What is glycolysis?

Structure and Functions

Glycolysis is the first step in the process that cells use to extract energy from food molecules. Although energy can be extracted from most types of food molecule, glycolysis is usually considered to begin with glucose. In fact, the term “glycolysis” actually means the splitting (lysis) of glucose (glyco). This is a good description for the process, since the glucose molecule is split into two halves. The glucose molecule consists of a backbone of six carbon atoms to which are attached, in various ways, twelve hydrogen atoms and six oxygen atoms. The glucose molecule is inherently stable and unlikely to split spontaneously at any appreciable rate.

When the energy is extracted from a glucose molecule, it is stored, for the short term, in a much less stable molecule called adenosine triphosphate (ATP). The ATP molecule consists of a complex organic molecule (adenosine) to which are attached three simple phosphate groups (see figure).

ATP consists of a five-carbon sugar called ribose, linked on one side to the nitrogenous base adenine and on the other side to a linear chain of phosphate groups. The molecule formed by the attachment of adenine to ribose is called adenosine, and the linkage of three phosphates generates adenosine triphosphate. The first phosphate is attached to the ribose sugar by means of a chemical bond whose energy is no greater than those bonds found anywhere else in the molecule. While the first phosphate is attached by what one could call a “normal” chemical bond, the second and third phosphates are attached by high-energy bonds. These are chemical bonds that require a considerable amount of energy to create. Thus ATP is an ideal energy storage molecule that provides readily available energy for the biosynthetic reactions of the cell and other energy-requiring processes.

When one of the high-energy bonds of ATP is broken, a large amount of energy is released. Usually, only the bond holding the last phosphate is broken, producing a molecule of adenosine diphosphate (ADP) and a free phosphate group. The phosphate group is only split from ATP at the precise moment when energy is required by some other process in the cell. This breaking of ATP provides the energy to drive cellular processes. The processes include activities such as the synthesis of molecules, the movement of molecules, and the contraction of muscle. The third phosphate can be reattached to ADP using energy released from glycolysis, or by other components of cellular respiration. The production of ATP can be diagrammed as follows: “energy from glycolysis + ADP + phosphate → ATP.” Similarly, the breakdown of ATP can be diagrammed as “ATP → ADP + phosphate + usable energy.” With this understanding of how ATP works, one can look at how it is generated in the cell by glycolysis.

The first step in the production of energy from sugar is really an energy-consuming process. Since glucose is inherently a stable molecule, it must be activated before it will split. It is activated by attaching a phosphate group to each end of the six-carbon backbone. These phosphate groups are supplied by ATP. Therefore, glycolysis begins by using the energy from two ATP molecules. The atoms of the glucose molecule are also rearranged during the activation process so that it is changed into a very similar sugar, fructose. A fructose molecule with a phosphate group on either end is called fructose 1,6-diphosphate. Thus one can summarize the activation process as “glucose + 2 ATP → fructose 1,6-diphosphate + 2 ADP.”

Fructose 1,6-diphosphate is a much more reactive molecule and can be readily split by an enzyme called aldolase into two three-carbon compounds called dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). DHAP is converted into G3P by an enzyme called triose phosphate isomerase, which makes G3P the starting point for all the following steps of glycolysis. Each G3P undergoes several reactions, but only the more consequential reactions will be mentioned. G3P undergoes an oxidation reaction, catalyzed by an enzyme called glyceraldehyde 3-phosphate dehydrogenase. Oxidation reactions involve the loss of high-energy electrons. Electrons are highly energetic and have a negative electrical charge. They are picked up and carried by molecules specially designed for this purpose.

These energy-carrying molecules are called nicotinamide adenine dinucleotide (NAD). Biologists have agreed on a conventional notation for this molecule to allow the reader to know whether the molecule is carrying electrons or is empty. Since the empty molecule has a net positive charge, it is denoted as NAD+. When full, it holds a pair of electrons. One electron would neutralize the positive charge, while two result in a negative charge. The negative charge attracts one of the many hydrogen ions (H+) in the cell. Thus when carrying electrons the molecule is denoted NADH. G3P surrenders two high-energy electrons to NAD+. The G3P molecule also picks up a free phosphate group at the end opposite from where one is already attached to form 1,3-bisphosphoglycerate. One can summarize the reaction as “2 Glyceraldehyde 3-phosphate + 2 NAD+ + 2 inorganic phosphates → ? 2 1,3-bisphosphoglycerate + NADH + H+.” The following reactions merely transfer the energy in these chemical bonds to high-energy bonds by transferring these phosphate groups to ADP molecules to produce ATP. Since each G3P eventually produces two ATPs, and two G3Ps are produced from each original glucose molecule, glycolysis produces four ATP molecules all together. However since two ATPs were used to activate the glucose, the cell has a net gain of two ATP molecules for each glucose molecule used.

The rearrangement of the atoms leaves them in a form called pyruvate. Pyruvate still contains much energy locked up in its chemical bonds. In most of the cells of the body and most of the time, pyruvate will be further broken down and all of its energy released. This further breakdown of pyruvate requires oxygen and is beyond the scope of this topic. It should be pointed out, however, that the complete breakdown of two molecules of pyruvate can produce more than thirty additional ATP molecules. With the addition of oxygen, the end products are the simple molecules of carbon dioxide and water.

The oxidative pathways that completely break down pyruvate are limited by the lack of oxygen in very active muscles. The ability to deal with electrons from NADH is also drastically reduced. Glycolysis can continue even in the absence of oxygen, but the electrons produced by glycolysis must be dealt with.

There is a very limited amount of NAD+ in each cell. NAD+ is designed to hold electrons briefly, while they are transferred to some other system. In the absence of oxygen, the electrons are transferred to pyruvate. Since pyruvate cannot be broken down without oxygen, there is an ample supply. Transferring electrons from NADH to pyruvate allows the empty NAD+ to pick up more electrons produced by glycolysis. Therefore, glycolysis can continue producing two ATP molecules from each glucose molecule used. While two ATPs per glucose molecule is a small amount compared to the more than thirty ATPs produced by oxidative metabolism, it is better than none at all.

