Classification of Vibration

CLASSIFICATION OF VIBRATION Vibration can be classified in several ways. Some of the important classifications are as follows. †¢Free Vibration. If a system, after an initial disturbance, is left to vibrate on its own, the ensuing vibration is known as free vibration. No external force acts on the system. The oscillation of a simple pendulum is an example of free vibration. †¢Forced Vibration. If a system is subjected to an external force (often, a repeating type of force), the resulting vibration is known as forced vibration. The oscillation that arises in machines such as diesel engines is an example of forced vibration.If the frequency of the external force coincides with one of the natural frequencies of the system, a condition known as resonance occurs, and the system undergoes dangerously large oscillations. Failures of such structures as buildings, bridges, turbines, and airplane wings have been associated with the occurrence of resonance. If no energy is lost or dis sipated in friction or other resistance during oscillation, the vibration is known as undamped vibration. If any energy is lost in this way, however, it is called damped vibration.In many physical systems, the amount of damping is so small that it can be disregarded for most engineering purposes. However, consideration of damping becomes extremely important in analyzing vibratory systems near resonance. If all the basic components of a vibratory system the spring, the mass, and the damper behave linearly, the resulting vibration is known as linear vibration. If, however, any of the basic components behave nonlinearly, the vibration is called nonlinear vibration. The differential equations that govern the behavior of linear and nonlinear vibratory systems are linear and nonlinear, respectively.If the vibration is linear, the principle of superposition holds, and the mathematical techniques of analysis are well developed. For nonlinear vibration, the superposition principle is not val id, and techniques of analysis are less well known. Since all vibratory systems tend to behave nonlinearly with increasing amplitude of oscillation, knowledge of nonlinear vibration is desirable in dealing with practical vibratory systems. If the value or magnitude of the excitation (force or motion) acting on a vibratory system is known at any given time, the excitation is called deterministic.The resulting vibration is called as deterministic vibration. In some cases, the excitation is nondeterministic or random; the value of the excitation at a given time cannot be predicted. In these cases, a large collection of records of the excitation may exhibit some statistical regularity. It is possible to estimate averages such as the mean and mean square values of the excitation. Examples of random excitations are wind velocity, road roughness, and ground motion during earthquakes. If the excitation is random, the resulting vibration is called random vibration. Reference link: http://cla ssof1. com/homework-help/engineering-homework-help

Dostoevsky and Maslow: Needs in Life, How They Are Prioritized, and the Exceptions

Dostoevsky has written, â€Å"Without a clear perception of his reasons for living, man will never consent to live, and will rather destroy himself than tarry on earth, though he be surrounded with bread.† (The Grand Inquisitor) With indirect opposition, Maslow's idea on these needs is stated in his quote, â€Å"A person lacking food, love, and self-esteem, would most likely hunger for food more strongly than anything else.† A number of instances stand as evidence to both Maslow and Dostoevsky's statements. First let us look at the claim Fyodor Dostoevsky has made. The Bible also has three references for a very similar idea. Scripture has expressed, in Deuteronomy 8:3, Matthew 4:4, and Luke 4:4, that ‘Man does not live on bread alone, but on every word that comes from the mouth of God.' (The Bible) All individuals have accepted the Bible as truth would feel this way and therefore approach life's needs as Dostoevsky. The act of fasting is also an example of how Fyodor's statement might come into play during an individual's life. Another group of individuals who might be observed to follow the Dostoevsky idea would be those who are suffering from serious mental disorders. A loss of regular and proper diet is a symptom of severe cases of depression, anxiety, and stress. (MayoClinic) They become so focused on their struggle to overcome these feelings, of being lost, or alone, or unorganized, and unsafe, that the priority of food becomes pushed aside. But in Maslow's Pyramid the feelings of safety and organization, love and belonging, are all placed higher, or less important, than the need to satisfy hunger. (Myers) Order of prioritization is the foundation of contradiction between the two statements. Abraham Maslow's idea seems to be more realistic to a majority of the remaining population. How is it reasonable to think a person would have the capability to even find their identity or â€Å"the purpose in life† without the energy supplied by fulfilling basic needs, like eating? This was a common reaction I heard from peers and adults after telling of Dostoevsky's statement. Gandhi said, â€Å"Even God cannot talk to a starving man except in terms of bread.† (Aldrich) Some needs take priority over others. (Myers) Our brain causes us to have feelings of motivation for needs; the most concrete are physiological needs, like our drive to eat. It would be unhealthy and tiring to suppress and ignore your bodies drive to eat while you find your identity. In extreme measures you could even die doing this. As we can see, neither Maslow nor Dostoevsky's claims can be applied to human beings as an entirety, as there are exceptions. The differences and personal circumstances attached to individuals are all too different. Even Abraham Maslow himself recognized that not all personalities followed his proposed hierarchy of needs. (Huitt) We have discovered though, that both of our statements tend to be more applicable to one group over the other. Religious individuals would be highly likely to side with Dostoevsky's views, where as people who do not value an identity outside their own would agree with Maslow's prioritization of needs. To build off of Abraham Maslow's hierarchy of needs, it has been proposed, (Norwood) a joint effort of trying to satisfy a single level of a need is also learning how to continue to satisfy this need. During this process an individual is forming part of their identity by developing and adopting a personalized method of reaching a need. For example, people at the esteem level seek out empowering information, and those at the safety level would need helping information. If Norwood's more currently proposed statement, that finding identity and satisfying needs are interrelated, is correct, then Maslow and Dostoevsky would both hart part in creating one universal statement. As for now, Fyodor Dostoevsky and Abraham Maslow's statements of needs in life and how they are prioritized stand separately. Across humanity, some people accept one over the other as true. In my research for the paper, I have been able to loosely affiliate certain groups of people with Maslow or Dostoevsky's claims. A number of instances stand as evidence to both statements. Each idea is held accountable in the correct situations. It is not a surprise to me how the controversy of deciding on a dominant idea has not been settled.

The Causes of the Financial Crisis in 2008 Essay

The Causes of the Financial Crisis in 2008 - Essay Example It played a striking role in the failure of key businesses. It also contributed to the decrease in consumer wealth estimated to be in trillions of US dollars and a downturn in economic activities that led to global recession of 2008 – 2012 and also contributed to the European sovereign – debt crisis. It led to the increase of the TED spread that reflected an increase in perceived credit risk. The TED spread is the difference between rates of interest on interbank loans and on short – term U.S government debt. The spread of TED increase is shown in the graph below: The spread (in red) increases significantly during the crisis. The spread size is usually denominated in basis points e.g. if the bill rate (T - bill) is 5.1% and ED trades at 5.5% then the TED spread is 40 basis points. The TED spread has fluctuated over time but generally has maintained the range of within 10 and 50 basis points except during the financial crisis. In general the financial crisis cause d a very big damage to the world economy and many researchers have carried out studies to explain the causes of this crisis. We try to look into some of the causes below. Imprudent mortgage lending is considered a cause to the crisis as compared to a backdrop of abundance in credit, reduced interest rates, and over the roof prices for houses, lending standard became hassle free enabling many people to engage in the purchase of houses they couldn’t afford. ... Competitive pressures contributed to the increase in the amount of subprime lending during the years preceding the crisis. Source: U.S census bureau, Harvard University. State of the nation’s housing report 2008 The graph shows the dramatic expansion of subprime lending in the U.S between 2004 and 2006. Another cause was the housing bubble where the Federal Reserve allowed housing prices to sour to an all-time high that was unsustainable. Once the bubble burst as it was bound to, it triggered the crisis. The Federal Reserve maintained interest rates artificially low, per month payments to mortgage were low too and housing prices went up. Home owners took equity loans to pay their initial mortgages and credit card debts until the home prices peaked and the house of cards started to crumble. Mortgage debts would not be increased to pay previous debts. Lack of transparency and accountability in mortgage financing also did contribute to the 2008 financial crisis. Many participants in the housing finance sector contributed to the crisis through the creation of bad mortgages and selling of bad securities with confidence that they won’t be held accountable. Lenders would sell exotic mortgages to home owners without considering the repercussions in case the mortgages failed. Similarly, a trader would sell to investors’ securities that are toxic with fear of personal responsibility in case the contracts failed. The system collapsed through the maximization of personal gains and passing of the problem down the chain from brokers, to realtors, to individuals in rating agencies, and to other market participants. The great promise of managing risk by the ‘originate – to – distribute’ model of finance failed with

Strategic Plan Assignment Example | Topics and Well Written Essays - 2500 words

Strategic Plan - Assignment Example External analysis of global car industry: [On the basis of MACRO (PESTEL) Analysis] (for reference see Appendix-1) The auto industry is often thought of as one of the most global of all industries. Car industry is experiencing rapid changes with globalization (Carson, 2004). Rapid changes are also altering the industry structure and attractiveness. The emerging markets include Latin America (Mainly Brazil), ASEAN countries, Eastern Europe, China and India. The fast growing emerging markets taken together, increased vehicle sales by 70-80% and production by almost 80-90%(Auto Industry Statistics). Car sales growth rate in US is around 3.5%, in Western Europe around 2.5% and in Japan around 1.5% while in China it is almost 9%. Globally the total car industry employment is predicated to reach 4.8 million by 2015. It is estimated that global car industry revenue reach 903 billion Euros by 2015. So the car industry has been focused on the potential of the emerging markets to offset the in dustries maturity and stagnation in the Triad economics of scale and spread the costs of developing new models. One of the main features of car industry experiencing is, manufacturers extending their operations in developing countries. For global producers, rapidly growing markets in developing countries were meant to provide for spreading vehicle development costs; for establishing cheap production sites for the production of selected vehicles and components; and for access to new markets for higher end vehicles. "Corporate strategies in regard to globalization vary depending on the starting point of individual firms, but there seems to be a large measure of convergence toward 1) building vehicles where they are sold, 2) designing vehicles with common 'global' under-body Platforms while retaining the ability to adapt bodies, trim levels and ride characteristics to a wide range of local conditions" (Sturgeon and Florida, 1999). Now we are going to analyze in short, different strategic tools, which are available to analyze global car industry. The strategic tools and different analysis techniques that we used to critically analyze the industry are: Macro environment: PESTEL analysis Industry: Porter's five forces Strategic groups and Cognitive map Key Factors for Success Marketplace: Market Segmentation, Targeting & Positioning Telescopic Observation Matrix Political forces as well as WTO regime plays major role in opening of the markets for foreign players. Change in the regulations of the market due to governments policies, foreign direct investment increased and also funds started to flow towards developing countries to establish new manufacturing plants. Due to these political and economical changes North American & European manufacturers opened new plants in Eastern Europe, Asia and South

