Sports And Children Essays - Childhood, Parenting, Learning

Sports And Children We no longer live in a society where kids run around actively throughout the neighborhood. The sandlot baseball games, pick up games in the park, and innocence in the children are gone in sports. Today children are more interested in television, computers, and video games and parents are afraid of letting their children run around the streets because of kidnapping. Kids are simply no longer interested in physical activity. A poll of over a thousand parents and one with students was done and the results show they blame inactivity on lack of time and homework. Whatever the cause is, we can see results with studies throughout the last few years. * 22% of children are physically active everyday of the week. * 49% in grade 4-12 are moderately to vigorously active. * 34% attend Physical Education classes daily. * 23% don't have these classes offered, because no all states have educational requirements for PE and some have budget cuts in the program. * 54% of children ages 6-11 are obese, with the obesity rates till on the rise (Hellmich 1997). * There are a number of federal, state, and local school programs to help students reach fitness goals. The missing link in having physically fit children seems to be the parents. They are allowing children to remain sedentary with the television and computers. Not enough children have parents who monitor their child's activity schedules, expose them to physical activity, and who serve as role models in being active themselves. Sports involvement and competition is very important in a child's life, but sometimes can go too far. Physical activity offers both positive and negative aspects in a child's life. Physical activity is an integral part of the learning process at all grade levels/ Unfit children develop low opinions of themselves, dislike activity, and develop antisocial attitudes. Children need the physical and mental benefits of sports. Kids involved in sports will physically feel better about their bodies by being fit, they are less likely to have the risk of obesity later in life, and more likely to learn new skills (Krucoff 1998). Mentally, sports stimulate the intellectual development, sharpen motor skills, provide emotional and social growth, help with depression, and increase self-confidence. A non-active child that becomes active in a sport program find increased energy, longer attention span, improved self-esteem, and better communication skills (Sports Psychology). Students learn about their bodies and want to improve them to lead a fulfilling life. Overall most children in sports enjoy themselves because they are having fun and meeting new friends. Athletics allow th ese children to interact with children of the same age with this similar interest thereby improving their social skills for later in life. This experience in sports will serve as a positive model to follow when approaching other challenges and obstacles throughout life. There is a strong connection between academic success and athletics. Athletes especially in high school perform better and remain in school more than non-athletes (Krucoff 1998). In middle school, high school, and college there is an athletic eligibility grade point average. If the student doesn't make the grades, they aren't entitled to participate in sports. With this push in academics students now work harder in the classroom so they can participate. Many students have sports to thank for being a college student. Without the athletic money from the talent in the sport most children of low-income families can't afford college. These students at the college athlete level tend to be successful because of the high demands and expectations of grades. In most schools the athletic eligibility is actually higher than graduation requirements. Studies also show in high school women have sew later, lowering the risk of pregnancy and disease. Young females also have higher self-esteem and a power to say no (Krucoff 1998). Competition is a very vital aspect of children involved in sports that offers many positive outcomes and teaches a variety of life skills. Competition is necessary for excellence and a child needs competitors who are not much better or worse at sports for this development to be essential. Without worthy opponent and challenges sports I not so much fun. The better the challenge the better opportunity a child has to go beyond his or her

Why is the UKs relationship with the rest of the EU so difficult

Why is the UKs relationship with the rest of the EU so difficult Introduction European countries have witnessed great political and economic integration with a Union of 27 European countries being currently in existence. This vibrant European Union can trace its roots to the post World War II years when integration among European nations was seen as necessary to end the devastating wars between neighbours.Advertising We will write a custom essay sample on Why is the UK’s relationship with the rest of the EU so difficult? specifically for you for only $16.05 $11/page Learn More The European Union has achieved significant growth from an initial membership of 6 nations to the current membership of 27 nations. It has emerged as a major political and economic force in the world, even threatening to compete with the traditional superpower, the United States of America. Of the 27 members making up the European Union, the UK has set itself apart as the nation that has a problematic relationship with the EU. While the other nations have a good relationship within the union and mostly support its policies, the UK continues to have a mostly adversarial relationship with the union. This paper will set out to discuss the major reasons for the difficult relationship between the UK and the rest of the EU. Reasons for the Difficult Relationship The UK is more concerned with the economic aspect of the EU than the political dimension. From the onset, the UK has been reluctant to foster stronger political ties with other European countries instead emphasizing on the economic dimension of the union. This is in contrast with the view of the other EU countries that view political goals as being equally important for the union (Chalmers 23). The main motivation of the UK to join the union was economic and the country never strived for political integration. Margaret Thatcher who served as the British Prime Minister from 1979 to 1990 expressed the concerns that Britain had regarding political integration. Thatcher s tated that British was constantly losing her independence and sovereignty as more decision-making power was transferred from