Walt Disney :: essays research papers

Walt Disney   Ã‚  Ã‚  Ã‚  Ã‚  Walt Disney was one of the famous motion-picture producers in history. He first became known in the 1920's and 1930's for creating such cartoon film characters as Mickey Mouse and Donald Duck. He later produced feature length cartoon films, movies about wild animals in their natural surroundings, and films starring human actors. Disney won 32 Academy Awards for his movies and for scientific and technical contributions to filmmaking. He also gained fame for his development of theme parks.   Ã‚  Ã‚  Ã‚  Ã‚  Walter Elias Disney was born on Dec. 5, 1901, in Chicago, Illinois. His family moved to Missouri, and he spent much of his boyhood on a farm near Marceline. At the age of 16, Disney studied art in Chicago. In 1920, he joined the Kansas City Film Ad Company, where he helped make cartoon advertisements to be shown in movie theaters.   Ã‚  Ã‚  Ã‚  Ã‚  In 1923, Disney moved to Los Angeles to become a film producer or director. When he failed to find a job, he returned to producing cartoons. He set up his first studio in the back half of a real estate office. For several years, Disney stuggled to pay his expenses. He gained success in 1928, when he released the first short cartoons that featured Mickey Mouse. Earlier filmmakers had found that animals were easier to animate than people. Mickey Mouse, drawn with a series of circles, proved ideal for animation.   Ã‚  Ã‚  Ã‚  Ã‚  In 1927, sound that had been added to motion pictures, and a process for making movies in color was developed a few years later. Disney and his staff made imaginative use of sound and color. Disney himself provided Mickey Mouse's voice for Steamboat Willie (1928), the first cartoon to use synchronized sound. His cartoon Flowers and Trees (1932) was the first cartoon in full Technicolor.   Ã‚  Ã‚  Ã‚  Ã‚  From 1929 to 1939, Disney produced a cartoon series called Silly Symphonies, which played in theaters along with other animated films featuring Mickey Mouse and other characters, like Donald Duck, Goofy, and Pluto. After 1924, Disney actually did more of the drawing necessary for his animated films. His genius lay in creating, organizing, and directing the films.   Ã‚  Ã‚  Ã‚  Ã‚  In 1937, Disney issued the first full-length animated feature film to be produced by a studio, Snow White and the Seven Dwarfs. It became one of the most popular movies in history. Disney's later full-length animated films included Pinocchio (1940), Fantasia (1940), Dumbo (1941), Bambi (1942), Cinderella (1950), Alice in Wonderland (1951), Peter Pan (1953), Lady and the Tramp (1955), Sleeping Beauty (1959), 101 Dalmations (1961), and the Jungle Book (released in 1967, after his death). In 1950, Disney released Treasure Island, his first full-length movie to use only human actors.

Douglas McGregor’s Theory X and Theory Y Essay -- Business Management

Douglas McGregor’s Theory X and Theory Y Biography of Douglas McGregor Douglas McGregor was born on 1906 in Detroit, America. In 1895, it was here that his grandfather, Thomas McGregor started his business and given its name as, McGregor Institute. The business provides assistance to Great Lakes sailors and other transient labour. The Institute provided shelter, warmth and food to approximately 100 men every year. When Thomas McGregor passed away, his son Murray McGregor (Douglas’s father) continued to manage the business. During high school, Douglas McGregor worked as a night clerk and played the piano and organ at the chapel services. At work, he became familiar with the employees and their problems. In 1936, McGregor Institute came to an end and it was sold for $100,000 to the Goodwill Industries. After high school, McGregor went to Oberlin College and then attended to Wayne University, where he had graduated in 1932. While at college, he was married and left his college work for about five years to save enough money to start a family. McGregor began as a gasoline station attendant in Buffalo and quickly progressed to district manager of stations in the Detroit region. In 1935, he received a PhD degree from Harvard University in Experimental Psychology. McGregor was a brilliant student at Harvard that; he achieved an A grade in every course. After his graduation from Harvard University, he became a Professor of Psychology and taught there f...