The process of generating energy (ATPs) in the absence of oxygen is referred to as fermentation. Most people are familiar with the fermentation of grapes to produce wine. Yeast has the enzymes to transfer electrons from NADH to a derivative of pyruvate and to convert the resulting molecule into alcohol and carbon dioxide. No further energy is obtained from this process. Alcohol still contains much of the energy that was in glucose. Humans and other mammals have different enzymes than yeast cells. These enzymes transfer the electrons from NADH to pyruvate, producing lactate.

Glycolysis and Muscle Activity

When yeast is fermented anaerobically (without oxygen), it will continue producing alcohol until it poisons itself. Most yeast cannot tolerate more than about 12 percent alcohol, the concentration found in most wine. The lactate produced by fermentation in humans is also poisonous. People, however, do not respire completely anaerobically. The two ATPs produced per glucose molecule used are simply not enough to supply the energy needs of most human cells. Muscle cells have to be somewhat of an exception. There are times when one asks the muscle cells to use energy much faster than one can supply them with oxygen. One may consider a muscle working under various levels of physical activity and examine its oxygen requirements and waste products.

At rest, a muscle requires very little ATP energy. For an individual sitting on the couch watching television, energy demands are minimal. The lungs inhale and exhale slowly and take in enough oxygen to keep its concentration in the blood high. A relatively slow heart rate can pump enough of this oxygen-rich blood to the muscles to supply their very minimal needs. As soon as one uses a muscle, however, its ATP consumption increases dramatically. Even if an individual simply walks as far as the refrigerator, large quantities of ATP are required to cause the leg muscles to contract. Muscle cells maintain a constant level of ATP so that, as soon as one asks a muscle to contract, it can do so. The ATP that is broken down is almost instantly regenerated from an additional energy store peculiar to muscle cells. Creatine phosphate is a molecule similar to ATP, in that the phosphate group is attached by a high-energy bond. There is more creatine phosphate in muscle cells than ATP. As soon as ATP is broken down, phosphates, and their high-energy bonds, are transferred from
creatine phosphate. Within the first few seconds of activity, the ATP concentration in a muscle cell remains almost constant, but the creatine phosphate level begins to drop.

As soon as the creatine phosphate concentration drops, the aerobic (oxygen-requiring) respiratory processes speed up. These processes break down glucose all the way to carbon dioxide and water and release plenty of ATP. This ATP can then be used for muscle contraction. If the muscle has now stopped contracting, the new ATP produced will be used to rebuild the store of creatine phosphate.

Within the first minute or so of muscle contraction, the use of oxygen can be quite high. The circulatory system has not yet responded to this increased oxygen demand. Muscle tissue, however, has a reserve of oxygen. The red color of most mammalian muscles is attributable to the presence of myoglobin, which is similar to hemoglobin in that it has a strong affinity for oxygen. The myoglobin stores oxygen directly in the muscle, so that the muscle can operate aerobically while the circulatory and respiratory systems adjust to the increased oxygen demand.

At low or moderate muscle activity, the carbon dioxide produced by aerobic respiration in muscles will trigger an increase in the activity of both the circulatory and the respiratory systems. The increased demand for oxygen by the muscles is supplied by an increased blood flow. Jogging around a track or participating in aerobic exercises would be considered low to moderate muscular activity. Respiration rate and pulse rate both increase with jogging. This increase in oxygen supply to the muscles provides all that they need. The level of creatine phosphate will be lower than that in resting muscles, but it will soon be replenished when the activity is stopped. The muscle cells have a good supply of food molecules in the form of glycogen. Glycogen is simply a long string of glucose molecules connected together for convenient storage. At a rate of activity such as that created by jogging, the glycogen supply can last for hours. Even after it is used up, glycogen stored in the liver can be broken down to glucose and carried
to the muscles by the blood. An individual will probably want to stop jogging before his or her muscles will want to quit.

High levels of muscular activity pose a different set of problems. After more than about a minute of vigorous exercise, the muscles begin to use ATP faster than oxygen can be supplied to regenerate it. The additional ATP is supplied by lactic acid fermentation. Glucose is only broken down as far as pyruvate, then converted to lactate by the addition of electrons from NADH. Lactate begins to accumulate in the muscle tissue. Since the body is still using large amounts of ATP but not taking in enough oxygen, it is said to enter a state of oxygen debt. When the muscular activity ends, the oxygen debt is repaid.

One can use an example of someone running to catch a bus, sprinting for fifty yards at full speed. That is not enough time for the circulation and lungs to respond to the increased demand for oxygen. The muscles have made up the difference between supply and demand with lactic acid fermentation. The individual now sits down in the bus and pants—to repay his or her oxygen debt.

Some of the oxygen will go to replenish the store in muscle myoglobin. Some of it will be used in oxidative metabolism in the muscle to replenish the reserves of creatine phosphate. The rest will be used to deal with the accumulated lactate. The lactate is not all dealt with in the muscle where it was produced. Being a small molecule, it easily enters the bloodstream. In muscles throughout the body, it can be converted back to pyruvate. Pyruvate can then reenter the oxidative pathway and be used to generate ATP, with the use of oxygen. The lactate, then, is being used as a food molecule to supply the needs of resting muscle. Much of the lactate is metabolized in the liver. Some of it will be metabolized with oxygen to produce the energy to convert the rest of it back to glucose. The glucose can then be circulated in the blood or stored in the liver or muscles as glycogen. A minimal amount of lactate is excreted in the urine or in sweat.