Assessment and decision making regarding depresion in dementia Assignment

Assessment and decision making regarding depresion in dementia - Assignment Example Among the signs and symptoms of dementia are despaired cognitive capabilities in memory, language, depression and poor problem-solving attention (Wang et al., 2007). The depressive nature of dementia makes it a rather delicate condition, requiring medical practitioners such as psychotherapists and physicians to make certain critical decisions regarding its management and treatment (Weiner et al., 2007). Consequently, guidelines for the evaluation of and decision-making on depression in dementia patients have since been developed. It is the prevalence, the depressive nature of dementia and its increased importance as a psychological concern in the health industry that has prompted stakeholders in psychology to establish certain guidelines for dementia evaluation and decision-making by psychotherapists (Hasegawa et al., 2005). An important aspect of these guidelines is that they conform to the ethical principles and codes of conduct most of the world’s psychological professions and associations such as the American Psychological Association. Decision-making by health care professionals while attending to depressed dementia patients is one of the core areas targeted by the guidelines. In this regard, professional conduct and endeavors by psychotherapists while making decisions on dementia treatment have been emphasized in most of the guidelines (McKellar & Gauthier, 2005). These guidelines on decision-making and engagement with dementia patients are particularly important given the role psychotherapists play in evaluating the memory changes and complaints that are characteristic of dementia (Stanley, 2008). However, the fact that most of the reduced cognitive performances occur in older people does not imply that the performance lapses are more pathological than they are physiological (Fago 2011). Instead, the decreased cognitive performances are directly proportional to the decrease in older peoples’ physiological functions (Wakisaka et al., 2003). Fortunately, psychologists are trained and equipped with skills in decision-making on dementia, supported by specialized neuropsychological tests that evaluate lapses and changes in dementia patients’ cognitive functioning (Barker, 2003). The main objective of the decision-making guidelines, however, remains the identification and specification of the most appropriate cautions, concerns and course of action for all clinicians. While engaging in decision-making on dementia treatment, psychotherapists are also advised to employ their expertise, uphold ethical values and consider patient choices and frames of mind/thought (Anthea & McCabe, 2006). In addition, various decision-making approaches such as categorical and probabilistic reasoning should be applied by psychotherapists when handling dementia patients. This paper thus explores the expertise, values, choices, probabilistic judgment and ethical engagement in decision-making for caring for depressed dementia patients. Decis ion-Making in Dementia Management Recent times have realized the replacement of the hitherto applied traditional approach of basing all medical decision-making processes on professional paternalism with more viable decision-making methods (Monahan, 2000). In the contemporary medical profession, most decisions made regarding the management of depression in dementia patie

A Negative Adjustment Letter Essay Example | Topics and Well Written Essays - 250 words

A Negative Adjustment Letter - Essay Example It is unfortunate that you are dissatisfied with the Gannon speakers you recently bought. Although the speakers have a sharp upward peak that might extend up to 5db above the normal smooth curve, they have other interesting features, considering that they have efficient transient response, satisfactory damping at the bass frequency, and sufficient capacity to handle power unlike other speakers. In addition, failures in midrange, tweeters, and midbass speakers due to mechanical or electrical issues can cause bass distortion. In that case, you should avoid applying immense power to the voice coil. On the same note, distortion of the bass sound can occur when the speaker is tampered with as was in your case. We found out that the booster magnets and insulation were missing and you had replaced the lead wires. Therefore, you should have avoided interfering with the speakers and maintain it in the right manner to avoid disappointments as was stated in the manual. We regret that we cannot comply with your recent requests to honor the three year warranty. This is because our warranty clearly states that if the speakers are sold at a clearance rate or if they are tampered with, then, the warranty becomes void. Nevertheless, we will be delighted to honor the maintenance and service agreement; hence, will offer 30% discount on repairs as your satisfaction is our major priority. Since you are among our esteemed consumers, we welcome you to our five day seminar, which will be free, on 3rd to 7th March. It will give more details on the different speakers we supply, how to maintain them, and offer a platform to air your concerns, advise, and opinions in regard to our

Effect of recession or credit crunch on telecom companies case study Research Proposal

Effect of recession or credit crunch on telecom companies case study ORANGE - Research Proposal Example The cascading effect has made the companies to think about the ways and means to handle the crisis. The telecom sector which initially gave indications of defying the recessionary trends has also started feeling the pinch. Saverio Romeo, the ICT analyst at Frost & Sullivan recently said that, the IT sector is going to be hit mainly in two ways1; Technology has brought about many changes in almost all spheres of life. Information technology in particular has proved to be a great influence towards transforming the way we communicate, listen to radio broadcasts, watch television broadcasts, impart education, search for information, track the movement of processes and services etc. Telecom sector is the key beneficiary of the IT revolution. Today, a simple mobile instrument can be used for services like, mobile-banking, storing songs, m-commerce, handy television receiver, net-surfing etc. besides serving as a telephone instrument. Telecom companies are making fullest use of this fusion in ICT by coming out with a number of schemes for retaining the existing customers as well as for attracting the potential customers. Reputed brands like 'Orange' have been investing in Research and Developmental activities as well. 'Orange Labs' from the France Telecom-Orange Group play a leading role in carrying this trend forward. With the he lp of a strong team of about 5,000 researchers, marketers, and engineers the company has been actively on way to provide best available services to its customers. But the moot question is how long they can sustain such efforts if recession continues longer. Efforts will be made through this study to figure out how companies are moving forward to contain the damage. Objectives of the Study This study is primarily being undertaken to study the telecom sector in general and how the recessionary trends are impacting the sector. With the help of examples like that of Orange, efforts will be made to find out concrete policies, if any, being undertaken by the companies in this direction. The study will try to seek answers to the following key objectives; i. Analysing the growth of the telecom sector in the last couple of years ii. Analysing some of the previous challenging situations that the telecom sector went through, and how the sector was able to pass thru iii. Analysing how some of the leading telecom companies have been performing in the recent past. iv. Analysing the policies being adopted by some of the governments in different parts of the world to help the telecom sector. v. What constructive role the Government as well as other stakeholders can play to see that the telecom sector is able to sustain the crisis like situation. Research Methodology The research will be carried out with the help of; i. Existing literature on the subject from government database, telecom sector companies, international organisations or other reliable sources available on the internet. ii. By going out in the field and assessing the ground reality by way of soliciting the views of users/ consumers in the sector iii. By seeking the opinion of the some of the experts in the field, from private sector as well as from the

MRSA Infection Research Paper Example | Topics and Well Written Essays - 2000 words

MRSA Infection - Research Paper Example Antibiotics used to treat ordinary S. aureus infections are rendered useless in case of MRSA. Infection occurring in healthcare settings is called health care-associated MRSA (HA-MRSA) while that occurring in the community, among healthy individuals, is called community-associated MRSA (CA-MRSA) (mayoclinic.org 1). HA-MRSA infections are generally acquired through invasive procedures or clinical devices such as artificial joints, surgeries, intravenous tubings, and catheters while CA-MRSA generally spreads through skin contact among child care workers, high school wrestlers and people living in crowded areas (mayoclinic.org 1). MRSA infection occurs in various parts of the body and owing to its antibiotic resistance, it is difficult to treat. Mild infections result in boils and sores on the skin. MRSA can also infect lungs, urinary tract, and bloodstream (webmd.com 1). There has been an alarming spread in the incidence of tough MRSA strains and because of its antibiotic resistance, MRSA is also called superbug (webmd.com 1). As per CDC, less than 2% of the US population carries MRSA (mayoclinic.org 3). MRSA was discovered in 1961 and research has shown that, like ordinary strains of S. aureus, it is also carried by many healthy people on their bodies, especially their noses (Matheson et al. 299). MRSA infection is common among those with a weaker immune system and while it is commonly a hospital-acquired the infection, its incidence in people who have not been hospitalized has become recently significant (webmd.com 1).

Malaysian Economy Essay Example for Free

Malaysian Economy Essay The Malaysian economy is expected to strengthen further and projected to grow at a faster rate of 4.5% to 5.5% in 2013 supported by improving exports and strong domestic demand. In the Economic Report 2012/2013 released by the Ministry of Finance (MoF) last Friday, it said the assumption was based on the global growth that will pick up especially during the second-half of 2013 (2H13). It said that it was also premised upon the expectation of an improvement in the resolution of a debt crisis in the euro-area and stronger growth in the economies of Malaysia’s major trading partners. The Economic Report 2012/2013 was released in conjunction with the national Budget 2013 that was presented by the prime minister last Friday. It said that given that the domestic economy is expected to strengthen further in 2013; inflation is estimated to increase moderately mitigated by further capacity expansion in the economy. On the supply side, growth in 2013 is expected to be broad-based supported by expansion in all sectors of the economy. Of significance, the external trade-related industries are envisaged to benefit from stronger global growth, particularly during the 2H13. It said that the services and manufacturing sectors are expected to contribute 4.2 percentage points to the gross domestic product growth. MoF said that the prospects in the services sector are expected to remain upbeat in 2013, with the accelerated implementation with major initiatives under the National Key Result Areas and continued investment in the seven services subsectors under the National Key Economic Areas. It said that these initiatives are expected to drive the wholesale and retail trade, finance and insurance, and communication subsectors, which are expected to grow 6.8%, 5.2% and 8.2% (2012 :5.7%; 4.2%; 9.3%) respectively. On the value-added of the manufacturing sector, MoF said that it is expected to grow 4.9%, (2012 :4.2%) with export oriented industries expected to  benefit from the higher growth of global trade, while domestic oriented industries expand in line with better consumer sentiment and business confidence. MoF said that the electrical and electronic (EE) subsector is expected to grow further, driven by higher demand for electronic equipment and parts as well as semiconductors in line with recovery in advanced economies. On the agricultural sector, MoF said that it is expected to grow 2.4% (2012:0.6%) following the recovery in the output of plantation commodities. MoF said that the production of crude palm oil is envisaged to rebound 2.5% to 18.9 million tonnes (2012: -2.5%; 18.4 million tonnes) on account of expanded matured areas to 4.44 million hectares (2012: 4.38 million hectares). On the mining sector, the report said that it is expected to expand 2.7% (2012: 1.5%) on account of higher production of crude oil and natural gas. â€Å"Production of crude oil is projected to increase 3.6% to 600,000 barrels per day (bpd) (2012: 1.6%; 579,000 bpd) due to higher regional demand,† said MoF. It added that several new oil fields are expected to start production in 2013, contributing to higher production of crude oil. On the construction sector, MoF said that it is envisaged to expand strongly at 11.2% (2012: 15.5%) with all the subsectors registering steady growth. On the domestic demand, MoF said that it is expected to grow at 5.6% (2012: 9.4%) and will remain the main driver of growth in 2013 underpinned by strong private sector expenditure. The report added that private consumption is projected to expand 5.7% (2012: 7%) on account of higher disposable income arising from better employment outlook, firm commodity prices and the wealth effect from the stable performance on the stock market following strong domestic economic activities. On private investment, Malaysia is expected to post a strong growth of 13.3% in 2013 (2012: 11.7%) attributed to the ongoing implementation of the Economic Transformation Programme projects. MoF said that public investment will continue to support growth and is expected to expand 4.2% in 2013 (2012: 15.9%) driven by higher capital outlays by the non-financial public enterprises (NFPE’s) and development expenditure by the federal government. It said that capital of the NFPEs will focus on the upstream oil and gas, transport, communication and utility industries. It added that in line with the expansion in domestic economic activities, national income in current prices is expected to increase 7.8% in 2013. The report also said that gross national savings is expected to expand strongly by 11.1%, with the private sector accounting 72.3% of total savings. On the balance of payments, MoF said that it is projected to remain favourable with current account continuing to record a higher surplus of RM71.9 billion or 7.3% of the gross national income. It said that the surplus in the goods account is projected to expand RM126.5 billion. â€Å"In 2013, exports are estimated to grow 3.9% (2012: 2.4%) supported by higher commodity exports and improving global EE demand. The MoF said that inline with increased domestic activity as as to meet increased inputs for the manufacturing sector, imports are projected to grow at a faster rate of 5.2% (2012: 6.5%). On the services account, the report said that it is expected to improve with a lower deficit of RM8.2 billion driven by large surplus in the travel account, following expectations higher tourist arrivals. MoF said that other components in the services account are expected to remain a deficit.

