Who was King Louis XIV?

King Louis XIV was the monarch of France for almost seventy-five years. He ruled from the mid-1600s until the early 1700s. He was sometimes called the Sun King because he was one of the longest reigning monarchs in the history of Europe. Among major European powers, King Louis XIV was the longest reigning monarch in history.  

King Louis XIV became king of France when he was four years old. His age prevented Louis XIV from ruling his kingdom for many years. Instead, he relied upon advisors, ministers, and his mother (who served as regent) to govern France.  hen Louis XIV did gain power as a young man, he made it his mission to change many things in France. He focused on tax reform, the arts, and foreign policy. During his reign, he led his country through several wars. These wars were very costly for France. Overall, though, France became a stronger foreign power during his reign. King Louis XIV was a devout Catholic and persecuted those who were not, most notably the Huguenots.  

What are ligaments?

Structure and Functions

Structurally, ligaments appear to be strap-like bands or round cords. They are strong yet somewhat pliable. In terms of the musculoskeletal system, they serve to stabilize the adjoining bones making up what is referred to as an articulating joint. Ligaments consist of a cellular component called fibroblasts, making up 20 percent of their total tissue volume. The remaining 80 percent of the tissue volume is outside the fibroblast cells and consists of collagen and elastin. The relative proportion of collagen to elastin varies among ligaments. The degree of stabilization also varies and depends on each particular joint, such as shoulder and ankle joint ligaments. This degree of stabilization may be one which limits the amount of movement or prevents certain movements entirely. Some ligaments surround an entire joint filled with a lubricating fluid called synovium and are termed capsular ligaments. Ligaments located outside this joint capsule are called extracapsular and provide joint stability, while ligaments located inside the capsular ligament are called intracapsular and permit much more movement of the joint.

Other locations outside the musculoskeletal system that consist of ligaments for supporting structures include the broad ligament for the uterus and Fallopian tubes, which attaches these organs to the pelvic wall. Suspensory ligaments are also found in the body supporting a variety of organs, including the eyeball and breasts.

Disorders and Diseases

Ligaments are elastic, and they gradually lengthen when under tension. The term sprain
describes an injury to a ligament caused by forces that stretch some or all of the ligament’s fibers beyond their limit. This type of ligament injury can result in some degree of rupture of some or all of the fibers. In some instances, the ligament injury includes the possibility of pulling attachments from the bones. The classification for grading ligament injuries is based on two factors, the numbers of fibers ruptured and the resulting instability of the joint involved. Ligament injuries are also classified clinically as first degree (mild), second degree (moderate), or third degree (severe).

A consequence of a stretched or ruptured ligament can be instability of the joint. Not all injured ligaments require surgery, but if surgery is needed to stabilize the joint, the torn ligament can be repaired. Instability of a joint can, over time, lead to wear to the cartilage and eventually to osteoarthritis.

Joint inflammation from trauma or other medical reasons can stiffen the joint ligaments, resulting in restricted motion. In contrast, a group of rare inherited diseases called Ehlers-Danlos syndrome can lead to abnormal collagen, resulting in loss of joint stability because of laxity in the joint capsule.

Several immune diseases can affect the ligaments of the body’s joints. Rheumatoid arthritis is a chronic disease that affects the synovial
membrane of the joint, which produces the joint’s lubricant synovium. This fluid becomes thickened and fleshy and erodes the joint structures, including the articular ligaments.

Perspective and Prospects

The discovery of joint structures is credited to early anatomists such as Andreas Vesalius, who published De fabrica humana in 1543. Until this time, his contemporaries had claimed that ligaments and tendons were types of nerve units. Three centuries later, in 1858, Henry Gray’s writings on dissection, Gray’s Anatomy, described and illustrated the anatomy and function of the human body, including the role of ligaments.

Advances in orthopedic medicine and the development of sports medicine have introduced specific braces to protect major joint ligaments during athletic and nonathletic activities. In addition, the continuing development of surgical procedures for the repair of damaged ligaments can help the individual return to an optimal level of function after the ligament injury. Research is ongoing to provide information to treat and find a cure for the many pathologies that affect ligaments and associated connective tissues.

Bibliography

Hoppenfeld, Stanley. Physical Examination of the Spine and Extremities. Norwalk, Conn.: Appleton-Century-Crofts, 1976.

Leach, Robert E. "Sprain." Health Library, March 18, 2013.

Malone, T. R., T. McPoil, and A. J. Nitz. Orthopedic and Sports Physical Therapy. 3d ed. St. Louis: Mosby Year Books, 1997.

MedlinePlus. "Sprains and Strains." MedlinePlus, June 24, 2013.

Norkin C. C. Joint Structure and Function. 4th ed. Philadelphia: F. A. Davis, 2005.

Scuderi, Giles R. Sports Medicine: A Comprehensive Approach. 2d ed. Philadelphia: Mosby/Elsevier, 2005.

Gray, Henry, H. V. Carter, et. al. Gray’s Anatomy. 15th ed. London: Bounty, 2012.

Vorvick, Linda J. "Tendon vs. Ligament." MedlinePlus, August 14, 2012.

Elements are pure substances, because all the atoms of a specific element are ____.

Substances can be categorized into three classes: elements, compounds and mixtures. An element is the purest form of a substance, since all the atoms of an element are identical. This means that they have the same number of protons, neutrons and electrons. While this may be true for elements that do not have isotopes (atoms that have the same atomic number but different numbers of neutrons), elements with isotopes may have atoms with different mass numbers. In general, one isotope dominates a given element and hence we can assume that all the atoms are identical to each other. Since atoms are identical to each other, they have exactly the same properties, thus making an element a pure substance and also incapable of further sub-division.

Some examples of elements are iron, copper, oxygen, sodium, chlorine, lead, uranium, etc.

Hope this helps. 

After they find the soap dolls, what does Jem realize that Scout does not yet understand?

At the beginning of Chapter 7, Scout asks Jem about what happened the night he went back to the Radley's yard to get is pants. He says, "They’d been sewed up. Not like a lady sewed ‘em, like somethin’ I’d try to do. All crooked." When they find the ball of twine in the knothole, Scout thinks it is another child's hiding spot. However, Jem thinks otherwise. He doesn't specify what he means by this but the indication is that, if it is not a hiding spot, the twine was put there to be found (by he and Scout).  

When they find the soap dolls, Jem and Scout rule out Mr. Avery and Miss Stephanie's sweetheart. After finding the pants sewn together and now these surprises in the tree, the reader can suppose that Jem might think it is Boo Radley who is behind these gifts. Jem never says this aloud or to Scout. And there is no direct textual evidence to absolutely prove that Jem thinks this. But there are hints. The fact that he never tells Scout what he's thinking or who he thinks is responsible is important.

He had been on the verge of telling me something all evening; his face would brighten and he would lean toward me, then he would change his mind. He changed it again. “Oh, nothin‘.” 

Scout, on the other hand, seems to have no clue that Boo is the one putting things in the tree. When they start to write the letter to thank the mystery giver, Jem says it should begin "Dear Mister." Scout asks why he assumes it is a man. 

How does weight-loss fasting differ from fasting for religious purposes in terms of personal experience and the attitudes of society?

What a great question! Religious fasting and weight-loss fasting differ primarily in their motivations, but also to some degree in the lived, personal experience of the fast and the opinions others may have of a fasting person. Fasting is a spiritual practice in many religions, and in the Abrahamic traditions it may even be demanded of those who are physically capable during certain holy days, weeks, or months. Depending on the tradition and personal preference, fasting may involve only eating at certain times of day for an extended period of time, eating very plain food, and/or limiting the liquids one consumes. Religious fasting is typically performed as a means of re-orienting or "touching base" with one's faith and as a demonstration of devotion. For example, the Muslim holy month of Ramadan is a time for fasting during the hours of daylight and an increased attentiveness to prayer and charity. 

Weight-loss fasting, on the other hand, is performed with the goal of shedding body weight for health or aesthetic purposes. People who engage in weight-loss fasting may also restrict their eating to certain times of day, very small quantities, and/ or very plain foods. Some people will "fast" by consuming only liquids for an extended period of time. The idea behind the practice of fasting for weight loss is that the body will go into "starvation mode" and begin burning excess fat through a process called ketosis. Some people feel that fasting and entering a state of ketosis gives their digestive tract a chance to rest and heal itself.

So, how do the personal experiences of religious fasting and weight-loss fasting differ? For one, the lifestyle activities which may surround the act of fasting are very different. People who fast for religious reasons spend a lot of time in prayer or meditation. People who fast for the purpose of weight loss do not typically engage in more prayer than they might otherwise, but may be interested in other activities which they feel benefit their process, such as gentle exercise. (Some people do engage in strenuous exercise to burn calories, but this is not necessary and can be hazardous to health.) 

As far as the physical, mental, and emotional experience of fasting, both people who fast for religious and weight-loss reasons report initial feelings of fatigue, followed by a sense of determination, focus, and purpose. Fasting stimulates the growth of neurons in the brain, and in the state of ketosis, ketones in the blood stream are like a superfood for brain activity! Some people feel they experience a rather dreamy sense of awareness for the duration of their fast. The particularities of brain and body chemistry and what this means in terms of experience has more to do with the amount and frequency of any food being taken in rather than the act of (or motivation behind) fasting. That is, someone who fasts on only water for a week would experience a more significantly altered mental state than someone who only abstains from food during the daylight hours.

As far as the attitudes of society, especially people close to the person engaging in fasting, most people have equal parts respect and worry for those who fast. Religious fasting is offered a little more honor in most cases because it is perceived as being for unselfish and spiritually beneficial reasons. With weight-loss fasting, however, some people are judgmental and believe it will cause damage to a person's health or is a sign of an unwillingness to participate in other means of weight loss. Some people who fast for weight loss have been criticized as "lazy" because others think they are not willing to put in the effort to exercise or make longer-term changes in their diet. Recent studies showing some of the health benefits of fasting have helped to shift this attitude a little bit more toward the positive end of the spectrum, but the thought of weight-loss fasting can still worry loved ones. That's not to say that people don't worry about their loved ones who fast for religious reasons—these people are just as at risk for health troubles as someone who fasts for weight loss. Where attitudes toward people fasting differ, it really seems to be more of a judgment of the motivation for fasting rather than the act of abstaining from food in itself. 

Explain how the concept of price elasticity can be useful to the government in its determination of taxation policy.

The question asks how the concept of price elasticity can be useful to the government in its determination of taxation policy. First, let’s review the concept of price elasticity. It is defined as the percent change in quantity demanded or supplied divided by the percent change in price which caused the change in quantity. Note that it applies to both the supply and demand curves. Finally, it is related to the slope of the curve in question, but it is not identical.

