What can David do about his position in relation to the other partners?

Introduction In considering what rights David has in respect of the other partners, it will first need to be determined whether a partnership has actually been created. For a partnership to be created two or more persons must conduct business with a view to profit. Partnerships are defined under s. 1(1) Partnership Act (PA) 1890 as a â€Å"relation subsisting between persons carrying on business in common with a view of profit†. Since David, Clive and Jane have all started a business in advertising with a view to profit; it is evident that a partnership has been created. As a partnership agreement has not been created by the partners, the partnership will be governed by the PA 1890. David will thus be able to rely on the PA 1890 in order to establish his rights and duties. It is contained within s. 19 PA 1890 that â€Å"the mutual rights and duties of partners whether ascertained by agreement or defined by this Act may be varied by the consent of all of the partners, and such consent may be either express or inferred from a course of dealing†.[1] Therefore, the rights and duties of David will have been capable of being varied with the mutual consent of all the partners. As the partners do not have a partnership agreement in place, it is clear that they have not varied the terms of their rights and duties that are contained under the Act. Given that a partnership is based upon the mutual trust of all the partners, they each owe a duty of good faith. This has been exemplified in the case of Const v Harris[2] when it was held by Lord Eldon that; â€Å"in all partnerships, whether it is expressed in the deed or not, the partners are bound to be true and faithful to each other†. Therefore, each partner must be required to act in the interests of the partnership as a whole and not in the interests of themselves. As Jane is a director of a company that runs corporate events, called Eventbright Ltd, which has been regularly used by the partners, it is questionable whether Jane is acting in the interests of the partnership. This is because Jane may only be using Eventbright Ltd in order to increase profits in her own company. This can be seen in Trimble v Goldberg[3] where it was made clear that all partners must act in good faith for the benefit of the partnership. There are three requirements that must be fulfilled by the partners when acting in good faith of the partnership. These are; 1) the duty to disclose information, 2) the duty to account for benefits received, and 3) the duty in respect of competing business.[4] Whether the latter two duties are being fulfilled by Jane is debatable. This is because Jane may be benefiting from using her company to which she is a director in order to gain profits (s. 29 PA 1890) and her company may be considered a competing business (s. 30 PA 1890). If this is the case, Jane will be required to disclose this information to the other partners and must account for and pay over to the firm all profits made by her. In respect of the restrictions Jane and Clive want to impose upon David’s work, it is likely that David will be able to assert his rights contained under s. 24 PA 1890. Here, it provided that; every partner may take part in the business (24(5)) and that decisions are to be taken by a majority but unanimity is required to change the nature of the business (24(8)). David may therefore take part in the business, yet because Jane and Clive have suggested he take a more administrative role, it is arguable whether this will be sufficient. This is because Clive and Jane will be capable of making a majority decision as to how the business is being run, although they cannot change the nature o f the business without David’s consent. In effect, David may not be able to oppose the decision that is being made by Clive and Jane as they will be able to take a majority vote as to how they think the business should be run. And, if they feel that it is in the best interests of the business, then David may not have any right to argue against this unless they acted in bad faith or attempted to change the nature of the business. If David is not happy with the new arrangements, he may be capable of bringing the partnership to an end. This can be done by giving notice to the other partners (s. 26 and 32 PA 1890). If David decides to bring the partnership to an end, any partner will have the right to publicly notify the dissolution (s. 37 PA 1890). After the partnership has been dissolved, each partner will be entitled to have the partnership property applied so that the debts and liabilities can be discharged. Once this has been done, any surplus will be distributed equally between the partners. Because not all property is partnership property, a distinction will have to be made between personal and partnership property as personal property will not be able to help meet partnership debts (s. 20 PA 1890). Overall, it seems as though David may not be able to oppose the decision of Clive and Jane to restrict his work to more clerical and administrative matters. If David is not happy with this decision he may be able to bring the partnership to an end by giving notice to the partners. Once this has been done, the partnership property will be distributed equally between all three partners. What is the partnership propertyWhy does it matter? The amount of money and property the partners have contributed to the partnership to use in the enterprise is known as partnership capital.[5] This represents the partner’s equity in the partnership and has noted in Reed v Young[6]; â€Å"The capital of a partnership is the aggregate of the contributions made by the partners. It is important to distinguish between the capital of a partnership, a fixed sum, on the one hand and its assets, which may vary from day to day and include everything belonging to the firm having any money value, on the other.† Partnership capital is thereby distinguished from partnership property which is the property that has been acquired by the partnership. This includes a transfer of property to; a) the partnership in its name, b) one of the partners in their capacity as partnership, or c) one of the partners indicating their capacity as a partner.[7] It is vital that partners indicate their intent as to whether the property is to be consider ed capital or property as this will determine who is entitled to the property once the partnership is dissolved. If the property is partnership capital, then the individuals will be entitled to take their share of the property.[8] If the property is partnership property, then the property will be distributed equally between the partners. As pointed out by Lord Andrews LCJ in McClelland v Hyde[9]; â€Å"the capital of a partnership is something different from its property or its assets†. 20(1) PA 1890 states that partnership property includes â€Å"property originally brought into the partnership stock or acquired for the purposes and in the course of the partnership business†. It is important for partners to specify what property belongs to whom in order to avoid any undesirable consequences. The original owners of the property may not be entitled to recover the property in the event that the partnership comes to an end.[10] On the insolvency or bankruptcy of a partnership, there are two sets of creditors; joint and separate. The partnerships assets are referred to as the â€Å"joint estate† in the Insolvency Act 1986 (as amended by the Insolvent Partnerships Order 1994 (SI 1994 2421)) and are used in the first instance to pay the partnerships creditors. If an asset increases in value, the increase will belong to the firm if the asset is partnership property. If the asset is owned by the individual partner, then the increase will belong to the individu al.[11] As a partnership does not have its own separate legal entity, partnerships cannot own property in its own name. Instead, partnership property will be held in the names of the individual partners who will be deemed to be holding the property in their names as agents for the purposes of, and as trustees for, the partnership as shown in Burdick v Garrick[12] where property held on trust for the partners was considered partnership property. There is also a presumption, unless expressly stated otherwise, that partnership property is held by partners as tenants’ in common and not as joint tenants (except for land; s. 39(4) Law of Property Act 1925). This was evidenced in Bathhurst v Scarborough[14] when it was noted that the general rule is that property bought with partnership money belongs to the partnership and will be held by the partners as tenants in common. The accounts of the partnership will usually make it clear which assets are to be considered partnership property and which assets are merely individual property that is to be used by the partnership as in Barton v Morris[15] where it was clear from the partnership’s accounts which assets were to be treated as partnership and individual property. In the instant scenario it would appear as though the office equipment and stationary is partnership property, whilst the rest of the partner’s assets are personal property. However, because there i s no partnership agreement in place that specifies which separates the assets between ‘partnership property’ and ‘partnership capital’ it seems as though s. 20(1) PA 1890 will apply. This means that all of the property that has been brought into the partnership stock will also be called partnership property. This has been recognised by Deards who stated that; â€Å"property brought into the partnership stock will cover property brought in as capital by a partner†.[16] Nevertheless, because s.21 of PA 1890 provides that property brought with the partnership’s money is presumed to have been brought for the partnership, any property that is itemised in the partnerships accounts will be deemed partnership property. This suggests that if the property is not itemised in the partnerships accounts and is merely being used by the partnership, then in the absence of any agreement by the partners, the use of any property by the partners will not be regar ded as partnership property.[17] Consequently, if any of the assets are not itemised in the partnerships accounts it cannot be said that they will be classed as partnership property. In Waterer v Waterer[18], however, the use of land was considered partnership property because of the nature of the partnership. In effect, unless David’s assets are itemised in the partnerships accounts, they will not be considered partnership property. The premises by which the company operates will most likely be considered partnership property in light of the Waterer v Waterer[19] case, whilst the use of Eventbright Ltd will not be. Any assets that are considered partnership property will be shared equally between the partners. Bibliography Books E Deards., Practice Notes on Partnership Law, (Cavendish Publishing, Business & Economics, 1999). E MacIntyre., Business Law, (Essex: Pearson, 6th Edition, 2012). R Mann., Essentials of Business Law and the Legal Environment, (London: Cengage Learning, Business & Economics, 2009). Journals K Killington., ‘Partnerships – All Are Equal?’ (2008) Tax Journal, Issue 916, 14-16. P Beasang., ‘Partnerships: Legal Issues’ (2008) Tax Journal, Issue 916, 13-14. T M Lewin., ‘What is Partnership Property?’ (2011) [25 July, 2014]. Legislation Partnership Act 1890 Case Law Barton v Morris [1985] 1 WLR 1257 Bathhurst v Scarborough [2004] EWCA Civ 411 Brown v Inland Revenue Commissioners [1965] AC 244 Burdick v Garrick (1869-1870) LR 5 Ch App 233 Const v Harris (1924) Turn & R 496 McClelland v Hyde [1997] 3 All ER 800, CA Reed v Young [1984] STC 38, 57-58 Trimble v Goldberg [1906] AC 494, PC Waterer v Waterer (1872-73) 15 LR Eq 402

