Pseudis paradoxa, inhabiting Trinidad and the Amazon basin (Olson et al 2001). Pseudins, a subfamily of the Frog Secreted Active Peptides (FSAP) are cationic, amphipathic and helical (Olson et al 2001). Pseudin-2, the most abundant and powerful 2685. 4 Da peptide comprises 24 residues (GLNALKKVFQGIHEAIKLINNHVQ). In aqueous solutions pseudin-2 coils randomly while in those emulating the hydrophobicity of the cell membrane e. g. 50% trifluoroethanol/water, it assumes an a-helical conformation (Yasser et al 2008). Antimicrobial activity of Pseudin-2 As testified by Olson et al (2001), Pseudin-2 effective against Escherichia coli (MIC=2. 5 Â µM), Staphylococcus aureus (80 Â µM) and Candida albicans (130 Â µM) and has very weak haemolytic activity against human erythrocytes in contrast to other frog antimicrobial peptides (Colon 2004). Another study by Pal et al (2005) showed that strains of several pathogenic bacteria Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus were also effectively acted upon by multi-l-lysine-substituted analogues. They also demonstrated that gradually raising the cationicity of pseudin-2 by replacement of several residues with l-lysine in the hydrophilic part of the peptide enhanced the antimicrobial property. An analogue [D-Lys3, D-Lys10, D-Lys14]pseudin-2 in particular, in contrast to others had a significantly increased antimicrobial effect against E. coli and S. aureus and, low haemolytic and cytolytic activity against human erythrocy tes. Replacing Asn with Lys at codon 3 was found to double the antimicrobial activity against E. coli and S. aureus from a reduction in destabilisation of the a-helix besides greater positive charge (Pal et al 2005). Kim et al (2007), in a study attempting to link structure to mechanical action of pseudin-2 in microorganisms and liposomes, suggested that the antimicrobial activity of Pseudin-2 is ascribed to the punching of holes in the target cell membrane through its oligomerisation according to the toroidal pore model in zwitterionic liposomes and the barrel-stave model in anionic liposomes. Pseudin-2 as an anti-diabetic peptide Besides antimicrobial features, Pseudin is seen as promising, prospective insulinotropic agent for treating type 2 diabetes as an incretin mimetic (Abdel-Wahab et al 2008). Yasser et al (2008) demonstrated that Pseudin-2 and derivatives, particularly a [Lys18]-pseudin-2 derivative, enhanced release of insulin from a clonal B-cell line, BRIN-BD11 via Ca2+ independent pathways. The insulin- releasing features of [Lys18]-pseudin-2 are very similar to the gut hormones GLP-1(7-36) amide and GIP (McClenaghan and Flatt 1999) Mutagenesis Site-directed mutagenesis Initially, DNA mutation was based on generation of random mutations in chromosomal DNA using X-rays and chemicals or error-prone PCR which suffered from the major drawback of not targeting the mutation to a specific gene, leading to the emergence of site-directed mutagenesis. This technique has become instrumental for altering DNA sequences in molecular biology and genetic engineering, and for investigating how protein structure relates to function (Zheng et al 2004). In vitro approaches to site-directed mutagenesis can be generally grouped into three categories (Botstein and Shortle 1985):(i) localized random mutagenesis (ii) oligonucleotide-directed mutagenesis (Cosby and Lesley 1997) and (ii) techniques restructuring DNA fragments e. g cassette mutagenesis (Lo et al 1984). Single amino acid substitutions in proteins can be produced by oligonucleotide-directed mutagenesis. One or more amino acids at specific desired locations in the polypeptide chain can be substituted with no length change. Any residue, chemically reactive or inert, buried or exposed can be targeted, and size can be replaced without altering polarity, or polarity without altering size (e. g. aspartate to asparagine). Often, different multiple substitutions are introduced at one specific position or at several locations to study their effect on protein function (Kegler et al 1994). Saturation mutagenesis Using saturation mutagenesis, which often involves