Splitting a message, and processing and gathering

This recipe will show you how you how to split a message into individual fragments, process each fragment individually, and re-aggregate the processed exchanges back Into a single exchange. In EIP terms, this is known as a Composed Message Processor, and Is made up of a combination of a Splitter and an Aggregated. How to do It†¦ In order to split and aggregate (Join) a message, combine a split DSL statement with an associated Congo as follows: 1. Define an Segregationist's Instance as described In the Aggregating related messages recipe.For this example, we will reuse theSetAggregationStrategy Implementation from that recipe: 2. Define a regular split block as per the Splitting a message into fragments recipe, breaking up the payload as you see fit through the use of an expression. Reference the Segregationist's instance through the strategy attribute in the split element: ${body) In the Java DSL, refer to the Segregationist's instance as the second parameter to the split() stat ement: from(â€Å"direct:in†) . Split(body(), new Straightforwardness()) . End() . To(â€Å"mock:out†); How it works†¦When an exchange reaches the split statement, It Is broken up Into Individual fragments as expected, each of which Is processed through the steps defined within the block. When each split fragment's exchange reaches the end of the split block, It Is passed Into theAggregationStrategy for aggregation. When all of the fragments have been processed, the final aggregated message proceeds down the route from the split block. This Is different from the normal Splitter behavior, which forwards the original message to that statement after the split statement.TIP By default, all processing Is performed by a single thread. You can parallelize the processing of each message fragment by using theparallelprocesslng option as described in the Processing split messages in parallel recipe. There's more†¦ An Segregationist's. When an exception is thrown during the processing of the fragment, the exchange will be immediately passed to Segregationist's. It is then up to the strategy to decide what to do with this information.