Poicies and Procedures That Are in Place to Protect Children and Young People

Explain policies and procedures that are in place to protect children and young people and adults who work with them Policies and procedures in place at Northfield primary to protect the children and those that work with them are the child protection policy, equalities policy, PSHE and citizenship policy safeguarding policy and anti-bullying policy. Strategies from all of these policies are combined in all areas of the school day to protect all who work and learn in school.Northfield believes that promoting positive behaviour is the way forward as children learn best and behave best when they know what is expected of them and when they are positively encouraged to behave well. They need to have opportunities to experience success and also need to be aware that if they do not behave appropriately they will be consistently but fairly treated. Each child knows the code of conduct which is displayed around the school, included in the home/school agreement and is reiterated during assembl y/PHSE times.Children that are bullied are not singled out or treated differently, they are comforted and encouraged to talk openly about what has happened and reassured that everything will be done to resolve the situation with the best possible outcome. Buddy systems are in place so that no one has to be alone at playtimes and older children look out for children on their own and help them to join in with others.As well as the children the policies and procedures are there to also protect the adults that work with children. It is essential that all professionals follow safe working practices too, as this protects everyone. For example if a disclosure is made by a child it must always be taken seriously and the correct procedure followed as in the safeguarding policy even if this turns out to be a mistake or untrue.An example of this happened to a friend of mine a few years back who is a nurse, her daughter had gone back to nursery school after the weekend having been absent for a few days beforehand, when asked what the children had been doing over the weekend the child had replied â€Å"Daddy been putting smarties up me bum†. Child services were called in and in the end it turned out that my friend had been doing the weekend shift at the hospital and her husband had been left the job of administering the suppository when required.This turned out to be a misunderstanding but was taken seriously as it could quite easily have been sexual abuse and was quickly sorted out. The child should be listened to in a calm, supportive manner and they should be allowed to speak openly. They should be reassured and the designated safeguarding officer should be told as soon as possible. When adults working within the school adhere to the policies and procedures while working they are not putting themselves into a position where allegations can be made true or false.For example if a child needs a nappy change there should always be two members of staff present, or if a child has an injury the adult should query it if it has not happened at school and inform the class teacher or safeguarding officer as necessary. If the injury has occurred at school then an accident form should be filled in and the appropriate first aid carried out by the designated first aider. All injuries should be timed and dated and an explanation or drawing of the injury should be documented for future reference.

Business strategic management Assignment Example | Topics and Well Written Essays - 1500 words

Business strategic management - Assignment Example The global business environment is offering a broad range of business opportunities and new clients, and thus allowing Starbucks to create different brands to cater for its market needs. The company is continuing to work towards realizing its long-term goals so as to emerge as the most reputable coffee company across the globe. However, despite the growth that the company is realizing, questions arise as to whether Starbucks is growing in the best way or whether it is exceeding its quest for growth (Richard Ivey School of Business, 2009). This paper will address the various issues that face Starbucks in its quest to emerge as the most preferred company in the world. Every company that undertakes its operations in the global market place encounters a number of issues that hinder their progress, even in the case of the most profitable companies such as Starbucks. Though the company has managed to witness outstanding reputation, it is still facing a number of issues like any other company in the global market place. For instance, with the advent of financial crisis, most companies suffer from the state of the economy, and Starbucks is no exception. There has been a number of store closures as a result of poor economic performance in major economies around the world. The number of stores that Starbucks depended on various factors such as finalization of third party agreements, income tax, expected cost savings as well as other benefits that are affiliated with the closure of stores. For instance, with the growing competition, from various companies in different parts of the globe, Starbucks has been unable to cope with the deteriorating performance of its stores, and hence leading to their closure (Richard Ivey School of Business, 2009). Competition is a common state of affairs in every business enterprise. There are a large number of coffee stores in various parts of the world. As a result, it

Paper on Abuse Reporting Essay Example | Topics and Well Written Essays - 500 words

Paper on Abuse Reporting - Essay Example This paper will supply an overview of the child reporting laws of the state of California. This paper will further discuss these laws in relation to my thoughts on confidentiality and the duty to protect others from harm. It will refer to ethical standards of human service s professionals and other codes of ethics. The Office of Child Abuse and Prevention under the California Department of Social Services, is responsible for executing the child abuse and neglect reporting law. According to a Summit (1983), California enacted its first child abuse reporting law in 1963. Earlier laws mandated that physical abuse should only be reported by physicians. The definition of child abuse has however been expanded by the numerous amendments that have been taking place over the years. Laws have also clarified the procedures for reporting various categories of child abuse (Summit, 1983). In California, there are certain professionals who are required to report known cases or suspected cases of child abuse. However, other citizens who are not required by law to do so may also be allowed to do so. Mandated reports and practitioners must therefore be kept updated on amendments made to these laws from time to time so that they can be well informed on what is required of them under all circumstances (Gil, 2001). The California laws on abuse reporting provide for why reporting is necessary, what should be reported, who should report, when reporting should be done and to whom it should be done. The laws also give ways of identifying incidences that need to be reporting and signs to look out for to know when to report. There are guidelines to determine suspicion of the various forms of abuse such as physical abuse, sexual abuse, neglect and emotional abuse among others (Summit, 1983). In relation to my thoughts on confidentiality and protecting the rights of others, I am of the opinion that it

Community and Domestic Violence Essay Example | Topics and Well Written Essays - 500 words

Community and Domestic Violence - Essay Example Also, they should concentrate on building a family time which allows the entire family to sit together and talk. This bonding with the family will prevent the young child from needing comfort or guidance outside the house as it will be readily available at home. Also, gang violence is presented as a romanticized idea in the youth culture today: songs, movies or books. Children are easily motivated to participate in an idea that is shown as being courageous. But, telling the child to stop listening to music or go to the movies will prove to be an unfruitful idea. Social scientists and criminologists have come to the conclusion that gang violence cannot be curbed through suppression.(Goldstein & Huff 1993) Instead, talk to the child of the cons of gang violence and emphasize the need to stay away from it. Thus, prevention and intervention will prove to be a far more successful communicator than force (Conley 1993). A lot of gangs are created as a need for the individual to be recognized. The young child might see the gang as his way to achieve three minutes of fame. Parents must ensure that their child has his priorities set straight. He must be taught the difference between famous and infamous.

Building technology Essay Example | Topics and Well Written Essays - 2000 words

Building technology - Essay Example Iron was in priority in UK during the early times. . â€Å"Mass produced cast iron components such as classical columns, Gothic window-tracery, nave arcading and even roof trusses were used in an increasing growing number of buildings†[Faculty 2006]. One of the best example for building constructed of cast and wrought iron is Crystal Palace. While cast and wrought iron were utilised for construction, steel took its full accumulation in construction only during the later part of the 19th century, there are many buildings that are made of steel one among them is St.Mary Axe, at London. This is considered as one of the best illustrations that reflects the skills in construction field of today. The use of cast and wrought iron could be found in buildings of the earlier times, until the 19th century the system excited. However, at present cast and wrought iron are used in building bridges and dams. This is mainly due to the fact that the advent of steel has occupied the place of iron in residential as well as industrial buildings. Nevertheless, in some of the industrial constructions cast and wrought iron are used to set the roofing. In the beginning of 18th century cast iron was used a lot and the prefabricated construction technique was practised by using the above form of iron. The property of the cast iron is that it is obtained as a natural source and it has high quantity of carbon in it. Though why cast iron was used in spit of bring brittle is that it does get rust formation when exposed to water and other climatic changes. Wrought iron is strong when get compressed and ductile. In some of the ear4lier buildings, wrought iron was used for roofing. Crystal Palace is one such building, constructed with cast and wrought iron. The load bearing system determines the technological aspect of bearing the whole weight of the walls. As far as Crystal Palace is concerned, â€Å"vertical load bearing† had been constructed. This vertical load bearing was fixed

Nursing research Essay Example | Topics and Well Written Essays - 1000 words - 2

Nursing research - Essay Example In line with this, the objectives of the study were to investigate whether staffing predicted nursing teamwork and determine the relationship between the levels of staffing and the subscales teamwork. Hence, the study focused on two research questions that were based on the research objectives. The first question asked, â€Å"Does the level of staffing predict nursing teamwork?† Conversely, the second question asked, â€Å"Does the level of staffing predict subscales of teamwork† (Kalisch & Lee, 2011, p.83). Based on the research study, the hypothesis was that in instances when the unit level case mix index (CMI) and the size of the healthcare facility were controlled, the levels of staffing had an effect on the levels of teamwork. In addition, the researchers also hypothesized that the size of the hospital affected teamwork exhibited by the staff members (Kalisch & Lee, 2011). Independent variable An independent variable in a research study is the factor that causes ch ange or an effect on another variable, which in most cases is change on the dependent variable in the research study (Polit & Beck, 2004). In this research study, staffing is the independent variable in the study since the levels of staffing in an organization affected the outcome in terms of teamwork. In this case, it is evident from the research findings that hospitals with high staffing levels experienced high levels of teamwork. On the other hand, since big hospitals have high staffing levels, they experienced high levels of teamwork. Dependent variable The dependent variable in a research study is the variable that may be changed or influenced by the independent variable (Polit & Beck, 2004). In line with this, the dependent variable of the research study by Kalisch and Lee (2011) is the level of teamwork in a hospital, which is a result of the staffing levels in the hospital. Research variables In a research study, research variables are concepts in a study, and these are conc epts that vary as the name suggests (Polit & Beck, 2004). One concept, or research variable in this study, is the skills mix among nurses, which affect the level of teamwork in nurses and vary from one hospital to another hospital. On the other hand, the size of the hospital is another research variable since all hospitals are not equal in size. In fact, this research study identifies the importance of the size of the hospitals remaining controlled. Research attributes and demographic variables Research attributes and demographic variables are the characteristics of the subjects in the study (Polit & Beck, 2004). In this regard, the research attributes and the demographic variables in this study are the age and professional qualifications of the research subjects. In this case, the age of the nurses is essential in evaluating their skills mix, which influences the teamwork of the nurses in a hospital. On the other hand, it is essential to point out that the professional qualificatio ns of the nurses play a crucial role in the skills of the nurses. In this case, the professional qualifications of nurses classify the nurses in the study as those who possessed a degree or a higher qualification, and those who did not hold a degree. In effect, these qualifications provide nurses with skills that contribute to trust among nurses, team orientation, and team leadership with these factors affecting the levels of teamwor