If the subject of the preceding example kept running at full speed, having missed the bus and run all the way to the office, lactate would build up in the muscles and in the blood. If the office was far enough away, the subject would eventually reach the point of exhaustion and stop running. At that point, the level of lactate in the leg muscles would be high enough to inhibit the enzymes of glycolysis. Glycolysis would slow down so that lactate would not become any more concentrated. The muscles’ supply of creatine phosphate would be almost exhausted, but the ATP supply would be only slightly lower than in a resting muscle. The body is protected from damaging itself: Too much lactate would lower the pH to dangerous levels, and the absolute lack of ATP causes muscles to lock, as in rigor mortis. The body’s self-protection mechanisms force one to stop before either of these conditions exists. Once the subject stops running, and pants long enough, he or she can continue. The additional oxygen taken in by increased respiration will have metabolized a sufficient amount of lactate to allow the muscles to start working again.

In cases where an individual has an inherited deficiency of particular enzymes of glycolysis, the consequences for muscle tissue are rather dire. Muscles, which depend heavily on glycolysis when operating under conditions of oxygen debt, fail to perform well if any of the glycolytic enzymes are defective. Symptoms include frequent muscle cramps, easy fatigability, and evidence of heavy muscle damage after strenuous exertion.

Glycolysis and Red Blood Cell Function

Red blood cells are the oxygen-ferrying units of the bloodstream and are filled with an iron-containing protein called hemoglobin. Hemoglobin binds oxygen tightly when oxygen concentrations are high and releases oxygen when oxygen concentrations are low. To perform their task successfully, red blood cells must maintain the health and functionality of their hemoglobin stores, and glycolysis helps them do that. In red blood cells, approximately 90 to 95 percent of the glucose that enters the cell is metabolized to lactate by means of glycolysis and lactate dehydrogenase. The ATP generated by glycolysis is used to bring charged atoms into the cell such as calcium, potassium, and others. The NADH generated by glycolysis is also used to maintain the iron found in hemoglobin in a state that allows it to bind oxygen. Glycolysis is also used to form the metabolite 2,3-DPG (2,3-Diphosphoglycerate). 2,3-DPG binds to hemoglobin and forces it to release oxygen more readily when oxygen concentrations are low. Thus 2,3-DPG aids hemoglobin delivery of oxygen to the tissues.

Abnormalities in the enzymes that catalyze the reactions of glycolysis are inherited. Individuals who inherit two copies of a gene that encodes a mutant form of a glycolytic enzyme experience uncontrolled destruction of red blood cells (hemolysis). The red blood cell destruction that results from defects in glycolytic enzymes is chronic and not ameliorated by drugs. An enlarged spleen is a typical symptom of glycolytic enzyme abnormalities, as the spleen tends to fill with dying red blood cells. The red blood cell destruction can be so severe that blood transfusions might be necessary. Removal of the spleen reduces red blood cell destruction.

Insulin, Diabetes, and Glycolysis

Glycolysis is heavily regulated by the hormones insulin and glucagon. Insulin, a hormone made and released by the beta cells of the pancreatic islets, stimulates the insertion of the GLUT4 glucose transporter into the membranes of cells. People with type 1 diabetes mellitus, who are incapable of making sufficient quantities of insulin, tend to have very high blood sugar readings, since their cells cannot receive the signal to insert the glucose transporter into their membranes and take up glucose from the blood. This prevents the removal of glucose from the blood, and in type 1 diabetics the blood glucose level climbs to abnormally high levels. GLUT4 allows the uptake of glucose without the input of energy. Therefore, glycolysis occurs as fast as the cells can take up glucose.

Insulin also stimulates the synthesis of a metabolite called fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate is a potent activator of phosphofructokinase, and activation of this enzyme ensures the activation of glycolysis. Insulin also activates the expression of genes that encode the protein involved in glycolysis. During uncontrolled diabetes, reduced glucose transport in muscle inhibits muscle cell glycolysis. In liver cells, reduced glycolytic gene expression and attenuation of the levels of fructose 2,6-bisphosphate reduce glycolysis. This contributes to the voluntary muscle weakness, liver dysfunction, and heart problems that are sometimes observed in diabetics.

Glycolysis and Cancer

The uptake of glucose and its degradation by glycolysis occurs ten times faster in tumor cells than in nontumor cells. This phenomenon, called the Warburg effect, seems to benefit tumor cells, since they lack an extensive capillary network to feed them oxygen and must rely on anaerobic glycolysis to generate ATP.

Oxygen-poor conditions also induce the synthesis of a protein called hypoxia-inducible factor (HIF). HIF is a transcription factor that helps turn on the expression of specific genes that help cells survive oxygen-poor conditions. The synthesis of at least eight glycolytic enzymes are activated by HIF. These fundamental observations of cancer cells have shown that glycolytic enzymes are excellent potential drug targets for anticancer agents.

Perspective and Prospects

Cellular respiration is the process by which organisms harvest usable energy in the form of ATP molecules from food molecules. Lactic acid fermentation is the form of respiration used by human muscles when oxygen is in limited supply. Glycolysis is the energy-producing component of lactic acid fermentation, which is much less efficient than aerobic cellular respiration. Fermentation harvests only two molecules of ATP for every glucose molecule used, while aerobic respiration produces a yield of more than thirty molecules of ATP. Most forms of life will resort to fermentation only when oxygen is absent or in short supply. While higher forms of life such as humans can obtain energy by fermentation for short periods, they incur an oxygen debt that must eventually be repaid. The yield of two molecules of ATP for each glucose molecule used is simply not enough to sustain their high demand for energy.

Nevertheless, lactic acid fermentation is an important source of ATP for humans during strenuous physical exercise. Even though it is an inefficient use of glucose, it can provide enough ATP for a short burst of activity. After the activity is over, the lactate produced must be dealt with, which usually requires the use of oxygen.

Most popular exercise programs focus on aerobic activity. Aerobic exercises do not place stress on muscles to the point where the blood cannot supply enough oxygen. These exercises are designed to improve the efficiency of the oxygen delivery system so that there is less need for anaerobic metabolism. Training programs in general attempt to tune the body so that the need for lactic acid fermentation is reduced. They concentrate on improving the delivery of oxygen to the muscles, storing oxygen in the muscles, or increasing the efficiency of muscular contraction.