the British Parliament to Brussels. The UK’s lack of commitment to political integration, which is a core aspiration for the other EU member states, has increased the difficulty in relationship between it and the EU.Advertising Looking for essay on international relations? Let's see if we can help you! Get your first paper with 15% OFF Learn More Britain’s relationship with the EU is complicated by the fact that Britain was not involved in the founding of the European Union. When the six European countries, France, Germany, Belgium, Netherlands, and Luxembourg, founded the EU, Britain choose to isolate herself from this union. British did not feel the need to engage in a union with other European countries since her economy was larger than that of countries such as Germany or France. Therefore, Britain disregarded the oppo rtunities she was given to participate in the process of establishing the EU during its formative years. Watts and Pilkington note that because of this disregard, Britain had excluded itself from the decisive events taking place on its doorstep (21). This created a hurdle for the UK since it did not have a part in the setting up of the basic rules that govern the EU (Watts and Pilkington 127). The formation of the Union led to an acceleration in economic growth for the member states and the six member states were going from strength to strength. This growth persuaded Britain to finally join the Union but by then, the six founding states had shaped the community to serve their best interests. As a new arrival to the Union, Britain had to be content with adapting itself to the rules that had already been put in place by the founding club of states. When a country chooses to be a member of the EU, it gives up some of its national sovereignty and agrees to be bound by some policies that dictate the policies of countries within the union on social, economic, and political matters. Unlike other EU countries, which are ready to give up their local powers and accept the authority of the European Court of Justice, the UK wishes to repatriate power back to Westminster. The UK currently feels exposed to EU integration and is therefore looking for ways to limit this exposure and therefore protect itself (Chalmers 132). The UK has tried to remove itself from some of the agreements of the EU in order to increase its autonomy.Advertising We will write a custom essay sample on Why is the UK’s relationship with the rest of the EU so difficult? specifically for you for only $16.05 $11/page Learn More Britain’s move towards limiting the authority of EU bodies can be seen from the Conservative Parties 2009 election manifesto, which clearly highlighted their commitment to limiting the power of the European Court of Justice over Britains cour ts (Brady 3). In line with this ambition, Britain intends to pull out of most of the EUs crime and policing co-operation in order to avoid having the European Court of Justice undermine Britains common law traditions. Brady observes that the UK wants to remain part of specific elements of EU crime and policing while disregarding those that are deemed unfavourable for the UK (2). This move has made many EU member states hostile to the UK. Britains politicians have played a significant role in making the relationship between the UK and the EU difficult. Begg observes that there is little support for the EU among British politicians with the anti-Europe politicians commanding a substantial political base while those in favour of the EU having little influence in the political system of the country (1). British parliamentarians are constantly calling for a referendum in the country to decide on whether the UK should maintain its EU membership. Public support for the European Union has a lways been low among Britons and this makes the relationship with other EU member states difficult since Britain is perceived to be an undedicated member. From the onset, the British did not unanimously favour membership to the European Community and legislation in support of the European integration was voted into Britain through a small majority in favour. The UK is constantly renegotiating the terms of its membership to the EU, an action that is frustrating the other members of the EU.Advertising Looking for essay on international relations? Let's see if we can help you! Get your first paper with 15% OFF Learn More Begg notes that the UK government is carrying out an audit of its relationship with the EU with the aim of making changes to suit the interests of Britain (1). This need for renegotiation has been necessitated by the alleged disenchantment of Britons with the EU. For EU member states, such actions are seen as a move towards more exceptional ism by British instead of fostering deeper integration. The special relationship between the UK and the US has made Britains relationship with the rest of the EU difficult since UK foreign policy traditionally started out by trying to build an Anglo-US position. Britain has for decades developed a close and special bilateral relationship with the US and the two governments have constantly sort to cooperate with each other and engage in deep consultation. Niblett notes that the UK and the US has many common foreign policy objectives that they collaboratively pursue (637). These strong bilateral relations tend to make the EU a secondary party to th e US as far as UK policy makers are concerned. The negative perception of deep US-UK relationships by EU member states can be seen by the historical attempt by French President Charles de Gaulle to veto Britains application to join the community in 1961 where President de Gaulle asserted that Britain’s ties with the US would be hindrance to the UKs dedication to the European Union. Nationalism acts as a major undermining force for Britain’s involvement in the EU. Watts and Pilkington states that Britain is the EU member that has mostly employed euroscepticism to defend national sovereignty against the encroachment of an alien Europe (110). In 1994, Leon Brittan, a former British Commissioner expressed the unease about Brussels due to the perception that it was interfering where it should not do so and the belief that Brussels lacked sufficient democratic legitimacy. Following the EU enlargement, the UKs influence in the Union has reduced considerably and it is no longe r able to moderate the EU debate or easily mediate with the majority of EU members. This lack of significant power in the union has increased nationalistic tendencies at the expense of involvement in the EU. Britains idea of her role in the world also contributes to making the relationship between the country and