Fundamentally, elasticity measures the sensitivity of quantity to price changes. Taxes have the effect of adding an additional cost to an item on top of what the supplying firm charges. That is, they have the effect of changing the price of the item or service, ceteris paribus. Therefore, if demand is highly elastic (relatively flat demand curve), small tax increases will cause large declines in quantity demanded. This in turn may cause suppliers to lower price to compensate for this effect, that is to attempt to increase the quantity demanded back toward the previous equilibrium. In essence, the suppliers have then absorbed some of the tax increase, because the overall price paid by the consumer does not go up by the full amount of the tax increase. Conversely, if demand is highly inelastic, the quantity demanded will change little due to the tax increase and the consumer’s price will go up by almost the full amount of that increase.

These examples illustrate that the concept of price elasticity will define how the burden of taxes is spread between consumers and suppliers. Additionally, this analysis can be used to estimate where the new equilibrium quantity will be. This in turn will affect both the total value of goods produced (with effects on employment, etc.) and the amount of tax revenue collected. For example, it does little good to dramatically increase tax rates on something if the result is to crush the market for that good, thus eliminating tax revenues from it.

How does Circe know who Odysseus is?

When Odysseus is on his way to Circe's home, Hermes gives him an herb called moly, and he tells Odysseus that it will protect him against her magic and prevent him from being turned into a pig like his crew were.  (This is actually where the expression "holy moly" comes from!)  Odysseus arrives at Circe's and she gives him a cup to drink from, and when he finishes, she flicks her wand at him and orders him off to the sties with his fellows.  Instead, however, he draws his blade and moves as though he is going to kill her, just as Hermes told him to do, and she begs him to spare her life.  She says, "Surely you are adventurous Odysseus, who the god of the golden wand, the killer of Argus, always declared would come upon his way from Troy, -- he and his swift black ship."  In other words, Hermes (the god to whom she alludes) has foretold the coming of Odysseus to Circe, and she recalls his words now.  She would be aware that the Trojan war has ended, and so it would make sense, according to what Hermes foretold to her, that this man is Odysseus on his way home.

In "The Vagabond," what does the line "white as the frosty field" mean?

The vagabond referred to in the title of this poem serves also as its speaker.  He is one who desires nothing more than to be a wanderer, living and sleeping outdoors, taking advantage of the freedoms allowed him by the road.  The second and fourth stanzas are the same, ending in these two lines:  “All I seek, the heaven above/And the road below me.”  Life on the road is all the speaker needs, in good times and in bad.  The line cited in your question falls in the third stanza, and is an image of those bad times.  The vagabond exclaims, “Not to autumn will I yield/Not to winter, even!”  By mentioning “White as meal, the frosty field,” the poet creates an image of winter, a field cold and frozen stiff, turned the color of porridge by the frost.  This image is used in conjunction with others, to the same effect – birds migrating away with the fall season, fingers turning blue with cold – and despite all these discomforts of the harsher season, the vagabond carries on with his wandering.  He refuses to be subdued, to fall prey to the warm comforts of a fire-lit room, but instead continues on in the elements, because it is in his very nature.  “There’s the life for a man like me,” he says at the end of the first verse, “There’s the life forever.”  And forever most certainly includes the freezing fields of winter.

How can "Kubla Khan" be considered a dream poem?

Samuel Taylor Coleridge's "Kubla Khan" is often thought to be a dream poem, and for good reason. A short, descriptive line before the beginning of the poem describes it as "a vision in a dream," while Coleridge himself claimed to have "composed" the poem in response to a vision he had while sleeping. Thus, it is reasonable to suppose that the poem is either meant to describe a dream sequence or, at the very least, a fantastical dream world. 

Furthermore, the imagery within the poem suggests a magical dreamscape. For example, Coleridge describes "A stately pleasure-dome" (2), "gardens bright.../ Where blossomed many an incense-bearing tree" (9), "Ancestral voices prophesying war" (30), and "A damsel with a dulcimer/ In a vision" (37-8). All in all, the poem takes us on a tour of various fantastical images, many of which seem to spring to life spontaneously and without prior explanation, just like images in a dream. As such, given the fragmented, exotic, and almost magical nature of the poem, it would be perfectly plausible to assume that Coleridge is, at least in part, describing a dream sequence. 

How does Shakespeare hold up a mirror to humanity through Macbeth?

Shakespeare holds up a mirror to humanity by showing his audience how relatively simple and easy it is for a good person to become corrupted by ambition and pride and greed.  Many of us would like to think that we could never become as crooked as Macbeth does, but Shakespeare shows us that it only takes one odd interaction and then a push from someone we trust to swell our ambition so that it becomes a real danger.  When Macbeth is fighting bravely in the two battles that begin the text, no one would have imagined that he would kill the king whose realm he defends.  Everyone is happy for Macbeth when Duncan rewards him with a new title, the Thane of Cawdor, and no one thought that Macbeth would turn traitor just as the former thane did.  It doesn't take much, though, for Macbeth to give up his best and most admirable qualities, and so Shakespeare implies that the same could be said for many more of us, if we are manipulated in the right way.

How could I go about discussing the following prompt: Henry VIII might have made himself supreme head of the Church of England, but he did...

Henry VIII broke from Rome during the period of the rise of Protestantism. As a result, there were essentially two different issues at stake: papal authority and the theology and hierarchy of the nascent state church. While the new Church of England rejected Papal authority, it created a "via media" or middle path between Roman theology and more extreme forms of Protestantism. In general, the new Church of England had weaker clerical authority than the Roman churches, but a more vertical hierarchical structure than some radical Protestant churches.

Liturgically, the major shift was from a Latin to a vernacular liturgy. The Eucharistic service in the Church of England is actually an English translation of a slightly modified form of the Sarum rite, the Roman Catholic liturgy as performed in the Cathedral of Salisbury. The Bible was now read in English rather than Latin, making it accessible to the laity. While Roman priests typically faced eastward (in the same direction as the congregation, and thus with their backs to the congregation), priests in the English church faced towards the congregation. Unlike the Roman church where communion was only given to the laity in one kind (bread but not wine), in the English church the laity communicated in both kinds. 

While the English church did maintain the older Roman parish system and episcopal hierarchy, it made fundamental changes in theology, including rejection of the doctrine of purgatory and indulgences, a belief in salvation through grace, and a belief in single predestination (you may be predestined to salvation, but the 39 Articles do not mention predestination to damnation). Critically, the English church subscribed to a "sola scriptura" doctrine (that scripture was all that was needed for salvation), reducing the importance of the clergy.

What happened at Pearl Harbor and why is it significant?

December 7, 1941, was an important day in U.S. History. On that day, Japan attacked the United States by launching an attack at our main military base in the Pacific Ocean at Pearl Harbor.

The United States and Japan had been heading toward conflict prior to the attack on Pearl Harbor. The United States stopped selling Japan oil and scrap metal once the Export Control Act was passed in 1940. The United States also froze the financial assets of Japan that were in US banks.

The attack on Pearl Harbor brought the United States into World War II. The US could now openly help Great Britain in its fight against Germany and Italy. The US also had to respond to the Japanese attack on Pearl Harbor. The US went into wartime mode, producing materials to rebuild its military in the Pacific and help the Allies fight in Europe. People within the US had to make sacrifice; certain products were rationed, and people loaned money to the government. People also grew their own vegetables in Victory Gardens to help conserve food and make more food available for the military. The US instituted a battle strategy against Germany, Italy, and Japan. This strategy included fighting in North Africa, seizing Italy, controlling the Atlantic, freeing France, and invading Germany. In the Pacific, the US wanted to recapture islands one at a time in a strategy known as island hopping. This would then set the US up for an attack on Japan. With the United States' help, the Allies were able to defeat the Axis Powers in World War II.

What are Mr. Braithwaite's character and appearance in To Sir, With Love by E. R. Braithwaite?

Ricky Braithwaite is an educated and intelligent engineer from British Guiana who served in the RAF in Britain during World War II. He can't find a job after the war because of racial prejudice in England, so he decides to teach at Greenslade, a school in London's East End. While he claims to be quick to anger, in reality he handles racism with intelligence and perseverance. For example, when he's on the bus to the East End in Chapter 1, a woman refuses to sit next to him because of the color of his skin. The bus driver wants to force her to do so, but Ricky decides to get off at the next stop instead, as he senses that this is not a woman he'd like to deal with. He is inherently respectful of the students at the school and treats them like adults, expecting respect in return. He has high standards, but he holds himself to the same high standards. He is carefully observant of what works with each student, and he is willing to work hard to help his students improve. 

What did Senator Joseph McCarthy do to become famous in the 1950s?

Senator Joseph McCarthy from Wisconsin became famous in the 1950s because he claimed that there were communists in our government. There had been a growing concern about the spread of communism in the United States after World War II ended. The Loyalty Review Program was initiated to check to see if federal employees were loyal to our country. While a small number of federal workers were fired, most government employees were cleared. However, this program played into the fear that communism was spreading in our country.

Senator McCarthy held hearings to determine if communists were working for our government. Senator McCarthy’s tactics were very intimidating. Few people were willing to stand up to him for fear that they would be labeled as a communist. Over 2,000 people lost their government jobs because of McCarthy’s actions, even though the evidence wasn’t that strong. 

However, when he claimed that there were communists in the Army, his power began to fade. People watched on television how he challenged and intimidated witnesses. The attorney for the Army took McCarthy head on and asked him if he had any sense of decency after he attacked a young attorney who worked for the Army. He lost his support, his power faded, and the Senate censured him. He died a few years later in 1957.

Define economics using the following terms: allocation, distribution, goods, resources, production, and services.

One way to define economics using these words is to say that economics is the study of the allocation of limited resources to the production and distribution of goods and services that are produced in order to try to satisfy people’s unlimited needs and wants.  Let us examine this definition to see what the important words mean.

Resources are the things that can be used to make goods and services.  These are usually divided into three categories.  The categories are land (natural resources), labor (human work), and capital (things, like tools, that are used to actually make the goods and services).  Resources are limited.  There are not enough resources to produce everything that people could conceivably want.

Resources are used to make (produce) and distribute goods and services.  Goods and services are the two categories of things that consumers might buy.  Goods are tangible things that you can pick up and leave the store with.  An example of a good is a smart phone.  Services are things that people do for you.  For example, part of what you pay for in a restaurant is the service that the cooks do in preparing your food and the service that the wait staff does in delivering the food to you.  These are not tangible things as you cannot pick up the cook’s actions and take them home.

One of the things that we have to do in any economic system is to allocate resources.  If I have ten farm workers, how many will work raising cattle and how many will work growing corn?  If I have a certain amount of corn, how much of it will go to feed animals and how much will be made into ethanol?  Someone has to make these types of decisions.

Economics is the discipline that studies these issues.  It asks how resources get allocated.  It asks what sorts of decisions people make when trying to fulfill their unlimited wants and needs with the limited resources that are available to them.

I have a literary analysis paper and my topic is the loss of innocence from the book To Kill A Mockingbird. I need some examples of metaphors that...