oligonucleotide-directed mutagenesis (Zoller and Smith 1982), a library of mutants with all possible mutations at one or more pre-determined key positions in a gene can be created. In conjunction with high-throughput screening, saturation mutagenesis has numerous applications. For example, it has been used in enhancing the stability of the Rhizopus oryzae prolipase enzyme towards lipid oxidation products such as aldehydes (Lorenzo et al 2007) and to increase enantioselectivity of Pseudomonas fluorescens esterase (Park et al 2005). The ligand-binding specificity of the human oestrogen receptor for a resveratrol-like synthetic compound has also been successfully enhanced by saturation mutagenesis (Islam et al 2009). Randomised gene libraries are usually created by replacing part of the parental gene with a synthetic DNA cassette with specific randomised codons (Hine et al 2003). Cassette Mutagenesis is a means of creating a library by targeting a specific site or sites of any length or sequence and replacing them with new sequences; degenerate oligonucleotides are used for inserting the predetermined degeneracy into the peptide. Cassette Mutagenesis involves cutting the original gene contained in a plasmid with two endonucleases at identified, appropriate restriction sites to remove a small section from the plasmid. To make the sequence more amenable to mutations at any region along it, unique restriction sites around 40 nucleotides apart can be inserted into the plasmid (Stryer 2002). The gap is subsequently replaced with a synthetic double-stranded oligonucleotide (the cassette) with sticky ends which is then ligated to the plasmid which now has the required mutation. The new mutated insert allows protein structures or nucleic acid sequences to be studied. Bakir et al (1993) found cassette mutagenesis to be useful for mutating nine single amino acids in the active site of Aspergillus awamori glucoamylase to modify pH dependence of the enzyme and investigate the functions of the mutated residues. Xiang and Sampson (2004) used cassette mutagenesis to screen libraries for establishing specificity of the substrate in a cholesterol oxidase-catalyzed reaction. Oligonucleotide synthesis or screening can be costly for cassette mutagenesis, especially if several parts of a gene are targeted for saturation mutagenesis, since for each region to be mutated, a different batch of oligonucleotide cassettes containing the mutated codon must be produced (Kegler-Ebo et al 1994). Codon randomisation High throughput substitution can be accomplished through randomisation of codons, resulting in a randomised gene library including all possible amino acid substitutions for the target amino acid residue. Conventional codon randomization uses oligonucleotides containing NNN-, NNB-, NNK- or NNS (N: A/C/G/T; B: C/G/T; K: G/T; S: G/C) since each of these combinations code for all 20 amino acids (Patrick and Firth 2003). Creating NNN libraries from oligonucleotides by employing an equimolar mixture of the four nucleotides at each position represents the easiest approach to codon randomisation (Bosley et al 2005) but a sizeable portion of the library contains premature stop codons especially in the event of multiple codon-randomisations. Additionally, the most common protein mutants with Arg, Leu and Ser (with six degenerate codons) are immensely over-represented in contrast to the rarest mutant with Met or Trp at each randomized position (Patrick and Firth 2003). By employing reduced codon sets, the quality and diversity of the protein library can be enhanced. NNB codons have the lowest likelihood of 1 in 48 of coding for stop codon. NNK and NNS codons reduce the over-representation of the commonly-occurring variants (Patrick and Firth 2003). Although NNK and NNS give rise to a similar distribution of amino acids, NNK is preferred for libraries hosted by E. coli and S. cerevisiae by virtue of their favourite codon use but the NNK codon distributes the 20 amino acids unequally and generates 3% termination codons. Neuner et al (1998) mutated codons with dinucleotide phosphoramidite which has the