Jury Trail Analysis Essay Example for Free

Jury Trail Analysis Essay A Jury Trail is a trial that proceeds like any other trial however the judges do not determine guilt or innocence in the case. A group of people that have been selected by both the defense and the prosecution sides in the case. These people that have been selected have sworn to inquire into matters of fact and reach a verdict on the basis of the evidence that during the case has been presented to them(Thefreedictionary, 2013). The trial by jury has become the central role in the criminal justice system. The Jury Trail has been known as an impartial was for a person to get a fair trial. This is based on that the person being tried having people just like them minus the crime being the one to decided guilt of innocence. The steps in a jury trial are as follows, selection of jury, the trial, the judge charge, deliberation, the verdict (Thefreedictionary, 2013). The jury selection process is quite a process. It starts with the county calling in its citizens for what is called a Voir Dire. This is the process by which citizens are questioned before being selected to hear evidence as juror (Thefreedictionary, 2013). After the questioning process the selected jury will be sworn in to hear evidence in the case. The trial is where both sides will present their evidence and arguments in the case. This is also were the judge may give remarks to the jury. Sides will give opening speeches, witnesses are called for direct and cross-examination and exhibits are presented (Thefreedictionary, 2013). Once both sided have presented their sides of the arguments they will give summary and closing arguments. The judge’s charge is after the defense and the prosecutions have presented their case and have given their closing arguments. The judge instructs the jury as to what laws apply to the case and what those laws mean(Nolo, 2013). The judge could also give the jury more information on the case and allow them to see evidence that was presented in the case. The Deliberation is when the jury goes into a private room to discuss the case and reach a decision. They may talk to no one except the Judge if they have questions. The verdict is when the jury returns to the courtroom and the foreperson announces the decision. The attorneys may ask that the jury be polled(Nolo, 2013). This is when each juror is asked separately there decision on each charge in the case. After the jury has made and read their decision on the case the judge will decide what the sentence will be for each count in the case. The selection of a fair and unbiased jury has a process that may take some time. The court that is handling the trial will bring in many different people that live in the area. Then they are asked a set of questions pertaining to their thoughts about certain topics that may or may not pertain to the case that they will or will not hear. The jury that is picked has to be chosen by both sides, the prosecutor and the defense team have to agree for the person to be made a jury member. A person has to show the courts that they don’t hold resentment towards a certain action, class of people, groups, actions on a person or the courts itself. The jury that is then chosen is taken to a room and sworn in and given instructions on what the do’s and don’ts are during their duty. The sixth amendment is a part of the constitution that gives the public the right to a public trial in criminal cases. These are where the court room is open to friends and family of the defendant and the victim of the crime. It also allow for a person to get a jury trial and a speedy trial. The confrontation clause of the Sixth Amendment gives defendants the right to be confronted by the witnesses against them. This gives defendants the right to cross-examine witnesses that is, the right to require the witnesses to come to court, look the defendant in the eye, and subject themselves to questioning by the defense(Nolo, 2013). The sixth amendment also provides that all people have the right to be represented by and attorney. A defendant shall provide their own defense; if they cannot afford a attorney the judge will appoint one for them at no cost to them. They also have the right to adequate representation. If there attorney of the one appointed to them by the courts does not, call favorable witnesses, object to mistakes, uses drugs, or a attorney that no long can handle cases, then they do not have adequate representation. There is a clause in the Fifth Amendment that states a person will be subject for the same offence to be twice put in jeopardy of life or limb.