In Chapter 22, Jem speaks with Miss Maudie about the outcome of the trial. He is distraught that Tom Robinson was found guilty and convicted. At the beginning of the chapter, he is crying and telling Atticus that it "ain't right." This is shocking for Jem who, prior to the trial, held the assumption that the world (namely the adult world) generally made sense and was fair. With the incorrect decision of the biased jurors, Jem learns that the world is not always fair. Speaking with Miss Maudie, he uses an analogy of a caterpillar to describe how he'd once felt safe and warm in his innocent perspective of things and now he feels exposed to the truth: 

"It’s like bein‘ a caterpillar in a cocoon, that’s what it is,” he said. “Like somethin’ asleep wrapped up in a warm place. I always thought Maycomb folks were the best folks in the world, least that’s what they seemed like." 

In Chapter 15, Scout, Jem, and Dill awkwardly but effectively get the mob to leave Atticus alone. Atticus was at the Maycomb jail making sure no harm would come to Tom Robinson. In the next chapter, Jem notes that he is convinced Walter and his mob would have killed Atticus. Scout responds, saying she will beat up Walter Cunningham Jr. the next chance she gets. Atticus makes her promise not to touch him. Here, Scout and Jem are taught to avoid violence after learning that, in the adult world, Walter and his mob had been expected to threaten violence. Atticus says that Walter Sr. has "blind spots." 

"Mr. Cunningham’s basically a good man,” he said, “he just has his blind spots along with the rest of us." 

This is Atticus' metaphorical way of saying that Walter is uneducated and ignorant in some ways. The children learn that these "blind spots" can turn a friend into an enemy. Racism can be a blind spot in this metaphorical sense. 

How has Katniss's life in District 12 changed since the Hunger Games?

Katniss's life was irrevocably changed when she became a Victor in the Hunger Games. To understand, first we need to discuss what her life was like before. Her father died when she was young, and because of the way her mother behaved she was forced to become the provider for the family. She illegally hunted and gathered plants to sell. Every day, Katniss had to fight to make sure her family stayed alive.

Once Katniss became a Victor, her life became that of luxury. She no longer needed to earn money or make sure her family had enough food to eat. They were able to afford everything they needed and more. Though Katniss still hunted, it was to help her friend Gale support his own family. 

On another level, she could no longer hide in the shadows as she had in the past. As a Victor, she would always be a prominent member of society. But the berries at the end of the 74th Hunger Games were viewed as an act of defiance by many members of society. Because of this, Katniss became a pawn in a game that she didn't understand. President Snow threatened her family and friends if she was unable to convince the districts that the berries were the desperate act of a girl in love. All sense of security in her life left as soon as she offered Peeta those berries, and it changed the face of Panem forever.

What are genomic libraries?

What Is a Genomic Library?

Scientists often need to search through all the genetic information present in an organism to find a specific gene. It is thus convenient to have collections of genetic sequences stored so that such information is readily available. These collections are known as genomic libraries.

The library metaphor is useful in explaining both the structure and function of these information-storage centers. If one were interested in finding a specific literary phrase, one could go to a conventional library and search through the collected works. In such a library, the information is made up of letters organized in a linear fashion to form words, sentences, and chapters. It would not be useful to store this information as individual words or letters or as words collected in a random, jumbled fashion, as the information’s meaning could not then be determined. The more books a library has, the closer it can come to having the complete literary collection, although no collection can guarantee that it has every piece of written word. The same is true of a genomic library. The stored pieces of genetic information cannot be individual bits but must be ordered sequences that are long enough to define a gene. The longer the string of information, the easier it is to make sense of the gene they make up, or “encode.” The more pieces of genetic information a library has, the more likely it is to contain all the information present in a cell. Even a large
collection of sequences, however, cannot guarantee that it contains every piece of genetic information.

How Is a Genomic Library Created?

In order for a genomic library to be practical, some method must be developed to put an entire genome into discrete units, each of which contains sufficiently large amounts of information to be useful but which are also easily replicated and studied. The method must also generate fragments that overlap one another for short stretches. The information exists in the form of chromosomes composed of millions of units known as base pairs. If the information were fragmented in a regular fashion—for example, if it were cut every ten thousand base pairs—there would be no way to identify each fragment’s immediate neighbors. It would be like owning a huge, multivolume novel without any numbering system: it would be almost impossible to determine with which book to start and which to proceed to next. Similarly, without some way of tracking the order of the genetic information, it would be impossible to assemble the sequence of each subfragment into the big continuum of the entire chromosome. The fragments are thus cut so that their ends overlap. With even a few hundred base pairs of overlap, the shared sequences at the end of the fragments can be used to determine the relative position of the different fragments. The different pieces can then be connected into one long unit, or sequence.

There are two common ways to fragment DNA, the basic unit of genetic information, to generate a library. The first is to disrupt the long strands of DNA by forcing them rapidly through a narrow hypodermic needle, creating forces that tear, or shear, the strands into short fragments. The advantage of this method is that the fragment ends are completely random. The disadvantage is that the sheared ends must be modified for easy joining, or ligation. The other method is to use restriction endonucleases, enzymes that recognize specific short stretches of DNA and cleave the DNA at specific positions. To create a library, scientists employ restriction enzymes that recognize four-base-pair sequences for cutting. Normally, the result of cleavage with such an enzyme would be fragments with an average size of 256 base pairs. If the amount of enzyme in the reaction is limited, however, only a limited number of sites will
be cut, and much longer fragments can be generated. The ends created by this cleavage are usable for direct ligation into vectors, but the distribution of cleavage sites is not as random as that produced by shearing.

In a conventional library, information is imprinted on paper pages that can be easily replicated by a printing press and easily bound into a complete unit such as a book. Genetic information is stored in the form of DNA. How can the pieces of a genome be stored in such a way that they can be easily replicated and maintained in identical units? The answer is to take the DNA fragments and attach, or ligate, them into lambda phage
DNA. When the phage infects bacteria, it makes copies of itself. If the genomic fragment is inserted into the phage DNA, then it will be replicated also, making multiple exact copies (or clones) of itself.

To make an actual library, DNA is isolated from an organism and fragmented as described. Each fragment is then randomly ligated into a lambda phage. The pool of lambda phage containing the inserts is then spread onto an agar plate coated with a “lawn” or confluent layer of bacteria. Wherever a phage lands, it begins to infect and kill bacteria, leaving a clear spot, or “plaque,” in the lawn. Each plaque contains millions of phages with millions of identical copies of one fragment from the original genome. If enough plaques are generated on the plate, each one containing some random piece of the genome, then the entire genome may be represented in the summation of the DNA present in all the plaques. Since the fragment generation is random, however, the completeness of the genomic library can only be estimated. It takes 800,000 plaques containing an average genomic fragment of 17,000 base pairs to give a 99-percent probability that the total will contain a specific human gene. While this may sound like a large number, it takes only fifteen teacup-sized agar plates to produce this many plaques. A genetic library pool of phage can be stored in a refrigerator and plated out onto agar petri dishes whenever needed.

How Can a Specific Gene Be Pulled Out of a Library?

Once the entire genome is spread out as a collection of plaques, it is necessary to isolate the one plaque containing the specific sequences desired from the large collection. To accomplish this, a dry filter paper is laid onto the agar dish covered with plaques. As the moisture from the plate wicks into the paper, it carries with it some of the phage. An ink-dipped needle is pushed through the filter at several spots on the edge, marking the same spot on the filter and the agar. These will serve as common reference points. The filter is treated with a strong base that releases the DNA from the phage and denatures it into single-stranded form. The base is neutralized, and the filter is incubated in a salt buffer containing radioactive single-stranded DNA. The radioactive DNA, or “probe,” is a short stretch of sequence from the gene to be isolated. If the full gene is present on the filter, the probe will hybridize with it and become attached to the filter. The filter is washed, removing all the radioactivity except where the probe has hybridized. The filters are exposed to film, and a dark spot develops
over the location of the positive plaque. The ink spots on the filter can then be used to align the spot on the filter with the positive plaque on the plate. The plaque can be purified, and the genomic DNA can then be isolated for further study.

It may turn out that the entire gene is not contained in the fragment isolated from one phage. Since the library was designed so that the ends of one fragment overlap with the adjacent fragment, the ends can be used as a probe to isolate neighboring fragments that contain the rest of the gene. This process of increasing the amount of the genome isolated is called genomic walking.

Key Terms



genome

:

all the genetic material carried by a cell




lambda (λ) phage

:

a virus that infects bacteria and then makes multiple copies of itself by taking over the infected bacterium’s cellular machinery




ligation

:

the joining together of two pieces of DNA using the enzyme ligase





Bibliography

Bird, R. Curtis, and Bruce F. Smith, eds. Genetic Library Construction and Screening: Advanced Techniques and Applications. New York: Springer, 2002. Print.

Bishop, Martin J., ed. Guide to Human Genome Computing. 2nd ed. San Diego: Academic, 1998. Print.

Cooper, Necia Grant, ed. The Human Genome Project: Deciphering the Blueprint of Heredity. Foreword by Paul Berg. Mill Valley: University Science, 1994. Print.

Dale, Jeremy, Malcolm von Schantz, and Nick Plant. “Genomic and cDNA Libraries.” From Genes to Genomes: Concepts and Applications of DNA Technology. 3rd ed. Chichester: Wiley, 2012. Print.

Danchin, Antoine. The Delphic Boat: What Genomes Tell Us. Trans. Alison Quayle. Cambridge: Harvard UP, 2002. Print.

Hoogenboom, H. R. “Designing and Optimizing Library Selection Strategies for Generating High-Affinity Antibodies.” Trends in Biotechnology 15.2 (1997): 62–70. Print.

Klug, William S., et al. Essentials of Genetics. 8th ed. Boston: Pearson, 2013. Print.

Primrose, S. B., and R. M. Twyman. “Genomic DNA Libraries Are Generated by Fragmenting the Genome and Cloning Overlapping Fragments in Vectors.” Principles of Gene Manipulation and Genomics. 7th ed. Malden: Blackwell, 2006. Print.

Sambrook, Joseph, and David W. Russell. Molecular Cloning: A Laboratory Manual. 4th ed. Cold Spring Harbor: Cold Spring Harbor Laboratory, 2012. Print.

Sandor, Suhai, ed. Theoretical and Computational Methods in Genome Research. New York: Plenum, 1997. Print.

Watson, James D., et al. Recombinant DNA: Genes and Genomes: A Short Course. 3rd ed. New York: Freeman, 2007. Print.

Who lives with Charlie Bucket?

Charlie Bucket, the protagonist of Charlie and the Chocolate Factory, lives with his parents and both sets of his grandparents in a flat in London. Although the novel is set in the present, in the modern era, the impoverished conditions of Charlie's living situation call to mind a Victorian London, similar to the city portrayed by Charles Dickens in his novels. This is a London where people live in desperate conditions, and something as simple as a bar of chocolate is seen as a luxurious treat.

In the film adaptation called Willy Wonka and the Chocolate Factory, Charlie does not appear to have a father living at home; this underlines his role as the "man of the house" and this portrayal makes his attempt to win the golden ticket even more important, because it is seen as a way to lift his family out of poverty. In the film version as in the novel, Charlie's mother works hard taking care of his grandparents who are all elderly and bedridden, although lively and loving as a family.

Is it possible to die of feeling overjoyed by someone's death?