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Case Study Example Due to having a good reputation and success Creative Bus Service management must ensure that they come up with a good strategic plan. With the board meeting’s conclusion of expansion of profits they have to choose a good strategy that will ensure growth of profits. Mr. Ghosh market survey can be presented clearly through the Internal Rate of return (IRR), Net Present Value (NPV) and Modified Internal Rate of Return (MIRR). These will clearly state the outcome of the proposed projects by the Creative Travel Bus service. The success of the company revolves around the top management ability to manage effectively projects B operating from Delhi to Patna and A operating from Delhi to Joypur. Mr. Ghash should address congestion that hinders bus transport to the management to seek a way out in order to ensure their customers enjoy efficient services and they maintain the good reputation and name the company possesses (The World Bank, 2011). Being the most reliable transport system in India it has to make a decision so as to uphold their name and services to customers. The World Bank, (2011). India Transport sector. Retrieved on 27th November 2012

Political philosophies of Utilitarianism, Libertarianism, and Research Paper

Political philosophies of Utilitarianism, Libertarianism, and Egalitarianism - Research Paper Example Nevertheless, there are varying ethical perspectives on the roles of the government in provisions to citizens and the citizens’ own individual rights. Some of these ethical perspectives are Utilitarianism, Libertarianism, and Egalitarianism. Utilitarian perspective The fundamental doctrine of utilitarian is that people should make the society as well as they can; this can be done by making people’s lives worthwhile. A utilitarian believes that government resources should be allocated in such a way that they will have the greatest impact to most people. Stuart Mills argued that just distribution of resources provides the maximum good to most people. Mills held that people should not just think about the utility of isolated acts but the convention of conduct, which if adopted and adhered to would capitalize on utility (Irudayam 5). According to the principle of utility, we always ought to do whatever will maximize on the total amount of happiness. For a utilitarian, a jus t distribution of wealth is the one that maximizes on the total amount of happiness. ... s that such very unequal distribution of wealth would not maximize contentment and would not, on utilitarian grounds, be morally optimal or just (Irudayam 7). Utilitarianism would advocate for progressive taxing based on the principle of diminishing marginal utility designed at maximizing happiness. Utilitarians believe in taxing the wealthy and giving subsidies to the underprivileged to lessen the level of income disparity and increase total happiness. However, this can only work up to a point. If the tax is excessively repulsive, it will dent incentives to work, hence, production of fewer possessions; as a result, reduce the overall happiness. Therefore, from the utilitarian perspective, the superlative solution is the one that maximizes on overall happiness and this maximal point will be achieved when the tax rates are precisely put at the point where additional gain from the redistribution would be offset by bigger losses resulting from undermining of incentive (Irudayam 9). Libe rtarian response The core hypothesis of libertarianism is that persons have strong moral claim to the serene enjoyment of their own persons, as well as an accomplishment of their voluntary agreement with others. Christian Libertarians insist that the government should not be concerned with the business of redistributing any possessions. They argue that every resource distribution should be communitarian in nature, voluntary and non state sponsored. Libertarians critically object state compelled wealth redistribution since they argue that property rights are so vigorous that they do not give way to the attention that motivate demand for redistribution (Benkler 38). To some libertarians, property rights seem to comprise the full personification of some individuals’ rights and are the only

Orwell Essay Example | Topics and Well Written Essays - 1000 words

Orwell - Essay Example ger of a lumber company in Burma, is stationed along with a dozen or so British citizens in Kyauktada, a small village which one of the British refers to as â€Å"a filthy hole.†(184) The social center for these minor government officials and company managers stationed in the â€Å"bloody, bloody hole† (18) is the Club whose policy is Whites Only, for it is whites who administer government in this outpost of imperialistic British rule of the subcontinent. The amount of liquor consumed in the Club by its male members, most of them infantile and cynical, is staggering. When the British Commissioner suggests the Club elect one non-white to membership, most of the Englishmen are enraged. But the news has filtered into the native community where two men, U Po Kyin and Dr. Veraswami, wish to be honored by joining. U Po Kyin is a Subdivisional Magistrate of Kyauktada who prospers by graft and plotting, while the doctor respects everything British; his ardor for Englishmen impels him to call them â€Å"torchbearers upon the path of progress.†(42) But the grossly obese U Po Kyin sees the doctor as an enemy and methodically destroys his reputation. Flory is the doctor’s friend and is criticized for being so by racist members of the Club. He is also, consequently, a ‘mark’ for U Po Kyin and, like the doctor, is ultimately so disgraced (as well as disconsolate over Elizabeth Lackertseen’s rejection) that he commits suicide. â€Å"Absolute power corrupts, but absolute powerlessness corrupts absolutely.† This observation, made by once Presidential candidate Adlai Stevenson, encapsulates what most often occurs when Third World countries are conquered and then ruled by more ‘advanced’ countries. Ugandan President and criminal, Idi Amin, for example, has been thought by many to be merely aping, though perhaps without their subtlety, what he’d learned from the British during their occupation of his country. This is apparent in Orwell’s depiction of the British in