Cardiac Muscle Structure and Function

Cardiac Muscle Structure and Function The structure of cardiac muscle The capacity for cells to utilize biochemical energy to generate both mechanical force and movement of the human body is a dominant feature found in muscle cells. There exist three distinct categories of muscle tissue, each differing by specific structural and functional properties. These categories include smooth muscles, skeletal muscles and cardiac muscles. Smooth muscles are involuntarily contracting, non-striated muscles that surround the inside walls of hollow organs such as the urinary bladder, reproductive organs, and both the gastrointestinal and respiratory tracts. Its contraction enables and regulates the progression of liquid content, such as food, urine and blood, along the internal passageways. Skeletal muscles are voluntarily contracting, striated muscles that attach to bones of the skeleton. The contraction of skeletal muscle is primarily responsible for the movement of the skeleton, but also has roles in heat production and protection of internal organs. Cardiac musc les are an involuntarily contracting, striated muscle found exclusively in the walls of the heart, more specifically in the myocardium. Contraction of cardiac muscles propel oxygenated blood into the circulatory system to deliver oxygen to the body, as well as regulates blood pressure (Martini et al., 2009). Cardiac muscle tissue is composed of a network of individual cardiac muscle cells, called cardiomyocytes. Cardiomyocytes are small in size, averaging 10-20ÃŽ ¼m in diameter and 50-100ÃŽ ¼m in length, have a single centrally positioned nucleus and connect to adjacent cells in a branched manner through specialized sites known as intercalated discs (Martini et al., 2009). Two structures that are found within the intercalated discs are  desmosomes and gap junctions. Desmosomes are specialized structures involved in cell-to-cell adhesion and gap junctions are intercellular channels that connect the cytoplasm of adjacent cells, allowing the free passage of molecules, ions and electrical signals. Within the cytoplasm of striated muscle cells are long, cylindrical organelles termed myofibrils. With a diameter of 1 to 2ÃŽ ¼m and numbering between hundreds to thousands in a cell, myofibrils are enveloped and grouped together by connective tissue called the fasciculus, which forms bundles of myofibrils that spans the length of the cell (Widmaier et al., 2006). Individual myofibrils can be further divided into two types of contractile filaments: thin filaments and thick filaments. These filaments are composed primarily of actin and myosin proteins, respectfully. The thin and thick filaments are aligned in a manner where they form repeating structural units along the length of the myofibril. Among these structures is the sarcomere, which is a Ca2+-dependent contractile unit responsible for muscle contraction and relaxation (Widmaier et al., 2006). An increase in cytoplasmic Ca2+ influx causes the thin and thick filaments to overlap each other, causing a shortening of the sarcomere, leading to a muscle contraction. Alternatively, a decrease in cytoplasmic Ca2+ levels causes the thin and thick filaments to pull away from each other, leading to relaxation of the myofilaments. The specific arrangement of the thin and thick myofilaments is responsible for the striated appearance of both skeletal and cardiac muscle tissue. Electrical stimuli, called action potentials, are required for striated muscle cell contraction. In skeletal muscles, action potentials are derived from neurons in the brain and spinal cord that transmits the signal through the nervous system and innervates muscle fibers, causing contraction. However, unlike skeletal muscles, the contraction of cardiac muscles occurs without neural stimulation, a property called automaticity (Martini et al., 2009). This is because the heart contains pacemaker cells, which are specialized cells that have no contractile function; rather having the ability to initiate and conduct action potentials to neighboring cardiomyocytes. The cardiac action potential propagates across cardiomyocytes through gap junctions, allowing the cells to contract in tandem, which enables the heart to contract as one muscle. Cells which have pacemaker activity constitute 1% of cardiac muscle cells, whereas the other 99% are contractile cells (Sherwood, 2006). The conversion of an electrical stimulus into a mechanical response is performed through a physiological process known as the excitation-contracting coupling or the ECC. This phenomenon has a critical role in muscle cells as it allows a propagating action potential to cause shortening of the sarcomere, leading to muscle cell contraction. When action potentials are produced by pacemaker cells, they conduct across the heart by traveling along the length of the myofibril on the muscle sarcolemma. An action potential will transmit on the sarcolemma until it reaches a transverse-tubule (T-tubule). T-tubules are defined as deep invaginations into the sarcolemma that contact the cisternae of the sarcoplasmic reticulum (SR), an organelle that functions as a Ca2+ storing body. Upon penetrating the T-tubules, the action potential will cause a depolarization of the membrane voltage potential, leading to an increased influx of Ca2+ into the cytoplasm. Resting within the T-tubules are many ion tr ansporters such voltage-gated L-type Ca2+ channels and Na+ / Ca2+ exchangers (D. Bers, 2002). These Ca2+-transporters are opened/activated when stimulated by action potentials, prompting the entry of extracellular Ca2+ into specific microdomains in the cytosol (Berridge, 2006). An elevation of cytoplasmic Ca2+ levels will trigger the opening of ryanodine receptors (RyR), which are intracellular Ca2+ channels present on the membrane of the SR, allowing stored Ca2+ to exit the SR and enter the cytosol. The mechanism of how Ca2+ ions triggers Ca2+ release from the SR was identified by several groups in the 1960s, and appropriately termed Ca2+-induced- Ca2+-release (Endo et al., 1968; Ford et al., 1968). An overall increase in intracellular Ca2+ level causes Ca2+ to bind and cause a conformational change in Troponin C, a protein present on actin filaments. This conformational change causes a displacement of Tropomyosin, which prevents the interaction of myosin protein with actin filaments, thereby allowing myosin to contact actin, which promotes sarcomeric contraction. Alternatively, Ca2+ sequestration from myofilaments and cytoplasmic depletion prompts a relaxation of the sarcomere. Such a decrease of cytoplasmic Ca2+ occurs by either by re-entering the lumen of organelles, such as the SR and mitochondria, or cellular export by Ca2+ pumps and Na+/ Ca2+ exchangers on the sarcolemma (D. Bers, 2002). The efficiency of muscle contraction is partly depicted by the type of myosin heavy chain (MyHC) that the cell expresses. MyHC are enzymes, found on the head of myosin proteins, which catalyze the hydrolysis of ATP. The rate at which MyHC can hydrolyze ATP ultimately depicts the speed at which the myofilaments contract, as well as the overall energy efficiency of that cell. In cardiomyocytes, two types of MyHC proteins are expressed: ÃŽ ±-MyHC and ÃŽ ²-MyHC. The following table represents the distinguishing features of the cells that express either ÃŽ ±-MyHC or ÃŽ ²-MyHC: Similar to skeletal muscles, cardiomyocytes are categorized into two distinct classes, based on the type of myosin heavy chain (MyHC) that is expressed. Those who predominantly express ÃŽ ±-MyHC are found in adult hearts, contract in a more energy inefficient manner and are quicker to fatigue. In contrast, cardiomyocytes that express more ÃŽ ²-MyHC are present in developing hearts, have a more energy efficient contraction and are more resistant to fatigue. Cardiovascular diseases and pathological cardiac hypertrophy Cardiovascular diseases are disorders that prevent the proper function of the heart and blood vessels, causing abnormalities of the cardiovascular system, which lead to defects in the brain, kidneys, lungs and other parts of the body (Public Health Agency of Canada, 2009). According to the World Health Organization, cardiovascular diseases accounted for 29% of global deaths in 2004, making it the leading cause of death in the world (World Health Organization, 2009). Furthermore, with an aging population, the number of patients diagnosed with heart disease in America is expected to double within the next 30 years, from 5 million to 10 million (Hobbs, 2004). In Canada, this disease was responsible for 31% (or >70,000) of total deaths in 2005 (Statistics Canada, 2009). Amongst the numerous categories of cardiovascular diseases, heart failure is the most prevalent, with the fastest spreading rate and the highest mortality rate over the past decade (Heineke et al., 2006). Heart failure is defined by defects in cardiomyocyte structure, function, rhythm or conduction, which prevents the heart to pump adequate amounts of oxygenated blood and nutrients to meet the bodys demands (McMurray et al., 2005). Individuals living with a failing heart suffer from severe coughing, shortness of breath and edema, leading to a decreased tolerance to exercise and an overall diminishment in physical and mental health. As the disease progresses, patients may develop further pathophysiologies due to detrimental effects on the function of vital organs, ultimately resulting in death. A common abnormality that precedes heart failure is the pathological enlargement of the heart, a condition known as cardiac hypertrophy. Cardiac hypertrophy is induced by the release of hormones, cytokines, chemokines and peptide growth factors, which act on cardiomyocytes in an endocrine, paracrine and autocrine manner (Heineke et al., 2006). The release of these factors occurs in response to increased cardiac workload, myocardial injury or defects in the contractibility of cardiomyocytes (J. Molkentin, 2000). The initial stage leading to cardiac hypertrophy is increased size and cell volume of cardiomyocytes in order to sustain the increased cardiac output demanded by the hypertrophied heart. Such a process is referred to as compensatory hypertrophy. At later stages of cardiac hypertrophy, the hypertrophied heart can no longer keep up with the increased workload, which subjects patients to heart failure, cardiac arrhythmias and sudden death (Berenji et al., 2005). It should be noted physiological cardiac hypertrophy, which occurs during pregnancy, adolescence growth and aerobic training, does not share the same detrimental consequences on cardiomyocytes as pathophysiological heart growth (Oakley, 2001). A characteristic of pathologically hypertrophied hearts is cardiomyocyte disarray, which is a disorder of heart cells. Misaligned cardiomyocytes prompts a disruption in the conduction of action potentials across cells, leading to compromised intracellular Ca2+ kinetics and decreased shortening of the sarcomere, which ultimately compromises the contractions of the heart. The molecular signaling pathways, responsible for cardiac hypertrophy, are being extensively studied by researchers with the hopes of developing therapies to treat cardiac hypertrophy. Calcineurin-NFAT signaling pathway The availability of intracellular calcium (Ca2+) in mammalian cells is critical for their existence and proper function. In addition to its role in muscle cell electrophysiology and contraction, Ca2+ acts as a secondary messenger in many signal transduction pathways, involved in physiological processes such as fertilization, memory, apoptosis, membrane trafficking and cell division (D. M. Bers, 2008). Furthermore, at the molecular level, Ca2+ has been implicated in regulation of gene transcription, DNA replication, DNA repair and both protein synthesis and degradation. A common question in muscle cell biology is that, with its numerous downstream targets, how does Ca2+ specify and activate a particular signaling pathway. It is generally understood that Ca2+ influxes into the cytoplasm through Ca2+ transporters on the sarcolemma as waves of Ca2+. In the 1990s, researchers have identified that depending on the amplitude and frequency at which Ca2+ waves penetrate the cell, different Ca2+-dependent signaling pathways are activated, which also affects gene expression and cell differentiation (Berridge, 1997; Dolmetsch et al., 1997; Dolmetsch et al., 1998). However, the exact molecular mechanisms in which specific Ca2+-dependent pathways in contracting cardiomyocytes are regulated remains disputed due to the highly specialized rhythmic cycling of Ca2+ involved in the hearts ECC. Molkentins group have postulated the existence of Ca2+ microdomains in the cytoplasm, which are relatively independent of the Ca2+ involved in the ECC. Within these microdomains , Ca2+ is locally regulated and can activate protein signaling pathways in that particular region (Houser et al., 2008). Many proteins that require Ca2+ to be active cannot readily bind Ca2+, thus use Calmodulin (CaM), a high affinity Ca2+-binding protein, as a Ca2+ sensor and signal transducer. Expressed in all eukaryotic cells, CaM is a 17kDa protein composed of four EF-hand motifs, each capable of binding a single Ca2+ ion. The affinity to which Ca2+ binds CaM depends on changes in intracellular Ca2+ concentrations. When cytoplasmic Ca2+ level are low, CaM exists in a closed conformation, where the EF-hand motifs are packed together, hiding the Ca2+ binding sites. Alternatively, when intracellular Ca2+ level are high, Ca2+ ions bind to the EF hand motifs on CaM, causing a conformational change that allow Ca2+ to bind more readily to the other motifs, allowing CaM to attain an open configuration (Chin et al., 2000). Because CaM is a small, flexible molecule with numerous targets, such conformational changes are required to expose specific hydrophobic regions on each domain, which allow the Ca2+-CaM c omplex to bind and activate specific proteins (Al-Shanti et al., 2009). One of the most recognized signaling pathways that require the Ca2+-CaM complex to be activated is the Calcineurin Nuclear Factor of Activated T-Cells cascade. Calcineurin (Cn), also referred to as protein phosphatase 2B (PP2B), is a Ca2+-dependent serine/threonine phosphatase that was first discovered in 1979 as a CaM binding protein in brain extracts (Klee et al., 1979). Further research by Schreibers group identified that Cn played a prominent role in the immune system, where the addition of immunosuppressive drugs, cyclosporine A (CsA) and FK506, decreased Cns activity (Liu et al., 1991). Cn is ubiquitously expressed in all cells and the gene that encodes the Cn protein is conserved from yeast to mammals, suggesting a common mode of regulation (Al-Shanti et al., 2009; Rusnak et al., 2000). Once active, Cn can de-phosphorylate a number of transcription factors such as myocyte enhancer factor 2 (MEF2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFÃŽ ºB) and nuclear factor of activated T-cells (NFAT) (Alzuherri et al., 2003; Blaeser et al., 2000; Jain et al., 1993; Michel et al., 2004). In addition to transcription factors, Cn has been identified as a direct regulator of the pro-apoptotic factor, Bcl-2 (Wang et al., 1999). The most characterized downstream target of Cn is the family of NFAT transcription factors. In the heart, the role of the Cn-NFAT signaling pathway in mediating pathological cardiac hypertrophy in vitro and in vivo has been extensively studied (Bueno et al., 2002; De Windt et al., 2001; Hill et al., 2002; Molkentin et al., 1998; Sussman et al., 1998; Zou et al., 2001). Once de-phosphorylated, NFAT transcription factors translocate to the nucleus and dimerize with other transcription factors to re-activate cardiac fetal genes, leadin g to hypertrophy of the adult heart. The structure of Calcineurin Human Cn was first crystallized in 1995 by the Villafranca group (Kissinger et al., 1995). Although it shares similar sequence homology to other serine/threonine protein phosphatases, PP1 and