the rest of the EU difficult. George suggests that due to her impressive historical legacy, the British population and its politicians feels superior to the other European countries and are therefore unwilling to relate on an equal footing with them (42). For centuries, the British Empire significantly influenced the world with Britain having colonies on every continent at the height of her imperial era. With such a legacy, entering the EU for Britain meant a loss of some of its worldwide influence. This has created a psychological barrier that has greatly strained Britains relationship with the rest of the EU. The UK has always conducted itself as an independent party to t he EU instead of a member state. This perception was best articulated during Margaret Thatchers rule, which was characterized by increased political isolation. During this period, the UK sort to highlight her sovereignty and opposition to political and social integration with the rest of Europe. Barely 3 years after UKs entry into the EU, the Britons were calling for a renegotiation of their terms of entry (Bideleux 143). This move had the support of the political establishment of the country and its citizenry therefore demonstrating the outsider status that UK aspired for. Financial considerations have made the relationship between the UK and other EU member states problematic. The UK has sort to reduce its financial responsibilities in the Europe and ensure that its financial well-being is not tied up with that of the other European nations (Eudey 15). This stance is best demonstrated by the refusal of the UK to give up its currency, the British Pound in favour of the common curre ncy of the EU, the Euro (Tavlas 37). The Eurozone crisis, which nearly triggered the collapse of the EURO currency, has increased the difficulty of the relationship between the UK and the rest of the EU. This crisis has been costly to the unions big economies with countries such as Germany and France having to shoulder enormous financial responsibilities in order to preserve the integrity of the common currency since its collapse would be devastating. Instead of taking on a more helpful approach, Britain has continually pointed to this event as justification for her scepticism about deep economic integration in the union. Most of the EU members have perceived Britain as being unhelpful during the crisis and this has reduced the goodwill that the UK enjoys with the EU. British officials are not very open with their EU counterparts and this has led to some of their actions been regarded as adversarial. Brady reveals that when taking actions that influence the EU, British ministers hav e not taken the time to articulate their position and enable the other EU members to better understand them (3). This lack of openness has antagonized many EU member states who are at times irritated by the actions of the Britons. Without open communication between British national officials and their EU counterparts, the EU officials can only guess at the motivation behind the actions of the UK government. Discussion Due to the numerous troubles that the UK has been having with the EU, there have been talks of Britain opting out of the union. Such a move would be detrimental to both the UK and the EU. The UK is important to the EUs continued political and economic growth. Without its involvement, the EU would lose some of its global powers and its ability to develop a more dynamic economy. Exclusion from the EU would also see Britain reduce itself to a second-class status in Europe and lack the power to influence the future decisions of the Union. Britain’s role in the EU is crucial to her economic well-being. Cottret states that while most of Britain’s foreign investment comes from outside the EU, the country is regarded as the most suitable launch pad for entry into the European market (192). Britains withdrawal from the EU would therefore seriously damage her advantage and lead to a significant decline in foreign investment. It is therefore in the best interest of Europe for the UK to continue being a member of the EU. However, the difficulties experienced in the relationship between the EU and the rest of the Union need to be mitigated. For the to occur, the UK will have to concede that it cannot maintain its identity entirely and accept to adopt a European identity. The nation will also have to accept the fact that the sovereignty of the British Parliament will be challenged and surpassed by the European Court of Justice from time to time. While this will be an infringement on the fundamental principle of the British community, it will be a small price to pay for the advantages of being in the EU. Conclusion This paper has discussed the difficult relationship between Britain and the EU. It has highlighted the many reasons that make Britains involvement in the EU difficult. The UKs historical legacy makes it difficult for the country to accept narrowing its political interests primarily to the European continent. The lack of involvement in the formative years of the Union also means that Britain did not have a say in the establishment of the core policies and rules that govern the EU. These difficulties have mitigated the role of the UK in the union and led to speculations about its future membership to the EU. This paper has noted that if the UK leaves the EU, there will be significant loses especially for the UK. Action therefore needs to be taken to make the relationship between Britain and the EU less problematic. Begg, Iain. It is entirely possible that Britain could leave the European Union within the next decad e. Feb. 2012. Web. Bideleux, Robert. European Integration and Disintegration: East and West. NY: Routledge, 1996. Print. Brady, Hugo. Britains 2014 justice opt-out: Why it bodes ill for Camerons EU strategy. Brussels: Centre for European Reform, 2013. Print. Chalmers, Daniel. European Union law: text and materials. Cambridge: Cambridge University Press, 2006. Print. Cottret, Bernard. Civilization of Modern Britain. Vienna: Breal Publishers, 2004. Print. Eudey, Greg. â€Å"Why Is Europe Forming A Monetary Union.† Business Review 3.1 (1999): 13-21. Web. George, Stephen. An awkward Partner: Britain in the European Community. Oxford: Oxford University Press, 1998. Print. Niblett, Robin. â€Å"Choosing between America and Europe: a new context for British foreign policy.† International Affairs 83.4 (2007): 627–641. Tavlas, Grant. â€Å"Benefits and costs of entering the Eurozone.† CATO Journal 24.2 (2004): 34-54. Web. Watts, Duncan and Pilkington, Colin. Brita in in the European Union Today. Manchester: Manchester University Press, 2005. Print.