Critical Analysis of The Iceman Cometh Essay

It is a basic law of storytelling that in order for an author to capture and maintain the reader’s interest, the author must create â€Å"realistic† characters, ones that are relatable, genuine, and plainly likeable. In the works of Eugene O’Neill, he takes that rule of realistic character development and proceeds to warp and twist it into a beautifully mangled paradigm of raw humanity and pessimism. He formulates characters that are utter derelicts to society, each one desperately hanging on to their hopeless dreams, each one hauntingly familiar to us. O’Neill, one of the more well-known twentieth century American playwrights, borrows from the thinking of Nietzsche to strip away the fluff of human personality, exposing the basic, eternally somber inner workings of the human psyche. In his plays, such as The Ice Man Cometh, O’Neill consistently portrays a classic nihilistic theme that there is no God, one of the first in his field to toy with the idea. He preaches that there is no great reward in life, that even after years, perhaps even a lifetime of suffering, there is no pay off – the only thing you get is the relief that is death. O’Neill’s The Ice Man Cometh, a play brought to Broadway which went on to celebrated success, is the story of, more or less, drunken slobs. The play’s epicenter is a bar/boarding house where a group of drunken derelicts seem to live. The hotel being named after the owner, Harry Hope, is laughably ironic, seeing as how most all of the bar flies have little or no hope left in there lives, yet they all dream of their tomorrows – paying their bills tomorrow, getting their job back tomorrow, making a fresh start tomorrow. The plot revolves around the many bar attendees, but sixty year old Larry Slade plays the role of the bitter objective commentator, a person who has decidedly removed himself from the anarchist group called â€Å"The Movement† and the responsibilities of mainstream life. He and his companions eagerly await the arrival of their salesman friend Hickey, who comes down twice a year to waste all off his money on buying everyone drinks. However before Hickey arrives, Don Parrit, the son of an ex-lover of Larry’s, a woman who was also in the Movement, comes to Larry seeking help. Apparently the Movement has nearly collapsed on account of someone selling the group out, resulting in the arrest of Parrit’s mother, Rosa. Shortly afterwards, Hickey arrives, which would usually put the men in good spirits. Hickey has changed though, and instead of being his usual enjoyable self, his is sullen and depressed, evangelically preaching to the others that they should renounce their â€Å"pipe dreams† as he has; that it is only when this is done can one truly obtain free will, a doctrine that Larry has already put into effect. That night, they celebrate Harry’s birthday, but everyone has become irritable and quarrelsome, what with Hickey’s grouchiness and unwillingness to drink. The story reaches its climax when Hickey announces the death of his wife, and all the character become infuriated with Hickey for reminding them of their pathetic grasp on pipe dreams, prompting them all to finally get moving towards turning those pipe dreams into realities. However their dreams fall apart the second they start, and they all return to the bar in the end; however their shreds of hope have been dashed by their confrontations with reality, and they all resent Hickey. Hickey then tells them that he actually killed his wife out of sheer hatred for constant forgiveness, and Parrit admits that he sold out his mother and the movement for similar reasons. Overcome with guilt, Parrit asks Larry to sentence his punishment, while Harry turns himself into the police, believing himself to be insane. Larry finally confronts his own fear of death by ordering Parrit’s suicide, in the end leaving Larry with his own desire for death. The characters in The Ice Man Cometh are essentially sad and entirely pathetic; the dynamics that exist between them seem so raw and primitive that it borders on the unreal. Although containing a well-sized cast, the play mainly focuses on the interactions between Larry, Parrit and Hickey (Bogard 51). From the beginning of the play, we are introduced to Larry as a man removed from society, one who cares not to create any more bonds or relationships with the world and its inhabitants. Larry tells us this himself when he says: †¦ So I said to the world, God bless all here, and may the best man win nd die of gluttony! And I took a seat in the grandstand of philosophical detachment to fall asleep observing the cannibals do their death dance. (O’Neill: Plays of Our time 12) Larry attempts to play the part of the coolly detached â€Å"Ubermensch† or â€Å"Overman† as proposed by Nietzsche. Nietzsche describes the Ubermensch as, â€Å"the meaning of the earth. Let your will say: the overman shall be the meaning of the earth! I beseech you, my brothers, remain faithful to the earth, and do not believe those who speak to you of otherworldly hopes! (â€Å"Towards the Ubermensch†). What Nietzsche basically illustrates is a man who lives in reality, and does not expect anything more from it; he does not expect an afterlife, nor any reward for his life – he is a man living by his own morals, not buying into â€Å"slave morality†, the basic set of ethics impressed upon society (Wilcox 13). However it should be noted that Larry attempts to play this role; he successfully does so, up until Don Parrit enters his life and tugs at the few heartstrings Larry has left. In the past, Larry was a father figure to Parrit, and now Parrit has come back trying to fill that paternal void in his life. After symbolically killing his mother by selling her out to the cops, Parrit yearns to find some semblance of a reliable parent. Although Larry clearly declares his new outlook on life, he is eventually convinced by Hickey to kill that pipe dream of his, his own fear of death, and takes responsibility for Parrit’s betrayal by sentencing him to his suicide. In his line â€Å"Go! Get the hell out of life, God damn you, before I choke it out of you! Go up-! † Larry is in theory sucked back into the real world by acknowledging that bond he shares with Parrit (O’Neill : Plays of Our time 138). Hickey, like Larry, is another example of the influence Nietzsche had on O’Neill. When Hickey finally returns, he preaches to the rest of the men to give up their dreams, and it is only then can one be totally free. This sudden quest to destroy the American dream is similar to Nietzsche’s rejection of the Judeo-Christian faith and it’s ideals of redemption (Orr 91). By refusing the notion of an afterlife, one is truly free in that you realize your actions have no real consequence. John Orr goes as far as to describe Hickey as both a Christ and an Antichrist figure to the barflies. His preaching offers no one salvation because they all end up back at the bar, mentally worse off than before, symbolically dead, but he himself is crucified when he turns himself in to the police. Edmund Wilson said, â€Å"†¦ [Eugene O’Neill], nearly always, with whatever crudeness, is expressing some real experience, some impact directly from life. † (382). And Wilson is right; many, if not all of O’Neill’s plays serve as a personal reflection of his thoughts and experiences in life. In cases like The Ice Man Cometh, Bogard suggests that the characters he writes about mimic the people he encountered while he spent his days in the saloons of New Orleans. As one notices in the early stage directions, the characters are described as specific â€Å"types† of people: Joe Mott being â€Å"mildly negroid in type; Piet Wetjoen â€Å"A Dutch farmer type†; and claiming McGloin has â€Å"the occupation of policeman stamped all over him† (51). There is no doubt these characters were based on people or groups of certain people he has encountered in his life. The motif of alcoholism is obvious in The Ice Man Cometh, and of course, O’Neill had first hand experience with alcohol problems. It was his constant drinking that mollified the shock of learning of his mother’s morphine addiction, and what also got him thrown out of Princeton University. Even O’Neill’s nihilistic rejection of Christianity stems from his early childhood, when he insisted that he no longer attend Catholic school, but instead go to a secular boarding school. Also, the suicide attempt of Jimmy Tomorrow and the successful suicide of Don Parrit are reflective of O’Neill’s own struggle with suicide back in 1912, ironically the same year The Ice Man Cometh takes place. With this knowledge of O’Neill’s troubled and mentally disturbed past, we are able to discern the basic themes of The Ice Man Cometh. However this in itself is no easy task, the play is multi-layered, dealing with themes that involve dreams of death, and the existence of God; however they all stem from a focal point which is the inner turmoil that exists within man. In the beginning of the play, Larry describes Hope’s Hotel to Parrit, which coincidentally enough is a perfect metaphor for the mens’ lives: What is it? It’s the No Chance Saloon. The Bedrock Bar, The End of the Line Cafe, The Bottom of the Sea Rathskellar! Don’t you notice the beautiful calm in the atmosphere? That’s because it’s the last harbor. No one here has to worry about where they’re going next, because there is no farther they can go. It’s a great comfort to them. Although even here they keep up the appearances of life with a few harmless pipe dreams about their yesterdays and tomorrows, as you’ll see for yourself if you’re here long. (O’Neill: Plays of Our Time 19). Larry repeats the idea that the hotel is â€Å"the end of the line†, that inside it’s walls there lies â€Å"no chance†, that it’s â€Å"the last harbor†. And so it is, the hotel symbolically becoming a sort of limbo, a hole in the wall place where the burnouts and ruined lives come to kill some time as they subconsciously wait for their deaths. Even O’Neill describes the hotel in the first few lines of his stage directions as: â€Å"The back room and a section of the bar of Harry Hope’s saloon on an early morning in summer, 1912. The right wall of the back room is a dirty black curtain which separates the bar†¦The back room is crammed with round tables and chairs placed so close together that it is a difficult squeeze to pass between them†¦The walls and ceiling once were white, but it was a long time ago, and they are now so splotched, peeled, stained and dusty that their color can best be described at dirty. (O’Neill: Plays of Our Time 7). The hotel exists as a microcosm removed from society; the cramped back room full of dirty furniture and even dirtier people, representing the grim reality of death that lies in the dark recesses of the inhabitants minds. To end up at this bar is to acknowledge your death. However all the hotel’s inhabitants hold on to their pipe dreams, their last great memories of reality, all making empty promises to get back on their feet. However, they still sit, waiting for the relief of death. Their relief is that they can finally end the suffering of day-to-day existence and leave this earth. Nietzsche pushes the notion that the only world that truly exists is the physical one. There remains no great dramatic ending, no glorious redemption, there is no higher being that any of us must answer to or any grand jury that is weighing our every action, â€Å"the ‘apparent’ world is the only one: the ‘true; world is mere added by a lie† (Wilcox 73). These men finally meet their death-bringer when salesman Theodore Hickman, to them known as Hickey, enters the hotel. Yearly coming by for Harry Hope’s birthday, always a bringer of life and vitality (and especially alcohol), Larry and the others notice a gross change in Hickey. He begins to unnervingly preach the glory of killing your pipe dreams. Hickey convinces the drunkards to forget those great memories of reality, forget those promises to start anew, and accept the fact that they are physically and mentally paralyzed; forever stuck in the limbo of Harry Hope’s hotel until their death (Bogard 54). Travis Bogard best explained it by saying: â€Å"Their dreams hold at least an illusion of life’s essence: movement in purposive action. Action, to be sure, will never be taken, but the dreams reveal a basic human truth: to foster life, man must preserve a minimal dream of movement†¦showing the dreamers that they will never take action†¦brings the peace of death. †