White Privilege Essay Example for Free

White Privilege Essay How America came about is fascinating, and learning about immigration, rights, laws, and racism makes learning more beneficial. It helps you to understand why we, as a nation, are they way we are today, and why we will continue to be stuck in our ways. According to James Barrett and David Roediger, â€Å"The Story of Americanization is vital and compelling, but it took place in a nation also obsessed by race†¦the process of â€Å"becoming white† and â€Å"becoming American† were connected at every turn (36). † One of the most controversial topics is white privilege and discrimination. Segregation within school systems has been a dominant problem in the past and will always continue to be. Being privileged is a something that individuals should be conscious of due to their past and understand that it is a privilege to be white rather than to be discriminated against. Becoming conscious of one’s own white privilege is the first step to understand the deeper meaning of racism and discrimination. My intentions of writing this paper were to describe a situation in which I was conscious of my own white privilege. White privilege was always on my side until high school where I felt as though I was discriminated against as being a petite, white girl, from upper-class Allendale leaving me to been seen as an easy target. While at my locker one day during lunch, I was approached by two of the black students (one male and one female) and a Latino girl, and they tried to convince me something hurtful was written about me in the bathroom. Being that I am not the type to care, get involved, or respond, I turned to walk away. The Latino girl proceeded to grab my hair causing me to turn and face her and she punched me square in the face. After several minutes of back and forth wrestling and punches, the fight was broken up my teachers. It turns out that there was nothing written about me, they were just trying to get me into the bathroom to fight me, opposed to the hallway which is out in the open. All three of the students that were there were taken to the principal’s office immediately and suspended for two days whereas I got off free and I was allowed to go back to my day. During the duration of the day, one of the African American men left the principal’s office in rage and had a mission to destroy all my belongings in my locker. The boy pried open my locked and poured a bottle of soda all over my books, note books and belongings. After I reported this to our principal, he held the three students involved in the fight until one person came clean about who had been at fault for ruining my locker. It turned out, that no one admitted to it, and they were all suspended even longer than originally for not fessing up. The following week, none of the three students attended my high school anymore and I was told by my principal that they left to attend other high schools in surrounding towns. After this incident, I have never come into contact with any of them ever again. However, several of my male friends found out what happened that day and wanted nothing but to get revenge and retaliate against them and show them who runs the high school, being that whites are minority. I became very conscious of my white privilege growing up in a one-square mile suburban town of Allendale, New Jersey. My entire educational career through eighth grade consisted of white, middle-to-upper-class Americans. All the people were similar, with the same morals, values and beliefs. Everyone dressed similar and drove similar cars, partook in the same activities and hung out in specific niches. At this point in my life, I could say I could correlate my life to Peggy McIntosh’s article when she describes the matrix of white privilege; There was one main piece of cultural turf; it was my own turf, and I was among those who could the turf. I could measure up to the cultural standards and take advantage of the many options I saw around me to make what the culture would call a success of my life†¦I could think of myself as â€Å"belong† in major ways, and of making social systems work for me. I could†¦be oblivious to anything outside of the dominant cultural forms (295). It wasn’t until high school where I thought I would potentially move out of my small town bubble. My high school is regional; students from Allendale, along with the surrounding towns of Ho-Ho-Kus, Upper Saddle River and half of Saddle River attended. Being that I came from such a white school system, the thought of going onto high school and being surrounded by students of other races and ethnicities is something that never crossed my mind. I was never taught about the disadvantages of being white, but rather I learned about blacks and their disadvantages of dealing with racism. Over the years, little was taught about racism and what it stood for, instead we were just told that this is what happened to people when they were of different races and ethnicities back in the day. The article by Peggy McIntosh describes how whites are taught to think of blacks; â€Å"As a white person, I realized I had never been taught about racism as something which put others at a disadvantage, but had been taught not to see one of its corollary aspects, white privilege , which puts me at an advantage†(291). Being white was never something that I had to deal with in or outside of school, or even within my community. I wasn’t necessarily shocked to walk into high school my first day to find only a select few of Latinos and African Americans. However, these were things that I never thought about or even had to think about. The few Latinos and African Americans came from Upper Saddle River and Saddle River. I was never stereotypical of these groups of people until I was surrounded with people from towns that had engaged with these people all the way up through high school. The Latinos in my school all stuck together, as well as the three African Americans that attended my high school. I feel as though this particular situation involved me having the white privilege advantage and it seems as though my white privilege helped to get me out of trouble. I should have gotten in trouble for â€Å"self defense† and throwing punches back, but I feel as though since I had never caused problems before, and they had been the center of most of the problems I was let go with no punishment. The students that got in trouble, were seen as troublesome students because of their past, where I had a clean record with no reason to suspect I was the start of the brawl. Considering my school is mostly made up of white students and entirely white faculty, when the three students got in trouble, it was probably a stereotypical decision based on non-whites. Blacks have always endured pain and agony as, â€Å"†¦victims of discrimination, segregation, and violence, blacks in the North encountered a powerful cluster of negative racial images. These stereotypes contributed to the conditions of racial degradation and poverty, which, in turn, reinforced prejudice† (Takaki 107). This excerpt further explains that stereotypes stick and the negative racial images will forever be a part of the everyday lives of blacks. The primary reason of why the situation occurred, I believe dates back to sundown towns. Beginning in about 1890 and continuing until 1968, white Americans established thousands of towns across the United States for whites only. A ‘sundown town’ is any organized influence that, for decades, was all-white on purpose. Many towns drove out their black populations, and then posted sundown signs. Other towns passed ordinances barring African-Americans after dark or prohibiting them from owning or renting property. Evelyn Nakano Glenn helps to further explain the regulations, â€Å"White controlled municipalities passed ordinances creating racial zones. When these laws were found to be unconstitutional, whites formed neighborhood associations and turned to â€Å"private† arrangements such as economic boycotts, violence, and restrictive covenants. These restrictions deprived blacks of a central element of liberal citizenship, namely property rights† (37-38). This is proof that the African-American populations had no choice but to leave because they weren’t welcome. No one would support their businesses or wanted anything to do with them; they were literally driven out of these towns and wouldn’t stand a chance if they stayed. Being that the town of Allendale where I grew up was a sundown town, which is the most obvious explanation as to why I grew up surrounded by all whites. Moving onto high school, the other regional towns of Ho-Ho-Kus and Upper Saddle River were sundown towns as well. This plays a huge role in the situation at my high school because people of color and different races are focused on more and white students carry all the dominant privilege. If I had been a different race I think the entire situation would have never occurred because I would probably be a person that was known for affiliating with them. If I had been black, I would have probably felt like I should stick with the other three black students in the high school. The situation would have been the same if I were Latino or another race. Segregation still takes place in America and being one of only a few black families within your community will be a repetitive cycle for black families looking to move to our dominantly white community. According to Douglas Massey; â€Å"When avenues of spatial assimilation are systematically blocked my prejudice, and discrimination, however, residential segmentation increases and persists over time. New Minorities arrive in the city and settle within enclaves, but their subsequent spatial mobility is stymied, and ethnic concentrations increase†¦whereupon group members are forced to adjacent areas, thus expanding the boundaries of the enclave† (225). I feel as though since my region of New Jersey is predominantly white, what would things change now? Why would blacks and ethnic families feel inclined to move to a neighborhood where they stand out? Especially for African-American families, my town along with the surrounding towns do not sell African-American hair products in any of my supermarkets or pharmacies nor are there salons where African-American women can go to get their hair braided. My community has adjusted to the white population and being that my town is so small, I feel as though it would take dramatic lengths to change the way our community functions. Being white, I feel as though I benefited from the whole situation because I did not get in trouble for punching the girl back, and I did not get suspended. I was allowed to return to my day at school as though nothing happened while they were kept in the front office until school was let out and were suspended for the rest of the week (2 days). This experience made me think about my race in a different way because I had never encountered issues with non-white people, because I was never around them. Coming from a primarily white school, white students stand to make white privilege stick out like a sore thumb. It helped me to understand that white people dominated my school population and that this would have never been an issue if the school had always been made up of a majority of other races and ethnicities. It is as if the select few minorities felt as though they needed to stand up for themselves and prove that just because there are so few of them they can still â€Å"run† the school. The three students involved, I feel, chose to leave due to feeling like they were discriminated against and treated differently than other students. They could have felt mistreated or felt that being out numbered was a disadvantage for them. Moving to surrounding schools definitely made them feel like they belonged better because I know there were mixed groups of people outside of our high school district. Being that ninety-nine percent of my school was white could have made the few students feel intimidated and make the white students angrier and feel the need to gang up on them after this incident, almost to prove their white privilege. This incident correlates to issues of citizenship and my ability to participate as a full and equal member of American society because I suffered no consequences from the incident except for a bloody nose. A bloody nose is a temporarily occurrence but because of what happened, it hasn’t affected me being a full and equal member in the American society. It has however, affected the minority students at my high school, and drove them away. As described by Evelyn Glenn, â€Å"At its most general level, citizenship refers to full membership in the community in which one lives. Membership in turn implies certain†¦reciprocal duties toward the community (37). † These black students are citizens but they do not live in a community with other African-Americans reside. They can be still be involved in the community but the families as a whole might not be as eager to get involved as they are outnumbered and may feel their voices may not be heard or make a difference. There are a few potential long term consequences of white privilege for myself that will be with me as long as I live. Being that Quinnipiac University is not very diverse, but more diverse than my high school, it was difficult to get used to seeing people of color and different ethnicities every day. I do not believe growing up in an all white community has been beneficial to me, and I wish I was more natural around people of different races and ethnicities. It is unrealistic to say that I will never have to deal with this, but in the real world, and when finding a job, you will be presented with a variety of people that may even become more of friends rather than co-workers. Someone’s accent or skin color does not determine what kind of person they are, it is their personality that makes them who they are. I also believe in regards to the incident, if I had been at fault, and was suspended for my actions of self defense, I would have not been able to attend a prestigious school such as Quinnipiac. When applying for colleges, most applications ask if you have ever been suspended, such as the Quinnipiac application which asks if you have ever been suspended or missed significant time from school. I would have then had to explain the situation and how I was suspended for self defense. If colleges see that you are a troubled student, and have a record for misbehaving, they will not accept you to their school. Community colleges of lower rankings will be more willing to accept a student with a past, rather than a private school like Quinnipiac University. Discrimination and segregation still exist today. The past makes up the present so learning about what people of all races and ethnicities went through in history is important as a citizen of the United States. Everyone, in some way, or somehow, has dealt with discrimination whether it is you or friends and family. While on the other hand, it is imperative to pay attention to your privileges and understand what it means to be American. Works Cited Barrett, James E. , and David Roediger. 2005. How White People Became White. Pg. 35-40 in White Privilege: Essential Reading on the Other Side of Racism, 2nd Ed. , Paula S. Rothenberg, Ed. New York: Worth Publishers. Glenn, Evelyn, Nakano. Citizenship: Universalism and Exclusion. Pg. 18-55 in Unequal Freedom: How Race and Gender Shaped American Citizenship and Labor. Cambridge: Harvard. Massey, Douglas S. How Space Gets Raced. Rethinking the Color Line. By Charles A. Gallagher. 3rd Ed. New York, NY: McGraw-Hill, 2007. 225. McIntosh, Peggy. 1997 White Privilege and Male Privilege: A Personal Account of Coming to See Correspondences through Work in Womens Studies. Pg. 290-99 in Critical White Studies: Looking Behind the Mirror. Richard Delgado Jean Stefancic, Eds. Philadephia: Temple University Press. Takaki, Ronald T. A Different Mirror: A History of Multicultural America. New York, NY: Back Bay, 1994. 108.

Cause and Effect Essay Essay Example for Free

Cause and Effect Essay Essay In Act Four Scene One Friar Lawrence explains the plan to Juliet, â€Å" Take thou this vial, being then in bed, And this distilled liquor drink thou off, When presently through all thy veins shall run A cold and drowsy humor, for no pulse Shall keep his native progress, but surcease. No warmth, no breath shall testify thou livest. The roses in thy lips and cheeks shall fade To paly ashes, thy eyes windows fall Like death when he shuts up the day of life. Each part, deprived of supple government, Shall, stiff and stark and cold, appear like death. And in this borrowed likeness of shrunk death Thou shalt continue two and forty hours,And then awake as from a pleasant sleep. Now, when the bridegroom in the morning comes To rouse thee from thy bed, there art thou dead. Then, as the manner of our country is, In thy best robes uncovered on the bier Thou shalt be borne to that same ancient vault Where all the kindred of the Capulets lie. In the meantime, against thou shalt awake, Shall Romeo by my letters know our drift,And hither shall he come, and he and I Will watch thy waking, and that very night Shall Romeo bear thee hence to Mantua. In Act Four Scene One Friar Lawrence explains the plan to Juliet, â€Å" Take thou this vial, being then in bed, And this distilled liquor drink thou off, When presently through all thy veins shall run A cold and drowsy humor, for no pulse Shall keep his native progress, but surcease. No warmth, no breath shall testify thou livest. The roses in thy lips and cheeks shall fade To paly ashes, thy eyes windows fall Like death when he shuts up the day of life. Each part, deprived of supple government, Shall, stiff and stark and cold, appear like death. And in this borrowed likeness of shrunk death Thou shalt continue two and forty hours,And then awake as from a pleasant sleep. Now, when the bridegroom in the morning comes To rouse thee from thy bed, there art thou dead. Then, as the manner of our country is, In thy best robes uncovered on the bier Thou shalt be borne to that same ancient vault Where all the kindred of the Capulets lie. In the meantime, against thou shalt awake, Shall Romeo by my letters know our drift,And hither shall he come, and he and I Will watch thy waking, and that very night Shall Romeo bear thee hence to Mantua. †