Insulin signaling activates glycolysis whereas another pancreatic peptide hormone, glucagon, inhibits glycolysis. Diabetics can suffer from inadequate glycolytic activity in particular organs, which can result in organ dysfunction. Expression of mutant forms of various glycolytic enzymes or supporting enzymes in transgenic mice has elucidated the link between abnormalities in glycolysis and the pathology of diabetes mellitus.

In the 1920s the German biochemist Otto Warburg demonstrated that cancer cells voraciously take up glucose and metabolize to lactate. Glycolysis is very active in cancer cells and helps them flourish under low-oxygen conditions. The development of new glycolytic inhibitors may constitute a new class of anticancer drugs that have wide-ranging therapeutic applications.

Bibliography

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Campbell, Neil A., et al. Biology: Concepts and Connections. 6th ed. San Francisco: Pearson/Benjamin Cummings, 2009.

Fox, Stuart Ira. Human Physiology. 13th ed. Boston: McGraw-Hill, 2013.

Nelson, David L., and Michael A. Cox. Lehninger Principles of Biochemistry. 5th ed. New York: W. H. Freeman, 2009.

Sackheim, George I., and Dennis D. Lehman. Chemistry for the Health Sciences. 8th ed. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2009.

Shephard, Roy J. Biochemistry of Physical Activity. Springfield, Ill.: Charles C Thomas, 1984.

Wu, Chaodong, et al. “Regulation of Glycolysis: The Role of Insulin.” Experimental Gerontology 40 (2005): 894–899.

After Duncan's death, Macbeth says "all is but toys". Explain what his words mean and whether they are sincere.

In Act II, scene 3, Macbeth, having just killed Duncan, observes:

"Had I but died an hour before this chance,

I had lived a blessèd time, for from this instant

There’s nothing serious in mortality.

All is but toys. Renown and grace is dead.

The wine of life is drawn, and the mere lees

Is left this vault to brag of."

Here, Macbeth expresses a fatalistic belief that in killing Duncan, he has robbed his own life of dignity, purpose, and meaning.  He is immediately remorseful, and his words are sincere.  He realizes that he has betrayed his king and country, and in doing so, doomed himself.  "All is but toys" expresses his belief that whatever he will do henceforward will be meaningless and transient. In killing Duncan he has discarded his own fame and respect. Whatever lays in his future will be a brief, trifling amusement. He believes that the best of life, living under Duncan's rule,  is behind him, and that he will never be able to rise to the nobility and morality of the great man he has murdered.  

`a_0 = 7, a_1 = 6, a_3 = 10` Find a quadratic model for the sequence with the indicated terms.

You need to remember what a quadratic model is, such that:

`a_n = f(n) = a*n^2 + b*n + c`

The problem provides the following information, such that:

`a_0 = 7 => f(0) = a*0^2 + b*0 + c =>  c = 7`

`a_1 = 6 => f(1) = a*1^2 + b*1 + c => a + b + c =6`

`a_3 = 10 => f(3) = a*3^2 + b*3 + c => 9a + 3b + c = 10`

You need to replace 7 for c in equation `a + b + c = 6` :

`a + b +7 =6=> a + b = -1`

You need to replace 7 for c in equation `9a + 3b + c = 10:`

`9a + 3b +7 = 10=> 9a + 3b = 3 => 3a + b = 1`

Subtract `a + b =-1 ` from `3a + b = 1` , such that:

`3a + b - a - b= 1 + 1`

`2a = 2=> a = 1`

Replace 1 for a in equation `a + b =-1`  such that:

`1+ b = -1 => b = -2`

Hence, the quadratic model for the given sequence is `a_n = n^2 - 2n + 7.`

What is the tone of the poem "The Emperor of Ice-Cream" by Wallace Stevens?

This is one of Wallace Stevens' best-known short poems. It is very evocative and the imagery is very unusual. It is understood to be a poem about death. The descriptions are very sensual and yet there is a formality and coldness about them. The ice cream of the title is mentioned not only in the phrase "the emperor of ice-cream," but also in the opening lines, "Call the roller of big cigars, the muscular one, and bid him whip in kitchen cups concupiscent curds." The image suggests a muscular man making ice cream (the "curds" suggest milk curdling or thickening); the word "concupiscent" is odd as it refers to sexual desire. This imagery that opens the poem is full of life: muscle, sexuality, smoking, making food. The ice cream may be being prepared for the funeral described, for a woman who will no longer know any of these activities enjoyed by the living.

The repetition of the line ending each stanza, "The only emperor is the emperor of ice-cream," is a rather sad and cynical statement. It may mean that even at an event honoring someone who has died, people really only care about those still living, and the physical pleasures of life. The finality of death is described throughout the poem, but the reference to an "emperor of ice-cream" suggests that we do not think of death or prepare for it properly, and that the rituals we observe after people die are somewhat hollow and selfish.

Personally, I find this poem rather haunting, and also quite depressing, but thought-provoking.

What is the significance of the title of Bharati Mukherjee's story, "The Management of Grief"?

The title "The Management of Grief" encapsulates the plot of a story that is about how people, particularly the main character, Shaila Bhave, manage grief, and yet it is ironic too: it is only when Shaila gives up trying to "manage" and "assess" her situation and accept uncertainty that she is free to move on with her life.

As the story opens, a Canadian social worker named Judith Templeton has been hired to help the Indians who have lost their loved ones in a plane disaster. Her goal is to help them manage their grief: she fully believes grief can be "managed" and will later talk to Shaila about the stages of grief. Judith has little idea what to do, as she freely admits: she has never dealt with a disaster of this magnitude and she doesn't understand the Indian culture of the survivors. She is critical of the ways the Indians manage, calling some of the women "hysterical" and later wondering that some of the men remarry so quickly. When Judith asks Shaila for help in helping people to cope, Shaila responds that "we must all grieve in our own way." 