Advantages and Disadvantages of Free International Trade

Advantages and Disadvantages of Free International Trade    Title of Coursework (please provide whole question) 2(a) Explain why free international trade can be good for countries’ economies, and examine the attempts to reduce trade barriers in the past decade. (maximum 1,000 words) 2 (b) What negative effects might free international trade have upon countries’ economies, and why might counties adopt protectionist policies? (maximum 1,000 words)    Question 2a, Explain why free international trade can be good for countries’ economies, and examine the attempts to reduce trade barriers in the past decade. Trade is a major engine of growth, both in developed and developing countries. Correspondingly, the opening of markets to allow for free trade internationally has been cited as a key factor boosting trade and economic growth globally over the years (OECD, 1999; 2003). There are a number of theories that highlight the reasons why countries should engage in international trade, and which cons equently enhance support for the argument for free trade. These include Adam Smith’s theory of absolute advantage, the theory of comparative advantage by David Ricardo, and other more recent theories (Mankiw, 2010). The theory of comparative advantage which is one of the most popular theories advocating free trade, posits that nations should specialise in the production of goods for which they have relative/comparative advantage, and exchange them for products from other countries with relative advantage in other products (Reuvid and Sherlock, 2011). Although this theory has some flaws, one of them being that it ignores limits in international demand that may exist for the specialised outputs of some countries (Reuvid and Sherlock, 2011), it nevertheless provides a strong argument for the promotion of free trade. Beyond theoretical reasons, statistics lend further support to the benefits of engaging in international trade. Sachs and Warner (1995), in a study to determine whet her nations open to trade are more prosperous, over a period from 1970 to 1989, reported that for developed countries, the rate of growth for open economies was 2.3% per year, and compared with 0.7% for closed economies. In developing countries, the gains were even higher, with a growth rate of 4.5% for open countries, as against 0.7% for closed countries. The OECD (2003) highlights other potential benefits of removing barriers to trade. They state that removing all tariffs on merchandise trade, and reducing the costs of trade by 1% of global trade value will boost overall welfare globally by over $170 billion a year, and this could add the equivalent of up to 2% to the current GDP of some regions. Other advantages of promoting free international trade through the removal of barriers are as follows: It gives customers greater choice by making available a wider variety of products, and also access to potentially cheaper and/or better quality goods. Removing price distortions encourag es the use of resources in a way that maximises the advantages offered by a country’s strengths/resources. In developing countries, these improvements in resource allocation and increased revenue from exports contribute to the national income and increase the resources available for further investments in development. It also enhances a country’s productivity and wealth (Love and Lattimore, 2009; Reuvid and Sherlock, 2011; The Economist, 2013b). These benefits have led to considerable attempts to reduce trade barriers, some of which shall be discussed subsequently.