I would imagine that, if one has an underlying condition such as heart disease, high blood pressure, or the like, it is possible to "die of" any extreme emotion that would aggravate such a condition.  If joy can excite one enough to raise one's blood pressure or increase one's heart rate, then I would think that it is possible to die as a result of that emotion, but we might more likely attribute it to that underlying condition than we would the emotion that triggered it. 

However, one of the great ironies of this story is that Louise Mallard doesn't die of the "joy that kills" when she sees her husband alive, but none of the other characters in the story know this.  Only the reader, who has been privy to her innermost thoughts and feelings during her immediate response to the news that her husband has been killed in a train accident, knows that it isn't joy she's feeling; it's terrible, terrible disappointment because she realizes that the freedom she thought she'd gained is once again out of her reach.

How do body systems interact with each other?

There are 11 different organ systems in the human body and each system must work with all other systems in order to sustain life for the individual. Some work more closely with others, but they all must interact. Some examples include:

Respiratory and Circulatory systems: Your respiratory system includes your airways from your mouth and nose to your lungs. Its major job is to bring in oxygen and release CO2 from your system. Oxygen is needed in every cell of the body in order to use ATP and fuel the body, without it our cells could not take their stored energy sources and actually use the energy. To get the oxygen around our body our alveoli (little popcorn-shaped structures in our lungs) drop it off in capillaries, tiny blood vessels, that surround them. This is where the circulatory system takes over, which includes your blood, blood vessels, and your heart. Your blood is a super highway and a connective tissue, connecting every living cell in the human body. All things, especially oxygen and fuel, are sent along your blood in order to feed the body. The heart pumps the blood around the body and red blood cells carry the oxygen to the cells. As the cells are using up energy, they create carbon dioxide (CO2) which is toxic and needs to be released. The blood picks this up and takes it back to the lungs to be released with your exhales. 

Muscular and Skeletal systems: This one is a bit easier to conceptualize. Your skeleton has many jobs, but one of its biggest is to support your body and give you shape, structure, and to help you move. Your muscles work around joints, or places where 2 or more bones meet, and pull the bones around the joints. This causes your body to move. Without bones to tug at, the muscles would just contract and writhe uselessly. Without muscles to pull on them the bones could not move and would be at the mercy of any outside forces. 

There are many other examples you could use to help understand. A few systems, like the circulatory and the nervous, interact with every system in the body and are completely interconnected. Other systems, like the urinary (excretory) or the lymphatic, may be more paired to one or 2 systems, but they still require other systems to fully perform their functions. Just like in large scale factories or businesses it takes many different departments and parts in order to make sure the operation is working at its best. I hope this helps! 

What are bionics and biotechnology?

Indications and Procedures

Bionics and biotechnology are part of the larger arena of
bioengineering. This broad interdisciplinary field integrates the many disciplines of biology, physics, and engineering for use in the medical sciences, as well as in other areas such as agriculture, chemical manufacturing, environmental studies, and mining. Because of the interdisciplinary nature of these studies, an often-confusing array of terms may be used, such as biochemical engineering, bioelectronics,
biofeedback, biological modeling, biomaterials, biophysics, biomechanics, environmental health engineering,
genetic engineering, human engineering, and medical engineering. When applied to the medical sciences, these various areas of knowledge can be integrated under the headings of bionics and biotechnology when considering the diagnosis, investigation, prevention, or treatment of diseases and damaged biological
systems.

Within the medical sciences, bionics is concerned with applying physics and engineering concepts and methodology to constructing artificial systems, such as organs or limbs, in order to replace damaged or diseased natural systems. To duplicate biological systems and replace them successfully, knowledge of how these systems function biologically, chemically, and mechanically is required. Creating artificial systems has evolved from the making of crude imitations, such as an artificial kidney machine, to the making of sophisticated replicas of the natural system, with the replacement being made in the living organism. While it is necessary to apply physics and engineering knowledge to duplicate these natural systems, the fact that these are natural systems requires the application of biological knowledge to the engineering effort. Some animals have the ability to regenerate lost or destroyed limbs; humans, however, must rely on their ingenuity. Biotechnology is an interdisciplinary field that seeks to replace, if not re-create, nature.

Within the medical sciences, biotechnology is concerned with the manipulation and study of biological systems at the molecular and genetic level. In addition to a basic understanding of how these systems function at these levels, biotechnology is used for practical purposes as well, including noninvasive diagnostic methods, cardiovascular measurements, bio-optics, medical imaging, modeling in physiology, and microsurgical techniques. A significant application is the synthesis of biological products, such as antibiotics, biochemicals used in diagnostic tests, drugs, enzymes, vaccines, and vitamins. This field is also concerned with the manipulation of genetic material to improve this synthetic process, as well as the study of
genetic diseases and the manipulation of the associated genes to prevent or cure these diseases. These kinds of syntheses and studies involve the use of molecules, cells, or genes as raw materials in biological processes that are duplicated under artificial conditions in order to improve or increase the quantities of needed biological products. The techniques and methodologies used to achieve these results are the basis of
the technology. Thus, once again, a thorough knowledge of biology and engineering is needed to understand the natural system and to improve the process by which the natural system works in order to accomplish an imposed artificial result.

Much of this work has been carried out through the use of recombinant DNA technology. Since genes provide the instructions controlling those processes by which biological products are made, it is possible to change the processes, or the rate of the processes, by changing the genes. Through genetic engineering, cell cloning, and other techniques, it is possible to make naturally produced antibiotics, vaccines, vitamins, and other needed biological products rather than duplicating these products with artificial materials using artificial means. Also, the rate at which these products are naturally produced can be increased so that large quantities can be obtained (under natural conditions, these products are produced in extremely small amounts). Another aspect of recombinant DNA technology has to do with diseases that result from biological processes that are improperly controlled by genes at critical points. Genetic engineering is used to replace or correct the genetic structure in order to replace or correct the instructions used to guide the biological process.

There is still much to be learned about biological processes and about the genetic material. It is estimated that there are about 100,000 genes constructed from some 3 billion base pairs. Discovering how these genes interact and the biological processes that each controls is a formidable task. By 2003, the
Human Genome Project had successfully mapped the entire human genetic structure from which all biological processes are controlled, including the flawed ones that cause diseases. Eventually, studies of other genomes, such as those of bacteria and viruses, will treat or prevent diseases and illnesses caused by them as well. This study of genetic material and the use of the tools of proteomics, whereby proteins produced from this genetic material are identified and their functions are elucidated, along with the ongoing study of genetic diseases and of other diseases at the molecular level, will have an increasingly important impact on the overall diagnosis, prevention, and treatment of diseases.

Biotechnology has contributed much to the medical sciences in a relatively short time. It has provided a better understanding of human physiology and an improved fundamental knowledge of disease itself. Knowledge has been gained about the physiological control networks (in part resulting from related studies in cybernetics), the key regulatory agents and processes, the target molecules needed for therapeutic intervention, and the molecular and genetic causes of disease.

With rapid advances in biotechnology, however, the scientific and medical professions are entering sensitive and controversial areas that have raised legal and regulatory concerns. The alteration of genes, the creation of modified organisms, the development of new drugs, the safety and side effects of new biochemicals, the detection of genetic diseases in the fetus, experimental therapies, the ability to clone, the ability to enhance brain functions, and the national and international competition to produce pharmaceuticals are some of the concerns facing medical practitioners, the biomedical industry, government, society, and the individual. These concerns will escalate as biotechnological advances delve even deeper into the molecular and genetic basis of life in order to achieve improved health benefits.

Uses and Complications

Most of the applications of bionics have been centered on replacing damaged or diseased natural systems. Bionic implants, either in development or commercially available, include retinal implants, urinary implants, cochlear implants, hippocampus replacements, larynx implants, and advanced hand replacements.

The learning retinal implant system includes an implant that replaces the function of a defective retina in individuals with retinal degeneration, including, for example, those with retinitis pigmentosa and macular degeneration. A normal retina includes cells that are stimulated by light to produce a signal that is transmitted to the brain and converted into a visual perception. When such cells do not function, vision is affected. A relatively system includes a retinal stimulator implanted in the eye, a pocket processor, and glasses that contain a small camera. The processor includes a microcomputer responsible for translating image data into retinal stimulation commands. Initial studies with four patients using a prototype system, which included all the above components except the camera, have been positive in that the patients were able to see light as well as simple patterns.

The urinary implant is an implantable pacemaker for the bladder. It will be marketed for bladder dysfunctions caused by spinal cord injury. The device allows for urine storage and full bladder control without the use of catheters.

The cochlear implant

is commercially available and consists of an implant that delivers electrical signals to an electrode array. Unlike hearing
aids, which act to amplify sound, the cochlear implant sends sound signals directly to the auditory nerve, thus bypassing the damaged portion of the ear.

A neural interface system is being developed that allows severely motor-impaired individuals to communicate with a computer through their thoughts. The system includes a sensor that attaches to a portion of the brain
and a device that analyzes brain signals. The signals are translated and allow an individual to control a computer cursor. In the future, it is hoped that the device will allow an individual to control other devices, including lights, telephones, and television sets.

Yet another brain implant being developed is a hippocampus replacement. The hippocampus is a portion of the brain that is important, among other things, in learning and memory; it is the first portion of the brain damaged in Alzheimer’s disease. The silicon hippocampus replacement is considered the first prosthesis to replace a damaged area of the brain. In 2007, it was tested in rats, and tests in humans were projected to take place sometime in the near future.

A further application being developed is the implantable artificial electrolarynx

communication system. The system is designed for patients who have had a complete laryngectomy. Approaches will be used to attempt to approximate normal voice and speech production.

The Cyberhand Project is developing a cybernetic prosthesis that is controlled by brain signals. Therefore, the hand will allow amputees to use their thoughts to move it and use it to grasp objects naturally. Additionally, the user will also be able to feel objects with which the device comes in contact.

While there are many applications of biotechnology, some of the more significant ones include the production of pharmaceuticals and biochemicals, the production of monoclonal antibodies, the improved understanding and control of complex diseases such as cancer and Acquired immunodeficiency syndrome (AIDS), and the improved understanding of genetic diseases. Many of the biotechnology techniques and methodologies are still experimental, as are the resulting products (for example, antibodies, drugs, enzymes, vaccines, vitamins, cloned cells, and recombinant DNA). Some are considered useful and practical, but are not yet approved for use.

The production of pharmaceuticals and biochemicals has been one of the most practical outgrowths of biotechnology research. It has produced both the knowledge of what needs to be done to correct a certain disease process and the ability to make the needed corrections. Some diseases result from deficiencies in particular proteins, as is the case with diabetes, hemophilia, and dwarfism. Others result from deficiencies in enzymes that would normally break down other chemicals, thus resulting in an accumulation of these chemicals, such as in Fabry’s, Gaucher’s, and Tay-Sachs disease. Still others result from a lack of cellular control, such as cancers.