The Law of Negligence Essay Example | Topics and Well Written Essays - 2000 words

The Law of Negligence - Essay Example 1The decision of Donoghue v. Stevenson was the point from where carelessness or a general duty for carelessness was recognized. In the case it was recognized that a manufacturer owed a duty to ensure that the produce were free from defect, to the ultimate consumer, and that any damage to property or personal injury should have been foreseen by him. In the particular case the claimant argued that she was poisoned due to drinking the ginger beer, purchased by her friend, due to the fact that the opaque form of bottle did not allow her to notice that the beer had a decomposed snail in it. The House of Lords by a bare majority found that a duty of care was owed to her, thereby overturning the previous decisions. Lord Atkin formulated on the general conception on which a duty of care was determined upon or in other word the famous "neighbor principle". The principle said that all reasonable care should taken to avoid acts or omissions from which it was reasonably foreseeable would injure the neighbor. This case started to recognize what had been termed the social wrong and so based negligent liability by determining the fault. Damage also is an essential part for proving neglige3nce and so the claimant must prove that an injury was sustained as a result of the defendant's negligence. Fault, damage ad causation is necessary but not sufficient condition of liability. The focus therefore in claims of negligence is that a duty has to be established for any claims for possible liability. Thus even if it can be shown that there has been a damage caused to the claimant the courts may nevertheless not grant negligence if it is found that there is no duty situation. Further there have been restrictions imposed by courts for claims of pure economic loss. 2In Murphy v. Brentwood DC the courts limited the scope for claiming economic loss but there are possibilities of claiming it in a number of situations. Further the courts have created a distinction between acts and omissions, liability for positive acts have been long recognize but this has not been so for omissions which are only allowed in very exceptional circumstances. 3The duty of care attaches with it the concept of foresee ability as Lord Wright said in Bourhill v. Young that the concept of foresee ability is always relative to the individual affected . However it is further stressed that foresee ability in itself is not adequate for establishing duty of care. Even though Lord Atkin place great emphasis on reasonable contemplation or foresee ability of harm as a precondition for establishing duty of care it fails to explain many claims under physical, non-physical and property damage which are even though foreseeable but still fall outside the head of negligence. The test for causation limits liability and so the courts are allowed to make value judgments when ascertaining damages. The courts have at times used the but for test for establishing liability- would the loss have occurred but for the negligence of the defendant. This limits the liability of defendants to the extent of his personal responsibility. The question of whether a duty of care is owed by the defendant is a matter of law and so is ascertained by the

Digital Business Management Essay Example | Topics and Well Written Essays - 2250 words

Digital Business Management - Essay Example To achieve this, the paper has selected www.origin.com as the site for analysis. An analysis of the website is conducted with a focus on how it is implementing digital information systems. The paper then reviews the business model of the website showing its online value proposition. The paper then goes ahead to identify the target audience of the website and how the website is trying to access them. Lastly, the paper evaluates the customer relationship management strategy employed and makes recommendations based on what has been observed. Origin.com is Origin’s official website. Origin provides free gaming services and a platform for games shopping that allows user to shop, access and play varied video games. Origin also acts as a social networking platform which enables users to connect, network and invite one another to play games across different platforms (Origin.com, 2014). The site is also connected to a cloud service that enables a user to save a game and resume from where it was stopped. It, therefore, allows for exchange of information and feedback, hence, creating a fully functional digital information system (Gitman and McDaniel, 2006). A digital information system is defined as arrangement of hardware, software, liveware and information resources that enables inputting of data, processing, outputting and storage of information often for a definite purpose (Kathy, Zhwei and Agrusa, 2004). There are many types of information systems; the transaction processing system, management information system, decision support system and executive support system (El-Sawy and Pereira, 2012). This websites acts as a decision support system since it provides information that is then used by a customer to make decisions based on information provided (Preece, 2001). The same information can be used by the Origin management team to note and analyse problems and come up with sustainable solutions for the same. The website implements digital information systems in

Auto Cad And STAAD Pro

Auto Cad And STAAD Pro This chapter gives an insight into the topics involved in this dissertation, it starts with a review of the key items involved to complete this project such as the programs used to design and analyze the structure as in Auto cad, and STAAD pro. The chapter further develops in reviewing the euro codes in which the building will be designed to. Auto Cad This is a design and documentation software program that was founded in 1982, 28years ago. It is the most commonly used piece of software of its kind and it is constantly being enhanced and improving its software to meet the current needs of its users. It is used for drawing objects to a very high degree of precision in either 2D or 3D format using polar coordinates. Almost any object conceivable like the 3D model shown in figure 2.7 can be produced on todays Auto cad thanks to its extensive array of tools and when trained, easy to use interface. Its tool base may be used in both the 2D and 3D