PP2A, the structure of Cn was found to be unque due to its dependence on Ca2+ for optimal activity (Griffith et al., 1995; Kincaid et al., 1988; Klee et al., 1988). From its structure, it was discovered that Cn exists as a heterodimeric protein, consisting of two subunits: the 59kDa catalytic subunit, calcineurin A (CnA), and the 19kDa regulatory subunit, calcineurin B (CnB) (Kissinger et al., 1995). The structure of CnA consists of two domains: a catalytic region which is found on the N-terminal and the regulatory domain which is present on the C-terminal region (Al-Shanti et al., 2009). The regulatory domain of CnA consists of three sub-domains: a CnB binding domain), a CaM binding domain) and an autoinhibitory domain (AI) as depicted in Figure 1.4 (Ke et al., 2003; Klee et al., 1998). Alternatively, the structure of CnB shares a 35% sequence identity to CaM and contains four EF-hand motifs, allowing it to bind Ca2+ ions in a similar mechanism as CaM (Klee et al., 1988; Kretsinger et al., 1973). In non-stimulated muscle cells, Cn is present in its inactive conformation, in the cytoplasm, where the autoinhibitory domain sterically blocks CnAs catalytic domain, rendering the phosphatase inactive. Upon stimulation, cytoplasmic Ca2+ will bind CnB, causing a conformational change, which exposes the CaM binding domain on CnA. Once the Ca2+-CaM complex docks onto its respective binding domain, another conformation change occurs which displaces the autoinhibitory domain from the catalytic domain, enabling the enzyme to be active. The crystal structure of full length human Cn was solved with a resolution of 2.1Ç º. The globular structure of CnA consists of 521 residues, where residues 14-342 form the catalytic domain and residues 343-373 form the CnB binding helical domain (Kissinger et al., 1995). Residues 374-468 and 487-521 are not visible in the crystal structure because they are presumed to exist in a random conformation(Ke et al., 2003). The AI domain is represented by a segment of 18 residues (Ser469-Arg486) that lie over the substrate-binding cleft on the C-terminus of CnA. The AI domain consists of two conserved short ÃŽ ±-helical domains, with five additional residues in its extended form. The residues of the AI domain that have the strongest interactions with the substrate-binding cleft of CnA were identified as Glu481-Arg-Met-Pro484, where Glu481 hydrogen-bonds with water molecules bound to the dimetal site in Cns active site (Kissinger et al., 1995). Residues 343-373 form an extended amphipathic ÃŽ ±-helical region that interacts with hydrophobic residues within the CnB binding cleft. In mammals, CnA is encoded by three genes (CnAÃŽ ±, CnAÃŽ ², CnAÃŽ ³) and CnB by two genes (CnB1, CnB2). Yet in the heart, only CnAÃŽ ±, CnAÃŽ ² and CnB1 are expressed (J. Molkentin, 2000). NFAT proteins NFAT transcription factors were first identified by the Crabtree group where, similar to Cn, NFAT played an important role in the regulation of early T-cell activation genes (Shaw et al., 1988). Since its discovery, researchers have provided evidence that the role of NFAT proteins was not restricted to T-cells, having been implicated in the central nervous system, blood vessels, heart, kidney, bone, skeletal muscle and haematopoietic stem cells (Crabtree et al., 2002; Graef et al., 2001; Hogan et al., 2003; Kiani et al., 2004; Macian, 2005). NFAT proteins are part of the Rel-family of transcription factors. The molecular mass of NFAT ranges from 70-200kDa, which is due to alternative splicing of genes resulting in varying protein sizes and differential phosphorylation states (van Rooij et al., 2002). The primary structure of NFAT consists of a moderately conserved N-homology region (NHR), a conserved Rel-homology region (RHR) and a non-conserved C-terminal domain (CTD). Firstly, the NHR (residues 1-407) contains a transactivation domain (TAD), a Cn docking site, a nuclear localization signal (NLS), a nuclear export signal (NES), serine-rich regions (SRR) and Ser-Pro-X-X-repeating motifs (SP), where X denotes any amino acid. The TAD is required for NFAT to bind the promoter region of genes to initiate transcriptional events. The Cn docking domain contains a SPRIEIT sequence, a variant of PxIxIT, which allows Cn to bind to NFAT and de-phosphorylate serine residues, mediating the nuclear shuttling of NFAT. Secondly, the RHR (residues 408-677), which is conserved among all Rel proteins, confers to a shared DNA binding specificity (L. Chen et al., 1998). The C-terminus of the RHR contains a DNA binding motif, which permit Rel-proteins to bind the 5-GGAAA-3 consensus sequence (Rao, 1994). The N-terminus of the RHR contains a domain that allows NFAT to interact with other transcription factors in the nucleus. Such molecular partners include the leucine zipper protein activator protein-1 (Fos, Jun), the Zn-finger protein GATA-4, the MADS box protein MEF2 and many others (L. Chen et al., 1998; Crabtree et al., 2002; Hogan et al., 2003; Molkentin et al., 1998). Lastly, although the exact role of the CTD (residues 678-928) remains ill defined, due to the differences in the length of the CTD between NFAT isoforms, it is possible that the CTD is responsible for the different transcriptional activity of the NFAT isoforms, as shown by several groups (Calabria et al., 2009; Rinne et al., 2010). NFAT transcription factors are ubiquitously expressed and consists of five isoforms: NFATc1, NFATc2, NFATc3, NFATc4 and NFAT5 (also known as tonicity-responsive enhancer-binding protein or TonEBP) (Mancini et al., 2009). Of the five NFAT proteins, only NFATc1, NFATc2, NFATc3 and NFATc4 are regulated by Ca2+-Cn signaling and are have known roles in skeletal and cardiac muscles (Calabria et al., 2009; van Rooij et al., 2002). NFAT5 cannot interact with Cn due to the absence of a SPRIEIT domain and is therefore insensitive to Ca2+-Cn signaling (Lopez-Rodriguez et al., 1999). Rather, NFAT5 is regulated by osmotic stress and is known to control the expression of cytokines, such as tumor-necrosis factor (TNF) and lymphotoxin-ÃŽ ², in lymphocytes (Lopez-Rodriguez et al., 2001; Macian, 2005). Due to its insensitivity of Cn and unclear roles in muscle cells, for the remainder of this thesis, the focus will be on the Ca2+-Cn regulated NFAT isoforms: NFATc1, NFATc2, NFATc3 and NFATc4. The cellular localization of NFAT proteins depend on the phosphorylation state of approximately 14 serine residues on the NHR. Okamura et al. identified that of these residues, 13 phosphoserines are targeted by Cn and are located in motifs SRR1, SP2 and SP3 (Macian, 2005; Okamura et al., 2000). Upon de-phosphorylation, the NLS sequence of NFAT is exposed and the NES is masked, prompting nuclear entry. NFAT kinases are regulators of NFAT transcription factors, which can interact with NFAT and reversibly phosphorylate the same serine residues that are targeted by Cn. Known NFAT kinases include casein kinase-1 (CK-1), glycogen-synthase 3ÃŽ ² (GSK3-ÃŽ ²), p38 and JUN-N-terminal kinase (JNK) (Beals, Sheridan et al., 1997; Chow et al., 1997; Gomez del Arco et al., 2000; Zhu et al., 1998). Upon re-phosphorylation, the NES sequence is re-exposed whereas the NLS sequence is hidden, prompting cytoplasmic retention of NFAT (Okamura et al., 2000). These kinases can either be classified as mainte nance kinases, which phosphorylate NFAT in the cytosol to prevent nuclear import or export kinases, which target NFAT in the nucleus to promote nuclear export. Each kinase can phosphorylates serine residues on specific motifs. CK-1 acts as both an export and maintenance kinase on SRR1 of NFATc2 (Okamura et al., 2004). GSK3-ÃŽ ² functions as an export kinase on both SP2 and SP3 of NFATc1 and SP2 on NFATc2 (Beals, Clipstone et al., 1997; Macian, 2005). The mitogen activated protein kinase (MAPK) family consists of p38, JNK and extracellular-regulate-signal kinases (ERK) and can phosphorylate the first serine of SRR1 on different NFAT isoforms. JNK phosphorylates NFATc1, whereas p38 targets NFATc2 (Chow et al., 1997; Gomez del Arco et al., 2000). CK1 may be responsible for phosphorylating the remaining serines on SRR1 (Macian, 2005). Although a cell may have the potential to translate different NFAT isoforms, depending on which NFAT kinase is expressed, only certain NFATs may be nuclea r localized. Cn-NFAT signaling in cardiac hypertrophy Cn-NFAT signaling is described as a multifunctional regulator, where its function depends on the cell type in which this pathway is active. In the brain, Cn-NFAT signaling mediates numerous processes, which include memory, brain strokes, ischemic injury, Parkinson and Alzheimers disease and the regulation of the cAMP-response-element binding protein (CREB) (Shibasaki et al., 2002). In the lungs, Cn-NFAT signaling has been implicated in the perinatal lung maturation and function, and regulating genes involved in the homeostasis of pulmonary surfactant, which is required for proper breathing (Dave et al., 2006). In skeletal muscles, this pathway is required for functional-overload induced skeletal muscle hypertrophy and for mediating skeletal muscle-fiber type conversions from fast muscle fiber type to slow muscle fiber type (Dunn et al., 1999; Michel et al., 2004). In the cardiovascular system, Cn is required for the early development of the heart, specifically the cardiac septum and valves (de la Pompa et al., 1998; Ranger et al., 1998). During heart disease, Cn-NFAT signaling promotes the reactivation of cardiac fetal genes, which are responsible for cardiac growth during development. The reactivation of these genes in the adult heart is responsible for the pathological growth of the heart, and not physiological growth (Wilkins et al., 2004). In 1998, Molkentin et al. first reported the novel role that Cn-NFAT signaling played in mediating pathological cardiac hypertrophy (Molkentin et al., 1998). Among the major findings of this report was that Cn-induced the de-phosphorylation of NFATc4, prompting its nuclear entry and allowed NFATc4 to interact with the GATA-4 transcription factor, leading to cardiac hypertrophy. In addition, cultured cardiomyocytes, treated with Cn inhibitors CsA and FK-506 immunosuppressive drugs, blocked chemical-induced cardiac hypertrophy. To support their in vitro findings, transgenic mice that expressed a cardiac-specific constitutively active form of CnA were generated. The hearts of CnA overexpressing transgenic mice, compared to the hearts of wild-type counterparts, displayed a 2-to-3 fold increase in heart weight-to-body weight ratio, a thickening of the left ventricular wall and intraventicular septum, a 2-fold increase in cross-sectional area of cardiomyocytes and extensive fibrosis. Furth ermore, CnA overexpressing mice had a greater increased susceptibility to sudden death, mimicking the effects of heart failure in humans. Upon treatment with the Cn inhibitor, CsA, the hearts of CnA transgenic mice returned to normal size. Many genes and proteins that are re-employed in response to heart disease have prominent functions in embryonic and fetal heart development. For example, cardiac fetal genes are active during the physiological growth in developing hearts. This family of genes consists of atrial natriuretic factor (ANF), b-type natriuretic peptide (BNP), ÃŽ ±-myosin heavy chain (ÃŽ ±-MHC), ÃŽ ²-myosin heavy chain (ÃŽ ²-MHC), and many others (Oka et al., 2007). When the heart has fully matured into an adult heart, the expression of these genes becomes dormant. During heart disease, hypertrophic stimuli re-activate the expression of these genes in the adult heart, which enables the heart to grow to a pathological state. One of the most studied transcription factor that interacts with NFAT to initiate cardiac hypertrophy are GATA proteins. GATA transcription factors consist of two conserved zinc fingers that are required to bind to the consensus DNA sequence 5-(A/T)GATA(A/G)-3, as well as domains that allow GATA to interact with transcriptional cofactors (Ko et al., 1993; Merika et al., 1993; Oka et al., 2007). Of the six members of the GATA family (GATA-1 to GATA-6), GATA-4, GATA-5 and GATA-6 are expressed in the heart (J. D. Molkentin, 2000). Among the GATA proteins expressed in the heart, GATA-4 has been associated with embryonic cardiogenesis, such as heart tube formation, and pathological growth of the adult heart (Molkentin et al., 1997; Pikkarainen et al., 2004). In addition, GATA-4 is a known regulator of the expression of cardiac structural genes during development. GATA-4 gene targeted mice were embryonic lethal at E7-9.5 due to structural and functional defects of the heart (Molkentin et al., 1997). Alternatively, cultured cardiomyocytes overexpression of GATA-4 caused a 2-fold increase in cell surface area, whereas GATA-4 overexpressing transgenic mice lead to increased heart-weight-to-body weight ratio, cardiomyopathy features of the cells and upregulation in the expression of cardiac fetal genes (Liang, De Windt et al., 2001). The regulation of GATA-4 occurs post-translationally, where such modifications affect its DNA binding ability, transcriptional activity and cellular localization. A number of chemical stimuli that induce cardiac hypertrophy have been associated with the phosphorylation of GATA-4, which increases both its DNA binding and transcriptional activity (Oka et al., 2007; Pikkarainen et al., 2004). Molkentins group identified that phosphorylation of Ser105 on GATA-4 by the ERK1/2 and p38 MAPK was responsible for GATA-4 increased DNA binding affinity and transactivation during heart failure (Charron et al., 2001; Liang, Wiese et al., 2001). Another kinase that targets GATA-4 is GSK3-ÃŽ ², a known negative regulator of cardiac hypertrophy (Haq et al., 2000). GSK3-ÃŽ ²-mediated phosphorylation of GATA-4 prompts its export from the nucleus, rescuing Cn-mediated cardiac hypertrophy (Morisco et al., 2001). A second family of transcription factor that is re-activated during heart disease is the myocyte enhancer factor 2 (MEF2). There are four members of the MEF2 family expressed in vertebrates: MEF2A, MEF2B, MEF2C and MEF2D. MEF2 proteins can either homodimerize or heterodimerize with other transcription factors such as NFAT and GATA, which can then bind to the DNA sequence 5-CTA(A/T)4TAG-3 to carry out transcriptional events (Blaeser et al., 2000; McKinsey et al., 2002; Morin et al., 2000; Oka et al., 2007). Although the MEF2 proteins are expressed in most cell types, their transcriptional activity is restricted to the immune system, neurons and contractile muscle cells (Akazawa et al., 2003). In the heart, MEF2 have critical roles in cardiac differentiation. MEF2C null mice were embryonic lethal, due to cardiac looping defects, an absence of a right ventricle and a downregulation of cardiac structural genes (Bi et al., 1999; Lin et al., 1997; Oka et al., 2007). The majority of MEF2A null mice died 2-10 days after birth because of defects in conduction and architecture of the heart. Surviving MEF2A null mice displayed reduced mitochondrial content and a less efficient conductive system. (Naya et al., 2002). In addition, transgenic mice that express a dominant negative MEF2 died shortly after birth because of cardiomyocyte hypoplasia, thinning of the ventricular walls and heart chamber dilation (Kolodziejczyk et al., 1999; Oka et al., 2007). A greater workload imposed on the heart, a phenotype of cardiac hypertrophy, has been associated with increased MEF2-DNA binding (Molkentin et al., 1993; Nadruz et al., 2003). In cultured cardiomyocytes, adenoviral-mediated overexpression of MEF2A or MEF2C caused sarcomeric degeneration and cell elongation, both of which indicate cardiac dilatation. The hearts of transgenic mice overexpressing MEF2A or MEF2C were subject to contractile defects, ventricular dilation and were more readily hypertrophied when pressure overload stimulation was induced. However, when cells of the transgenic hearts were isolated, rather than having a greater cross-sectional area, the cardiomyocytes were more elliptical in shape, suggesting that MEF2 did not d