It has been possible to produce proteins (insulin for diabetes, factor VIII for hemophilia, and growth hormone for dwarfism), enzymes, and bioregulatory proteins (interferon for cancer). This is done by learning how these proteins are produced naturally and then engineering the cells or biochemical processes that can produce these proteins in quantity. In addition to these various kinds of proteins, other biochemical products can be made, including antibiotics, vaccines, and vitamins. Scientists may produce natural, unaltered biochemicals; altered biochemicals (for improved results); or synthetic versions of the biochemicals.

Monoclonal antibodies are a significant group of naturally produced, unaltered biochemicals. They are highly specific biochemicals used for the diagnosis of infectious diseases, for monitoring cancer therapy, for determining the blood concentrations of therapeutic drugs and hormones, for use in some pregnancy tests, for suppressing immune responses, and, to some extent, for disease therapy (for example, to kill cancer cells). Examples of monoclonal antibodies that have been approved by the Food and Drug Administration (FDA) include those used to treat transplant rejection, macular degeneration, multiple sclerosis, inflammatory diseases (including inflammatory bowel disease, rheumatoid arthritis, psoriasis, and allergy-related asthma), and a wide variety of cancers (including non-Hodgkin’s lymphoma, breast cancer, acute myelogenous leukemia, chronic lymphocytic leukemia, colorectal cancer, head and neck cancers, and non-small-cell lung cancer). While much of this work is still experimental, there is a great potential for the development of highly specific
vaccines and for reagents used in diagnostic tests. In addition to being highly specific, these vaccines and reagents would be free of any biological contamination and tend to be reliably stable at room temperature. The vaccines would also be safer since their production would not require the handling of large quantities of the pathogenic agent (which is how vaccines have traditionally been obtained). Possible uses could involve immunological protection against hepatitis B, herpes simplex, polio myelitis, rabies, and malaria.

Molecular pharmacologists also develop biochemicals from nonhuman sources. In fact, the diversity of animal and plant life in the world is a natural pharmacy of potentially useful biochemicals. Many medicinal plants are already known, and systematic studies of other species are under way. Animals also contribute useful biochemicals. For example, excretions from the skin of tropical frogs have been used to treat skin diseases, diabetic ulcers, eye infections, and cancers. Through the study of fifty species of poison arrow frogs, scientists have discovered more than three hundred chemicals. Biotechnology has made it possible to study natural biochemicals in small amounts and at the molecular level and has provided the necessary techniques and methodologies for using these biochemicals in the study of diseases.

Cancers form a complex group of diseases that continue to defy the best attempts to understand them. A cancer is composed of cells that have proliferated uncontrollably. This response may be caused by a mutated gene, by carcinogenic agents (for example, chemicals or ultraviolet light), or by viruses. Cancers develop in multiple stages that involve different physiological mechanisms. Understanding these mechanisms and the genes and biochemicals that are involved has been possible in large part because of the techniques and methodologies of biotechnology research. Gene therapy is showing great promise for curing some types of cancer.

The same can be said of the efforts to study AIDS. This syndrome is caused by a virus that infects and kills certain kinds of T lymphocytes that are needed to initiate and maintain normal immune system responses; therefore, AIDS is characterized by the occurrence of unusual infections or by Kaposi’s sarcoma (a rare cancer). The nucleotide sequence of the viral genome has been determined through recombinant DNA technology, and the functions of the genes are being characterized. Diagnostic tests to determine if blood is contaminated by the virus have been developed, and efforts are under way to develop a vaccine. The proteins used in these immunological investigations are made in large quantities by genetically engineered microorganisms. Other vaccine studies are concerned with using recombinant DNA technology to disable the AIDS virus genetically (by removing or altering its genes) so that it will
infect and generate protective immunity without actually causing the disease.

Genetic diseases are also beginning to be understood as a result of biotechnology. Many of these diseases are caused by gene mutations that cause the absence of a protein or the production of a defective protein, affecting biochemical processes. Recombinant DNA technology is providing methods of detecting these defects, as well as providing therapies for correcting or replacing them. Many of these defects can even be diagnosed in the fetus and in previously undetectable carriers. Some of the commonly known genetic diseases include Alzheimer’s disease, cystic fibrosis, hemophilia, Huntington’s disease, muscular dystrophy, sickle cell disease, and thalassemia. There are approximately three thousand genetic diseases resulting from single-gene mutations. In addition to studying these numerous mutations, efforts are being made to study diseases associated with specific normal genes (such as the susceptibility for heart attacks by individuals with genes producing specific cholesterol-carrying proteins) and to cure genetic disorders by replacing the mutated gene with a normal gene. This normal DNA acts as a template for production of a certain type of ribonucleic acid (RNA), messenger RNA (mRNA), which acts as a template for production of the normal protein.

One advantage of learning more about common genetic diseases is that more can be learned about normal genomes by comparing them with mutated genomes. These diseases are few in number, however, and much remains to be done. With a map of the human genome (as well as the genome of other animals, plants, bacteria, and viruses), biotechnology, and its usefulness to the medical sciences, will advance significantly. The Human Genome Project has essentially produced a map of the entire human genetic structure, including every gene in the twenty-three chromosome pairs. This accounts for about 100,000 genes with about 3 billion base pairs. In addition, there are about 3 million differences per genome from one individual to another. These differences are responsible for such things as personality differences and inherited diseases. To find and understand some of the rarest disease-causing genes, it is estimated that the differences between the genomes of some 4 billion individuals will need to be studied. This resulting database would strain even state-of-the-art computers, not to mention the researchers who will compile the database.

Study of the differences between the genomes of individuals, and in particular the differences in genes involved in drug metabolism, will be a starting place to provide researchers with a way to overcome adverse reactions to drugs from selected portions of the population by applying the tools of pharmacogenomics, the study of how a person’s genetic makeup (genotype) affects the response to drug treatment. After correlating the differences in the genes with a specific negative response, researchers will then need to determine the genotype of a specific individual and use that information to determine the treatment regime that will be most effective for that individual. Alternatively, such information will allow drugs to be developed that are customized for the population to which the individual belongs.

Although many therapeutic strategies involve replacing a mutated gene with a normal gene, other strategies that are currently being developed use short pieces of DNA, called oligonucleotides, to correct the underlying mutation in the DNA of an individual. For example, single-stranded oligonucleotides that include the correct sequence of nucleotides (the basic components of DNA) are introduced into a living cell and, through a process known as homologous recombination, are exchanged with the defective portion of the genomic DNA. Other methods include use of RNA of the proper sequence to substitute for defective RNA formed from defective DNA. Although these methods ensure a properly functioning protein will be produced, in some cases it is advantageous to stop production of selected proteins in various disease states, such as in various viral infections, cardiovascular disease, or cancer.

RNA may be used to prevent production of specified proteins. For example, using antisense technology, single-stranded RNA or DNA (called the antisense strand) is administered to an individual and binds to a portion of the mRNA that will produce a specified protein. Once bound, it will physically block production of the protein, and the double-stranded molecule formed will then be degraded. Other methods to prevent protein synthesis utilizing RNA include RNA interference. In this method, double-stranded RNA is administered to an individual and it ultimately causes the target mRNA to be degraded, thereby preventing protein production, by a different mechanism than found in antisense technology. Vitravene (fomivirsen) is the first, and presently the only, antisense drug that the FDA has allowed to be marketed. It is used to treat a particular viral infection, cytomegalovirus retinitis, in individuals with AIDS. Many other antisense drugs are currently in various stages of development to treat a variety of other viral infections,
cardiovascular diseases, or cancers, including cancer of the colon, skin, lung, and prostate.

Perspective and Prospects

Artificial limbs have been in use for centuries, but no attempt was made to duplicate natural limbs except in the crudest sense. The use of microorganisms for the production of fermented beverages (such as beer, wine, and vinegar) and food (such as bread) goes back many centuries. Likewise, folk medicine made use of natural biochemicals to treat diseases for many centuries. These traditional processes, however, did not involve an understanding of what was occurring and may only be considered biotechnology by default. The knowledge needed for biotechnology required the development of several scientific disciplines, all of which only occurred after the 1950s, when scientifically understood and controlled processes were developed to produce biological products. It was not until the 1970s that recombinant DNA technology allowed significant advances in the understanding of many molecular and genetic processes.

The advancement of bionics and biotechnology after the 1950s was the result of advances made in related scientific fields during earlier decades, primarily after 1900. These developments included the discovery that enzymes were proteins and the theory of enzyme action; the discovery of the structure and function of vitamins; the discovery of the composition of nucleic acids; the discovery of the structure of carbohydrates; the development of a better understanding of the cellular infrastructure; work on natural and experimentally induced mutation; the study of hereditary metabolic errors; a better understanding of immunology, viral and bacterial diseases, tumors, and cell pathology; the realization that genes were found in the chromosomes; early studies concerning chromosome recombinations and the mechanisms of genetic expression; the ultraviolet analysis of DNA and RNA; the increased use of electron microscopy; the development of the technology involved in the large-scale production of penicillin; and the further development and integration of studies in genetics, biochemistry, and physiology.

The 1950s and 1960s saw important advances in the discovery of the structure of DNA, the breaking of the genetic code, the discovery of how gene actions were regulated, the structure of the gene and of numerous proteins, the discovery and study of numerous hereditary diseases, the development of medical procedures for organ transplants, the evolution of the branch of science known as molecular biology, and the continuing synthesis of discoveries and theories from a variety of scientific disciplines. The 1970s saw the development of technologies that further developed these areas of study, in particular recombinant DNA technology and monoclonal antibody technology. The future will see an increased refinement of these technologies and further developments resulting from the success of the Human Genome Project.

Bibliography

Albertini, Alberto, Claude Lenfant, and Rodolfo Paoletti, eds. Biotechnology in Clinical Medicine. New York: Raven Press, 1987.

Borem, Aluizo, et al. Understanding Biotechnology. Upper Saddle River, N.J.: Prentice Hall, 2003.

Glick, Bernard R., Jack J. Pasternak, and Cheryl L. Patten. Molecular Biotechnology: Principles and Applications of Recombinant DNA. 4th ed. Washington, D.C.: ASM Press, 2010.

Hodge, Russ. The Future of Genetics: Beyond the Human Genome Project. New York: Facts On File, 2010.

McElheny , Victor K. Drawing the Map of Life: Inside the Human Genome Project. New York: Basic Books, 2010.

Murray, Thomas H., and Maxwell J. Mehlman, eds. Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology. New York: John Wiley & Sons, 2000.

Vasil, Indra K. Biotechnology: Science, Education, and Commercialization. New York: Elsevier, 1990.

Walker, Sharon. Biotechnology Demystified. New York: McGraw-Hill, 2007.

Why is Aunt Alexandra so old fashioned in To Kill a Mockingbird?

Aunt Alexandra, Atticus's sister, quickly establishes herself as a conservative, old-fashioned presence in the book. She disapproves of the way Atticus raises his children, especially Scout, and she attempts to "improve" Atticus's parenting style by coming to live with him and his children during the second half of the novel.