formats, some of the basic tools include, line, circle, arc, break, extend, mirror and copy. These are only a small fraction of the features of Auto cad, which make it possible to create and change or redesign models of any shape and complexity, in a relatively short period of time as compared to drawing by hand or using other software programs such as STAAD pro. This is the reason why auto cad was used to detail the design rather than STAAD pro because of its ease of use and the complexity of the design and then inputted into the STAAD pro software for the analysis. STAAD Pro This is a finite element analysis and design software program run on windows operating systems, which is used to analyse the structural stability of structures, under a variety of conditions. It allows the users to effectively analyse structures built from a number of different materials such as, timber, concrete, aluminium and steel, under different forces caused by, earthquake, soil interaction, and various dead loads and live loads, which are specified by the local design codes being used in whatever location the structure is being design, in this case Eurocodes. It is a very versatile piece of software that has being perfected over the past 25 years, it reduces the amount of man hours required to correctly analyse how a structure will behave when loaded using either 2D/3D model generation. The general steps involved in producing a successful model are as follows: Model generation: creating the structure model in either 2D or 3D which could involve importing an Auto Cad files and then choosing the material type and size for the members, applying a foundation types to correct locations and specifying loads and forces on the model. Calculations:-to obtain the analytical results. Code check:- creating parameters for design specification Running analysis:-to perform analysis and design. Verification of results:-displayed through graphs, diagrams and tables. Reporting and printing. Eurocodes: This chapter is intended to provide a brief introduction into the eurocodes. It will list the benefits, the problems, associated with the codes. It describes the general layout of the codes and discusses the difficulties with the drafting of the codes and how the difficulties were resolved, the national annex and their roles will also be discussed. It will advance to describe in detail to list the difference between the previous BS 8110 and the contents of Part 1.1 of Eurocode 2, which has superseded the above British standard. And will be the main eurocode used to design this concrete structure. The eurocodes are set of ten codes of practice for the design of building and civil engineering structures in concrete, steel, timber, masonry other building materials Table 2.1 lists these eurocode there titles and reference numbers. Similar to the previous codes of practice the British standards these codes come in a number of different parts, each containing different rules to the design of the different structures included in the codes. Table 2.1 EN1991 provides the characteristic values of the loads or actions as termed in the code, needed for the design. It is the head code of the world fist material independent design code providing guidance on determining the design value of actions and combination of actions, including partial safety factors for the actions. EN 1997 covers the foundation design with respect to the geotechnical side. EN1998 is devoted to the seismic design and provides guidance on achieving earthquake resistance in buildings and structures. These Eurocodes will have the same legal standing as the previous British standards and other approved documents. These codes were published first as preliminary standards; know as ENV (Norme Vornorme Europeenne), in the beginning of 1992. Now after being revised reissued as European standards, known as EN (Norme Europeenne), along with national annex which contains supplementary information, are coinciding with British standards but will eventually become mandatory and all conflicting standards will be withdrawn as in the British standards. Benefits of Eurocodes. There are many advantages of having design standards which are accepted by all member states how ever this is not a new initiative as the first draft Eurocode 2 for concrete structures was based on the CEB (Comite Europeen du Beton) Model Code of 1978 produced by a number of experts from various European countries, similarly Eurocode 3 was based on the 1977 Recommendations for design of steel structures published by ECCS (European Conventional for Constructional Steelwork). The original reason for this work was to improve the science of structural design. Recently though the drive is for political and economic unification of countries and these Eurocodes will help to lower the trade restrictions and barriers which exist between member states and allow for contractors and consultants to compete freely and fairly for work within Europe. Also the unification will enable products, materials, components, design programs to be marketed throughout member states. It will also improve interna tional standing of European engineers which should help in increasing their chances of wining work abroad. Prooduction of Eurocodes: Each Eurocode has been drafted by a team of experts from different member states. These groups are under contract to the CEN (Comite Europeen de Normalisation), the European standards organisation, whose members are the national standards bodies as in the British Standards Institute in the UK. During the ENV stage of production a liaision engineer from each member state was involved in evaluating the final document and discussing with the drafting team the acceptability of the eurocode in relation to the previous national code. Format of Codes: Problems associated with drafting the Eurocodes. There were many problems faced when the Eurocodes were being drafted mainly being the terminology that was to be used, different climate conditions, materials and different work practices from the different member states. The following details outline ways in which these problems were overcome. Terminology From the beginning it was inevitable that the terminology would have to be standardised in general the agreed terminology was found to be similar to that used in the UK national standards. The few minor differences include loads are now called actions while dead loads live