OBriens Things They Carried Essay: Truth, Fiction, and Human Emotion

The Things They Carried: Truth, Fiction, and Human Emotion  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   There are many levels of truth in Tim O'Brien's The Things They Carried. This novel deals with story-telling as an act of communication and therapy, rather than a mere recital of fact. In the telling of war stories, and instruction in their telling, O'Brien shows that truth is unimportant in communicating human emotion through stories. O'Brien's writing style is so vivid, the reader frequently finds himself accepting the events and details of this novel as absolute fact. To contrast truth and fiction, the author inserts reminders that the stories are not fact, but are mere representations of human emotion incommunicable as fact. O'Brien's most direct discussion of truth appears in Good Form. He begins with, "It's time to be blunt," and goes on to say that everything in the book but the very premise of a foot soldier in Vietnam is invented. This comes as a shock after reading what seems to be a stylized presentation of fact. In the sequence of Speaking of Courage followed by Notes, O'Brien adds a second dimension of truth to a story so vivid that the reader may have already accepted it as the original truth. In Notes, O'Brien steps out of the novel and addresses the reader to discuss the character, Norman Bowker, and the formation and history of the previous story, Speaking of Courage. In a letter from Norman Bowker, Tim O'Brien is asked to write a story about his part in the war. In discussing this, O'Brien presents an elaborate picture of the story's development and the main character's real-life demise: "Speaking of Courage" was written in 1975 at the suggestion of Norman Bowker, who three years later hanged himself in the locker room of a YMC... ...O'Brien goes beyond the telling of war stories in The Things They Carried to say something larger about the art and purpose of story-telling. Contrasting truth and fiction, O'Brien shows that the truth cannot always communicate human emotion. O'Brien's personal guilt at seeing a man die from a grenade blast is real, and must be communicated as such in a story. Norman Bowker's guilt at seeing Kiowa sink into the muck leaves him with a sense of direct personal failure. By incorporating this sense of failure into fictional events, O'Brien is able to communicate the true human emotion behind the story, rather than just the facts. Above and beyond a simple set of war stories, The Things They Carried reduces fiction to the very heart of why stories are told the way they are. Works Cited: O'Brien, Tim. The Things They Carried.New York: Penguin Books USA Inc., 1990.   

Humorous Wedding Toast by the Brides Brother Essay -- Wedding Toasts

Humorous Wedding Toast by the Bride's Brother Good evening Ladies and Gentlemen. Firstly, on behalf of the bridesmaids, I'd like to thank Mike for his kind words and reiterate how wonderful they look and what a fantastic job they have done today. I would also like to say that Sallie looks stunning - as I'm sure you'll all agree. Which really isn't that much of a surprise given we are related. Sallie is of course my sister, so I've known her much longer than I've known Mike. But I have been sternly warned not to delve into any of her terrible past relationships, her horrible pre- and post-teen attitude, her early problems with alcohol and the short spell she spent in a Singapore jail for drug trafficking. Instead, all I'll say is that, as I have seen her grow up, she has become...

Aids in the African American Community

In the mind of the public, the AIDS problem is undoubtedly linked to sexual behaviors and possibly perceived to be a result of promiscuity, nonmonogamous sexual activity, and a well-deserved problem that should affect gay and homosexual people.To a certain extent, efforts to combat AIDS in the African-American communities have also been hindered by the fact that we know very little, beyond stereotypes and myths, about the sexuality of African-Americans. These perceptions have provided much of the confusion about what we should do about HIV/AIDS, or for that matter any of the health problems that are at epidemic levels in the African American communities throughout the United States.It has also been the case that several of the important sources of leadership in the African-American communities have utilized the AIDS epidemic to develop and promote extremely conservative religious and moral agendas and punitive responses toward persons who are already considered to be unfit members of the community.For example, during the first wave of the AIDS epidemic there were several stories within the African-American communities across the United States about ministers who were preaching to their congregations about how AIDS is â€Å"God's punishment for homosexual people who sin.†While there is no way to determine the extent of this attitude among African-American ministers and preachers, approximately one-fourth of the sample (28 percent) of African-American college students was in agreement with this belief.â€Å"There is a long history in the United States of African-Americans and other minority groups being devalued and of having their behavior labeled deviant. In the case of AIDS, the victims are further socially ostracized.A prime example is the fact that Haitians were at one time considered a risk group. Because of this, many Haitians lost their jobs and experienced extreme levels of racial discrimination, not because they had AIDS, but because they were H aitians and therefore linked to AIDS† (Moore and LeBaron, 1986).So, it appears that efforts to combat HIV/AIDS have been hindered by (1) our lack of knowledge about the sexuality of African-Americans, (2) research that has not seriously examined the variability of behavior and attitudes within African-American groups, (3) community and religious leaders who view the AIDS problems as punishment from God, (4) our intolerance of gays and bisexuals within the African American community, and (5) the lack of attention directed at the prevention of sexually transmitted diseases prior to the HIV/AIDS epidemic.If one accepts these observations, then what are we to do in order to develop effective and culturally sensitive AIDS-prevention messages that will reach African-Americans, who are not monogamous, are not abstinent, and who do not use IV-drugs.One solution is to make sure that African-Americans have an adequate understanding of the factors associated with the transmission of HIV/ AIDS. Overall, the pattern of the results indicates that African Americans are very knowledgeable about AIDS, but there appears to be a gap between knowledge and risky sexual behaviors.The development of culturally sensitive AIDS-prevention programs for African-American college age adults may be facilitated by considering some of the insights gained from the study.For example, data suggest the gap between knowledge and risky sexual behavior is likely to be filled with different attitudes and beliefs for males versus females, or individuals with multiple versus non-multiple sexual partners, or individuals with or without a history of STDs, or individuals with or without HIV/AIDS. (Nikitta Foston, 2002).Information uncovered by this investigation revealed that males are less knowledgeable about several factors involved in the transmission of AIDS than females. On the other hand, individuals with multiple partners were more likely to believe that AIDS is caused by bacteria or the same virus that causes VD.Knowledge about the factors associated with the transmission of HIV/AIDS was essentially identical for subjects who practiced unprotected anal intercourse and those subjects who did not. Individuals with HIV/AIDS correctly answered only 55 percent of the questions concerning the transmission of AIDS while those not exposed correctly answered 85 percent of the AIDS knowledge questions.These data suggest that educational information and self-assessment instruments may need to be created for and targeted at specific African-American groups rather than rely on a wide-scale mass media campaign to reach all individuals. One way to accomplish this aim may be to create materials that enable African-Americans to actively question and evaluate their own risk.Perhaps one of the problems that has to be overcome in order to implement such a plan is to identify the explicitness needed in the HIV/AIDS prevention messages for African-Americans who are not monogamous and engagin g in risky sexual behaviors (e.g., anal intercourse).The possible means of how to minimize the gap between knowledge and risky behaviors could go on and on, but the one way that is likely to result in a more favorable outcome is to simply ask the people involved to provide solutions. Seldom have we taken this position around a major public health problem, but what can we lose by asking African-Americans to generate solutions to problems that are the focus of so much human suffering.One of the barriers to effective HIV/AIDS education programs in African-American communities is the fact that the people and organizations have not been encouraged to believe that HIV/AIDS prevention would be more effective when planned, executed, and propagated by members of their own community.In other words, African-American community members are not involved in the empowerment process which stresses both individual determinations over one's own life and strong democratic participation in the life of o ne's community. The notion of empowerment presupposes that African-American community members have the competency to intervene on their own behalf but lack the necessary resources.