Shaila tries denial, hoping that somehow her husband and sons managed to survive the plane explosion, and even refusing to identify what obviously must be the photo of her dead son Vinod. As her friend Dr. Ranganathan says, "it is a parent's duty to hope." After she accepts the deaths, she begins to bond with other survivors and she travels to India. In India with her wealthy parents, she realizes that she "flutter[s] between two worlds." 

Shaila finds some comfort and "management" through her faith, in which she communes with the spirits of her dead loved ones. Her dead husband tells her to go on with the work they began together. 

Back in Canada, Shaila continues to try to manage her grief. While "deep in the Toronto winter, grey skies, icy pavements," Shaila tries to "assess my situation, how best to live my life." Some of her Indian friends have literally moved on to Vancouver or to Texas. One "rare, beautiful, sunny day," Shaila walks through a park. She looks through the still barren branches up at "the clear blue sky." Against this clarity of nature, which mirrors the inner clarity she now experiences, she hears the voices of her family a final time, telling her "your time has come ... Go, be brave." At this point, she drops the idea of managing her grief and of needing to "assess my situation." This liberates her: "I do not know where this voyage I have begun will end. I do not know which direction I will take. I ... started walking." 

How does Thoreau use rhetorical questions in his argument in "Civil Disobedience"?

Among other rhetorical devices, Henry David Thoreau makes extensive use of rhetorical questions to further his argument in "Civil Disobedience."  For example, in the second paragraph of the essay, Throeau asks:

This American government- what is it but a tradition, though a recent one, endeavoring to transmit itself unimpaired to posterity, but each instant losing some of its integrity?

This passage highlights a difference that Thoreau identifies between the aims of "American government" not to become "[]impaired" through history and its actual practice which "each instant" impairs "some of its integrity." By setting up this distinction, he sets the stage for his analysis in the paragraph that follows of America's failings.

Several paragraphs later, Thoreau addresses the issue of majority rule and asks a sequence of rhetorical questions:

Can there not be a government in which majorities do not virtually decide right and wrong, but conscience?- in which majorities decide only those questions to which the rule of expediency is applicable? Must the citizen ever for a moment, or in the least degree, resign his conscience to the legislation? Why has every man a conscience, then?

Again, the goal is to point out the difference between the professed aims of government and its actual practice.  Pointing out that "conscience," which ought to guide the "majorities" does not articulate itself in "legislation."  Thus, majority rule fails because of the mediation of the legislative apparatus.

Finally, when honing in on Northern hypocrisy regarding slavery in America, Thoreau inquires:

What is the price-current of an honest man and patriot today?

This question both alludes to the practice of slavery--trafficking in human ownership--through the figure of "the price-current of an honest man" and implies that there are scarcely any "honest [men]" and "patriot[s]" in his antebellum America.  Just like the two other rhetorical questions, Thoreau uses this one to highlight the distance between ideals and reality.

Discuss how, in The Great Gatsby, Jay Gatsby’s dream of attaining Daisy’s affection can be seen as symbolic. How has his pursuit affected him?...

A symbol can be defined as a thing, person or situation which stands for, or signifies, something else. It may be the representation of another person, thing, idea or situation. Gatsby's dream of attaining Daisy is symbolic of the desire to attain the unattainable. As Nick Carraway himself explains in the novel, Daisy became Jay Gatsby's "holy grail."

The grail itself is a symbol of eternal life and happiness. Whoever finds it will experience everlasting joy. This much sought-after object has never been found, even though millions have been spent in searching for it. Many believe that its existence is only a legend. This is exactly what Jay is searching for. Attaining Daisy would ensure his lifelong happiness.

In order to achieve this ideal, Jay does everything he possibly can. Having been born into poverty has made his dream much harder to achieve. However, he does succeed in attaining what he believes are the qualifying criteria to ensure the realisation of his ideal. He becomes enormously wealthy, albeit by way of illegal activities. For example, he becomes involved with characters from the underworld, such as Meyer Wolfsheim, and opens a number of drugstores to conduct an illicit bootlegging business.    

Furthermore, he becomes involved in selling fake or junk bonds which are highly profitable. This ensures the creation of his enormous wealth, which further enables him to build an impressive mansion and buy extremely expensive items such as a lavish car and expensive clothes. It also provides him with the means to throw huge, over-the-top parties every week, in the hope that these will pique Daisy's interest and that she may turn up. He will then get an opportunity to approach her and recreate the past.

When Nick Carraway tells him that he cannot reclaim the past, Jay becomes very upset and insists that 'of course you can.' Nick, however, knows that Jay's dream is an impossible one and it is kept alive by an undefinable, resolute and invincible hope that Jay nurses and nourishes throughout the novel. Nick admires him for this hope.   

Even the reality of his and Daisy's situations does not deter Jay from seeking his ideal. She is married to the enormously wealthy Tom Buchanan, who comes from old money, and she has a child as well. He ignores these facts, and when he and Daisy start a clandestine affair, he is enormously happy. His grail is within his grasp.

Unfortunately, when reality hits home during his confrontation with Tom Buchanan in New York, Jay does not know how to accept it, especially when Daisy tells him that she had loved Tom too. It is as if everything has come crashing down, and he starts talking almost incoherently, but Daisy drifts farther and farther away from him. She is not prepared to leave behind her life of privilege and luxury, no matter what.

Tom Buchanan knows that he has won the battle for Daisy and he confidently allows her to travel with Jay, knowing that nothing his adversary can say or do will take his wife away from him. It is this brief journey that spells the end of Jay Gatsby, for, during their trip home, Daisy drives his car and accidentally kills Myrtle Wilson. In the end, Jay is killed by the vengeful Mr Wilson, who is led to believe, by the malicious Tom, that Jay is responsible for his wife's untimely demise.

Jay Gatsby's unfortunate tale makes us aware of the risks in indulging a fanciful and fantastical ideal. One can dream, but within that dream, one must also be realistic and pragmatic. Jay refused to accept reality and foolishly blundered on, and, in the end, his dream was forced to die even before he did.