Essay about Hip-Hop Beyond beats and Rhymes directed by Byron Hurt

About Hip-Hop Beyond beats and Rhymes directed by Byron Hurt (movie) - Essay Example Men with their bling-bling paraphernalia, for instance, threw money promiscuously in front of the camera while women in scanty dress dance erotically in the background. These images imply four things: (1) Amassing a great amount of money is men’s ultimate goal. The privilege of wealth and comfort seems to belong only to men. (2) Men’s and women’s roles, as it appears, are codified through paper money. While men search for money, on the other hand, women passively wait for men to come for their rescue. (3) The role of women is placed underneath or behind men’s. As a background, a woman only becomes a woman if she puts her place in the arms of a man. (4) Women are tagged with price on their body. Here, women are transformed into objects. In contrast to men, women seem to have no power and will. Activist Hurt realized the sharp conflict between his ideals and the ideas propagated by hip-hop culture. He believes that life’s goal is men’s and women’s equality in the access of comfort and resources. Money is just a human invention. Like money, role-giving belongs to humans, both men and women. Hurt confessed that the more he deciphered about the reproduction of sexism and masculinity in the hip-hop songs, â€Å"the more those lyrics became unacceptable to

Managing the Environment (MEWK3 DQ1) Essay Example | Topics and Well Written Essays - 500 words

Managing the Environment (MEWK3 DQ1) - Essay Example In other words, the bank had successfully created a holistic marketing strategy and was able to follow through. As it is building "the world's local bank" brand, the bank is very vulnerable to making that brand work. Hence, it must focus on acquiring local knowledge in each area it operates in, and put that local knowledge to customizing the bank's marketing activities to the locality's preferences and characteristics. Another vulnerability is that competitor banks might leverage on their being 'local' in designing marketing activities and compete head on with the bank's "the world's local bank" strategy. This will surely questions the integrity of such campaign - say, hw can HSBC be that area's local bank wherein the competitor bank is truly local in every sense Going forward and aligned with the company's "the world's local bank" image, a more decentralized structure with regard its marketing department should be adopted. This way the branch is given the authority to design and implement its marketing plans.

Choose a topic from your personal knowledge and experience Essay

Choose a topic from your personal knowledge and experience - Essay Example The most important thing when learning English as a second language is to learn to be a good listener. Effective listening is very important since it helps you to understand some of the words and concepts that may appear challenging. I have realised that when you carefully listen to others, you may be in a position to quickly understand what they are trying to say. When you listen carefully, you are also able to ask questions to the speaker so that he or she may explain the points that you may require clarification. I have also observed that if you are a good listener, mutual understanding is likely to be created with the person you are communicating with. If there is mutual understanding between the two parties involved, it is quite easy to exchange information. From my own experience, I have observed my level of understanding of different terms has significantly improved following the adoption of this strategy. I can now easily understand the main subject of discussion without aski ng the speaker to repeat what he or she has said. The other important point I must emphasize in this particular case is that you should not shun the way of behaviour of the people in the host country if you are an international student. This can only create hostility and it is counterproductive. Therefore, I have noted that you must be as cooperative as much as possible in order to avoid conflicts of interest. If you treat other people as important, there are likely chances of learning quickly their culture as well as language. From my own perspective, I have rapidly developed cordial relationships with other students than I ever anticipated. When you are learning English as a second language, I have realised that learning by observing other people is very effective in as far as acquiring new knowledge is concerned. One important thing I

Short Answer (strategic planning) Coursework Example | Topics and Well Written Essays - 500 words

Short Answer (strategic planning) - Coursework Example It further provides a practical guide for setting goals and making decisions. During stressful times, a vision helps groups to maintain focus and stick together. A strategy is a plan of action that an organisation chooses to give it direction and scope in order for it to attain its vision or goals. Strategies deal with strategic issues by focusing on the need to come up with a new set of rules or revise an existing one; create a process that will develop a mission, vision, and goals and achieve them; produce services, products, projects and programs to be followed; offer controls for the current strategy delivery and develop future capabilities while working on relations with stakeholders. Main purpose of strategy formulation is to develop strategies that will successfully connect an organisation to its environment and help it offer solutions to the public. Secondly, to offer a plan that an organisation will follow in response to strategic issues and help it reach its vision. Planning is the process of identifying and defining an organisation’s purpose, pursuit and methods of achieving them. Implementation is putting into action and following the identified strategies so as to realize the goals and objective. This leads an entity achieve a competitive advantage and better performance. If an organisation does not allocate enough resources to execute its strategy successfully, the strategy is bound to fail irrespective of how delightful it is. These resources include time and people. Secondly, a strategy may fail because the conditions that were to be exploited change before the strategy is effective. Ignoring reality and assuming that no changes are occurring in your business environment. A third reason is an overload of information from too many policies and strategies intended to solve a specific problem. Human resources tend to run away from this information overload since it

Austrian and Post-Keynesian Criticisms of the Standard Neoclassical Essay - 1

Austrian and Post-Keynesian Criticisms of the Standard Neoclassical View of the Competitive Process - Essay Example This research will begin with the statement that the neo-classical view of the competitive process believes that the perfectly competitive approach it describes the essence of capitalist competition in the market. The attributes of the process are viewed as exceptional and typically arising from government intervention, which includes protection and nationalization. The criticism points out that the basic motivator of the capitalist process, competition, ensures that if any firm enjoys super-normal profits, rivals will soon enter to bid away those profits. They will succeed to undermine any temporally market dominance that the incumbent enjoys. According to Nolan, Post Keynesians school of thought has been criticized by many schools on the issue of economic policies of the evolution of power operating in the capital market. They argue that the changes in the strength of demand cause changes in the level of prices with the respect to costs. These changes tend to have a strong influenc e on the society propensity to save or to consume and thereby changing the level of effective demand to make it correspond with the available supply. Thus, capitalism naturally initiates full employment level provided the income distribution adjustment is allowed to adjust itself to the economy. In the short run, some kind of Keynesian policies will be required but the process will be essentially governed by price flexibility relatively to wage costs. The post-Keynesian believes that the changes in the strength of demand cause changes in the level of prices with the respect to costs. These changes lead to the great influence on the consumer propensity to save or to consume and thereby changing the level of effective demand to make it correspond with the available supply. On the other hand, the Austrian school of thoughts has received criticism on the way they view the strength of demand. They argue that market participants who obtain more and more on accurate and complete perfect kn owledge depend on potential demand and supply preferences.