loads are now referred to as permanent and variable actions respectively. Similarly bending moments axial loads are now called internal moments and internal forces respectively. Principles Application Rules This was the method used to divide the documents into sections ensuring documents were concise, described the overall aims of the design provided specific guidance as to how these aims can be achieved in practice. Principles comprise of general statements, definitions, requirements and models for which no alteration is allowed. Application Rules are generally recognised rules which follow the statements satisfy the requirements given in the principles. When the letter P is missing from the clause number it indicates an application rule. The use of alternate rules other than that in the eurocodes is permitted as long as hey do not effect the design requirements and are at least equivalent to those suggested. National Annexes Differences in work practices, climate conditions etc required the allowance for different parameters to be determined and specified at a national level such as safety factors, cover particular methods of construction etc. where these deviations are allowed a note in the code is provided in the accompanying annex, these parameters are know as NDPs (Nationally Determined Parameters). Eurocodes 2: Design of concrete structures. This will be the main Eurocode used to design this structure as the build will be mainly concrete this code is to replace the previous code of practice BS8110 and it is the European standard for the design of buildings in concrete, although the ultimate aim of Eurocode 2 and BS 8110 is largely the same to provide guidance on the design of buildings and civil engineering works in concrete, there are many new design procedures and differences, it is based on a limit state principles and comes in four parts as shown below in table 2.3 Liquid retaining containment structures Part 1.1 of Eurocode 2gives a general basis for design of structures and some detailing rules very similar to the previous BS8110, the design cannot not be completed without using reference to other documents such as EN 1990 (Eurocode 0) and Eurocode 1 to determine design values of actions (loads), Part 1.2 of Eurocode 2 for fire design, EN 206 for durability design Eurocode 7 for foundation design. The reason for this difference in structure and layout is to make the eurocodes more concise than BS 8110 and avoid repetition. Proposed Design: In the design process a number of different designs were considered and working with the requirements of the structure the most suitable one was chosen these requirements were as follows: Design a suitable multi-storey building containing retail units and accommodation units. The structure should be designed and built to modern codes of practice and standards. The building must be of modern aesthetics and be unique to surrounding buildings. Also the structure should fit the following criteria: Retail Floor Space ; between 1500 4000m2 Accommodation Space ; between 10000 30000m2 Maximum Footprint ; between 1500 3500m2 Maximum Height of Building; 40m. The following designs were considered and compared when choosing the final design. Proposal One; Retail space = 3161m2 Accommodation space = 11718m2 Footprint = 3161m2 Provision for lateral stability and vertically stability is provided by concrete columns and shear walls/shear cores within the structure. Proposal Two; Retail space = 2001m2 Accommodation space = 11674m2 Footprint = 2001m2 Provision for lateral stability and vertically stability is provided by concrete columns and shear walls/shear cores within the structure. Proposal Three; Retail space = 1558m2 Accommodation space = 28451m2 Footprint = 1558m2 Provision for lateral stability and vertically stability is provided by concrete columns and shear walls/shear cores within the structure. Chosen design: The design in proposal two was chosen finally because when it was compared with the other designs it was decided that it was more astethic than proposal three because of its falling design, it was then compared with design one and it was not considered to be more asthetic but it did accomodate the footprint requirments and space requirments better than proposal one did. Materials Methods: Elevator Elevator Shaft; The elevator shaft will provide latheral stability for the building and will direct forces into the ground, it will span from the base to the roof in each of the four shafts. There will be four elevator shafts positioned in the centre of each external face of the building, providing ease of acess to each floor. Each one will be of dimensions 3 x 2m and will utilise a electric cable borne method for lifting and will travel at a max speed of 2.5m/s. Each elevator will be able to accomondate a max of 10 peolple at a time. Latheral Stability: The elevator shafts incorporadted in this design provide for latheral stability caused by wind loads, these loads are created by the wind force on acting on the external face of the building transmiting the loads to the floor, these floors form horizontal diaghragms transfering the latheral load to the vertical rigid elevator shaft which acts as a vertical cantillever and subsequently transfers the loads to the foundations. The advantage of using the elevator shaft to provide lateral stability is that concrete walls tend to be thiner than other bracing systems used in medium sized multistorey construction and so save space in congested areas also they are very rigid and may be used as fire compartment walls, the disadvantge of using the elevator shaft for latheral stability is that construction is slower and less accurate and when constructed they are not easily modified, also it is difficult to provide connection between steel and concrete. Procedure STAAD Pro 1.1 Importing drawing Now that both the model had being created and the loads calculated, it was now time for the analysis of the model. To achieve this, first the model had to be imported into STAAD pro, this was done by saving the model in Auto cad as a R12/LT2 DXF file, which is compatible with STAAD pro, and then opening a new structure sheet in STAAD pro and using the import function located in the file drop down menu. When importing the file the following two pop up windows will appear shown in figure1.1 and figure 1.2, these let you define the orientation and units you want to analyse your model