Herb Brooks: Charismatic Motivation in Coaching Essay -- essays resear

Herb Brooks: Charismatic Motivation in Coaching In the following essay, I will argue that Herbert â€Å"Herb† Brooks was a charismatic leader due to his powerful motivation and his high expectations. He expected great things from the players he coached, but mostly, he expected them to think of the team and not themselves. He motivated with a powerful punch, mostly through fear, but was able to unite his teams and eventually the country. Herb Brooks was born on August 5, 1937 in St. Paul Minnesota (Herb Brooks). Growing up in Minnesota, he became attached to the sport of ice hockey. He spent years practicing and playing this sport, and in 1955, he led his high school team to the state championship. After three years of college at the University of Minnesota, he joined the 1960 Olympic hockey team, but was cut from the team just before the Olympic games. He played for the United States in the next two Olympic games, and in 1970 he picked up his coaching career at the University of Minnesota. In his six year’s of coaching at the university, he led the team to three national championships (Herb Brooks). In 1980, his United States Olympic hockey team, consisting of all college students, achieved one of the greatest spectacles in sports history: â€Å"The miracle on ice.† His team beat the Soviets in a white-knuckle, heart pounding game with a score of four to three. The Soviet’s were a well trai ned, terrifying team that were considered to be the greatest hockey team that has ever taken the ice. After leading his team to this miraculous victory, he continued his coaching career up until his tragic death in 2003. His high expectations for his team and his fearful, powerful motivational techniques led him down a path of greatness that helped him become an inspiration to all. Brooks' 1980 Olympic hockey team consisted of college students whose average age was 22 years, and was full of rivalry because of players being from different universities. This young team was being matched against some opponents who had played and practiced together year-round, for several years. The Soviets had beaten a team of National Hockey League all-stars the year before, and they triumphed over this young U.S. team at an exhibition game in New York a week before the Olympiad (Herb Brooks). Herb did not ... ...out the best in every player that played for him. Although he seemed harsh at first, the team members bought into his methods of motivation, and became united as a team. Herb communicated to them his goals and aspirations, and the team was able to set its sights on the future. He had many dreams, and once said, according to the ESPN website, "You know, Willie Wonka said it best: We are the makers of dreams, the dreamers of dreams. We should be dreaming. We grew up as kids having dreams, but now we're too sophisticated as adults, as a nation. We stopped dreaming. We should always have dreams. I’m a dreamer.† His dreams bringing out the best in every player became reality, and it not only united his team, but it united the country. Herb Brooks was a great inspiration to his many team members throughout the years, and now he is remembered as a powerful motivator and an inspiration to the nation as a strong charismatic leader. Works Cited Herb Brooks. Retrieved April 14, 2005 from the world wide web: http://galenet.galegroup.com. Coach Known Best for 1980 Hockey Gold. (2003, August). The Associated Press. Retrieved April 14, 2005 from the World Wide Web: http://www.espn.com.

It is inhuman and offers no solution to unwanted pregnancies

Abortion is the act by which a pregnancy is prematurely terminated to result in the death of a foetus or unborn child. The life of the developing child is destroyed and the child therefore loses the chance of being born into this world.Various methods are used to perform or carry out an abortion such as use of medicine, surgery or any other methods of extraction some of which are very crude. Abortion dates way back into history and has been a social evil that society has had to put up with for a long time. In traditional society such methods as botanical products, exerting pressure on the abdomen and use of sharpened tools were used to perform abortion.With advanced civilization   these methods have changed to result to more modern methods that are medically safe. Crude methods however cannot be ruled as many women will tend to maintain secrecy about the whole issue or they may not afford to visit clinics (Riddle ,John M.).Several reasons lead to abortion but the most common one is unwanted pregnancies. Such pregnancies result from failed methods of contraception, rape, incest or even careless or unprotected sex.Special cases such as complications arising from a pregnancy also result in abortion where the urgency to save the life of the mother becomes inevitable. In the course of medical examination doctors may also detect complications in the development of a foetus and decide to terminate a pregnancy depending on the degree of destruction to the foetus.Pro-abortion activists argue that there is no need of bringing an unwanted child into this world. Children resulting from rape and incest for example come at a time when the mother is least ready for the responsibility. They are not conceived through a relationship and in the event of conception through rape the fathers may not even be known.Many people find it unhealthy to bring such children into the world because of the injustices they are likely to face in society.   Of all the injustices faced by child ren in the world however,   abortion is the worst of them all as it denies an unborn child the most basic human right; to be born and be raised in this world.Denying a child the right to live means that such a child loses the chance to be anybody in society and society has therefore been denied the services of great men and women through abortion (Edward Richards P, Katharine Rathbun C.).Despite rigorous campaigns against abortion, the evil has been on the increase in present day society.. This is due to advance in the field of medicine that has made abortion safer thus reducing the risk of death during the process.As a result, it has become an easy way out for many women especially young adults who engage in careless sex due to the promiscuous nature of society today.   But how safe is safe remains a topic of discussion regarding abortion.Though abortions carried out medically may be safe, the side effects may be far reaching and may not be realised immediately. The reproductiv e system of a woman for example may be destroyed and she may not be able to have children in future.This is traumatic as the woman is unable to overcome the guilt of contributing to her barrenness and the lack of children may lead to the break up of marriage where the woman is in such a relationship. The frustrations and psychological torment may be too much for the woman to bear (Edward R. P, Katharine R.C.).Due to increased number of abortions, a lot of people have come up with the argument that it should be legalised. They argue that legalising abortion will help to reduce abortion related deaths that result from crude methods because clinically induced abortion would now be accessible to those who wish to have it.