CRM Prediction and CRM Validation Approaches

CRM Prediction and CRM Validation Approaches Since CRM is underlying the regulation of gene expression in tissue-specific manner, understanding the characteristics of CRMs is helpful to determine the potential CRM candidates for further applications such as tissue-specific gene therapy. As previously discussed the influential parameters to CRM activity include the types and arrangement of transcription factor binding sites (TFBSs) and epigenetic modification pattern[121, 124]. Therefore, these factors are taken into account for prediction of promising CRMs. Transcription factor binding sites are described as short DNA regions (6 to 10 bp in length) which are recognized and bound by various transcription factors[149]. One CRM can contain many TFBSs depended on its functionality[150]. Several experimental studies have been performed in order to map the TFBSs in DNA genome. Chromatin immunoprecipitation (ChIP) assay is a common method to identify the TFBSs in protein-bound DNA complexes in the solution[151, 152]. In addition, DNase footprinting, which relies on the digestion of exposed DNA region where it is not protected by target proteins, has also been used[153, 154]. The difference between these techniques is mainly involving resolution of transcription factor binding sites[155, 156]. To derive the TFBS motifs from raw data, these DNA sequences are used as the input to compute the similarity and the potential motifs are generated. To apply the information of transcription factor binding sites motifs on CRM prediction, it is relatively simple as this method requires solely genomic DNA sequences. The predicted motifs are mapped to the original genome and prospective CRMs containing clusters of TFBSs are identified[124, 157]. Due to the enormous spread of motifs in large genome, a lot of DNA regions showing the potency of being CRMs are indicated; however, only few DNA sequences are actually occupied by the target transcription factors[158]. In the erythroid cells of mouse genome showed approximately 8 million hits of GATA-binding factor1 (GATA1) binding site motifs, but only 15360 motifs were bound by GATA1 and all of bound motifs bore H3K4 monomethylation[159]. Indeed, relying on merely TFBS motifs is not sufficient to obtain the significant CRMs. The study on smaller-size genomes is one alternative to improve the quality of CRM prediction.[157] Another approach to determine the potential CRMs is the use of conservation of non-coding DNA among several species. The assumption is that the DNA sequences associate with gene expression are highly conserved in comparison to non-essential DNA after evolving through the purifying selection over time [157]. This method is not depended on the information on TFBS so that it offers another solution to prediction of CRMs in case tissue-specific enhancers have not been widely studied. At initial study about the DNA sequence alignment of more than 100 bp-long DNA between human and mouse, with the minimal conservation of 70%, was conducted and potential enhancers for certain genes such as interleukin-4, interleukin-13 and interleukin-5 were identified[160]. Later on this approach shows the promising results due to high validation rates in transgenic mouse embryo by using rigorous conservation constrain[160-163]. The conservation-based prediction is also applicable to discover novel TFBSs wh ere the information is not extensively elaborated. With the DNA sequence alignment between orthologous species, the short DNA sequences conserved in many species, namely phylogenetic footprints, could be the possible binding sites for transcription factors [164, 165], and mutations of the conserved boxes can lead to the reduction of gene expression as in the example of altered effect of variant E box on ÃŽ µ-globin reporter gene induction[166]. As the approach is mainly related to the evolutionary constrain among species it means that the use of this method may overlook the potential CRMs which are lately developed and the TFBS pattern cannot be aligned to the former population[157]. For example, in the ChIP-seq study the GHP68 enhancer, located at intragenic region of mouse abhydrolase domain containing2 (Abhd2) gene, does not contain the footprint of GATA-binding factor1 (GATA1) motif which is commonly found in Abhd2 genes of other non-primate species[167]. Indeed, the GHP68 enhan cer in primate genome possesses the unique protein binding pattern[157]. Another consideration on conservation-based prediction is that even though the conservation level of selected CRMs is extremely high among orthologous species, the actual activities of CRMs possibly vary from species to species in nature[168]. Due to the limitations of previous approaches regarding false positive prediction by highly redundant presence of TFBS motifs in large genome[158], as well as lineage-specific evolution of certain CRMs in different organisms[157], epigenetic regulation is considered the promising parameter of CRM prediction as a result of the strong correlation between hypersensitivity to DNA treatment/histone modification and enhancer activity[169-171]. Many CRMs have been found to localize at genome region where the response to DNase activity is very sensitive[153, 172]. In addition biochemical patterns of modification at enhancer are showed including histone acetylation[169], high H3K4me1 as well as low H3K4me3 modification[170], and occupancy of histone acetyltransferase p300[171, 173]. For active promoter, in contrast to usual enhancers, the major characteristic is the presence of nucleosome-free and high level of H3K3me3 modification[174, 175]. By using the reference genome database containing epigenetic as well as DNase hypersensitivity regions, where the information is obtained from ChIP seq [176], and DNase seq experiments, the substantial rate of validation of selected CRMs from 43 to 100% in many study models[169-171, 176, 177] indicates the robustness of the epigenetic-based approach. The idea is this method is optimized that the predicted conditions is not too stringent as evolutionary conservation method and the number of output is not too enormous as TFBS-based prediction[157]. Still, some potential CRMs can be overlooked using biochemical features[173, 178]. For instance, the study of heart enhancer identification showed that three different predictions yielded various amount of outputs. The possible CRMs were hardly obtained through comparative genomic DNA alignment while the use of p300 occupancy to identify the potential sequences gave rise to 130 output sequences with 75% validation rate[173]. In another TFBS-based study in heart by Narlikar and colleagues, the classifier, where its database relied on predicted and validated TFBS, was generated to select the putative CRMs from the non-functional DNA[178]. This prediction allowed them to distinguish 40,000 CRMs from genome and the validation rate was relatively considerable in comparison to the epigenetic approach[178]. This suggests the need of additional further study on biochemical pattern prediction to cover the missing CRMs. Using experimental and computational study, scientists are able to collect the extensive information about TFBSs, epigenetic modification and conservation of DNA among species. This data has been widely deposited in many open-access database websites, which become the significant information resources for further CRM identification[179]. The Ensembl Regulatory Build is recently developed to integrate the previous discovery of epigenetic marks and occupancy of transcription factors from different projects and build the better-defined regulatory regions in human genome[180]. Another commonly used database website is the University of California Santa Cruz (UCSC) Genome Browser Database, which provide all aspects of information for CRM prediction including experimental (DNase hypersensitivity clusters, epigenetic marks of histone proteins, and binding of transcription factors from ChIP seq) as well as computational (conservation level among vertebrates from DNA sequence alignment) study [181]. This aids the feasibility of enhancer prediction since the use combinatorial information would suggest more significant CRM outputs with higher validation rate[182-184]. For example, the sophisticated protocol designed by Nair and team to identify the liver-specific CRM was derived from the integration of experimental study from UCSC genome browser and the putative TFBS motifs from computational analysis[182]. To obtain predicted liver-specific TFBS motifs, the presumptive promoters, which are 1000-bp DNA sequences located upstream of transcription start sites, from highly-expressed genes were initially compared to ones from low-expressed genes in the liver, followed by computing the potential TFBS motifs which are likely to associate with liver-targeted gene induction based on distance difference matrix (DDM) and multidimensional scaling (MDS)[182, 185]. The DDM was primarily used to identify the difference between two protein structures by calculating the distance differenc e values from low distance matrices[186]. Ultimately the predicted TFBS motifs were mapped to the corresponding DNA sequences of liver-specific genes in UCSC genome browser where the experimental data of such genes was previously described[182]. The ideal CRMs were expected to show the coexistence of predicted motifs together with dense DNase clusters, high conservation level in vertebrates, and explicit histone modification patterns. In addition, the putative motifs should be consistent to the transcription factor lists from ChIP-seq experiment. The promising liver-specific transcriptional module from prediction was further validated and showed the remarkable activity to up-regulate hFIX expression up to 15 fold compared to control, reflecting the robustness of the prediction method[182]. The same approach has also been applied to design the CRMs targeting other target cells such as cardiomyocytes, and the 10-fold augmented expression of cardiac genes was noted upon validation in m ouse model[183]. Taken together, this suggests the increased power of using multiple parameters to determine transcriptional modules, and the combined data provided in UCSC genome browser is valid; the integrated data is nicely standardized so that the summary of information is reliable. However, the feasibility of combinatorial approach, relying on both computational data and previous experimental study, is the major concern due to the requirement of strong expertise on bioinformatics knowledge for computation of TFBS motifs. One possible alternative to circumvent this limitation would be the direct use of available information on UCSC Genome Browser for CRM selection by taking associated determinants (DNase hypersensitivity, transcription factor binding, histone modification, and conservation level among vertebrate) into consideration. There are several validation assays that have been performed to investigate the potency of CRMs to enhance gene expression. In general, the plasmids containing minimal core promoters and reporter genes such as lacZ, encoding ÃŽ ²-galactosidase, luciferase, and green fluorescence protein (GFP), are the backbone constructs, and the predicted CRM are cloned into certain position based on the validation methods[149]. Usually CRM sequences are inserted at the upstream of the promoters and the increased strength of overall construct expression is assessed after transfection or integration of plasmids[187-196]. In order to develop the downstream process to identify the target cells where CRMs are active, the use of heterologous barcode has been done so that the number of CRM high-throughput screening is up to hundreds or thousands [191-194, 196]. In some studies, the need of barcode is eliminated by targeting at enhancers directly, and the method is called self-transcribing active regulator y region sequencing (STARR-seq) [197]. Both transgenic animal embryos and specific cell lines [187-191, 193-196] are commonly used to study CRM activity. For example, transgenic mouse or fly (D.melanogaster) containing putative CRMs as well as reporter genes are initially generated, and the development of reporter gene signals later observed at the certain parts of embryos is identified depended on tissue specificity of CRMs[198]. To improve time and cost-effectiveness of the current approach, Gisselbrecht and colleagues developed the technique called enhancer-FACS-Seq (eFS), which makes use of the distribution of GFP signaling based on the tissue-specific CRM enhancement, to sort out the GFP-positive cells from the negative population using fluorescence activated cell sorting (FACS)[190]. Validation of the effect of CRMs on gene expression has also been reported in animal models and the delivery methods of CRMs are adjusted to be tissue-specific. AAV is the example of tissue-target ed delivery system since its tropism is relied on the serotype[182-184]. The use of AAV vectors to carry the predicted CRMs to the specific organs has been done in heart and liver enhancers by using AAV9, and the follow-up process was achieved through the reporter hFIX protein expression in the blood. In murine models, to reduce the cost of virus production, HD injection of plasmids containing CRMs in mice can be primarily done for initial screening[182]. This method is distinctive since the model simulates the actual situation of CRM activity in animal body for gene therapy application[182-184]. In addition, another advantage of using this approach is the longevity and the expression level can be observed continuously for long-term study as the mouse sacrifice is not required. Biology of hepatocellular carcinoma (HCC) Hepatocellular carcinoma (HCC) is one type of liver cancers which is highly prevalent in many regions such as East Asia, Africa, and United State[199]. Even though the incidence of HCC ranks the sixth in comparison to other cancers the rate of mortality is relatively high[200]. There are several etiological factors describing HCC development including Hepatitis B (HBV) and C (HBC) infection, aflatoxin-directed induction, alcohol consumption, accumulation of fat in the liver resulting in non-alcoholic steatohepatitis (NASH), sex-related influence, unbalance of microbes in gastrointestinal tract, and type II diabetes[201]. Each factor has specific mechanism to cause HCC, but in general most of factors ultimately lead to liver cirrhosis formation and subsequently HCC[202]. A number of staging system to classify HCC disease development stage have been designed for diagnosis; however, the gold-standard for staging remains challenging due to heterogeneity of HCC population[203]. To study the molecular mechanism underlying HCC development, copy number genomic[204-206], exomic[207, 208], whole-genome sequencing[209, 210], and transcriptomic[211, 212] studies have been conducted in liver cancer tissues. In copy number alteration analysis, both deletion (i.e. TNFAIP3, CDKN2C, WRN, PTEN, BRCA2) and duplication (MDM4, BCL9, ARNT, MET) of specific genes are found in HCC genomes[213]. Exome and whole-genome sequencing in HCC allow detailed investigation of genome structures at the levels of mutation in both coding and non-coding regions[213, 214]. For example, mutation of NFE2L2-KEAP1 and MLL genes were identified from 87 cases with HCC development using exomic approach[214]. Transcriptomic study gives another insight into HCC regarding the change of expression profiling compared to normal hepatocytes. Using in combination with whole-genome sequencing, transcriptome revealed the RNA editing mechanism implicating in up-regulation of gene expression in cancer developm ent[215, 216]. Taken together, the aberrant genes found in HCC are mapped to cellular pathways to explain the molecular mechanisms underlying disease development. The pathways which are postulated as the keys for hepatocarcinogenesis include cell cycle regulation (i.e RB[217], CDKN2A[218]), WNT pathway (i.e. APC[219], AXIN1[220, 221]), chromatin remodeling (i.e. ARID2[208, 210], MLL[222]), tyrosine kinase signaling (i.e. SOCS-1[223], IGF[224]), and NOTCH[225, 226] pathways. Apart from structural genes, miRNAs, small non-coding RNAs which control gene expression at post-transcriptional level through hybridization with the mRNA templates and subsequently leading to translation inhibition or RNA degradation[227], are implicated in HCC progression due to the evidences on differential miRNA expression between HCC and normal hepatocytes[228, 229]. In general, miR-92, miR-18 and miR-20 are significant in HCC stage progression[229]. Some altered miRNA expression is associated with etiological factors. For[MC1] instance, there is correlation between miR-126 down regulation and alcohol consumption[230]. The functions of miRNA in HCC pathogenesis are divided into two groups; oncogenic miRNAs and tumor-suppressor miRNAs. For oncogenenic miRNAs, three miRNAs including miR-221, miR-224 and miR-21 have been showed to enhance hepatocarcinogenesis. The miR-221 plays role in cancer invasion using two mechanisms; increasing cell proliferation targeting CDKN1B/p27 expressi on[231], and enhancing cell migration through AKT signaling[232]. The invasion of HCC is also supported by miR-224, but its mechanism of action is involved with homeobox D10 downregulation and induction of inflammatory pathway[233]. Another oncogenic miRNA miR-21 is reported to suppress expression of program cell death 4 (PCD4) [234, 235]protein which functions as tumor suppressor protein, and to increases cell proliferation through the regulation of mitogen-activated protein kinase-kinase 3 (MAP2K3) activity[236]. Apart from individual miRNAs, certain clusters of miRNA have been identified to contribute to HCC progression. For instance, the up-regulation of miR-17-92 cluster, which is composed of miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1[237], was found in HCC, and the attenuation of its expression diminished the ability of malignancy transformation[238]. The activity of miR-17-92 cluster affects the expressions of certain genes usually found in HCC such as PTEN, E2F1, and E-cadherin[239]. However, the individual miRNA members may function in the different ways. For example, up-regulation of miR-19 suppressed the formation of liver fibrogenesis through TFF-ÃŽ ² signaling[240]. A number of tumor suppressive miRNAs have also been discovered to diminish HCC development. The miR-122 function is to control the genes associated with tumor formation and metastasis including VEGF[241], RHOA[241], PKM[242] whereas miR-375 exerts its activity by suppression of ATG7 expression to block autophagy[243], the essential mechanism of cancerous cells to survive under hypoxic environment. The miR-125b prevents cancer proliferation by activation of p21(WAF1/Cip1) G1/S cell cycle arrest as well as repression of SIRT7 gene induction[244]. G1/S transition of cancer cells is also controlled by miR-26a activity[235]. The overall functions of HCC-associated miRNAs are implicated in STAT3, by modulating Bcl-2 and Mcl-1 functions, and NF-ÃŽ ºB inflammatory pathways, le ading to hepatocacinogenesis[245].