in. For the structure model meters and kilo Newton were chosen with a standard orientation of the Y axis pointing upward. After that the model will appear on the main STAAD Pro interface as shown in figure 1.3. As can be seen from figure 1.3, STAAD Pro has a vast array of tools and functions that make it possible not only to, analyse almost any structure in almost any situation, but also to draw structures. For simple structures it would be worth while using STAAD Pro, however for more complicated structures it is better to use Auto cad, because it is specifically tailored for drawing almost any structure or object with ease, for the trained user. Now that the model was now in STAAD pro, it was now time to proceed with further developing the model for analysis. On the left hand side of the main window containing the model, there is a tool bar called modelling, this toolbar contains functions for modifying the model, like design, support, general, load, material etc. 1.2 Adding supports For the model, supports were required at every base node position. To achieve this, the support window was selected from the general toolbar, figure 7.5 shows the window that pops up for adding support to your structure. For this model fiixed support was required so the create button was selected, and fixed support in the sub menu was chosen as shown in figure 1.4. Now that the option for fixed support was now in our main support window, it was now time to apply the support. STAAD pro gives you a number of different options of assigning the support, like, assign to view, use cursor to assign and assign to edit list, and assign to select nodes. First the node function was selected from the cursor toolbar as shown in figure 1.6, this option allows you only to selected nodes and not beams. When this was done, the bottom layer of nodes on the model, were select and the assign to selected nodes function was used. Now fixed support were applied to the model in the correct position as shown in figure 1.7, and it was time to proceed with the next step. 7.3 Member selection From the general toolbar, the properties window was selected. From here you can assign any style of member in accordance with many different regions building codes using the section database function, and apply any number of different sections to different members in the same model. You may also design the dimensions as in this case a 300mm by 280mm rectangular concrete section was chosen for the beam and a 300mm by 300mm concrete section for the column was detailed. Once selected, the section chosen appears in the properties window, and from here you are given the same option as applying support i.e. (assign to view, use cursor to assign and assign to edit list, and assign to select beams). First the beam function from the cursor toolbar was chosen, this allows you to only select beams and not nodes. Then the columns were assigned using the same process with the different section assigned, figure 1.9 shows the model with the beams and columns applied. Now that this was completed it was now time to move on to applying the various loads to the model. 7.4 Applying loads Loads are used to estimate how a structure will behave if constructed. Since the loads had being previous calculated with the aid of eourcodes, it was now possible to apply them to the structure. In the general toolbar, the load window was selected, from here all types of load may be applied to the structure, for the dome the loads calculated were, dead load, live load, and wind load. From the load window, the load cases icon was selected, a pop up window as shown in figure 1.10 was activated. From here all the three types of loads were identified and added to the main load window. Each load name was then picked individually by used of a pop up window known as load items which is shown in figure 1.11 and the specific load applied. Now that the loads had being picked and values assigned to them in the appropriate direction, it was now time to apply the loads to the model. In the load window the same options exist as for the support and properties window for applying items to the model, for the dead and imposed load, the assign to view function was used. For the wind load only the side facing the wind is loaded, so the node cursor was selected from the cursor toolbar and all the nodes on wind facing side of the structure was selected as shown in figure 1.12. 7.5 Running analyse First the analysis/print toolbar was selected from the modelling menu, which resulted in two windows being activated, the print analysis commands window and analysis whole structure window, which are shown in figure 1.13. In the analysis commands window the no print option was selected and added to the analysis whole structure window, which shows the processes involved in the analysis. After this was completed the analyse toolbar located at the top of the user face was selected, and the run analyse option selected as shown circled in red in figure 1.14. After the analysis in completed a window the STAAD analysis and design window shows the processes carried out and whether there are any errors or warnings related to the model. Any problems relating to the model may be checked by selecting the errors or warning in the window, and the exact problems with the members they are related to, will be displayed. Figure 7.15, shows the final analysis of the dome model which took 16 seconds with no errors or warnings, after all the errors and warnings were corrected. 7.6 Post processing On the bottom left of the STAAD analysis and design window, there is a set of options on where to go after the analysis, the go to Post Processing Mode option was selected and done button pressed. Form here, the post processing window as shown in figure 7.16 the results of the analysis may be viewed for both the beams and the nodes. Graphs and reaction tables along with visual representation can be viewed for the nodes, showing things like the max displacement of a node. Stresses, graphs and forces can be viewed for beams showing such things as max axial forces, max bending, max shear and max stresses. 7.7 Producing reports The number of results including structure type, No. of nodes, No of members etc can be put into a report format. This is a useful tool for an engineer to document any findings to produce to clients or planners, an example of a node report for the dome is shown in figure 1.17.