Marketing Synopsis

After the Initial success of the casual shoes, GOES expanded its market towards the apparel and the sports shoe market as well, thereby demonstrating the power of Innovation. Since then, GOES had carved out a niche for itself through distinctive innovation. It has been adopting strategies to ensure that it could successfully renew its technology, products and process, and maintain long term competitiveness. Key Issues and Fact Finding: * According to us, first issue was, Polecat had no prior knowledge in the field of engineering and shoe industry. The research process was exhaustive.After insulting various publications and encyclopedias he recognized that a watertight breathing membrane worn by NASA astronauts can act as a prototype for his shoes. * After patenting the new technology, second issue was that none of any shoe leading companies in Italy showed interests in his product. This led him to manufacture the shoes all by himself. * Third Issue was that after diversifying Its pro duct portfolio and expanding Internationally, GOES could not enter sports shoe market as it had intense competition and it required a very different technology.Polecat felt that every sector requires a different mind-set, but in response to nonuser requests, Golf Shoe range was launched in 2009. * The last and the major key Issue was that shoe market was highly competitive and to maintain Its position, only innovation could not help. The shoes must be stylish and trendy enough to match the style offered by others. Thus GOES had to constantly work on product differentiation while maintaining its quality and costs. Key Learning: * The very first thing this case teaches us is that â€Å"Necessity is the mother of invention†.We must be constantly aware of our surroundings. One should have zeal and enough confidence on oneself to convert the opportunity in potential offering. Polecat realized the necessity of the shoes that breathes and created a new market altogether. * Take smal l steps and have full faith in your potential. Polecat initially 1 OFF small. This gave him an opportunity to test the response of the customers in limited period of time. After getting satisfactory response, he then switched over to men and women wear and expanded the market gradually. * â€Å"Think big†.Initially he started locally and then expanded its target market by entering in apparels and sport shoes. The company then, internationally diversified its product portfolio. Polecat realized his true potential and knew to what extent he could go. Questions: IQ . What do creativity and innovation Signify and entail? What are the key types of innovation? SQ. Analyses Goose's innovative strategy in detail. What are features of this strategy that have made Goes shoes a success? What factors, other than product innovation, does Goes owe its competitive advantage to?Q. 3. Assess the market environment of the industries Goes operate in. Who are Goose's key competitors? What Strate gies and options are available to Goes for sustaining its position in these industries? ANSI : Creativity: The process of generating ideas and new ways of doing things is called as creativity. This term is more frequently used in arts. It more refers to the thought process. Innovation: The process of generating ideas and filtering them checking the feasibility of the idea and implementing the idea to create value is called innovation.In simple terms it is the process of creating value by generating new ideas or changing existing ideas. Creativity is a part of innovation. Types of Innovation: Product Innovation: It involves the process of creating new products or altering existing product with new technology in order to create value to the customer. Process Innovation: It involves the key changes in the way of doing business. Impact of process innovation would be big. It should be communicated with the end user effectively.Service Innovation: Creating new service applications which e nables the customer much convenience. NAS:2 Innovation strategy for GOES: A good idea, constant collaboration with universities in order to see if idea is feasible and improve it and a patent to protect the innovation. Success Factors: * Company invested heavily in R&D. In 2008 GOES spent SIS$ 20. Million on R&D expenses. * GOES emphasized on the value of the patents. It made development of â€Å"Breathing Technology' its mission and held over 50 patents in this field.These 50 include Rubber soles patent, Leather soles patent, Apparel patent, patents related to processes, equipment and machinery and material. These patents helped in gaining competitive edge. Factors that Gave Competitive advantage: They positioned themselves as one of a kind catering to the entire family. Product categories were based on the target customer Target customer: Male, Female, Pricing: Medium to medium-high price range of market Product Categories: Classic products which were elegant and traditional.Casu al products which were wearable and adaptable. Production: High quality standards, continuously improving flexibility and time to market, Cost leadership. Marketing: They concentrated around the product features I. E. Technology rather than only concentrating in the fashion and style thus making a clear differentiation from other products. They advertised using the images of product and breathable sole technology. Distribution System: Very efficient and adaptable distribution system for each country they operate in based on their structure.

Final Assignment