Sigmund Freud Essay -- essays research papers

Sigmund Freud was born may 6, 1856. He was the first of six children he also had two older half brothers from his fathers previous marriage. This was his father’s second marriage and in this one he was much older than his wife was about twenty years older than he was. When Sigmund was just 4 years old his family moved to Vienna, it was a tough childhood for Sigmund growing up in a large Jewish family with not to much income it was a struggle for everyone in the family. He was nicknamed the golden child at one point in his childhood and the meant he was to achieve great success, from that point on his family did everything they could to give Freud a chance to succeed. Freud excelled at his studies at an early age, earning top marks in all of his classes. He excelled in everything but especially languages he could speak five languages at a young age. Freud was so dedicated to his work sometimes he would have meals sent to his room just so he could study. To prove how much his parents did for him the golden child a younger sibling was learning to play piano but Freud complained about the noise so they had the piano removed from the house. Like most geniuses Freud had a hobby that he was very passionate about he used to keep a record of all his dreams in a logbook and he would read them over and analyse them. At the tender age of 18 Freud entered medical school, he studied a lot of things including fish and seals. He graduated from medical school with top marks in his class....

The Probability of a Major Hurrican Hitting New Orleans :: essays research papers

The Probability of a Major Hurricane Hitting New Orleans   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Table of Contents Executive Summary  Ã‚  Ã‚  Ã‚  Ã‚  3 Introduction  Ã‚  Ã‚  Ã‚  Ã‚  3 Hypothesis  Ã‚  Ã‚  Ã‚  Ã‚  7 Analysis & Method  Ã‚  Ã‚  Ã‚  Ã‚  8 Conclusion  Ã‚  Ã‚  Ã‚  Ã‚  10 References  Ã‚  Ã‚  Ã‚  Ã‚  12 Appendix  Ã‚  Ã‚  Ã‚  Ã‚  14 Executive Summary New Orleans, Louisiana lies at the second lowest elevation among major cities in the United States. It is a city surrounded by water, making it almost like an island. To counter this dangerous combination of the low elevation along with the lakes, rivers and swamps surrounding it, the Army Corps of Engineers built a series of levees around the city to foster its protection. It is these very same levees however that might doom the city should a Category 3 hurricane ever hit. Our statistical analyses examined the current belief that there is a 39% probability that New Orleans will be hit by a major hurricane and based on the resulting Z-score, rejected that belief. We did find however that the probability, while not 39%, was still in the 30th percentile range, which should still be a major cause for concern among the leaders and residences of the city of New Orleans. Introduction New Orleans is a city that is rich in culture as well as history. The city is in effect, an island – Lake Pontchartrain surrounds the city to the north, the Mississippi River to the west and south, and a bevy of lakes – including Lake Borne to the east. Surrounding the city is a series of levees to keep these bodies of water at bay. In addition to these levees, the only defense the city has is a series of canals and a very antiquated pumping system. However, the same levees that protect the city, makes it a death trap should a major hurricane make a direct hit to the metropolitan area. The risk of intense flooding brought forth by storm surges of 20+ feet would wipe the city out. New Orleans was founded to be a port to the world – with its intersection at the Mississippi River and the Gulf of Mexico, it was a great location for world trade. However, it was also a cesspool of disease, floods, and other problems. Despite this, the city was a major economic powerhouse and the city grew and prospered despite of the problems. As the city expanded, swampland was reclaimed to expand the city. To protect its citizens, the Army Corp of Engineers built a series of levees around the city. These levees form a bowl around the city. It is precisely this architecture that was meant to protect the city will in effect destroy the city.