The Tet Offensive through the strategic eyes of the Viet Cong and Research Paper

The Tet Offensive through the strategic eyes of the Viet Cong and North Vietnamese - Research Paper Example However, the communist north decided to stage an offensive in what came to be regarded as the biggest attacks ever, since the Vietnamese war began. During this attack, the communists attacked major towns of the South to a tune of more than 100 towns, including the southern capital, while also spreading the attacks to over 36 provincial capitals of the south, using a brigade of more than 80,000 troops (Donaldson, 161). Despite the South Vietnamese and the USA army being caught by surprise, they responded to the offensive and eventually overcame the communists, although the whole scenario took two more months, with the worst occasion being the Battle of Hue, where the whole of the city was destroyed and thousands of residents, to a tune of 7600 executed by the communists, in what came to be referred as the Hue massacre (Collins, 42). There are three main aspects that have made the Tet Offensive stand out, in the whole episode of the Vietnamese war. First, the Tet offensive was launched by the North Vietnam against South Vietnam by surprise, allowing the communists to inflict more damage on the South, on the initial face of the offensive. Secondly, the offensive stands out as the largest military operation that was ever conducted by either the north or the south in the Vietnamese war. Thirdly, it stands out as the worst attack on the civilians, since the offensive did not only aim at the Southern Vietnamese and the USA armies, but also extended its attacks to the civilian command and control centers throughout South Vietnam, culminating with the horrific Hue massacre that left over 7000 civilians dead (Anderson, 183). Such a massive attack operation could not have just come on board, without efficient and effective planning and execution of the attacks. The Tet Offensive occurred at a time when the pressure was mounting on the USA military and government to consider dropping its involvement in the Vietnamese war, considering that close to 45% of the Americans beli eved that the war was not worth being pursued, mainly due to the losses it had inflicted on the USA, in terms of the number of the casualties of its soldiers, the increment in taxation to the citizens, and the lack of a slightest indication that the war was coming to an end (Robbins, 12). With such disgruntling within the public, and even some sections of the government and intelligence, the military command needed to act decisively in bringing the whole issue to a halt. The USA military command therefore reacted by mounting the success offensive in 1967, where it sought to assert to the public that the USA would win the war, and brings it to a speedy end. This was achieved through media propaganda where the army generals misled the American public on the capabilities of the Northern Vietnamese Army and the Viet Cong, by asserting that they were losing ground and therefore were not in a position to launch any major attack. To curb it all, and give more confidence to the people, the US army General called on the communists to try something, because the USA was actually looking for a fight (Donaldson, 155). Therefore, the anti-war sentiments by the American public, coupled by the underestimation of the communists ability

Romeo and Juliet Courage Essay Example for Free

Romeo and Juliet Courage Essay Romeo and Juliet, a story of two families. A story about two lovers that are willing to die for each other. A story where courage plays a huge and important role in. Life itself also involves a lot of courage Just to get by day to day. This essay will explain how courage plays an important role in literature and life. One example of how courage plays a role in literature is in shakespheres Romeo and Juliet. Romeo and Juliet both express their love for each other in a huge way. This shows a ton of courage because they would likely be killed or hated because they are with the other family. Romeo and Juliet are willing to die for each other with shows so much courage because they are very likely to be banished or killed for their actions. Another example of how courage plays an important role in literature is how much courage the Nurse in the play Romeo and Juliet shows. The nurse knows about Romeos love for Juliet and Juliets love for Romeo. Yet the Nurse keeps it a secret from the Capulet family even though she could be fired and ruin Romeos change to be with Juliet if the Capulet family found out. The Nurse shows courage by doing this and it plays an important role in the play and in literature. An example of how courage plays an important role in life is when you make a new friend. Before you meet them you have no idea who they are or what kind of person they are. But instead of leaving them alone and never getting a chance to make a new friend you talk to them. After talking to them you realize they are a good person. This is important because without courage you would never had the guts to go out and meet a new friend of learn about other people. In this essay I have showed you Courage, the ability to do something that frightens one, is important in life and also very important is literature.