In a nutshell, Aunt Alexandra is old fashioned because she is highly preoccupied (one might even say obsessed) with the Finch family lineage. Despite the fact that Atticus is not terribly wealthy, the Finch family actually has a history of distinction in the novel and is known as one of the "good" families of Maycomb (this means that they have historically been wealthy). Atticus hardly seems concerned with the class of his family, but Aunt Alexandra seems anxious to preserve the family's image and maintain a place of distinction in Maycomb's social circles. As such, Aunt Alexandra seems old fashioned because she's obsessed with the past and its outdated class system and social hierarchy.

`int sqrt(x^2 - 9)/x^3 dx` Evaluate the integral

`intsqrt(x^2-9)/x^3dx`

Let's evaluate the integral: Apply integration by parts,

`intuv'=uv-intu'v`

Let `u=sqrt(x^2-9)`

`v'=1/x^3`

`u'=d/dx(sqrt(x^2-9))`

`u'=1/2(x^2-9)^(1/2-1)(2x)`

`u'=x/sqrt(x^2-9)`

`v=int1/x^3dx`

`v=x^(-3+1)/(-3+1)`

`v=-1/(2x^2)`

`intsqrt(x^2-9)/x^3dx=sqrt(x^2-9)(-1/(2x^2))-intx/sqrt(x^2-9)(-1/(2x^2))dx`

`=-sqrt(x^2-9)/(2x^2)+1/2int1/(xsqrt(x^2-9))dx`

Apply the integral substitution `y=sqrt(x^2-9)`

`dy=1/2(x^2-9)^(1/2-1)(2x)dx`

`dy=x/sqrt(x^2-9)dx`

`dy=(xdx)/y`

`=-sqrt(x^2-9)/(2x^2)+1/2int(ydy)/x(1/(xy))`

`=-sqrt(x^2-9)/(2x^2)+1/2intdy/x^2`

`=-sqrt(x^2-9)/(2x^2)+1/2intdy/(y^2+9)`

Now use the standard integral:`int1/(x^2+a^2)dx=1/aarctan(x/a)+C`

`=-sqrt(x^2-9)/(2x^2)+1/2(1/3arctan(y/3))`

Substitute back `y=sqrt(x^2-9)` and add a constant C to the solution,

`=-sqrt(x^2-9)/(2x^2)+1/6arctan(sqrt(x^2-9)/3)+C`

In Shakespeare's Romeo and Juliet, how are the gods seen as charitable in the way they allow certain events to happen?

To be charitable is to be giving. Just as we see in Greek and Roman mythology, the gods in Shakespeare's Romeo and Juliet are takers much more than they are givers. We can interpret at least a couple of moments in the play, however, as instances when the gods charitably give.

One of those instances concerns Romeo and Juliet's wedding night. Act III, Scene 2, opens with Juliet giving a monologue that can be seen as a prayer of petition to the sun god to allow night to arrive faster. The monologue opens with the following request:

Gallop apace, you fiery-footed steeds,
Towards Phoebus' lodging: such a wagoner
As Phaethon would whip you to the west,
And bring in cloudy night immediately (Act III, Scene 2, lines 1-4)

Phoebus is another name for Apollo, the Greek sun god. He was believed to drive the sun east and west using a golden chariot pulled by white horses. According to the myth, prior to taking this role previously held by his father Helios, Phaeton, Apollo's brother, stole the chariot and drove the sun to set in the west very early one morning. Juliet's allusion to Phaethon relays her eagerness for the setting sun so she can have her wedding night. Since her wedding night certainly does come, albeit at the normal hour, we can loosely interpret Apollo as having charitably granted her petition; at any rate, nothing occurred to prevent Juliet from having her wedding night.

Despite this interpretation, the gods still take far more than they give. Specifically, they take many lives. One example of taking can be seen during Romeo's exile. Romeo opens Act 5, Scene 1, by relaying a dream he had of Juliet kissing him, a dream he feels prophecies their union to come. Soon after, though, Juliet's faked death is announced. Unaware she has not actually died, Romeo feels he has been tricked by the gods and exclaims, "Is it even so? Then I defy you stars" (Act V, Scene 1, line 24)! The word stars can be interpreted as another term for fate, and fate is controlled by the gods. By saying he defies the stars, Romeo is saying he is challenging fate, or the gods, meaning he is not going to accept the fate the gods dealt him; he is going to take matters into his own hands by ending his life with his own hands. Romeo's reaction to the news of Juliet's death shows us how he feels the gods have taken from him, not given to him. In addition, Romeo's sentiment that the gods have taken from him leads to real deaths, showing us the gods truly do take lives.

What are astrocytomas?

Related conditions:
Primary brain tumors

Definition:


Astrocytomas, the most common gliomas, are primary malignant brain tumors that can occur in most parts of the brain and occasionally in the spinal cord. As the name implies, astrocytomas are derived from astrocytes nonneural support cells of the central nervous system. The types of astrocytomas based on clinical pathology include pilocytic astrocytoma, fibrillary astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Because astrocytomas are primary brain tumors formed in the brain, they rarely spread to other parts of the body; however, they usually grow rapidly and invade surrounding normal brain tissue and therefore are life-threatening.

Risk factors: Brain tumors are caused by mutated or missing genes that result in abnormal cells. High-dose ionizing radiation used over time to treat brain tumors may on occasion cause secondary tumors. Exposure to certain chemicals such as pesticides, petrochemicals, and formaldehyde, and to electromagnetic fields over time increase the risk of developing astrocytomas.

Etiology and the disease process: Generally, malignant brain tumors are caused by changes in genetic structure due to inherited or environmental factors. It was thought that only 5 percent of primary brain tumors, including astrocytomas, are inherited; however, one study has shown that 80 percent of patients with grade IV astrocytoma (glioblastoma multiforme) had anomalous copies of chromosome 7. Familial clustering of gliomas is also associated with defined inherited tumor syndrome, including Li-Fraumeni syndrome, Turcot syndrome, and the neurofibromatosis I syndrome.

Incidence:
Gliomas of both benign and malignant tumors account for 45 to 50 percent of all primary brain tumors; grade I and II astrocytomas account for 25 to 30 percent of all gliomas. Approximately 13,000 people in the United States die of malignant brain tumors every year, which represents about 2 percent of all cancer-related deaths.

Symptoms: Various symptoms may occur with astrocytomas, which depend largely on the location and size of the tumor. Seizure, focal neurologic deficits such as weakness or speech problems, and headaches are common symptoms. The headaches that are associated with brain tumors are typically worse in the morning and accompanied by vomiting. Sometimes increased pressure on the brain tissue can cause blurred, double, or even loss of vision. Behavioral changes may also follow with changes in mood and general state of well-being.

Screening and diagnosis: Methods of screening and diagnosing astrocytomas include computed tomography (CT) scans, magnetic resonance imaging (MRI), angiograms, X rays of the head and skull, and biopsies. Other brain scans, such as magnetic resonance spectroscopy (MRS), single-photon emission computed tomography (SPECT), or positron emission tomography (PET), provide a gauge of brain activity and blood flow. Brain tumors are graded based on the following criteria: mitotic index (growth rate), vascularity (blood supply), presence of necrotic center, invasive potential (border distinctness), and similarity to normal cells.

Accordingly, astrocytomas can be graded into four levels. Pilocytic astrocytoma are grade I tumors that are slow growing and do not invade the surrounding normal tissue, and are commonly diagnosed in children and young adults. Low-grade astrocytomas, including fibrillary or protoplasmic astrocytomas, are grade II tumors that grow slightly faster than grade I tumors and are invasive, with high incidence in the cerebrums of young adults and in the brain stems of children. Anaplastic astrocytomas are grade III, malignant and invasive tumors that occur in the same location as the low-grade astrocytomas and have a high recurrence rate. Glioblastomas multiforme are grade IV, a malignant type that is by far the most common glioma: Approximately 50 percent of astrocytomas are glioblastomas. The common sites of tumors are cerebral hemispheres in adults and the brain stem in children, and they typically contain more than one cell type.

Treatment and therapy: Treatment options differ according to size, grade, and location of the tumor. Tumors may be removed by craniotomy, an open-skull procedure. They may also be removed by ultrasonic aspiration, in which ultrasonic waves fragment the tumors, which are then aspirated. Alternatively, stereotactic radiosurgery may be performed with a Gamma Knife on benign, malignant, or metastatic tumors that are around 4 centimeters (cm) in size. Chemotherapy may be used as a primary therapy in young children or as an adjuvant after tumor removal with radiosurgery. For pilocytic and fibrillary astrocytomas, complete resection of the tumor is achieved; however, if excision is not possible because of the tumor’s location, chemotherapy is indicated in young children and radiotherapy in adults. The treatment options for anaplastic astrocytoma and glioblastoma multiforme include total resection followed by radiotherapy and chemotherapy after surgery.

Prognosis, prevention, and outcomes: The prognosis and outcome of astrocytomas largely depend on the age of the patient, histological features of the tumor, and degree of neurologic or functional impairment. In low-grade astrocytomas, the mean survival time after surgery is six to eight years with the prognosis depending on whether the tumor undergoes progression to a malignant phenotype. Complete recovery is possible in pilocytic astrocytoma if total resection is achieved, while fibrillary astrocytomas show frequent recurrence. In patients with anaplastic astrocytomas and glioblastoma multiforme, the extent of resection is a prognostic factor; generally, younger patients below the age of forty-five have a better prognosis.

Arjona, D., et al. “Early Genetic Changes Involved in Low-Grade Astrocytic Tumor Development.” Current Molecular Medicine 6 (2006): 645–50. Print.

“Astrocytoma.” American Brain Tumor Association. Amer. Brain Tumor Assn., n.d. Web. 27 Aug. 2014.

Compostella, A., et al. “Prognostic Factors for Anaplastic Astrocytomas.” Journal of Neuro-Oncology 81 (2007): 295–303. Print.

Keating, Robert F., James T. Goodrich, and Roger J. Packer. Tumors of the Pediatric Central Nervous System. 2nd ed. New York: Thieme, 2013. Print.

Kennedy, Benjamin. “Astrocytoma.” Medscape. WebMD, 15 May 2014. Web. 27 Aug. 2014.

Miller, C. R., and A. Perry. “Glioblastoma.” Archives of Pathology and Laboratory Medicine 131 (2007): 397–406. Print.

Robins, H. Ian, et al. “Therapeutic Advances for Glioblastoma Multiforme: Current Status and Future Prospects.” Current Oncology Reports 9.1 (2007): 66–70. Print.

Szeifert, G., et al. “The Role of the Gamma Knife in the Management of Cerebral Astrocytomas.” Progress in Neurological Surgery 20 (2007): 150–63. Print.

What ethnic/social/economic groups moved to the Great Plains? Why did they make this move? What challenges did they face?

The first groups to settle the Great Plains included people in lower economic classes, European immigrants, and African Americans. The main appeal of settling this region was large quantities of cheap land; the 1862 Homestead Act, which was passed to encourage the settlement of this region, made land in the area cheap and available in large quantities. This appealed to those who could not afford land in other states, Europeans whose countries had little unclaimed land to offer, and African Americans who wanted the opportunity to start farms despite generational poverty.