Compare and contrast the tragic hero qualities of Brutus and Caesar.

During Julius Caesar’s funeral, Antony repeats, “Brutus is an honorable man.” Though Antony’s intents are ironic, Brutus is, in fact, an honorable fellow. He loves his wife and the Roman Republic, but his strong principles cause him to assassinate one of his closest friends for fear that he will take the throne: “I slew my best lover for the good of Rome.” His ideals are more powerful than friendship.

They also make him ignorant to the manipulations and ill-intentions of Cassius and other senators. Brutus deludes himself into thinking that murder can be done “nicely”: “Let us be sacrificers, but not butchers.” Thus, he is not clear-sighted when it comes to a political assassination. Against the advice of Cassius, he lets Antony live and even speak at Caesar’s funeral, resulting in war and the deaths of the conspirators. Brutus’s downfall and primary characteristic seems to be his sense of honor.

Caesar, on the other hand, is more concerned with strength. He is strong-willed and decisive but subject to overconfidence and hubris. Like Brutus, Caesar also underestimates his ability to be manipulated. Decius says that he can sway Caesar by appealing to his pride: “when I tell him [Caesar] he hates flatterers, / He says he does, being then most flattered.” This independence and desire for power bring about his downfall. The crown entices him, and he describes himself as being superior to other men:

… men are flesh and blood, and apprehensive;
Yet in the number I do know but one
That unassailable holds on his rank,
Unshaked of motion: and that I am he…

This attitude elicits jealousy and fear in his fellow senators. It also draws him to the Capitol on the day of his assassination, in spite of multiple warnings. Caesar tells his wife, “Cowards die many times before their deaths; / The valiant never taste of death but once.” Decius praises and prods Caesar, saying, “If Caesar hide himself, shall they not whisper / 'Lo, Caesar is afraid'?” These compliments and subtle taunts succeed, and Caesar dies that day. Therefore, while Brutus’s weakness seems to be honor, Caesar’s is the need to prove his strength.

What is Gladwell's overall message about success?

Gladwell’s book “Outliers” focuses on the success of those people that succeed far above and beyond the norms of society. His message counters popular theory that success can be attributed to some basic personality traits, ambition and intelligence alone. Gladwell theorizes that success is much more influenced by the conditions under which one is born and raised than by any other element. It is his message that the culture, generation, or family one is born into or raised in, coupled with the life experiences that one has, will likely determine if a person becomes successful on the level of an outlier. At first glance, some of his theories seem to support traditional thought that for example, habits such as hard work can alone determine success. However, Gladwell looks deeper, beyond those habits to what allowed them to develop.

In explaining “The 10,000 Hour Rule,” Gladwell describes that it is not just about putting in the hours of practice or learning through college that make one successful but about having the lifestyle, support or means to put in that much time.

“You can’t be poor, because if you have to hold down a part-time job on the side to help make ends meet, there won’t be time left in the day to practice enough.“ 

What is the relationship between law and psychology?

Introduction

The study of psychology and law, specifically decision making by a jury, is a subset of social psychology. A man might be sitting in his living room watching television when, all of a sudden, a police officer knocks on his door, asks him to step outside, and then informs him that he is being arrested on suspicion of burglary. He claims that he is innocent, but six months later he finds himself on trial for this crime in front of a jury. Should it make any difference to the jury whether he has a good or bad character, whether he is attractive or unattractive, or whether he is white, black, or Latino? The US legal system is designed to yield objective, unbiased decisions based on a set of rules and procedures intended to focus on evidence presented at the trial. Yet Clarence Darrow, one of America’s most famous lawyers, bluntly saw it otherwise: “Jurymen seldom convict a person they like, or acquit one that they dislike. The main work of the trial lawyer is to make a jury like his client, or, at least, to feel sympathy for him; facts regarding the crime are relatively unimportant.” Research in the field of forensic psychology
confirms Darrow’s 1933 statement by indicating that human beings do not always conform to such idealistic principles as complete objectivity. Though moral character, lifestyle, attractiveness, race, and related factors have little, if anything, to do with the evidence presented in a given case, research shows that they nevertheless affect the outcome of both real and simulated trials.

The field of psychology and law is continually expanding. Research has focused on such topics as jury selection and jury functioning, social influence as it occurs in the courtroom, the deterrence value of capital punishment and the length of jail sentences, the validity of expert witnesses, and the effect of memory on eyewitness identifications. These areas of psychological application to the legal arena provide a wealth of information that not only will make people aware of potential problems within the judicial system but also will, it is hoped, help provide solutions to the make system as unbiased and objective as possible.

Jury Psychology

In trying to persuade a jury, a lawyer must discover jury preferences concerning the verdict or the issue to be decided in the case even before the jury is impaneled. Thus, the voir dire examination in which prospective jurors are questioned on their biases or prejudices is of extreme importance. Psychologists have shown in jury research that people decide between alternative explanations of someone else’s behavior by using attitudes already established. These attitudes concern the behavior under evaluation and the person being judged. This psychological insight about the importance of prior attitudes is the basis for trial strategy in general and for specific persuasion strategies and techniques in individual cases. The main objective of jury attitude research is to identify attitudes and values that determine which case facts or issues jurors will find most salient, how they will perceive the evidence gathered on those issues, and how those perceptions are likely to influence their decisions about the case. Moreover, in most research on juror decision making, it was found that jurors’ decisions tend to be determined by groups or clusters of attitudes related to the decision.