Types of Tissue and Muscle

Types of Tissue and Muscle Muscle Muscle is one of the four fundamental types of tissue present in animals. It is a soft tissue primarily responsible to produce movement of a body part. Its cells convert the chemical energy of ATP into the mechanical energy of motion and exert a useful pull on another tissue. More specifically, muscle contraction serves the following overlapping functions: movement and contractile move of body contents in the course of respiration, circulation, digestion, defecation, urination, and childbirth. Stability by resisting the pull of gravity. Communication. As well as the control of body openings and passages. And finally, producing around 85% of our body heat, which is vital for the metabolism (Carey Carpenter, 2007). Classification There are three histological types of muscle—cardiac, smooth and skeletal—which differ in appearance, physiology, and function. The cardiac muscle is essentially limited to the heart, though it extends slightly into the nearby blood vessels. It is involuntary and striated because of the regular arrangement of their actin and myosin filaments. Its cells are much shorter, so they are commonly called myocytes, and are mononuclated (Saladin, 2003). The myocytes assemble branches of adjoining cells and form a network by attaching to each other in attachment points called intercalated discs that provide strong mechanical adhesions between adjacent cells. Smooth muscle lacks striations and is involuntary. Smooth muscle cells are usually long and spindle-shaped, and each fusiform cell has a single and centered nucleus (Purves et al., 2004). Small amounts of smooth muscle are found in the iris of the eye and in the skin, but most of it, called visceral muscle, forms layers in the walls of the digestive, respiratory, and urinary tracts, blood vessels, the uterus, and other viscersa (Alberts et al., 2008). The skeletal muscle type is of special interest of this thesis and will be further studied in the following sections. Skeletal muscle Skeletal muscles are, as the name implies, are bound to the skeleton by means of tendons, which means that they are volitional. It is composed of both muscular tissue and connective. A skeletal muscle cell (muscle fiber) is about 10 to 100m in diameter and 30 cm long. It is surrounded by a sparse layer of areolar connective tissue called the endomysium, which allows room for blood capillaries and nerve fibers to reach each muscle fiber. Muscle fibers are grouped in bundles called fascicles, which are visible to the naked eye as parallel strands. Each fascicle is separated from neighboring ones by a connective tissue sheath called the perimysium, usually somewhat thicker than the endomysium. The muscle as a whole is surrounded by still another connective tissue layer, the epimysium. The epimysium grades imperceptibly into connective tissue sheets called fasciae, deep fasciae between adjacent muscles and a superficial fascia (hypodermis) between the muscles and skin. It is described as striated and voluntary (Saladin, 2003). Structure The skeletal muscle tissue consists of long and cylindrical cells called muscle fibers, which are actually huge single cells that form during development by the fusion of many separate cells, called myoblasts. Each cell contains multiple nuclei adjacent to the plasma membrane, and they are about 10 to 100m in diameter and 30 cm long. The bulk of the cytoplasm inside is made up of myofibrils, which is the name given to the basic contractile elements of the muscle cell. Within each myofibril are thin actin filaments and thick specific muscle isoforms of myosin II filaments (Alberts et al., 2008). Myosin filaments are bundles of molecules with globular heads and polypeptide tails. Actin filaments consist of two chains of actin monomers twisted together. They are wrapped by chains of the polypeptide tropomyosin and studded at intervals with another protein, troponin. In most regions of the myofibril, each thick myosin filament is surrounded by six thin actin filaments, and conversely, each thin actin filament sits within a triangle of three thick myosin filaments. The myofibril consists of repeating units, called sarcomeres, which are the units of contraction, built up of approximately 2.2 microns in length. Each sarcomere is made of overlapping filaments of actin and myosin, which create a distinct band pattern. As the muscle contracts, the sarcomeres shorten, and the appearance of the band pattern changes. Each sarcomere is bounded by Z-lines, which are structures that anchor the thin actin filaments. Centered in the sarcomere is the A-band, which contains all the myosin filaments. The H-zone and the I-band, are regions where actin and myosin filaments do not overlap in the relaxed muscle. The dark stripe within the H-zone is called the M-band; it contains proteins that help hold the myosin filaments in their regular arrangement. The bundles of myosin filaments are held in a centered position within the sarcomere by a protein called titin. Cardiac muscle and smooth muscle also contain sarcomeres, although the organization is not as regular as that in skeletal muscle (Alberts et al., 2008; Purves et al., 2004.). The plasma membrane, called the sarcolemma has tunnel-like infoldings called transverse (T) tubules that penetrate through the fiber and emerge on the other side. The function of a T tubule is to carry an electrical current from the surface of the cell to the interior when the cell is stimulated. Most other organelles of the cell, such as mitochondria and smooth endoplasmic reticulum (ER), are located between adjacent myofibrils. The sarcoplasm also contains an abundance of glycogen, which provides stored energy for the muscle to use during exercise, and a red pigment called myoglobin, which binds oxygen until it is needed for muscular activity. The smooth ER of a muscle fiber is called sarcoplasmic reticulum (SR). It forms a network around each myofibril, and alongside the T tubules it exhibits dilated sacs called terminal cisternae. The SR is a reservoir for calcium ions; it has gated