Psychopathy Essay

There have been many studies linking conduct disorder to antisocial personality disorder and sometimes to psychopathy as well. Conduct disorder appears in children and adolescents and involves behavior that violates rights of others and/or societal norms or rules. According to the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV), the individual’s behavior must include actions such as aggression to people or animals, destruction of property, deceitfulness or theft, serious violations of rules, as well as a clinically significant impairment in the adolescent’s social, academic, or occupational functioning. The DSM-IV states that in order for a child or adolescent to be found to be presenting Conduct Disorder he or she must present with three or more of the above listed behaviors in the past twelve months, including at least one in the past six months (McCaullum, pp. 6-12, 2001). Those who present with antisocial personality disorder may or may not present with psychopathy. There are two main assessment devices used to evaluate the level of psychopathy that a person exhibits. The Psychopathy Checklist-Revised (PCL-R) was developed by Robert Hare in 1980 and revised in 1991 (Blair et al, 2005). The Antisocial Process Screening Device (APSD) is another device used to assess psychopathy in adults (Frick & Hare, 2001a). Both of these assessments consist of twenty behavioral items, scored from zero to two, that are used to measure whether or not a person possesses certain traits that, when combined, are common to those of people diagnosed with psychopathy. There have been many research studies conducted over the years concerning the validity and effectiveness of the Psychopathy Checklist- Revised. One such study was aimed at assessing whether or not the level of psychopathy of an individual, as measured by the Psychopathy Checklist- Revised, was correlated to that individual’s probability of violent recidivism (Tengstrom, Grann, Langstrom, & Kullgren, 2000). The study had a sample size of 202 male violent offenders presenting with schizophrenia that ranged in ages from 16 to 67. The base rate for each individual’s Psychopathy Checklist- Revised score was 26 and the base rate for reconvictions during follow-up was 21% (Tengstrom, Grann, Langstrom, & Kullgren, 2000). Overall, his study showed a positive relationship between score on the Psychopathy Checklist- Revised and the level of violent recidivism. The implications of this research study show that the Psychopathy Checklist- Revised can be used as a tool to gauge the likelihood of reconvictions concerning violent crimes, at least when discussing male violent offenders that present with schizophrenia. Another study, conducted by Walters and colleagues (2003), strived to determine whether the Psychopathy Checklist- Revised or the Lifestyle Criminality Screening Form (LCSF) compared to each other when assessing levels of disciplinary adjustment and recidivism. Although the results of the study showed that the two tests were similar in results, the Lifestyle Criminality Screening Form only took about ten minutes to complete while the Psychopathy Checklist- Revised takes between two and three hours (Walters et al, 2003). Therefore, it was concluded in the study that if there was a high risk of offender recidivism or disciplinary maladjustment, the Lifestyle Criminality Screening Form would possibly be a better choice due to the cost-effectiveness of the inventory. Due to the abundance of characteristics tested for in the Psychopathy Checklist- Revised, there have been many studies to assess which of those have a greater effect than others when discussing propensity to commit violent offenses. According to Blair and associates (2002), one of the specific symptoms presented in individuals with psychopathy is a reduced level of empathic response. There has been a positive relationship found between high levels of antisocial behavior and low levels of empathetic response. This supports the reason that both the Psychopathy Checklist-Revised (PCL-R) and the Antisocial Process Screening Device for children include the lower levels of empathetic response to victims in their criteria of psychopathy (Blair et al, 2005). One of the most common methods in which this theory has been tested is by measuring the level of skin conductance in individuals while presenting them with images of people in distress. Both children with psychopathic tendencies and adults with psychopathy present reduced autonomic responsiveness (Blair et al, 1997). This study shows that while those not presenting with psychopathy show high levels of autonomic responsiveness through sweating due to empathy felt by viewing the disturbing images, those that present with psychopathy or psychopathic tendencies do not. According to a study conducted by Blair and Coles (2000), individuals presenting with psychopathic tendencies or psychopathy tend to have a reduced ability to name both fearful facial expressions and fearful vocal affect (Stevens et al, 2001). An interesting fact coinciding with this finding is that while both children with psychopathic tendencies as well as adults with psychopathy present with this lowered empathetic response to fear and sadness, they do not show impairment in responding to expressions of happiness, anger, or surprise (Blair et al, 2005). Another factor associated with psychopathic tendencies or psychopathy is a partially inhibited ability to make the distinction between moral and conventional transgressions. A moral transgression is explained by Turiel (1983) as one that is defined by its consequences pertaining to the rights and well-being of individuals, such as hurting a person. A conventional transgression is assessed by its consequences for the social order (Turiel, 1983). A person that is not presenting with psychopathy will not present with an inability to distinguish between moral and conventional transgressions. They tend to reference the victim in a moral or conventional transgression situation more frequently when explaining their reason as to why they believed the transgression to be wrong. In the case of those presenting with psychopathic tendencies, psychopathy, as well as some other antisocial disorders, individuals make less references to the victims included in the situation and also seem to have a more difficult time distinguishing between moral and conventional transgressions discussed in the situation (Blair et al 1995a). The second of the two previously mentioned deficiencies in the ability to distinguish between moral and conventional transgressions is even more prevalent when the rules banning the specific transgressions are removed from the scenario. Thus, if there is no law or rule prohibiting the act or transgression, children with psychopathic tendencies, adults with psychopathy, as well as other antisocial populations will show a decreased ability to distinguish between the two types of transgressions (Nucci & Herman, 1982). Another area that is studied in order to search for differences in populations that present with psychopathy is that of gender and ethnicity. In a study by McCoy and Edens (2006), researchers looked to test the theory that stated that individuals of African descent are more likely to present with psychopathy. The study included 945 Black and White youths who were assessed using the Psychopathy Checklist- Youth Version. There was a lack of results showing any significant difference between Caucasians and those of African descent. However, there was an unexplained heterogeneity among the individual races. The researchers from this study advised that more research should be conducted in this area of study in order to attempt to discover the reason for this similarity within the individual races. Another study, this one conducted by Kosson, Smith, and Newman (1990), used a combination of three separate research projects in order to come to a conclusion. The first study was aimed at examining the internal structure of the Psychopathy Checklist and and its scores in relation to several constructs relevant to psychopathy. This first study found that there were differences between Whites and Blacks in the distribution of psychopathy scores. It also noted a difference between the two groups in the relation of psychopathy to measures of impulsivity. The second study was focused on assessing patterns of passive avoidance manifestations as compared to the results in a study conducted by Newman and Kosson (1986). It found that the levels of passive avoidance manifestations were similar, but not identical, in the two groups. The third and final study consisted of assessing the levels of criminal charges received by both psychopaths and non-psychopaths. This portion of the study was particularly interesting in that it found that psychopaths do, in fact, receive more criminal charges than do non-psychopaths (Kosson, Smith, & Newman, 1990).

Elizabeth Bishop’s Poetry

Elizabeth Bishop poses interesting questions delivered by means of a unique style. Do you agree? Focus on themes and stylistic features. In my opinion, Elizabeth Bishop has a unique style of asking interesting questions. Bishop invites us along on the journey with her. She does this by her â€Å"painterly eye† which she has been praised for. In her poems she takes the ordinary and turns it into the extraordinary. As a reader, I wonder why she goes into so much detail. There is a story behind each of her poems. Her poems â€Å"First Death in Nova Scotia† and â€Å"In the Waiting Room† are about childhood experiences. She uses great detail in her poems and we feel like we are apart of it. This can be clearly seen in Bishop’s poem â€Å"The Fish†. â€Å"The Fish† is an example of where Bishop turns something so plain into the extraordinary. She takes fishing and turns it into a seventy-six-line poem. This poem recalls a time when Bishop went fish in a rented boat. Bishop makes a clear statement in the opening line of the poem, â€Å"I caught a tremendous fish†. The adjective tremendous is very effective, I feel. In the first four lines, Bishop stated how she caught a huge fish and stared at it beside her boat. She didn’t haul the fish into her boat. I question why she didn’t bring it straight on board. Bishop’s delight in catching the fish soon gives way to an emotional involvement with the fish. She compares his eyes to her own and she notes that the irises are â€Å"backed and packed with tarnished tinfoil†. The image is emphasized by assonance and alliteration. It was a big personal achievement to catch the huge fish. Bishop began to enjoy her triumph. It was a big moment for her. She imagined that her feeling of victory filled up the rented boat. Meanwhile, the big fish was still partly in the water. Then she did something unusual. She released the fish she had caught: ‘And I let the fish go’. I wonder why she had mercy on the fish and decided to let it go. â€Å"Filling Station† is another clear example of Bishop turning the ordinary into the extraordinary. In this poem Bishop is writing about a family petrol station. The voice in the poem is that of an outsider. The compound words â€Å"oil-soaked† and â€Å"oil-permeated† give us a clear vision of this petrol station. I wonder why Bishop is there in the first place. We become fascinated with the place. In verse two, the speaker sees the family. The image of everything covered in oil is continued. Alliteration is used to describe the sons, â€Å"several quick and saucy and greasy sons assist†, this suggests they have an oily appearance. The speaker begins to wonder if anyone lives here, â€Å"Do they live in the station? †. Bishop looks for and finds evidence of the female touch in verses four and five. We begin to see that there is beauty and love in the most unlikely places. In this male-dominated world, there is care to attention and detail with the mention of â€Å"daisy stitch†. In the final verse the repetition of â€Å"somebody† highlights the importance of the mother. The poem ends with the assurance that everybody is loved and worthy of love. Bishop recalls a childhood experience in her poem â€Å"In the Waiting Room†. This poem is similar to â€Å"First Death in Nova Scotia† as both have a theme of childhood innocence in them†. Perhaps the most immediately striking feature of Bishop's work is its child narrator describing the seemingly innocuous event of waiting at the dentist's office while her aunt is in the patient's room. In this setting, the memory revolves around the narrator reading a  National Geographic  magazine. Bishop writes in uncomplicated, declarative language like â€Å"It was winter. It got dark / early. † that mirrors her age at the time. The poem takes an interesting direction as the child-speaker sees herself as a young woman: â€Å"What took me / completely by surprise / was that it was me: / my voice, in my mouth†. Aunt Consuelo’s cry becomes the speaker’s own cry. The woman and the girl merge into one in a surreal leap of the imagination â€Å"I – we – were falling, falling†. This poem makes us question what it means to be a woman. In â€Å"First Death in Nova Scotia† Bishop presents an extraordinarily vivid memory of a disturbing personal experience. It is winter in Nova Scotia. The dead child has been laid out in a â€Å"cold, cold parlour†. As in â€Å"In the Waiting Room† the voice in this poem is that of a child-speaker.