An example of a powerful but supposedly irrelevant variable is the moral character or lifestyle of the person on trial. A study by David Landy and Elliot Aronson in 1969 provided support for this claim when people acting as jurors in a simulated courtroom read facts about a negligent homicide case in which a pedestrian was run over and killed on Christmas Eve. Mock jurors read either positive or negative character descriptions of the defendant. In the positive character case, the defendant was described as a widowed insurance adjuster going to spend Christmas Eve with his son and daughter-in-law. In the negative character case, the defendant was described as a janitor, twice divorced, possessing a criminal record, going to spend Christmas Eve with his girlfriend. Mock jurors were asked to judge whether the defendant was guilty or innocent and, if guilty, to decide how many years he should spend in jail. When the person on trial was described as having a positive character, mock jurors sentenced him to two years in jail; when he was described as having a negative character, they sentenced him to five years in jail. This clearly suggests that the lifestyle and moral character of people on trial do dramatically influence jury decisions.

The attractiveness of the person on trial has also been found to affect the verdict reached by jurors. Michael Efran in 1974 wondered whether physical attractiveness might bias students’ judgments of another student who was accused of cheating. He had college students act as school jurors. Students received a photograph of the fellow student and a written description of the cheating case. All students read the same case description. Half had an attractive photograph attached, whereas the other half saw an unattractive photograph. Those with the attractive photograph attached judged the student to be less guilty than did those with the unattractive photograph. For those found guilty of the crime, more severe sentencing was recommended for the less attractive photograph group. Evidence that attractiveness affects jury decision making is found not only in simulated, but also in real court cases. John Stewart in 1980 asked observers to rate the attractiveness of seventy-four male defendants tried in Pennsylvania. When he later examined the court records, he found that the more attractive defendants received the lighter sentences. Once convicted, the more attractive defendants were twice as likely to avoid prison as those who were less attractive.

Although attractiveness often helps, there are circumstances under which good looks can actually hurt a person on trial. In 1975, Harold Sigall and Nancy Ostrove found that when mock jurors judged a woman accused of stealing $2,200 they were more lenient in their sentencing decisions when she was attractive than when she was not. When she was said to have swindled the money by charming a middle-aged man into making a phony investment, however, the beautiful defendant was sentenced more severely than her less-attractive counterpart. Apparently, people react quite negatively toward someone who uses his or her appearance to commit a crime.

The race
of the person on trial also seems to affect the jury decision process. Stewart found that nonwhite defendants were more likely to be convicted than were whites for comparable crimes. Further, the convicted were much more likely to be sent to prison if they were nonwhite than if they were white. Louis Cohen, Laura Gray, and Marian Miller in 1990 had white students act as mock jurors in a burglary case. They all read the same burglary case, but the race of the person on trial varied among black, Latino, and white. When the defendant was black or Latino, a more severe sentence was awarded than when the defendant was white. Although the race of the defendant should theoretically be irrelevant to a court case, it does, in fact, appear to affect the verdict.

Much of the psychology associated with legal decision making is centered on trial tactics or strategy. The key to courtroom persuasion is understanding what jurors feel, know, and believe and providing them with information consistent with those predispositions. Jury persuasion is really strategy that depends on a trial lawyer’s ability to conceive, formulate, and convey information with which a jury will agree. This technique demands sophisticated insight into the complexities of human psychology combined with instincts, judgment, and oratory skills. Lawyers must act as advocates, shaping the argument in a fashion most favorable to their position. The ideas or premises jurors bring with them into the courtroom constitute what psychologists call cognitive structures. Cognition pertains to what people know; cognitive structures consist of what people think they know. Jurors are found to be inflexible because their cognitive structures act as a mechanism through which they admit information consistent with what is already there. Therefore, most jurors strive to reach verdicts that do not conflict with their cognitions (beliefs, attitudes, opinions, or values) at the beginning of the trial. Jurors’ perceptions of the trial process and their ultimate decisions are largely determined by their preexisting cognitions, which interpret, distort, or reinforce the information presented during the trial. In short, jurors view the evidence presented at the trial through their own value systems and the predisposed beliefs that they bring with them into the courtroom.

Attitudes and Value Systems

The main objective of jury attitude research is to identify attitudes and values that determine which facts or issues in the case the jurors will find most salient, how they will perceive the evidence presented to substantiate those issues, and how those perceptions are likely to influence their decisions about the case. Most psychologists agree that attitudes consist of three components: affect, cognition, and behavior. Affect refers to a person’s emotions, feelings, and “gut instincts” about something. Cognition refers to perceiving, thinking about, and interpreting information related to an object, person, or event. Behavior refers to the intention to act in ways that are consistent with an attitude. These three components are closely related. Attitude formation is acquired over time in three ways: It is learned from others, it is developed through experience, or it is the product of self-observation. Attitude salience refers to the strength with which attitudes are held. The way to determine what attitudes jurors hold and the salience of these attitudes is to undertake pretrial research focusing on what kinds of jurors hold which attitudes, their composition, and salience.

Attitudes linked to people’s key values play a significant role in shaping how they react to events both inside and outside the courtroom, including how jurors think and feel about the entire trial process and their decisions. Most attitudes are developed over a lifetime of experience with parents, friends, colleagues, teachers, books, television, and other direct and indirect sources. Attitudes vary in the intensity with which they are held, depending on how closely they relate to some underlying core value. These attitudes are the best predictors of behavior because people tend to act in ways consistent with their values.

Juror profiles based on demographics such as gender, income, age, education, religion, and political preference are desirable because they are readily observable factors. Attitude and personality, however, are said to be better predictors of juror behavior. Affective jurors decide on an emotional rather than a rational basis. They are impulsive decision makers, who often base their decisions on what they see and hear rather than waiting until all the facts have been gathered. They tend to reformulate information until it fits into their previously held worldview or set of conclusions based on how they feel about the matter at issue. They often draw conclusions without reviewing the facts or analyzing witness testimony. Affective jurors are generally deeply devoted to religious principles or philosophies of life. They are often not college educated and conduct business based on how they “feel,” what they believe, and what “ought to be.” Cognitive jurors are orderly and logical decision makers. They seek information and are organized and fastidious. They are methodical list makers who seek out facts and information. They are often college-educated and rely on detailed instruction and precision.