Additionally, it will show which changes will be made that will have a positive exult to our program not only now, but in the future as well. Readiness of our Leaders There are several leaders in this change the principal, H. O. S. T. Administration Migrant Education, Reading Teacher, several paraprofessionals, and our SST including myself. Together we identify the core elements and negotiate items in our change plan. The main change is to increase the time allotted students to do reading at our program.Program/practices for scale and sustainability Our program has and is having success in empowering students to grow al develop in a safe and caring environment. The area that can be improved the enriching environment, why? First, the program needs to have access computers in the area where HOST is located. Second because the student get computers time only three days out of the week and for 20 minutes a c while at HOST. Third, the students are given 30 minutes, but by the time t' go t o and from the computer lab, which takes them 10 minutes, they only 20 minutes at most.My personal feelings are that our children can benefit from having their own computer lab at HOST or tablets that they can access anytime they are in the aftershock program. Most of the students at our aerogram are of Hispanic decent some of them struggle in reading, comprehension and writing. I can only imagine what can be done to help them in those areas if we had our own computers or tablets. Our student have a 30 minute block in which reading is being implemented already, if v had reading and writing software on tablets Or Computers Our students cal reap the benefits. What is it?Why is it important? In order for our program to continue to empower students to grow and develop in a safe, caring, an educationally enriched environment feel that the students need more reading time. My thoughts are that if the students had tablets in our aftershock program to work with in reading that they would mak e rapid advancement in reading. The stakeholders that will approach are the principal at the school, since she is a person that commends a lot of power In other words when she speaks people listen, plus she knows other people as well that have that type of authority.Identifying the main change will assist us to determine whether or not all elements within this change are crucial. At this point our plan can be tweaked to fit the needs of our studs The need and wiliness of all stakeholders to relocate resources for the Ben f our change plan is amazing. In corporations or companies change is evitable and a must in order to stay in the game. The key to change is to b willing to listen to others opinions. How is it high quality and valued by stakeholders? This change is high quality because of the students that this change target!Most of the students are Engle sis Language Learners and struggle with comprehension. Some of them are behind in their level of reading and writing skills. What results are anticipated? This change will be enriching the students in that they will increase their level of reading, comprehension ND writing skills. The stakeholders will benefit because they will actually s the students progress. Non-negotiable elements of the program/practice There will be items in the change plan that is nonnegotiable in order to keep the integrity of the change.During our planning stages as a group we decided that reading and comprehension were nonnegotiable. These two items are non-negotiable since they are our focal point of interest. Without these two we would not have a need for the change plan. Scale and sustainability scores In order to define the scale and sustainability score of the change plan we ad to review the Scale and Sustainability scores located within the book â€Å"Leading Change Step-By-Step† by Jody Spiro. These results will let us know to what extent certain features have been merged into our program (Spiro, 201 1).Our results sho w that we have an all-inclusive plan, but not all stakeholders have bought into it yet. What this says about us is that we are good at working together and coming up with a plan. However, this does not mean that everyone agrees with it. There is still some resistance to the actual plan change. This of course is expected, since change is never easy, nonetheless a good way to get individuals on board is by communicating and educating them. Education & Communication: One of the best ways to overcome resistance to change is to educate people about the change effort beforehand.Being upfront with education and communication lets everyone have knowledge about the changes. â€Å"People tend to see things that are happening now as more urgent than those that will happen in the future. † (Weber, 2006). Sometimes individuals are afraid of something they do not understand, however once they learn how this change is to come or will be made they are not as afraid. It is only then that they will start asking questions once they are informed. This however is not a guarantee that they will accept the change right away, but now they are more ready to listen to what one has to say.The development of scale and sustainability strategies for the change strategy Creating an environment where there is open communication and providing them an outlet to speak about their concerns will minimize a lot of the resistance. Providing the team with a consistent and clear message will minimize resistance. If change my views or do not sound confident in my change plans, the message will be inconsistent. On the other hand, if I am consistent and clear; offering a clear vision and specific goals to achieve, the team will be focused and know what is expected of them.I will also make sure the â€Å"messages are communicated through the participants' ears† (Spiro, 201 1). Communication is a key element, for this element we scored a five. However, this needs to be on a continual basis i n order for the group to be informed throughout the school year. Communication is not something that happens last minute; it is something that is practice throughout with co- workers. In conclusion ‘Veneered you introduce change, you are sure to encounter barriers† (Drexel & Muskier, 2012). The best change leaders; will have a plan B for when things go wrong.Knowing your group, making sure you communicate with them and realizing you cannot make change happen alone will help your change effort become successful. Communication must be clear and consistent while your plan needs to have important feasible goals. Another area to be aware of is that the plan change is not written on stone and that there might be changes that will take place throughout the planning stages. What one might come up with at the end as a leader for hanger might be totally different than what one started with.

Alzheimer’s Disease Amyloid Precursor Protein Gene