channels in its membrane that can release a flood of calcium into the cytosol, where the calcium a ctivates the muscle contraction process (Saladin, 2003). Muscle contraction For contraction to occur, an action potentials spreads from the end plate and when it reaches the T tubules, it continues down them into the sarcoplasm. Action potentials open voltage-regulated ion gates in the T tubules. These are physically linked to calcium channels in the terminal cisternae of the sarcoplasmic reticulum (SR), so gates in the SR open as well and calcium ions diffuse out of the SR, down their concentration gradient and into the cytosol. The calcium ions bind to the troponin of the thin filaments. The troponin-tropomyosin complex changes shape and shifts to a new position. This exposes the active sites on the actin filaments and makes them available for binding to myosin heads; the myosin heads must have an ATP molecule bound to it to initiate the contraction process. Myosin ATPase, an enzyme in the head, hydrolyzes this ATP. The energy released by this process activates the head, which â€Å"cocks† into an extended, high-energy position. The head temporarily keeps the ADP and phosphate group bound to it. The cocked myosin binds to an active site on the thin filament. Myosin releases the ADP and phosphate and flexes into a bent, low-energy position, tugging the thin filament along with it. This is called the power stroke. The head remains bound to actin until it binds a new ATP. Upon binding more ATP, myosin releases the actin. It is now prepared to repeat the whole process—it will hydrolyze the ATP, recock (the recovery stroke), attach to a new active site farther down the  thin filament, and produce another power stroke (Saladin, 2003). Classes of muscle fibers Not all muscle fibers are metabolically alike or adapted to perform the same task. Some respond slowly but are relatively resistant to fatigue, while others respond more quickly but also fatigue quickly. Indeed, skeletal muscles can be divided into fast and slow twitch fibers and its myosin heavy chain (MHC) isoform expression. Type I (MHC-I): Also called slow oxidative (SO) or slow-twitch. These fibers have relatively abundant mitochondria, myoglobin, and blood capillaries, and therefore a relatively deep red color. They are well adapted to aerobic respiration, which does not generate lactic acid. Thus, these fibers do not fatigue easily. However, in response to a single stimulus, they exhibit a relatively long twitch, lasting about 100 milliseconds (msec). Type II (MHC-II): Also called fast glycolytic (FG) or fast-twitch. They are well adapted for quick responses but not for fatigue resistance. They are rich in enzymes of the phosphagen and glycogen–lactic acid systems. Their sarcoplasmic reticulum releases and reabsorbs Ca2 quickly, which partially accounts for their quick, forceful contractions. They are relatively pale (white fibers). These fibers produce twitches as short as 7.5 msec, but because of the lactic acid they generate, they fatigue more easily than SO fibers. Some authorities recognize two subtypes of FG fibers called types MHC-IIA and MHC-IIB. Type IIB is the common type just described, while IIA, or intermediate fibers, combine fast-twitch responses with aerobic fatigue-resistant metabolism. Type IIA fibers, however, are relatively rare except in some endurance-trained athletes (Saladin, 2003). Notably, human skeletal muscle does not contain MHCIIb (Spangenburg and Booth, 2003; Schiaffino and Reggiani, 1994; Smerdu et al., 1994). In addition, ‘‘hybrid’’ fibers containing two MHC isoforms (i.e., type I/IIA, IIAX, IIXB) can also be present in muscle (Schiaffino and Reggiani, 1994; Staron and Pette, 1993). The fiber types can be differentiated histologically by using stains for certain mitochondrial enzymes and other cellular components, like using immunohistochemical procedures with antibodies against the specific MHC isoforms (Schiaffino et al., 1989; Lucas et al., 2000). All muscle fibers of one motor unit belong to the same physiological type. Nearly all muscles are composed of both SO and FG fibers, but the proportions of these fiber types differ from one muscle to another. Muscle myogenesis Vertebrate skeletal myogenesis proceeds through three stages: determination of the muscle progenitor cells, called myoblasts; proliferation and in some cases migration of myoblasts; and their terminal differentiation into mature muscle by fusing to form multinucleated myotubes (Buckingham et al., 2003; Shi and Garry, 2006). Muscle development Muscle tissuesare derived from themesodermallayer of embryonicgerm cellsin a process known asmyogenesis. All muscles are derived fromparaxial mesoderm [8].The paraxial mesoderm is divided along the embryos length intosomites, corresponding to thesegmentationof the body.Muscle cells come from two cell lineages in the myotome somite, the epimere and hypomere, which formepaxialandhypaxialmuscles, respectively. Most muscles are hypaxial. During development,myoblasts either remain in the somite to form muscles associated with the vertebral column or migrate out into the body to form all other muscles. Myoblast migration is preceded by the formation ofconnective tissueframeworks, usually formed from the somaticlateral plate mesoderm.Myoblasts follow chemical signals to the appropriate locations, where they fuse into elongate skeletal muscle cells (Sweeney, 1997). Muscle differentiation Muscle fibersform from the fusion ofmyoblastsinto multi-nucleated fibers calledmyotubes. In the early development of an embryothese myoblasts will proliferate if enoughfibroblast growth factor(FGF) is present, without differentiating. When these factors are depleted, the myoblasts cease division and secretefibronectinonto theirextracellular matrix and bind to it through _5ÃŽ ²1 integrin, their major fibronectin receptor (Menko and Boettiger 1987; Boettiger et al. 1995). The second stage involves the alignment of the myoblasts together into chains and subsequently into myotubes. This step is mediated by cell membrane glycoproteins, including several cadherins and