The Causes and Effects of World War I Essay -- Papers

The Causes and Effects of World War I In 1914 through 1918, the entire world was at war. Due to many small, and some great incidents, the world powers went to war. During the war there were many events that drastically affected the outcome. Some of these events were very influential. From the assassination of Archduke Francis Ferdinand to the Treaty of Brest-Litovsk, the war was shaped by events like this. On June 28, 1914, the Archduke of Austria-Hungary, Francis Ferdinand, and his wife entered their car. About five minutes later a blast rang out. A bomb had been throw in front of his car. A Serbian nationalist and member of the Black Hand, Gavrilo Princip, ran up to the car and, with two shots, killed the Archduke and his wife. When news of the murder reached Austria-Hungary, they thought that the Black Hand was in some way associated with the Serbian government. The Austria-Hungarians gave the Serbs and ultimatum. The Serbians agreed to all but one condition. This wasn't acceptable for the Austrian-Hungarians. They declared war on Serbia. The system of alliances soon took effect and had all the Allied countries declaring war on the Central Powers and vice versa. On May 7, 1915, A British ocean liner is sailing off the Irish coast. Onboard are about 1,200 people, 125 of which are Americans. They boarded despite the fact that the German government had warned Americans not to take British ships. Suddenly a torpedo hits the side of the ship. A German U-Boat, U-20, had shot at her. Within 20 minutes the British Liner was at the bottom taking over 1,000 souls. The sinking of the Lusitania was one of the major reasons the United States was drawn into World War I. It swayed American public opinion in favor of joining t... ...ed. Vladimir Lenin wanted to end the fighting so he accepted the German demands. The German demands were even harsher this time. Russia would lose Poland, the Baltic states, and recognize Finland, Ukraine, and Georgia as independent states. After the treaty was signed, Russia lost 25% percent of it's total area and population. Also, since Germany no longer had to worry about the Eastern Front they could commit more troops and weaponry to the Western Front. The five mentioned events are some of the most significant of the war. From beginning to end, the war was shaped by events like this. The Treaty of Versailles all but ended the fighting. During the course of the war over 10 million soldiers lost their lives and 20 million were wounded. As Europe was trying to rebuild, the League of Nations was created to prevent something like this from ever happening again.