Alzheimer’s disease, AD, is a distressing condition that involves the decline in cognition of the mind which results to psychotic disorder, and affective and behavioral disturbances (Bloom 9). It is a progressive central nervous system disorder and the main cause of dementia (Stavljenic-Rukavina 1). Alois Alzheimer in 1907 reported the case of a 51-year old Frankfurt woman who died in dementia (Bloom 9). He described the neuropathological condition of the woman with neurofibrillary tangles or NFTs and amyloid plaques or NPs (Bloom10). NPs are extracellular beta-amyloid peptide or A?Spherical deposits closely related to dendrites, reactive astrocytes, dystrophic axons, and activated microglia (Felician and Sandson 19). Thus, for several decades, collaborative efforts of experts from different scientific and medicinal endeavors were devoted for the neurological and pathophysiological characterization of this disease (Bloom 9). As such, the roles of four specified genes, as well as the mechanism of oxidative stress, tau, inflammation, hormonal changes, and inflammation on the AD’s neurodegeneration have been the central theme of scientific studies conducted on this disease (Felician and Sandson 19).As experts continuously gained insights on the mechanisms of neurodegeneration, pharmacological strategies are concurrently devised for the development of appropriate drug treatment and interventions (Felician and Sandson 19). Molecular Mechanism Early and late onset ADs are types of familial AD which are genetically heterogeneous. Familial AD is accounted for 10% of AD cases from 30-60 year old patients and ascribed to three types of genes which included APP, presenilin-1 or PSEN1 and presenilin-2 or PSEN2 (Stavljenic-Rukavina, 1).Nonetheless, the mutations in these genes also cause A? -level increase; A? is generated by proteolytic APP fragment that was also observed in the brains of AD patients (Stavljenic-Rukavina, 2). However, not all AD cases can be attributed to the three identified genes. Genes are then the most important determinant of AD development (Stavljenic-Rukavina, 2). On the other hand, there is a great chance for children with parents having history of familial AD to inherit the genetic traits and develop either early-onset or late-onset AD (Jayadev et.al. 375). As well, AD development threat in the offspring is directly related to age; the tendency of AD occurrence among children of parents with historical AD background increases as the children gain progress in their growth and development (Jayadev et. al. 375). The pathogenesis of Alzheimer’s disease, on cellular level, has been consistently observed. The pyramidal neurons are the type of cortical cells that are fundamentally deteriorated in AD pathogenesis resulting to the spread of NPs and NFTs in cortex areas (Felician and Sandson 20).Both NPs and NFTs are normally found in brain areas in the aging process but their concentrations and densities are pecu liar in the case of AD (Felician and Sandson 20). Originally, NPs are found at the amygdala and concentrated in parietal association and order temporal cortex parts (Felician and Sandson 20). In the maturity of AD, NPs can also be observed in hippocampus, in other structures of mesial temporolimbic brain, and even in cortical and meningeal blood vessels (Felician and Sandson 20).Luckily, the areas for sensorimotor and visual are remained unaffected. Meanwhile, in the early stage of AD, NFTs can be found hippocampus, amygdala, and in entorhinal cortex, the association cortex has abundance of NFTs (Felician and Sandson 20). However, NFTs are not exclusively for the cases of AD, these are also detected in the several cerebral troubles like in dementia pugilistica, postencephalitic parkinsonism, and subacute sclerosing panencephalitis (Felician and Sandson 20). The formation of NPs is attributed to the A ? peptide deposition; A ?peptide types that only differ in C-terminal are common in cerebrovascular and extracellular plaques (Felician and Sandson 19). A ? peptide, made up of 39-43 amino acids, is normally generated from APP or amyloid precursor protein. In addition, the series of hydrophobic C-terminal is crucial in its solubility and amyloid formation rate (Felician and Sandson 19). As such, A ? with 40 amino acids, A ? 40, as well as A? peptide with 42 and 43 amino acids or A? 42 and A ? 43 respectively (Felician and Sandson 19). However, in vitro, the variants of A?42 and A? 43 can easily form insoluble fibrils as compared with the A? 40 variant (Felician and Sandson 19). Furthermore, the incubation of these A? variants can immediately lead to coalescence implying the possible amyloid plaque deposition through these components. In line with this, diffuse plaques have nonfibrillary and A? soluble constituents denoting the senile plaques’ early stage (Felician and Sandson 19). Likewise, diffuse plaques have A? deposits in the absence of neuritic degener ation (Felician and Sandson 19).On the other hand, neurofibrillary tangles, comprised of abnormal bundles of intraneuronal filaments, are made up of tau microtubule-associated protein with high degree of phosphorylation (Felician and Sandson 19). The degree of phosphorylation is largely dependent on the enzymatic activities of kinases that are not yet fully understood (Felician and Sandson 19). Nevertheless, the intraneuronal abnormal filaments arrange themselves in either parallel or helical bundles in perikaryotic cytoplasm that make them in contact with the dentritic processes (Felician and Sandson 19).The amyloid precursor protein, a membrane glycoprotein, is consisted of 28 A? extracellular residues and 12 to 15 putative transmembrane residues (Felician and Sandson 20). It also occurs as 695, 751, and 770-amino acid isoform. While the 695-amino acid isoform occurs mainly in neurons, 770 and 751-amino acid forms are seen on both non-neural and neural cells along with protease in hibitor domains (Felician and Sandson 20). APPs are carried into the cell membrane by secretory vesicles and may undergo proteolytic bond breakage through the action of ?