Stylistic analysis: One Stair Up by Campbell Nairne

The book â€Å"One stair up† was written by a Scottish novelist Campbell Nairne in 1934 and describes the life of a working-class family from Edinburgh. And we can see a fragment that shows fine style and good sense of humour. The scene takes place in one of the Broadway cinemas. Two young people – Andrew and Rosa – decided to watch some movie. The culminating point of this story is the moment when Andrew says in excitement, â€Å"Good, isn't it? †, but receives the answer, â€Å"I don't see anything funny in that†. In this scene we can see how different Rosa and Andrew are.From this fragment we don’t know anything about their origin and social status, but we can guess that Rosa was from richer family than Andrew, that’s why she had better taste and didn’t like the foolish comedy. We can also easily understand it from one sentence: â€Å"It pleased her to be seen in the dress circle, even with Andrew†. She hoped to see so me of her friends to spend more pleasant time with them, but as she couldn’t see anybody, she had to stay with Andrew. There is one more evidence for it: â€Å"Is he really so stupid, she wondered. Yes, I suppose he is†.All these facts show us that Andrew and Rosa had very different social status. So, we can say that the main idea of this small fragment is to show how difficult it is for people from different classes to understand each other. What is fun for one is absolutely fool for another. Some habits, like talking in the cinema, are absolutely normal for one and unacceptable for another. I think that the moral of the story can be very well illustrated with two proverbs: â€Å"Tastes differ† and â€Å"A place for everything and everything in its place†. In order to describe the scene properly author uses different stylistic devices.On the whole he describes the movies that the heroes watched in details, so the reader can easily imagine everything that happened on the screen. For this aim the author forms his speech into short sentences that follow one after another like the scenes of the movie. But to make the story more artistic he uses, first of all, different epithets: â€Å"shadowy faces†, â€Å"looped curtain†. Also there are similes: the carpet â€Å"yielded like springing turf†, â€Å"a hard-worked dog, for you saw it, or another like it, in dozens of these comic films† and other to recall some associations in the readers’ mind and to make the images more  Ã¢â‚¬Å"visible†.What is more, similes help the reader understand the way of thinking of different characters and the author, too. The author uses different set phrases like â€Å"The film seemed to have smashed all records. It drew tears from the hardest hearts. It sent thrills down the spine† and others. It is described even with some kind of sarcasm as a sample of bad taste. Also there is an oxymoron: the main part in the â€Å"mightiest drama of Broadway† has a â€Å"bewitching† actress named Minnie Haha.Also the author uses book and high lexicon for usual things, for example: â€Å"to-night he would resist that awful temptation to explain the story in a whisper†, so it’s a burlesque. As for me, I liked this story, but I feel pity to Andrew. It is better to have a good sense of humour than trying to show your tastes. And Andrew just wanted to have better social position and dated with a girl from a rich family. But it is really difficult to them to be together. So, I think that Campbell Nairne had shown everything really truly.

A role-playing video game Undertale

A role-playing video game Undertale Undertale is a role-playing video game created by American indie developer and composer Toby Fox. Usually this type of games are not very popular but undertale is not one of this cases. It has a very interesting and really complicated plot. In the game, players control a human child who has fallen into the Underground, a large, secluded region underneath the surface of the Earth, separated by a magic barrier. The player meets various monsters during a quest to return to the surface, mainly through the combat system; the player navigates through mini-bullet hell attacks by the opponent, and can opt to pacify or subdue monsters in order to spare them instead of murdering them. These choices affect the game, with the dialogue, characters, and story changing based on outcomes. Undertale has three main endings: true pacifist, neutral and genocide. A neutral ending occurs when one of these conditions are met: The protagonist does not befriend all plot pivotal characters (Papyrus, Undyne, Alphys) OR The protagonist kills any monster. The Neutral Route ends with the protagonist escaping the Underground alone. There are a variety of different possible variations of this ending depending on the choices made throughout the game. The true pacifist ending occurs when all of these conditions are met: A Neutral Route has been completed. No monsters were killed throughout the game. (The protagonist cannot gain any EXP, and as a result, they cannot progress past LV 1.) Papyrus, Undyne, and Alphys have been befriended. A Genocide Route has NOT been completed before. Doing a Pacifist run after a Genocide route will result in an altered Soulless Pacifist ending. The True Pacifist Route ends with the barrier being broken, and the protagonist and the monsters of the Underground being able to leave. Additionally, this route will feature the True Pacifist Ending Credits. This ending occurs only when all enemies in each area (Ruins, Snowdin Forest, Waterfall, Hotland/CORE) are killed until no one remains. This includes all bosses. Completing the Genocide Route leads to the destruction of the games world. Upon re-launching the game after a completed Genocide Route, the first human asks the protagonist to give up their SOUL to them in exchange for the recreation of the world. This effectively acts in the same way as a true reset, but it also permanently alters the endings of any later Genocide or Pacifist endings (Soulless Genocide Soulless Pacifist). Neutral endings after a Genocide run are unaffected. A very interesting fact of this game is that there are two characters know that they are inside a game and try to trick you psycologically not to complete the Genocide route. Another interesting fact is that EXP dosn’t mean experience as everyone believes, it means EXecution Points.

Analysis of the Theme for English B Essay Example | Topics and Well Written Essays - 2000 words

Analysis of the Theme for English B - Essay Example In similar situation where blacks were discriminated to a great extent, Hughes kept his spirit high for studying in good academic institutes, and moving on, and presently is studying in a college where all his fellows are white, and he is the only black in his class. The poet describes a day where the instructor asked the class to write a page on what the inner feel of the students is, as stated in the stanza as below: This is a clear depiction of how open ended the question was from the instructor, trying to understand what the students felt, and thought and to see their insight on things. The writer always had strong feelings about the issues related to racism, and therefore, had no option but to write on the same topic; the discriminatory feeling and the thoughts, all came out on that single paper, where by the writer illustrated the ideas associated with discrimination, feelings, experience, grudges, and finally, realizing the fact of equality. In clear terms, the writer stated that America is about equality to all, and no matter how much is disliked by black and/or the white, they are a part of each other since they are part of America. Towards the end, in a sorrow tone, the writer states that yesno matter how harsh it is but the fact remains that whites do have an edge over the blacks as he states: I guess you learn from me--- although you're older---and white--- and somewhat more free. 3. Research Question The underlying research questions for this analysis are as follows: i. What tone has been used in the poem and how is it justified ii. What role does the persona's sense of his race play in what he has to say about his paper iii. How does this persona seem to feel about education in general 4. Methodology The methodology adapted for this research includes primary and secondary research. Primary research constitutes reading the original poem and coming up with analysis of what I feel the writer is stating. Secondary research, on the contrary, implies that the existing research about the subject matter is studied, like books and articles. 5. Analysis & Discussion This section presents in-depth analysis and discussion about the poem. 5.1 A Generic Analysis of the Poem In Hughes' poem under consideration for this research, i.e. Theme for English B. there is heavy weight-age assigned to elements of literature such as the characters, the plot, the tone, symbolic representations, themes, view points, and the scenario set-up. The plot seems highly structured as it provides in depth background details, and is seamlessly associated to the scenario described as stated by the poet: "I am twenty-two, colored, born in Winston-Salem. I went to school there, then Durham, then here to this college on the hill above Harlem." This is a clear indication of the time period and the growing mode as the time moves on. The scenario setting initiates similar to the scenario whereby a student is direct to go

Rocks and Minerals Essay Example | Topics and Well Written Essays - 500 words - 1

Rocks and Minerals - Essay Example Crushed basalt is commonly used as aggregate in highway construction and railroad ballast. Basalt can also be found in asphalt. It is also used as floor tiles and stone monument. An evidence of basalt in mars is also noted as well as basaltic rocks in the moon. Basalt appearance is uniform but can be viewed under electron microscope to reveal its component silicate mineral. Dolerite is a type of basaltic rock. It is a fine grained igneous rock commonly called diabese. Dolerite is a medium grained igneous rocks commonly found in dikes and sills. It is composed mainly of plagioclase crystals, feldspar and clinopyroxene with augite and ilmenite as minor minerals. Unlike the common basalt, dolerite crystals can be viewed under a hand lens. This is an indication that dolerite was cooled slowly than basalt. Dolerite is noted for its resistance in weathering and therefore most commonly used to build roads and monumental stones. The Tasmanian peninsula in Tasmania, Australia has the world’s largest areas of dolerite. Most of the copper ore minerals are created by weathering and is mined as mineral chalcopyrite (CuFeS2). Chalcopyrite is the most abundant mineral ore of copper. When chalcopyrite is extracted for copper, it contains 34.5% by mass copper. Other copper mineral ores can be chalcocite Cu2S, covelite (CuS), bornite (2Cu2S*CuS*FeS), malachite (CuCO3†¢Cu(OH)2), and cuprite (Cu2O). Copper mineral ores is mined for copper. Vast mountain areas are quarried for chalcopyrite, malachite and cuprite. Conglomerate is a large chunk of rock that has different minerals or rock types embedded to it. This is a type of sedimentary rock that is commonly found I beaches, rivers, and glaciers. Pebbles and small rocks are the major components of a conglomerate rock. Quartz is the most common mineral of pebble so is conglomerate. Iron oxide, calcium carbonate and silica are also tied together with all the components. Conglomerates doesn’t have