Movies Represent Storytelling at Its Best Essay

Imagery, sounds, storytelling ability, excellent editing, serious acting and creative imaginations are all technically combined to make a good movie. Movies represent storytelling at its best. The writer gives a script to the director who interprets it and creates a core team of professionals that includes the cinematographer, the designer (and his team), the sound engineer, the actors, and the editor. They make ï ¬ lms to entertain, to express emotion, tell stories, deliver messages, to dream, to imagine, and it is all because they have a passion that drives them. Filmmaking takes time, patience, dedication, commitment, and an understanding of the process in its totality. If ï ¬ lmmakers are oriented toward story and performance, they must learn to visualize the narrative. The story must unfold in the mind’s eye, as it is conceived and created. The ï ¬ lmmaker has to see the movie while the screenplay is being written and during pre-production before the cameras roll. (LoBrutto 2002) Matthew Vaughn created a make-believe movie which insinuates that mutants are everyday people that exist among us; and there were times during the movie that the thought actually crossed my mind. Owing to the fact that, making a film is a most complex artistic enterprise and that, movie making is the only creative endeavor that encompasses all of the arts: writing, photography, painting, acting, music, dance, and architecture; the filmmaker must take on the challenge of telling a story via image and sound each time a movie is made. (LoBrutto 2002) Storytelling A movie is a story; it is as simple as that. Movies are really a category of art that use various kinds of technical combinations of imagery and sounds to tell stories. However, how the story is told, often make fictions seem real, non-fictions become personal, fantasy appear realistic and musicals, like Burlesque, http://youtu.be/9snF_LsF-OI expand into song and dance. There is always something that viewers can relate to in movies. Nevertheless, â€Å"Movies are not, and are not meant to be, blueprints for how to live our lives. They are, however, reflections of lives.† (Goodykoontz, & Jacobs 2011) The story, X-Men: First Class, is about former closeted mutants coming out and embracing their difference. However, the film began with a setting during the period of the holocaust when Magneto was a young boy in Poland. The boy’s name was Erik Lehnsherr (later named Magneto). The story highlights aspects of the enslavement of Jews by the German Gustapo. The close-up shots of the numbers that were branded on the arms of the Jewish people in the concentration camp align the story with an actual historical event. Those shots coupled with the boy’s forceful separation from his mother help to authenticate and solidify the director’s attempt at reality. His anger and fury at the separation triggered his mutant power of magnetism that caused him to rip the metal fence that stood between himself and his mother. The Gustapo commander’s name was Schmidt (later Sebastian Shaw). It was he who shot and killed Erik’s mother in cold blood, before the child; resulting in Erik’s mutant power of magnetism being triggered and magnified during his subsequent angry outburst. Sebastian Shaw murdered the boy’s mother because he wanted to see a demonstration of the boyâ€⠄¢s mutant powers. Mission accomplished, Shaw wanted to train and harness Erik’s mutant power to use it as a weapon. On the other hand, Charles Xavier was a brilliant academic who is of gentry stock. As we saw it when he was a boy, he had the power of telepathy. He also had the ability to read and control other people’s minds. In the beginning of the film, Charles was quite blatant and unapologetic about reading people’s minds without their permission as was the case when he was talking the woman at the bar, before Raven interrupted. He became a CIA consultant on humans with mutant abilities then later he and Erik (who became his close friend) recruited, trained and formed X-Men: First Class a department within the CIA. Both men, Charles and Erik formed a league of mutants to fight against the plans of the evil Sebastian Shaw. There were also minor storylines about interpersonal relationships and the mutants’ personal insecurities as it related to personal acceptance. Overal l the storyline of a Jew’s revenge against his former Gustapo torturers was good; revenge in this case was sweet. Acting Actors are the most visible elements in a film. The actors †¦. In X-Men: First Class There was wild card and character actors but there were no star actors (except for Hugh Jackman’s one clip appearance when he used the f word). The acting was mediocre because at times it did not come across as being natural. It appeared to be acting, more the type for a stage production than for the cinema. However, if I should compare the two main characters; Michael Fassbender did a good job of portraying Erik’s anger, loss and hurt that he suffered growing up in a concentration camp. McAvoy in Charles’ character on the other hand, did not have much negative experience to work with and his character came across as Erik’s boring telepathic side-kick. Kevin Bacon did justice to Sebastian Shaw’s character. With the exception of Raven, the other actors were not really given much screen time. There were many actors but not much solid acting, although there was a lot of action. Cinematography The director of cinematography’s job is to take the director’s view of how the movie should look and help the director to get the shots that he wants with ideas on camera angles, types of cameras, and lighting suggestions that will best serve the director in getting the type of feel he wants out of each scene in the movie. (Goodykoontz, & Jacobs 2011). The cinematographer is specifically responsible for its look, in very specific, shot-by-shot terms. He or she is responsible for the images that the camera sees, and by extension the images that the audience will see in the finished film. . Cinematography means â€Å"writing with movement.† (Goodykoontz, & Jacobs 2011). http://www.youtube.com/watch?v=IAbhclxSNTw The cinematographer demonstrated knowledge based brilliance and skillful use of all type of shots in this clip. He coupled it with the bright natural sunshine made the finale to this clip quite moving. The words â€Å"Never Again† were delivered in a deep focus close up shot of Magneto. The cinematographer used long, medium and close-up shots as well as deep focus. His variety of shots and choice of lightings made this film very entertaining. Editing â€Å"The film editor helps create the film, literally constructing it, piecing together different takes of individual scenes and then placing the selected scenes in the order that tells the story the director wants to tell. The editor’s role is crucial to the making of a successful film. Poor editing does the audience the ultimate disservice when it comes to film.† (Goodykoontz, 2009). The scenes were fast paced, action packed, story driven to the point where there was nothing noticeably wrong or out of place with the editing. It was done in an incongruous style and that added to the overall excitement. The fast movements created the desire to watch this film again and again. The editing was clean. There were no visible or audible hitches. The story flowed and it was quite riveting and entertaining because it reflected real life human struggles for acceptance. Sound â€Å"Music has been a crucial part of the movie going experience since before the advent of recorded sound in films. So important was its use that over time directors began inserting musical cues, or signals, for specific music to be played at specific times.† (Goodykoontz, & Jacobs 2011) I particularly favored the scene that brought Xavier and Erik together; it contained a variety of magnificent sounds. When Erik was in the sea and there was also a bevy of boats and ships around him; there were sounds of boat horns; there were natural sounds of water splashing against the sides of the ships and the ripping sounds of the speed boats dividing the water. During the destruction of Shaw’s ship, there were credible sound effects of the unreeling of the massive chain on the anchor; the crashing banging sounds and the explosive sounds. The complimentary sound of background orchestra music playing that loaded repeated andante beat (da-dap da-dap da-dap) that suggests action and then there was the dialogue. Overall, the music and sounds were seamlessly interwoven into each scene to further engage the audience’s attention. Added to that, amidst all the other sounds, the dialogue was clear and audible. The overall sound for this movie was good. Style and Directing A film director is the creative force behind a movie. He is the one who is responsible for the end product that the viewing public pays to see at the movie theatre. His word is final on the visuals, the sounds and the acting. According to Vincent LoBrutto in his book, The Filmmaker’s Guide to Production Design; â€Å"A good director must have a ï ¬ rm idea of how to translate the script cinematically.† (LoBrutto 2002) LoBrutto went on further to say that, directors read the script for an overall impression and impact. It does not matter who the scriptwriter(s) is/are, it is the director’s interpretation, shots and takes that viewers see at the movie theatres. The buck stops at the film director. (LoBrutto 2002) Director Matthew Vaughn has his own fast-paced action-packed style of directing. http://www.imdb.com/name/nm0891216/ He tried to make comic book characters seem real by fusing natural historic events like the holocaust (Erik was in the concentration camp during the Holocaust where his mom was killed) and the Cuban missile crisis into the plot. Vaughn created elaborate props and set designs and he used every computer graphics skill to enhance the story. X-Men: First Class doesn’t just rely on the usual fast paced scenes and top notch special effects that are typical of action movies; it raises the bar several notches. It doesn’t lose its sentimental core amidst the explosions and super feats but it continues to provide viewers a complex storyline to follow. This is Vaughn’s â€Å"Kick Ass† style. There is humor as in the training sessions when Banshee, after receiving clear instructions and encouragement; fell straight to ground without even attempting to try. There was much laughter at his expense. Humor is Vaughn style; as his previous work â€Å"Kick Ass† showed; that coupled with the elaborate props and high tech sound effects; complete his signature on the project. The director Matthew Vaughn placed his stamp on this movie through the production design, the acting, the dialogue, the cinematography and especially the sounds. http://www.imdb.com/name/nm0891216/ Impact of society on the film and vice versa Whether it is in appearance, fashion, or behavior, films romanticize a certain lifestyle that is eagerly imitated by audiences. Fashion magazines promise that we can â€Å"Get Angelina’s Look† if we follow the tips inside. Celebrity gossip publications keep readers up-to-date on the comings and goings of seemingly everyone who has appeared in a movie. The Internet and social media are practically choked with chatter about film— box-office results, reviews, gossip, and more. Beyond such obviously shallower aspects, film can influence how we live, our morality, and our behavior. (Goodykoontz, & Jacobs 2011) â€Å"Film can influence how we live, our morality, and our behavior.† (Goodykoontz, & Jacobs 2011) Filmmakers will argue that, this effect is unintentional because movies are a part of a make believe world but there are those who pattern what they see, and make it their reality. An example of society’s impact on film is portrayed in the indelible affect that the holocaust had on Erik; he was soaked with hatred and revenge for the former Gustapos who imprisoned him, especially Sebastian Shaw. This is a portrayal of the agony that the Jewish people suffered at the hands of the Germans. That intrinsic hatred became the fuel for his mutant powers. The others had to hide their difference from normal society, for fear of rejection but above all the fear of unknown reaction to them. Likewise, the film is highlighting the fact that some people among us who are different from us, want acceptance and they also want to feel a sense of belonging just like normal people. Their differences are as varied as the characters in the film and their needs are as similar. It is sending a message of acceptance, brotherhood and unity. Genre â€Å"A genre is so called because it tends to use familiar story formulas, character types, settings, and iconography (visual imagery with symbolic implications), all of which lead viewers to have certain expectations about what the movie will be like before actually watching it. .† (Goodykoontz, & Jacobs 2011) It is a type, or category of films that is usually easily recognizable as part of a certain genre. Genres tell the audience up front what to expect from the product they are buying. If they like a particular kind of story, chances are they will like this particular film, especially if the writer and director give the expectations a little twist. X-Men: First Class is an action-fantasy. It is loaded with action but it is also loaded with some fantastic comic book feats. At the start of the film, the MARVEL logo is shown; that is an indicator that it is a comic book story. The ability for humans to alter and mutate into other beings, is genre specific activities for fantasy. While the fast-paced actions during the confrontations/battles with good and evil are typical of action films. Therefore, it is difficult to place the film within any one genre because it can fit into several: drama (Erik’s beginning and the dramatic separation from his mother); fantasy (Erik’s control of the missiles in mid-air); action (the air and sea confrontation). Application of at least one approach to analysis and Interpretation Films are often used to express emotion, deliver a message, to dream and to imagine; all having to do with human psychology. A psychological approach to analyzing a film is especially concerned with how a film provides examples of various psychological theories and concepts, particularly those of Sigmund Freud and Carl Jung (e.g., sexual symbolism, subconscious repression and dreams, the id, ego, and superego, the collective unconscious). Identity crisis was an issue in the film. Psychologist Erik Erikson’s psychosocial theory of human growth and development at the fifth stage looks at Identity versus Identity confusion. This was played out so well by Raven. It states that adolescents must be allowed to explore different roles in a healthy manner in order to achieve a positive identity; or else they will experience identity confusion. (Santrock, 1989) Raven obviously received no previous parental guidance regarding self-acceptance and role explorations; she hid behind a morphed socially accepted form. She was more comfortable being someone else and she often abandoned her true identity. Accept Yourself: http://www.youtube.com/watch?v=Csii_f5f204 â€Å"You want society to accept you, but you can’t even accept yourself,† said Magneto to Raven. Raven had a serious problem of identity confusion and she struggled with self-acceptance. In the above clip Erik challenged her to accept herself in her true blue form. The movie embraced people who were physically different, while at the same time it was highlighting their struggles to gain social acceptance and their deep-down desire to be normal. This point was introduced as early as the meeting with Charles and Raven. http://www.youtube.com/watch?v=UEKxXYrb2Rk The insecurities about their difference continued to play out in the dialogue between Raven and Charles as well as Raven and Hank. http://youtu.be/PKnL_MwwU3o Charles Xavier, who like Erik, had no visible disability, seemed to have had a more rational approach to life in general. He was more in control of his behavior and his decisions than Erik. According to Psychiatrist Sigmund Freud, the ego makes rational decisions (Santrock, 1989 p. 34). An example of this was the scene where Charles was in his kitchen and Raven (who he looked upon as a sister) entered in her unclothed blue form, in a sensual rather sexual manner. Charles’ ego quickly assessed the situation and decided that it was wrong and he chided her with disgust in his voice. His conscious ego made a decision. Similarly, psychologist Albert Bandura’s social learning theory speaks to conforming to social behavior within the one’s environment (Witt & Mossler, 2010). Charles Xavier knew that society, especially the upper class to which he belonged, would definitely not accept Raven in her true form. His socialization caused him not to even consider having a relationship with a blue woman; blue blooded one, perhaps. Overall textual themes There are five categories that make up the theme of every film: the plot, the emotional mood, the character, style or texture, and ideas. (Goodykoontz, & Jacobs 2011) There were several themes in this film. †¢Self-Acceptance: The lack of social acceptance motivated the mutants to bond together as a brotherhood; and help each other to gain control of their super power as well as provide them with a safe non-judgmental environment. †¢Brotherhood and Unity: They watch out for and watch over each other; they literally function like a family with Erik and Charles as the parents. At Charles castle during the training days. †¢Inter-Personal Relationships: Charles and Erik seem to have a deep seated tenderness for each other as was seen in those close up shots when Charles was shot in his back. Erik held him in his arms and the moment captured a deep relationship. †¢Revenge: Erik hunted and killed all his torturers. Sebastian Shaw’s killing was the final reveng e and the sweetest. Conclusion Imagery, sounds, storytelling ability, excellent editing, serious acting and creative imaginations are all technically combined to make a good movie. Movies represent storytelling at its best. The writer gives a script to the director who interprets it and creates a core team of professionals that includes the cinematographer, the designer (and his team), the sound engineer, the actors, and the editor. They make ï ¬ lms to entertain, to express emotion, tell stories, deliver messages, to dream, to imagine, and it is all because they have a passion that drives them. Filmmaking takes time, patience, dedication, commitment, and an understanding of the process in its totality. If ï ¬ lmmakers are oriented toward story and performance, they must learn to visualize the narrative. The story must unfold in the mind’s eye, as it is conceived and created. The ï ¬ lmmaker has to see the movie while the screenplay is being written and during pre-production before the cameras roll. (LoBrutto 2002) The film was good, exciting, colorful, action packed and almost believable. However, due to its suggested sexual contents and the one time use of the f word, I cannot recommend it for the family. Twaitney O. Reference Goodykoontz, B., & Jacobs, C. P. (2011). Film: From Watching to Seeing. San Diego, CA: Bridgepoint Education, Inc. LoBrutto, V. (2002) The Filmmaker’s Guide to Production Design New York, NY: Allworth Press Santrock, J. W. (1995). Life-Span Development. Dubuque, IA: Brown & Benchmark Witt, G. A., & Mossler, R. A. (2010). Adult Development & Life Assessment. 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