The Great Depression Essay -- essays research papers

Carmack 2 The Great Depression   Ã‚  Ã‚  Ã‚  Ã‚  The Great Depression is known as a time of economic disaster, and for its impact on the social structure of families. As times got harder, the family way of life changed. Families that were well off did not suffer as much as those that were already struggling. When men lost their jobs they also lost the ability to support their families. Children were forced to leave home and find work without adequate schooling. The Great Depression affected people both physically and psychologically. It was an era of unemployment, family struggles, and the way they survived.   Ã‚  Ã‚  Ã‚  Ã‚  The Great Depression was an era of unemployment. One of the main causes of unemployment was the combination of the greatly unequal distribution of wealth throughout the twenties. The unequal distribution of wealth had gone on forever. Money was distributed disparately between the rich and the middle class, between the United States and Europe, and even between industries and agriculture. The unequal distribution of wealth had created an unstable economy. Companies were losing money because of this unstable economy so there for they had to make some changes. The first thing that had to be done was to save money and they did this by cut the pay role. Employees of many years were fired or took massive pay cuts. The employers only kept a select few workers that they had to have. Carmack 3 If one did not make the employer’s expectation, they were fired.   Ã‚  Ã‚  Ã‚  Ã‚  Monte Cristo had a list, a little roll call. And one by one he took them each for a ride Saying One and Two and Three and so on Till the names were all crossed off And he had cleabsed the world of a giving number Of betrayers who had personally wronged him. He was judge, jury, and executioner   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  (Sandburg 445) Finding a replacement was not difficult since everyone; men, women, children, and even grandparents, were looking for work. I’m not asking for social equality, †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦ All I want is a job with a decent wage, To exist now and provide for old age. So kindhearted employers, my case is up to you, Give me something to do. (Proudberg 9-16) With few job openings and so many people looking fo... ...yday study the buffalo on the nickel, †¦. Study before the nickel, the dime is spent.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  (Sandburg 456) A lot of the people today have long forgotten the lessons that their parents had taught them. Today people really do not appreciate the value of a dollar, but they know all about â€Å"plastic,† or commonly known as credit cards. I think a small dose of depression would do people today some good but not too much, because I think we would have a lot more people killing themselves and others just because people have fewer moral values today. Carmack 8 Worked Cited Hawes, Joseph M. Children Between the Wars. Ed. Joseph M. Hawes., N. Ray Hiner. New York: Twayne Publishers, 1997. Proudbeg, Jim. â€Å"Poor Nut Ambitious (too Proud To Beg).† 21 Apr. 2000. http://www.mudcat.org/!!-song99.cfm?stuff=fall99+9902682. Sandburg, Carl. The Complete Poems of Carl Sandburg. New York: Harcourt Brace Jovanovich, 1970. Underwood, Mark. â€Å"Black Thursday.† The New York Times on the web. 1 May. 1996. 4 Apr. 2000 . The Great Depression Essay -- essays research papers Carmack 2 The Great Depression   Ã‚  Ã‚  Ã‚  Ã‚  The Great Depression is known as a time of economic disaster, and for its impact on the social structure of families. As times got harder, the family way of life changed. Families that were well off did not suffer as much as those that were already struggling. When men lost their jobs they also lost the ability to support their families. Children were forced to leave home and find work without adequate schooling. The Great Depression affected people both physically and psychologically. It was an era of unemployment, family struggles, and the way they survived.   Ã‚  Ã‚  Ã‚  Ã‚  The Great Depression was an era of unemployment. One of the main causes of unemployment was the combination of the greatly unequal distribution of wealth throughout the twenties. The unequal distribution of wealth had gone on forever. Money was distributed disparately between the rich and the middle class, between the United States and Europe, and even between industries and agriculture. The unequal distribution of wealth had created an unstable economy. Companies were losing money because of this unstable economy so there for they had to make some changes. The first thing that had to be done was to save money and they did this by cut the pay role. Employees of many years were fired or took massive pay cuts. The employers only kept a select few workers that they had to have. Carmack 3 If one did not make the employer’s expectation, they were fired.   Ã‚  Ã‚  Ã‚  Ã‚  Monte Cristo had a list, a little roll call. And one by one he took them each for a ride Saying One and Two and Three and so on Till the names were all crossed off And he had cleabsed the world of a giving number Of betrayers who had personally wronged him. He was judge, jury, and executioner   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  (Sandburg 445) Finding a replacement was not difficult since everyone; men, women, children, and even grandparents, were looking for work. I’m not asking for social equality, †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦ All I want is a job with a decent wage, To exist now and provide for old age. So kindhearted employers, my case is up to you, Give me something to do. (Proudberg 9-16) With few job openings and so many people looking fo... ...yday study the buffalo on the nickel, †¦. Study before the nickel, the dime is spent.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  (Sandburg 456) A lot of the people today have long forgotten the lessons that their parents had taught them. Today people really do not appreciate the value of a dollar, but they know all about â€Å"plastic,† or commonly known as credit cards. I think a small dose of depression would do people today some good but not too much, because I think we would have a lot more people killing themselves and others just because people have fewer moral values today. Carmack 8 Worked Cited Hawes, Joseph M. Children Between the Wars. Ed. Joseph M. Hawes., N. Ray Hiner. New York: Twayne Publishers, 1997. Proudbeg, Jim. â€Å"Poor Nut Ambitious (too Proud To Beg).† 21 Apr. 2000. http://www.mudcat.org/!!-song99.cfm?stuff=fall99+9902682. Sandburg, Carl. The Complete Poems of Carl Sandburg. New York: Harcourt Brace Jovanovich, 1970. Underwood, Mark. â€Å"Black Thursday.† The New York Times on the web. 1 May. 1996. 4 Apr. 2000 .

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.