The settlers of the Great Plains often struggled with farming. The climate of the region was not ideal for agriculture; droughts were a common feature of the summer season, and it got very cold in the winter. Additionally, farmers had to break through layers of grass roots in order to plant, and grasshoppers often infected crops.

In Philbrick's Freak the Mighty, what does Max mean by "your basic chunk of chain-link heaven"?

The characters in Philbrick's Freak the Mighty are not luxurious millionaires in the least. Max's grandparents are lower-middle-class citizens who have probably lived in their home for a very long time. As neighborhoods age, they tend to show some wear and tear. The house must be small, too, because Grim made a makeshift bedroom for Max in the basement out of "cheap paneling" and it tends to stink. When Max grows bored with his room, he can go outside to the back yard. Max describes it as follows:

"So finally I get bored in the down under and I'm hanging out in the so-called back yard, your basic chunk of chain-link heaven" (6).

From the tone of this sentence, one can infer that Max isn't impressed with his yard. First, he demonstrates his disappointment by saying the yard is "so-called" because it isn't pretty or anything special to look at. Next, he uses the word "chunk" which suggests that there isn't a lot of space for him there. Finally, he mentions that the yard is framed by a chain-link fence, but in order to throw in a sarcastic twist of verbal irony at the end, he says "heaven." Therefore, the yard is small, probably old, and framed by a chain-link fence. It's not much, but it's all he has.

How does Macbeth's obsession with the witches lead to his downfall?

When Macbeth discovers that he has become Thane of Cawdor just like the witches prophesied, he cannot help but dwell on the other part of the witches' prediction -- whether he will become the king of Scotland or not. However, Macbeth succumbs to the destructive power of his ambitions and takes matters into his own hands. He does not want to wait to become the king lawfully, instead, he is the one who wants to fulfill the witches' prophecy. When he murders Duncan, we observe the beginning of his downfall. On the inside, he quickly becomes an unstable and vulnerable person, afraid he might lose his position as the king of Scotland. The reason for his unsettling thoughts lies in the fact that he feels threatened by the second part of the witches' prophecy, which states that Banquo's descendants will inherit the throne some day. This perturbs Macbeth greatly, and he begins to murder anyone who he thinks may jeopardize his position as the leader of the country.

Impatient to find out what awaits him in the future, he seeks out the witches and demands to find out what will happen. This shows how desperately dependent he has become on the witches because he does not want to allow nature to take its course. He wants to feel safe and immune to any threat and fear. However, his trust in the witches only shows how oblivious he is of the fact that their prophecy has a very destructive effect on him. He takes their words too literally, believing there is no such thing as a man not born of woman or woods that can move.

Although Macbeth is seduced by the witches' prophecy, the witches are not responsible for his downfall. They only sensed how corrupt he can become and encouraged such behavior. However, Macbeth's unbridled ambition is what makes him transform from a valiant and loyal subject to a treacherous and cold-blooded murderer.

In what way is Mr. Underwood's editorial in the Maycomb Tribune similar to Atticus' advice to Jem and Scout when they got their guns in To Kill A...

After Tom Robinson’s death, Mr. Underwood publishes an editorial. When Tom tried to escape, prison guards gunned him down, killing him instantly.

“Mr. Underwood didn't talk about miscarriages of justice, he was writing so children could understand. Mr. Underwood simply figured it was a sin to kill cripples, be they standing, sitting, or escaping. He likened Tom's death to the senseless slaughter of songbirds by hunters and children.” (Ch. 25)

Earlier, Atticus had told the children that it was a sin to kill a mockingbird. Miss Maudie explained why: because they did nothing but make beautiful music for people and "sing their hearts out for us.” They did not damage crops or bother people in any way.

Mr. Underwood’s editorial condemns the guards for their excessive violence. It was not necessary to shoot Tom twelve times—it wasn't necessary to shoot Tom at all. Tom Robinson was like a mockingbird. All he did was live a decent, honest life and help someone in need, like a mockingbird who did nothing but sing. Just as Atticus explained to the children that it was a sin to kill an innocent mockingbird, Mr. Underwood explained to the town it was a sin to kill an innocent cripple.

Tom Robinson was unjustly accused of committing a violent crime. People decided he was guilty before the trial even started, and he ended up dying for an act that was not really even committed. His only ‘crime’ was being an African American man who felt sorry for a white girl and so tried to make her life a little easier.

In "The Inchcape Rock" by Robert Southey, how does the character of Sir Ralph the Rover compare to that of the abbot?

In the poem, the Abbot of Aberbrothok has attached a bell to a buoy to warn sailors of the perilous Inchcape Rock. When mariners hear the bell, they know that they have the abbot to thank for their lives.

In the meantime, Sir Ralph the Rover is a pirate who appears to be completely unlike the abbot. The poem tells us that when Sir Ralph feels the 'cheering power of spring,' it makes him sing and whistle. However, his heart is 'mirthful to excess' and his mirth is 'wickedness.' The pirate is happy when he can commit wicked acts; the spring inspires him not to good works but to acts of sabotage.

Sir Ralph commands his men to row him over to the Inchcape Rock so that he can cut the bell from the 'Inchcape Float.' He is gleeful as he performs this dastardly act, announcing that 'The next who comes to the Rock, / Won’t bless the Abbot of Aberbrothok.' Sir Ralph is unrepentant as he sails away to plunder among the high seas. Soon after he has 'grown rich with plunder’d store,' he then 'steers his course for Scotland’s shore.'

However, because of the stormy sea, Sir Ralph and his men cannot tell where the shore is. Sir Ralph desperately wishes that he could hear the Inchcape Bell. His wish is not answered, of course, as he was the one who has cut the bell from its buoy. The irony is complete when Sir Ralph's vessel dashes itself against the Inchcape Rock; as the ship sinks, Sir Ralph tears his hair and curses in despair. So, while the abbot's chief aim in life appears to be to bring comfort and hope to others, Sir Ralph lived to cause others pain. As a pirate, he excelled in the arts of plunder and mayhem; his actions brought others woe, while the abbot's unselfish actions saved many lives.

Why does Vera ask Mr. Nuttel what he knows about her aunt and family?

Saki, the author, wanted to keep the reader in the dark as to Vera's intentions and motives. The girl seems to be making polite conversation with the visitor. It does not become apparent until much later in the story that Vera wants to be sure of Framton's ignorance of local history before she tells him the ghost story she has in mind. If such a tragedy had really occurred, it would have been known and talked about all over the region.

"Do you know many of the people round here?" asked the niece, when she judged that they had had sufficient silent communion.

"Hardly a soul," said Framton. "My sister was staying here, at the rectory, you know, some four years ago, and she gave me letters of introduction to some of the people here."

Once Vera has gotten the information she has been fishing for, she tells him her whole made-up story about the three hunters who got sucked into a bog exactly three years ago. Saki emphasizes that this young girl is "self-possessed," that is, poised, relaxed, sure of herself. She intends to lose her self-possession when the three hunters will appear outside, headed towards the open window. She will fake an expression of goggle-eyed horror to make it appear to the nervous Framton Nuttel that she is actually seeing ghosts. When her aunt, who has supposedly been waiting for them for three years, announces that she sees her men approaching:

Framton shivered slightly and turned towards the niece with a look intended to convey sympathetic comprehension. The child was staring out through the open window with a dazed horror in her eyes.

The girl's imagination and mischievous spirit have turned this stereotypical English country manor into a house of horrors. Framton flees for his life because he is sure the three returning hunters must be ghosts armed with shotguns. It is only after his flight that the reader is let in on Vera's practical joke. The three hunters are just ordinary men returning from a day's snipe-shooting in the marshes. 

"Here we are, my dear," said the bearer of the white mackintosh, coming in through the window, "fairly muddy, but most of it's dry. Who was that who bolted out as we came up?"

"A most extraordinary man, a Mr. Nuttel," said Mrs. Sappleton; "could only talk about his illnesses, and dashed off without a word of goodby or apology when you arrived. One would think he had seen a ghost."

What are ears?

Structure and Functions

The ear is composed of three parts: the outer ear, the middle ear, and the inner ear. All three parts are involved in hearing, while only the inner ear is involved in balance.

Sound can be thought of as pressure waves that travel through the air. These waves are collected by the fleshy part of the outer ear and are funneled down the ear canal to the eardrum. The eardrum, being a thin membrane, vibrates as it is hit by the sound waves. Attached to the eardrum is the first of the ossicles (the hammer or malleus), which moves when the eardrum moves. The second ossicle (the anvil or incus) is attached to the first, and the third to the second. Therefore, as the first bone moves, the others move also. The base of the third bone (the stirrup or stapes) is in contact with the oval window at the beginning of the inner ear. Movement of the oval window sets up vibrations in the fluid of the cochlea. These vibrations are detected by hair cells. Depending on their position in the cochlea, the
hair cells are sensitive to being moved by vibrations of different frequencies. When the hair of a hair cell is bent by the fluid, an impulse is generated. The impulses are transmitted to the brain via the auditory nerve. The nerve impulses are processed in the brain, and the result is the sensation of sound, in particular the sense of pitch. Thus the three parts of the ear turn sound waves into “sound” by changing air vibrations into eardrum vibrations, then ossicle movement, then fluid vibrations, and finally nerve impulses.

Disorders and Diseases

Each of the three parts of the ear can be affected by diseases that can lead to temporary or, in some cases, permanent hearing loss. Damage to the eardrum, ossicles, or any part of the ear before the cochlea results in conductive hearing loss
, as these structures conduct the sound or vibrations. Damage to the hair cells or to the auditory nerve results in sensorineural hearing loss
. Sound may be conducted normally but cannot be detected by the hair cells or transmitted as nerve impulses to the brain.

Disorders of the outer ear include cauliflower ear, blockage by earwax, otitis externa, and tumors. Cauliflower ear is a severe hematoma (bruise) to the outer ear. In some cases, the blood trapped beneath the skin does not resorb and instead turns into fibrous tissue that may become cartilaginous or even bonelike.

Earwax is secreted by the cells in the lining of the ear canal. Its function is to protect the eardrum from dust and dirt, and it normally works its way to the outer opening of the ear. The amount secreted varies from person to person. In some people, or in people who are continually exposed to dusty environments, excessive amounts of wax may be secreted and may block the ear canal sufficiently to interfere with its transmission of sound waves to the eardrum.

Otitis externa can take two forms, either localized or generalized. The localized form, a boil or abscess, is a bacterial infection that results from breaks in the lining of the ear canal and is often caused by attempts to scratch an itch in the ear or to remove wax. The generalized form can be a bacterial or fungal infection, known as otomycosis. Generalized otitis externa is also called swimmer’s ear because it often results from swimming in polluted waters or from chronic moisture in the ear canal.

Tumors of the ear can be benign (noncancerous) or malignant (cancerous) growths of either the soft tissues or the underlying bone. Bony growths, or osteomas, can cause sufficient blockage, by themselves or by leading to the buildup of earwax, to result in hearing loss.