-secretase (Felician and Sandson 20). Consequently, this cleavage generates ? -APP, a soluble ectodomain and the precursor for A? peptide production through cleavage in A? domain. As the generation of soluble APP is, in vitro, ascribed with the activity of protein kinase C, uncleaved APP is inferred to take the proteolytic pathway (Felician and Sandson 20). On the other hand, APP intracerllular recycling and management are done through endocytotic or endosome-lysosome means. The endocytotic route causes proteolytic cleavages by means of ?– and ? -secratases leading to the synthesis of A? (Felician and Sandson 20). Moreover, A? production is enhanced by intracellular calcium concentration which denoted the significance of calcium-rich proteases in A? production (Felician and Sandson 20). In vivo, APP cleavage occurs at N-terminus at the A? -region through the action of ? -secretase and at the C-terminus by means of ? -secretase activity (Mohan 1). Also, APP can take a pathway facilitated by ? -secretase at the A? -peptide domain producing soluble ? -APP (Mohan 1).Ezymes can also possibly attack APP without A? -peptide generation (Stavljenic-Rukavina, 1). Since the putative ? -secretase, under the control of kinase C, regulates the generation of soluble APP, any agents that supports this metabolism may hinder the A? production (Felician and Sandson 21). As well, A? deposition may also be lessened by drugs which inhibit APP cleavage into ? – and ? -secratases (Felician and Sandson 21). Nonetheless, agents that can impede A? coalescence would decrease its neurotoxicity effects (Felician and Sandson 21).After the formation of amyloid plaques, neurofibrillary tangles and inflammation dictates the death of neurons (Stavljenic-Rukavina 1). In relation to this, microglia and astrocytes ce lls of the brain are heavily affected by inflammatory process (Stavljenic-Rukavina 1). In AD patients, astrocytes are enlarged and produce prostaglandin which in turn sends signal to activate the inflammation mediated by arachidonic acid (Stavljenic-Rukavina, 1). On the other hand, microglia generates free radicals which cause neurons’ death (Stavljenic-Rukavina 1).Meanwhile, cell nutrients as well as its regulation components are transported through the microtubules in which structural properties are mainly dependent on tau protein (Stavljenic-Rukavina 1). In AD condition, the tau lessens its capability to bind with microtubules and binds with other tau protein resulting to knots of helical filaments called as neurofibrillary tangles (Stavljenic-Rukavina 1). APP Duplication is Sufficient to Cause Early Onset Alzheimer’s Dementia with Cerebral Amyloid Angiopathy Studies showed that A? encoding through APP gene expression leads to the development of Alzheimer-type demen tia (Sleegers et.al. 2977). APP genetic expression results to elevated levels of A? 42, a 42-amino acid product of the proteolytic process (Sleegers et. al. 2977). Aside from the cleavage of APP into alpha, beta, and gamma secretases, high APP genetic expression results to elevated levels of A? 42 and A? deposition (Sleegers et. al. 2977). Meanwhile, it has been long known that APP level triplication in Down’s syndrome patients results to the development of Alzheimer type dementia at early stage; the APP excessive expression leads to neurodegeneration and A? deposition (Sleegers et. al.2977). In relation to this, it was reported that families with cerebral amyloid angiopathy and early onset Alzheimer type dementia had APP genomic duplications which implied that APP over-expression, without full trisomy 21, has triggered the Alzheimer-type dementia (Sleegers et. al. 2977). In addition, Alzheimer-type dementia patients have elevated APP mRNA levels in their brains (Sleegers et. al. 2977). Further, the variation on the transcription of APP gene due to genetic factors was believed as the underpinning factor in the pathogenesis of the disease (Sleegers et.al. 2978). In fact, three APP mutations were observed on Alzheimer-type early-onset dementia patients. These mutations, as seen in vitro by means of trisomy 21, caused a two-fold elevation of in APP transcriptions (Sleegers et. al. 2978). With the aforementioned evidences on APP elevation through APP genomic mutations or duplications which resulted to the development of early onset AD, it could logically infer that A? has a crucial role in its aetiology (Sleegers et.al. 2978). Hence, for the evaluation of APP locus duplication on Alzheimer-type dementia cases, Sleegers et. al. conducted a study on Dutch population with early onset Alzheimer-type dementia patients. Material and Methods In the approval of the University of Antwerp medical ethical committee, the respondents of this research were recruited form an epidemiological study on early onset AD in several provinces of The Netherlands and in Rotterdam (Sleegers et. al. 2978).Patients with early-onset dementia diagnosis were enlisted based on the recommendation of medical experts and healthcare providers. As such, the assessment of the patients’ conditions was done in accordance with the standards of the Stroke-Alzheimer’s Disease and Related Disorders Association, and the National Institute of Neurological and Communicative Disorders (Sleegers et. al. 2978). Medical records of the patients and their respective relative with similar trait inheritance were made available for an in-depth examination.Meanwhile, for the assessment of genetic inheritance, 111 patients with ages 33 to 65 years old of which had 75 respondents with familial background of either late or early-onset of dementia and 10 of which have autosomal dominant inheritance history for several generations of their respective clans were studied (Sleegers et . al. 2978). The genomic DNA or gDNA was derived from lymphocytes and alleles of APP were measured by means of real-time polymerase chain reaction, PCR (Sleegers et. al. 2978).Also, the PrimerExpress software was utilized for the design of ? 