CAMs (Knudsen 1985: Knudsen et al. 1990). Recognition and alignment between cells takes place only if the two cells are myoblasts. However, identity of the species is not critical (Yaffe and Feldman, 1965). The third stage is the actual cell fusion itself. In this stage,calciumions are critical for development (Shainberg et al. 1969; David et al. 1981). Fusion is mediated by a set of metalloproteinasescalledmeltrins (e.g., c-Met).Myocyte enhancer factors(MEFs) promote myogenesis.Serum response factor(SRF) plays a central role during myogenesis, being required for the expression of striated alpha-actin genes (Wei et al., 1998).Expression of skeletalalpha-actinis also regulated by theandrogen receptor; steroids can thereby regulate myogenesis (Vlahopoulos et al., 2005). The specific extracellular signals that induce determination of each group of myoblasts are expressed only transiently. These signals trigger production of intracellular factors that maintain the myogenic program after the inducing signals are gone. We discuss the identification and functions of these myogenic proteins, and their interactions, in the next several sections. Muscle-specific transcription factors Pax family Satellite cells and proliferating myoblasts is characterized by the expression of Pax-genes, more specifically Pax7 and Pax3, which are transcription factors that regulate proliferation. Back to the developmental stage, in the lateral portion of the somite, which forms the hypaxial muscles, factors from the surrounding environment induce the Pax3 transcription factor. In the absence of other inhibitory transcription, Pax3 then activates the genes encoding two muscle-specific transcription factors, Myf5 and MyoD. In the medial region of the somite, which forms the epaxial muscles, MyoD is induced through a slightly different pathway[1]. Pax7 residing satellite cells proliferating stage and Pax7 knockout mice completely lack satellite cells (Seale et al., 2000). Cells expressing Pax7 is believed to be important for the regeneration of myoblasts. Also the expression of Pax3 has negative effect on the differentiation and it has been shown that this transcription factor is down-regulated in muscle by ubiquitination and proteasomal degradation before differentiation can proceed (Boutet et al., 2007). Pax genes have been shown to regulate the proliferation and survival even of certain cancers such as melanoma (Muratovska et al., 2003). Pax transcription factors are downregulated upon further differentiation and other proteins predominate. Meanwhile Pax3 _____, Pax7 appears only in muscle stem cells (___). MyoD family Muscle cells come from two cell lineages in the somite. In both instances, paracrine factors instruct the myotome cells to become muscles by inducing them to synthesize the MyoD proteins (Maroto et al. 1997; Tajbakhsh et al. 1997). Or also called the myogenic bHLH (basic helix-loop-helix) proteins. The proteins of this family all bind to similar sites on the DNA and activate muscle-specific genes (e.g. the muscle-specific creatine phosphokinase gene by binding to the DNA immediately upstream from it, or the chicken muscle acetylcholine receptor) (Lassar et al. 1989; Piette et al. 1990). MyoD and Myf5 belong to this family and are particularly important for muscle differentiation [2]. Their important role during differentiation is supported by the MyoD-/-/Myf-5-/- mice lacking fully developed skeletal muscle (Rudnicki et al., 1993). Myf-5 promotes myoblasts’ proliferation and is required for the cells to initiate differentiation (Ustanina et al., 2007). Absence of MyoD inhibits differentiation in cell culture and the protein is therefore considered to be a positive regulator of the process (Sabourin et al., 1999). While Pax3 is found in several other cell types, the myogenic bHLH proteins are specific for muscle cells. Any cell making a myogenic bHLH transcription factor such as MyoD or Myf5 is committed to becoming a muscle cell. Myogenic regulatory factors (proper name?) Later than the MyoD proteins expression during differentiation, the myogenin and the myogenic regulatory factor 4 (MRF4) are present. Mice with deleted myogenin in developing myoblasts can start the differentiation process but they cannot move and die soon after birth (Hasty et al., 1993). Among other things, this suggests that myogenin is required at a later stage of the process. Similarly, MRF4 is important for the growth of muscle tissue (Rhodes and Konieczny, 1989). It is noted that the MEF2 family of transcription factors also regulate differentiation (Olson et al., 1995), but their functions are not described in this context. In summary, Pax transcription factors help to sustain it from the stem cell stage of satellite cells, MyoD and Myf-5 act as myogenic determinants in the myoblast’s diet, and myogenin and MRF4 are known as regulators of the later differentiation and muscle fiber formation (Pallari, 2011). Other factors Although some factors that induce differentiation remain unknown, some growth factors and signaling molecules have been shown to regulate the process. Notch signaling is important in animal embryonic development, in that it participates in the cell fate determination (Alberts et al., 2008). Notch has a dual role of myoblasts in that the protein has an inhibitory effect on myoblasts differentiation (Shawber et al., 1996) and simultaneously stimulates their proliferation (Conboy and Rando, 2002). The chemoattractant SDF-1 also has an inhibitory effect on myoblasts differentiation and stimulates their proliferation by activation of the PKCÃŽ ¶ (Ãâ€"demiÃ…Å ¸ et al., 2007). Moreover, differentiation requires the expression and activity of cyclindependent kinase (Cdk) inhibitors, such as p21 and p27, critical for the withdrawal of myoblasts from the cell cycle (Kitzmann and Fernandez, 2001). To fully understand the factors that regulate, activate and inhibit satellite cells and their differentiation requires even much research (Kuang and Rudnicki, 2007; Shi and Garry, 2006.). [1] developmental biology Scott gilbert [2] developmental biology Scott gilbert