The middle ear consists of the eardrum, three small bones called the ossicles, and the eustachian tube. The bones of the middle ear move in an air-filled cavity. Air pressure within this cavity is normally the same as the outside air pressure because air is exchanged between the middle ear and the outside world via the eustachian tube. When this tube swells and closes, as it often does with a head cold, one experiences a stuffy feeling, decreased hearing, mild pain, and sometimes ringing in the ears (tinnitus) or dizziness. The middle ear is susceptible to infection, such as otitis media
, because bacteria and viruses can sometimes enter via the eustachian tube. Young children are especially prone to middle-ear infections because a child’s eustachian tubes are shorter and more directly in line with the back of the throat than those of adults. Untreated ear infections can sometimes spread into the surrounding bone (mastoiditis) or into the brain (meningitis).

Fluid in the middle ear during an ear infection interferes with the free movement of the ossicles, causing hearing loss that, although significant while it lasts, is temporary. In other instances, there is the prolonged presence of clear fluid in the middle ear, resulting from a combination of infection or allergy and eustachian tube dysfunction, which itself can result from swelling caused by an allergy. This condition, known as glue ear or persistent middle-ear effusion, can last long enough to cause detrimental effects on speech, particularly in young children. Middle-ear infections can sometimes become chronic, as in chronic otitis media; permanent damage to the hearing can result from the ossicles being dissolved away by the pus from these chronic infections.

During a middle-ear infection, fluid can build up and increase pressure within the middle-ear cavity sufficiently to rupture (perforate) the eardrum
. Very loud noises are another form of increased pressure, in this case from the outside. If a loud noise is very sudden, such as an explosion or gunshot, then pressure cannot be equalized fast enough and the eardrum can rupture. Scuba diving without clearing one’s ears (that is, getting the eustachian tube to open and allow airflow) can also result in ruptured eardrums. Other causes of ruptured eardrums include puncture by a sharp object inserted into the ear canal to remove wax or relieve itching, a blow to the ear, or a fractured skull. Some hearing is lost when the eardrum is ruptured, but if the damage is not too severe, the eardrum heals itself and hearing returns.

The middle ear does not always fill with fluid if the eustachian tube is blocked. In some instances, the middle-ear cavity remains filled with trapped air. This trapped air is taken up by the cells lining the middle-ear cavity, decreasing the air pressure inside the middle ear and allowing the eardrum to push inward. Cells that are constantly shed from the eardrum collect in this pocket and form a ball that can become infected. This infected ball, or cholesteatoma, produces pus, which can erode the ossicles. If left untreated, the erosion can continue through the roof of the middle-ear cavity (causing brain abscesses or meningitis) or through the walls (causing abscesses behind the ear). The symptoms of a cholesteatoma go beyond the symptoms of an earache to include headache, dizziness, and weakness of the facial muscles.

Permanent conductive hearing loss can also result from calcification of the ossicles, a condition called osteosclerosis. Abnormal spongy bone can form at the base of the stirrup bone, interfering with its normal movement against the oval window. Hearing loss caused by osteosclerosis occurs gradually over ten to fifteen years, although it may be accelerated in women by pregnancy. There is a hereditary component.

The inner ear begins at the oval window, which separates the air-filled cavity at the middle ear from the fluid-filled cavities of the inner ear. The inner ear consists of the cochlea, which is involved in hearing, and the labyrinth, which maintains balance.

Disorders of the cochlea result in permanent sensorineural hearing loss. Hair cells can be damaged by the high fever accompanying some diseases such as meningitis. They may also be damaged by some drugs. The largest, and most preventable, sources of damage to the hair cells are occupational and recreational exposure to loud sounds, particularly if they are prolonged. In some occupations, the hearing loss from working without ear protection may be confined to certain frequencies of sounds, while other occupations lead to general loss at all sound frequencies. Prolonged exposure to overamplified music will likewise cause permanent hearing loss at all frequencies. This is more severe and has much earlier onset than presbycusis—the progressive loss of hearing, particularly in the high frequencies, that occurs with normal aging.

The labyrinth is the part of the ear that maintains one’s balance; therefore the major system of disorders of the labyrinth is vertigo (dizziness). Labyrinthitis is an infection, generally viral, of the labyrinth. The vertigo can be severe but is temporary.

With Ménière disease, there is an increase in the volume of fluid in the labyrinth and a corresponding increase in internal pressure, which distorts or ruptures the membrane lining. The symptoms, which include vertigo, noises in the ear, and muffled or distorted hearing especially of low tones, flare up in attacks that may last from a few hours to several days. The frequency of these attacks varies from one individual to another, with some people having episodes every few weeks and others having them every few years. This condition, which may be accompanied by migraine headaches, usually clears spontaneously but in some people may result in deafness.

Diagnostic and Treatment Techniques

The most common ear disorders, outer-ear or middle-ear infections, are diagnosed visually with an otoscope. This handheld instrument is a very bright light with a removable tip. Tips of different sizes can be attached so that the doctor can look into ear canals of various sizes. Infections or obstructions in the outer ear are readily visible. Middle-ear infections can often be discerned by the appearance of the eardrum, which may appear red and inflamed. Fluid in the middle ear can sometimes be seen through the eardrum, or its presence can be surmised if the eardrum is bulging toward the ear canal. In other cases, the eardrum will be seen to be retracted or bulging inward toward the middle-ear cavity. Holes in the eardrum can also be seen, as can scars from previous ruptures that have since healed.

Impedance testing may be used in addition to the otoscope for the diagnosis of middle-ear problems. Impedance testing is based on the fact that, when sound waves hit the eardrum, some of the energy is transmitted as vibrations of the drum, while some of the energy is reflected. If the eardrum is stretched tight by fluid pushing against it or by being retracted, it will be less mobile and will reflect more sound waves than a normal eardrum. In the simplest form, the mobility of the eardrum is tested with a small air tube and bulb attached to an otoscope. The doctor gently squeezes a puff of air into the ear canal while watching through the otoscope to see how well the eardrum moves.

A far more quantitative version of impedance testing can be done in cases of suspected hearing loss. This type of impedance testing is generally administered by an audiologist, a professional trained in administering and interpreting hearing tests. The ear canal is blocked with an earplug containing a transmitter and receiver. The transmitter releases sounds of known frequency and intensity into the ear canal while also changing the pressure in the ear canal by pumping air into it. The receiver then measures the amount of energy reflected back. The machine analyzes the efficiency of reflection at various pressures and prints out a graph. By comparison of the graph to that from an eardrum with normal mobility, conclusions can be drawn about the degree of immobility and, consequently, about the stage of the middle-ear infection. Many pediatricians or family physicians have handheld versions of this instrument, which resembles an otoscope but is capable of transmitting sound and measuring reflected sound intensity.

When an ear infection has been diagnosed, the treatment is generally with antibiotics. For outer-ear infections, drops containing antibiotic or antifungal agents are prescribed. For middle-ear infections, antibiotics are prescribed that can be taken by mouth. The patient is rechecked in about three weeks to ensure that the ear has healed.

In some cases, the ear does not heal, or the fluid in the middle ear does not go away. This can occur if a new infection starts before the ear is fully recovered or if the infecting microorganisms are resistant to the antibiotic used for treatment. In cases of chronic or repeated otitis media, a surgical procedure called a myringotomy can be performed in which a small slit is made in the eardrum to release fluid from the middle ear. Often, a small tube is inserted into the slit. These ear tubes, or tympanostomy tubes, keep the middle ear ventilated, allowing it to dry and heal. In most cases, these tubes are spontaneously pushed out by the eardrum as healing takes place, usually within three to six months. Patients must be cautious to keep water out of their ears while the tubes are in place.

A permanently damaged eardrum—from an explosion, for example—can be replaced by a graft. This procedure is called tympanoplasty, and the tissue used for the graft is generally taken from a vein from the same person. If the ossicles are damaged, they too can be replaced, in this case by metal copies of the bones. For example, when otosclerosis has damaged the stapes (stirrup) bone, hearing can often be restored by replacing it with a metal substitute.

Tumors, osteomas in the ear canal, or cholesteatomas on the eardrum may need to be removed surgically. Surgery may also be needed if infections have spread into the surrounding bone. Bone infections or abnormalities of the inner ear are diagnosed by X-rays or by computed tomography (CT) scans.

For some persons who have complete sensorineural hearing loss, some awareness of sound can be restored with a cochlear implant. This electronic device is surgically implanted and takes the place of the nonexistent hair cells in detecting sound and generating nerve impulses.

Problems of balance may sometimes be treated successfully with drugs to limit the swelling in the labyrinth. Ringing in the ears (tinnitus) is usually resolved when the underlying condition is resolved. In some cases, tinnitus is caused by drugs (large doses of aspirin, for example) and will cease when the drugs are stopped. However, it is difficult to identify the cause of most tinnitus cases, and there is no specific cure.

Doctors who specialize in the diagnosis and treatment of disorders of the ear and who do these surgeries are called otorhinolaryngologists (ear, nose, and throat doctors; also called otolaryngologists). They are medical doctors who have several years of training beyond medical school in surgery and in problems of the ear, nose, and throat.

Perspective and Prospects

The basic anatomy of the ear has been known for some time. Bartolommeo Eustachio (1520–1574), an Italian anatomist, first described the eustachian tube as well as a number of the nerves and muscles involved in the functioning of the ear. An understanding of how the ear functions to discriminate the pitch of sounds, however, was not arrived at until the twentieth century. Georg von Békésy won the Nobel Prize in Physiology or Medicine in 1961 for his work on the acoustics of the ear and how it functions to analyze sounds of varying frequencies (pitch).

Treatment of diseases of the ear has been radically changed by the advent of antibiotics. Older texts describe rupture of the eardrum by middle-ear fluid as a desired outcome of middle-ear infection, one which would ensure that the infection drained and healed, rather than becoming chronic.

Chronic ear infections used to be associated with diseases such as tuberculosis, measles, and syphilis, which themselves became far less common with the widespread use of antibiotics or vaccines. In the past, chronic ear infections were much more likely to result in mastoiditis, or infection of the air spaces of the mastoid bone, requiring surgical removal of the infected portions of the mastoid bone.

Adenoids and tonsils
were frequently removed from patients with recurrent ear infections, as these were thought to be the source of the reinfection. It is now known that these tissues are involved in the formation of immunity to infectious bacteria and viruses. Their removal is not advocated in most circumstances—except, for example, when they are large enough to block the opening of the eustachian tube.

Reconstructive surgery began in the 1950s with the development by Samuel Rosen and others of the operation to free up the calcified stapes bone in cases of otosclerosis. Today, virtually all components of the middle ear can be replaced.

While ear infections used to be much more dangerous, perhaps there is an equal danger today of taking threats to the ears too lightly. Chronic ear infections can still cause permanent hearing loss and may even become life-threatening infections if left untreated. Damage involving the inner ear remains untreatable, as do many cases of tinnitus and loss of balance. Because the largest source of inner ear damage is prolonged exposure to noise, the prevention of damage is far more effective than treatment.

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