advantage of requiring only seven dinucleotide building blocks to code for all 20 amino acids. Besides being flexible, the technique can be used applied to various hosts with different codon usage patterns. Virnekas et al (1994) have reported use of trinucleotide phosphoramidites as well in random mutagenesis involving chemical DNA synthesis with a yield above 98%. MAX randomisation The MAX codon randomisation method designed and tested on three residues on a synthetic zing finger protein recently by Hine et al (2005) is a superior technique using simple primers efficiently to curtail library size. Using this technique specific synthetic oligonucleotides anneal to a template containing the codons targeted for mutagenesis which are each fully randomised conventionally (NNN)-to select the particular set of desired codons for E. coli. 20 oligonucleotides, each made up of a complementary region and a MAX codon encoding an amino acid, base-pair at each randomised codon. Specific selection primers are designed to cover the 5 region of each target codon and terminate with each specific codon whose presence in the library is necessary; a set of primers is synthesised for each targeted codon. These are hybridised to the template and ligated to give a single strand. 2 extra unique oligonucleotides are needed for serving as primer-binding and restriction sites at the cassette extremities, also ensuring that PCR amplification of only the selection strand occurs. The resulting double-stranded DNA can be subjected to restriction digestion, dephosphorylation followed by ligation into an expression construct or extended to regenerate the complete gene. One advantage of the MAX technique is that, despite the requirement for a large number of primers, their maximum number does not exceed 20 times the randomized codon-number, resulting in a library comprising 8000 mutants with the absence of codon bias and premature termination codons. While randomising NNN and NNG/T codons generates exponentially-rising redundant gene libraries with increasing randomised codons, MAX randomisation generates non-redundant libraries in essence. Amplification bias likely to arise from using PCR to generate the complementary strand can be minimised by synthesising a second strand instead of using PCR. MAX also allows circumvention of the use of a DNA synthesizer and is helpful when medium to large (103-106 variants) libraries have to be screened efficiently (Neylon 2004). Drawbacks MAX is not practical if only one codon needs to be randomized and cannot be used if the number of adjacent codons to be randomized exceeds two. Furthermore, it is a complicated technique (Hine et al 2003). References Abdel-Wahab, L. M. , et al. (2005) Isolation and structural characterisation of a novel 13-amino acid insulin-releasing peptide from the skin secretion of Agalychnis calcarifer. Biol Che. 386: 581-587. Amann and Brosius. (1985) ATG vectors for regulated high-level expression of cloned genes in Escherichia coli. Gene [Online]. 40: 83-190. Available from: http://www. sciencedirect. com/science?_ob=ArticleURL_udi=B6T39-47PH4H8-BJ_user=153063_coverDate=12%2F31%2F1985_rdoc=1_fmt=high_orig=search_sort=d_docanchor=view=c_searchStrId=1259545403_rerunOrigin=google_acct=C000012698_version=1_urlVersion=0_userid=153063md5=af56ff2270eff863a3062bdd46bc9a70 Amiche, M. , et al. (1999) The dermaseptin precursors: A protein family with a common preproregion and a variable C-terminal antimicrobial domain. FEBS Lett [Online]. 456: 352-356. Available from: http://apps. isiknowledge. com/InboundService. do?Func=Frameproduct=WOSaction=retrieveSrcApp=HighwireUT=000082079500002SID=Q2coKoP%40dF7jNOjpLkgInit=YesSrcAuth=Highwiremode=FullRecordcustomersID=HighwireDestFail=http%3A%2F%2Fwww. isiknowledge. com%3FDestApp%3DCEL%26DestParams%3D%253Faction%253Dretrieve%2526mode%253DFullRecord%2526product%253DCEL%2526UT%253D000082079500002%2526customersID%253DHighwire%26e%3DCkCYpwhLs4N6PGgAE_lYJ503Re6_mdcbI8LWGd6UH07UznpX03dChP3eV4e0frXM%26SrcApp%3DHighwire%26SrcAuth%3DHighwiresmartRedirect=yes[Accessed 25th Feb 2010] Andersons et al. (1991) Biologically a