2-microglubulin or hB2M, exon 5, 11, and 18, ubiquitin C or hUBC, ATP5J, APP, and GABPA (Sleegers et. al. 2978). As the APP alleles were normalized for hB2M and hUBC, 20 nanograms of genomic DNA were combined with the PCR and 400 nanomoles of the respective primers (Sleegers et. al. 2978). Finally, the duplication of the samples was done by means of dosage quotients or DQs calculation through six normal individuals and dementia patients.Patients with trisonomy 21 were also included as controls (Sleegers et. al. 2978). Fluorescence in situ hybridization, FISH, was utilized to determine APP genomic duplication (Sleegers et. al. 2978). FISH was performed on both interphase nuclei and metaphase chromosomes while the Epstein-Barr virus-transformed pa tients’ lymphoblasts were taken from the metaphase period by means of 0. 1 microgram/milliliter colcemid treatment and incubated, at 37 °C for 25 minutes, in hypotonic solution of 1 molar sodium hydroxide, 30 millimolar glycerol, 0.8 millimolar magnesium chloride, 2 millimolar HEPES, and 1 millimolar calcium chloride (Sleegers et. al. 2978). This suspension then was used for 106 cells per milliliter as the chromosomes’ mechanical stretching was done through cyto-centrifugation. On the other hand, the Multiplex Amplicon Quantification, MAQ, was applied in the detection of APP locus duplication. MAQ was comprised of multiplex PCR amplification of the reference amplicons and targets which were tainted with fluorescent substance (Sleegers et. al. 2978).After MAQ, DNA fragment analysis, and comparison target amplicon DQ between control individuals and the patients were done (Sleegers et. al. 2979). Results and Discussion Real-time PCR APP measurements of 10 probands showe d heterozygous duplication (Sleegers et. al. 2982). Based on the Dutch population sample, APP duplication along with segregation pattern and neuropathology tantamount to autosomal dominant inheritance and AD with excessive CAA were identified with APP duplication in a family (Sleegers et. al. 2982).Specifically, the genomic APP locus duplication were observed in five of the 65 family cases with early onset AD autosomal dominance while APP duplication was detected in a single out of ten family cases early-onset AD autosomal dominance (Sleegers et. al. 2982). Even though these numbers are small, the data generated from this study illuminated the significance of genomic APP locus duplication assessment when simple mutations were excluded in AD known genes (Sleegers et. al. 2982). In the 65 patients with familial AD history, a single genomic duplication was identified (Sleegers et. al. 2982).In addition, the genomic duplications among the Dutch samples have 1. 8% overall frequency and 2 . 7% frequency in AD patients and family (Sleegers et. al. 2982). In contrast, duplication was failed to be detected on 36 patients with irregular early-onset AD which denoted that the duplication of de novo genomic APP is a weak cause of early-onset Alzheimer-type dementia (Sleegers et. al. 2982). Moreover, the duplication observed among the Dutch family samples has only APP which proved that genomic APP duplication, regardless of adjacent genes, has the capacity for AD and CAA mixed phenotype (Sleegers et.al. 2982). As well, duplication size differences signified the non-specific recombination substrate from the genomic attributes of APP locus; APP rather is in increased recombination region as imparted by other factors such as low transcription repeats (Sleegers et. al. 2982). Nevertheless, the mutation that affects APP expression among 4. 5% of the Dutch participants that either genomic APP duplication or APP mutation promoter carrier, are the frequent cause of Alzheimer-type de mentia (Sleegers et. al. 2982). Polymorphism in the Promoter of the Human APP GeneThe cleavage of APP produces A? with associated neurotoxicity; hence, genetic studies postulated that abnormal A? deposition neuropathologic AD conditions (Athan, Lee, Arriaga, Mayeux, and Tyco1793). The abnormal deposition of A? in AD patients has been ascribed to APP gene missence mutations and the proteolytic APP cleavage producing A? 42 which in turn triggers the development of early-onset AD (Athan, Lee, Arriaga, Mayeux, and Tyco1793). The most solid proof for this notion is the case on trisomy 21 wherein the duplication of APP gene results to increased A?peptide level and aggregation of such in the amyloid plaques of the brain (Athan, Lee, Arriaga, Mayeux, and Tyco1793). While the presenilin enyzymes enhance fibrillogenic APP conversion, the APOE or alipolipoprotein-E elevates A? coalescence and deposition (Athan, Lee, Arriaga, Mayeux, and Tyco1793). Since A? production is associated with APP con centration and on other factors in both A? and APP syntheses, it was hypothesized that the expression of APP gene is a determinant of AD development (Athan, Lee, Arriaga, Mayeux, and Tyco1793).Recently, a study reported the weak relation between AD inheritance and microsatellite sequence in the APP first intron and a tetranucleotide non-association with AD (Athan, Lee, Arriaga, Mayeux, and Tyco1794). Hence, to further scrutinize this issue, Athan et. al. anchored their study on APP promoter variant screening in tri-ethnic populations which included white, Caribbean Hispanic, and African-American as they intended to determine APP promoter identities. MethodologyThe respondents in this study were Manhattan residents of Washington Heights with ages of more than 65 years (Athan, Lee, Arriaga, Mayeux, and Tyco1794). Personal interview and medical background check, neuropsychological, physical and neurological examinations were done on the participants. In addition, individuals with quest ionable dementia, Parkinson disease, and other types of dementia were excluded in the study. Consequently, a total of 1,077 participants was successfully enlisted, whereas, 16% of them has family history of stroke (Athan, Lee, Arriaga, Mayeux, and Tyco1794).For genotyping, DNA from 1,013 respondents was taken as the panel of neuropsychologists and physicians established the criteria for the identification of AD patients along with the Clinical Dementia Rating Scale (Athan, Lee, Arriaga, Mayeux, and Tyco1794). The oligonucleotide primers used for APP promoter PCR amplification came from GenBank (Athan, Lee, Arriaga, Mayeux, and Tyco1794). From genomic DNAs and by means of Platinum Taq DNA Polymerase, the fragments were amplified while the product sequence was determined through dye terminators (Athan, Lee, Arriaga, Mayeux, and Tyco1794).Meanwhile, 15 microliter of the PCR products was introduced into WAVE fragment DNA analyzer (Athan, Lee, Arriaga, Mayeux, and Tyco1794). The haplotyp es PCR products were individually cloned through pGL3 vector in between SacI and Bg III sites (Athan, Lee, Arriaga, Mayeux, and Tyco1794). On the other hand, U-87 MG glioma cells were cultured with the solution of Earle’s balanced salt and 2 millimolar L-glutamine with 10% fecal calf serum in EMEM medium (Athan, Lee, Arriaga, Mayeux, and Tyco1794).At 70% confluence, the cells were transferred by means of FuGene 6 reagent and pGL3 vectors were added to transfected DNA to maintain a constant concentration of about 1 microgram per plate of 35 squared millimeter (Athan, Lee, Arriaga, Mayeux, and Tyco1794). While the isotonic solution of phosphate-buffered sodium chloride was used to wash the U-87 cells, the 250 microliter Reporter Lysis Buffer was applied for cell lysis (Athan, Lee, Arriaga, Mayeux, and Tyco1794).After this, the centrifugation of the cell extract was done at 10,000 g for five minutes. From the supernatant, 20-microliter aliquot was taken and combined with 100 mic roliter Luciferase Assay Buffer for luciferase activity measurement (Athan, Lee, Arriaga, Mayeux, and Tyco1794). Then, with 10-20 microliters of the lysate ? -galactosidase assays were performed. This ? -galactosidase measurement was utilized for the normalization of the luciferase data (Athan, Lee, Arriaga, Mayeux, and Tyco1794).Each allele was counted and by sample proportion calculation, the frequencies were computed (Athan, Lee, Arriaga, Mayeux, and Tyco1794). For the ethic group comparison of allele frequency, chi square analysis was applied while logistic regression was utilized for APP promoter and AD polymorphisms odd-ratio calculation (Athan, Lee, Arriaga, Mayeux, and Tyco1794). As well, for each ethnic group, logistic regression was employed as the data were classified with respect to the APOE allele’s occurrence or non-occurrence as education and age discrepancies were adjusted.Finally, Hardy-Weinberg equilibrium was analyzed through chi square analysis while the e thnic comparison of APP promoter and AD polymorphisms odd-ratio calculation as their education, age, and sex were adjusted (Athan, Lee, Arriaga, Mayeux, and Tyco1794). Results and Discussion Two types of APP promoter polymorphisms were detected and identified, with respect to the starting site of the transcription, as G>C at +37 and G>C at -9 variants (Athan, Lee, Arriaga, Mayeux, and Tyco1797).In connection to this, +37C allele was typically observed among 18% African-American respondents while European and Caribbean-Hispanic have 3% and 10% respectively (Athan, Lee, Arriaga, Mayeux, and Tyco1797). Although +37C allele was commonly observed among AD patients, the adjustment of their socio-demographic attributes with respect to this allele produced non-significant observations (Athan, Lee, Arriaga, Mayeux, and Tyco1797). Also, -9C allele was hardly detected for disease association.On the other hand, even though the adjustment with respect to socio-demographic traits was made, still a strong link was found between APOE allele and AD (Athan, Lee, Arriaga, Mayeux, and Tyco1797). Moreover, the evaluation of both +37C and -9C allele variants in U-87 glioma cells through promoter-reporter assays has resulted to non-significant promoter activity (Athan, Lee, Arriaga, Mayeux, and Tyco1797). The early onset, less than 60 years old, of AD has been ascribed to APP, PSEN1 and PSEN2 while the late stage, greater than 65 years old, AD development has not yet fully explained by the genetic model (Waring and Rosenberg 329).The development of AD in late age stage was associated with APOE and to other reported genetic variants and alleles, however, they still insufficient to plausibly explain the mechanism involved in the AD occurrence (Waring and Rosenberg 329). Summary Alzheimer ’s disease is a progressive degeneration of the capacity of the mind for cognition thus affecting the psychological and affective attributes of the inflicted individual.Based on genome-wide stu dy, children of parents with familial Alzheimer’s disease are more prone to inherit and develop this condition either as they take progress in their growth and development or at the senescence stage of their lives (Jayadev et. al. 375). The primary pointed culprit for this cognitive deterioration is the beta-amyloid peptide which is a part of amyloid precursor protein. APP passes through the fatty membrane of the cells and delineated in the different areas of the brain, even though, the normal function has not yet been fully known.As APP is attacked by enzymes, fragments are generated including A? -peptide with associated neurotoxicity. Sleegers et. al. in 2006 found the coincidence of cerebral amyloid angiopathy with Alzheimer’s disease in a Dutch multigenerational family. This genomic duplication was attributed solely to APP gene expression that was also observed in 65 Dutch families with early-onset of AD cases. However, APP locus duplication was not observed in 36 AD patients that signified the case of de novo mutation. On the other hand, Athan et. al.in 2002 reported the two types of APP promoter polymorphism which involved +37C and –9C alleles. Moreover, they found a strong link between AD inheritance and the apolipoprotein-E role. In this connection, the genetic traits of every individual should be scientifically scrutinized for an accurate determination and identification of the substance involved in the development of the disease in parallel with its molecular mechanisms. Works Cited Athan, Eleni S. , Lee, Joseph H. , Arriaga, Alex, Mayeux, Richard P. , and Tyco, Benjamin. â€Å"Polymorphism in the Promoter of the Human APP Gene.† Archives of Neurology 59 (2002): 1793-1799. Bloom, Elin. Genetic Studies of Alzheimer’s Disease. Acta Universitatis Upsaliensis. Uppsala, Sweden: Uppsala University, 2008. Felician, Olivier and Sandson, Thomas A. â€Å"The Neurobiology and Pharmacotherapy of Alzheimer’s Disease. â⠂¬  Journal of Neuropsychiatry and Clinical Neurosciences 11, 1 (1999): 19-31. Jayadev, Suman, Steinbart, Ellen J. , Chi, Yueh-Yun, Kukull, Walter A. , Schellenberg, Gerard D. and Bird, Thomas D. â€Å"Conjugal Alzheimer Disease. † Archives of Neurology 65, 3 (2008): 373-378.