Keys to Persuasion

Understanding what jurors feel, know, and believe and providing them with messages consistent with these predispositions are keys to persuasion in the courtroom. What jurors see and hear in the courtroom depends on what meaning they attach to the information provided and its relevance according to their value systems. Jurors are not computers or automatons that store information and then later retrieve it verbatim. Rather, jurors store information according to their own ideas of its importance. As a general proposition, it is agreed that jurors tend to remember best the information heard first (primacy) and last (recency). Therefore, jurors tend to retain information presented at the beginning and the end of the trial better than information presented during the middle. Jurors generally argue deductively, from the general to the particular, fitting facts to premises as they are received.

Lawyers attempt to reinforce, change, or create some specific attitude, opinion, or behavior in jurors favorable to the position they are advocating. It is a dynamic process involving the relationship between those who attempt to persuade and their audience. For lawyers to be persuasive, they must adjust their strategies and tactics to the characteristics of the jury.

Jury decisions tend not to be completely objective, and factors irrelevant to the evidence presented in the case are often considered. That is, the character, physical attractiveness, and ethnicity of the defendant, as well as other factors such as attitude similarity between the jurors and the person on trial, all seem to impact the jury’s decision-making process, despite the fact that justice should be blind to these extraneous variables.

Although lawyers make use of their clients’ attractiveness, dressing and grooming them appropriately for a court appearance, the idea of a trial as a beauty contest is not an appealing one. Means of diminishing the impact of physical attractiveness on legal decisions need to be established. Some researchers have proposed that attractiveness has been found to be less powerful if a sufficient amount of factual information is presented to the jury, if the judge explicitly reminds the jury of the basis on which the verdict should be reached, and if the jury is presented with transcripts of the testimony rather than being directly exposed to those who testify. These same factors should diminish the subjective impact of race as well.

Words should be free of double or multiple meanings. A. Daniel Yarmey points out that the testimony “Mr. Brown shot Mr. Jones” depends on the witness’s perception, memory, and communications process and ability to relate what was seen and heard. Memory and language overlap. In another example, Yarmey points out that a witness who testifies to “seeing a black face” is drawing on questions of eyesight, how much light was present, the witness’s distance from the scene, other persons present, physical features, an interpretation of what constitutes “blackness,” and other such variable factors. For a jury to accept eyewitness testimony, the credibility of the eyewitness is always at issue. This is also apparent during expert testimony, when the lay jury is asked to determine the relative merit of often technical evidence. Credibility is often a deciding factor, coupled with other considerations. Other factors affecting eyewitness performance include the duration of the event, a stress or fear factor, the age of the witness, the length of the retention interval, postevent information, and the method of questioning. A lawyer who asks a witness to relate “what happened” and then asks questions is often more successful than the lawyer who attempts to draw out facts one by one.

Bibliography

Bradshaw, Brad. The Science of Persuasion: A Litigator's Guide to Juror Decision-Making. Chicago: American Bar Association, Criminal Justice Section, 2011. Print.

Costanzo, Mark, and Daniel Krauss. Forensic and Legal Psychology: Psychological Science Applied to Law. New York: Worth, 2012. Print.

Greene, Edie, and Kirk Heilbrun. Wrightman's Psychology and the Legal System. 8th ed. Belmont: Wadsworth, 2014. Print.

Hastie, Reid, Steven D. Penrod, and Nancy Pennington. Inside the Jury. Union: Lawbook Exchange, 2002. Print.

Kassin, Saul M., and Lawrence S. Wrightsman. The American Jury on Trial: Psychological Perspectives. New York: Hemisphere, 1988. Print.

Landy, David, and Elliot Aronson. “The Influence of the Character of the Criminal and His Victim on the Decisions of Simulated Jurors.” Journal of Experimental Social Psychology 5 (1969): 141–52. Print.

Loftus, Elizabeth F., and James M. Doyle. Eyewitness Testimony. 4th ed. Newark: LexisNexis, 2007. Print.

Loftus, Elizabeth F., and Katherine Ketcham. Witness for the Defense. New York: St. Martin’s, 1992. Print.

Nemeth, C. J. “Jury Trials: Psychology and Law.” Advances in Experimental Social Psychology. Ed. Leonard Berkowitz. New York: Academic Press, 1981. Print.

Ross, David Frank, J. Don Read, and Michael P. Toglia, eds. Adult Eyewitness Testimony: Current Trends and Developments. New York: Cambridge UP, 2007. Print.

Taylor, Lawrence. Eyewitness Identification. Charlottesville: Michie, 1982. Print.

Vinson, Dr. Donald E. Jury Persuasion: Psychological Strategies and Trial Techniques. 3d ed. Little Falls: Glasser LegalWorks, 1996. Print.

Yarmey, A. Daniel. The Psychology of Eyewitness Testimony. New York: Free Press, 1979. Print.

What is vector-borne disease?

Definition

Vector-borne disease is disease caused by microorganisms, such as bacteria,
viruses, or protozoa, that are transferred from one living thing (a host) to
another living thing (a recipient) through a third living thing (a vector).

Types and Examples

With vector-borne disease, the host and recipient can be of the same species; a
well-known example is malaria, in which the parasitic
protozoan is acquired from an infected person by a mosquito during a blood meal
and transferred to another human that the mosquito subsequently feeds on. The host
and recipient also can be of different species. An example is western equine
encephalitis, in which the host is a bird that is infected by the disease-causing
species of arbovirus and the recipient is a horse or a human; as with malaria, the
vector is a mosquito.

Another example of a vector-borne disease is dengue fever,
in which a flavivirus is transmitted from the host to the susceptible person by a
species of mosquito called
Aedes aegypti. Another vector-borne disease, and one that is
spreading in eastern North America, is Lyme disease. Caused by the bacterium
Borrelia burgdorferi, Lyme disease is transmitted from
contaminated animals, such as deer, to humans by the bite of several species of
tick. Although Lyme disease is easily treated early in the infection (when its
hallmark is a bulls-eye pattern at the point of the tick bite), the disease
becomes difficult to treat and is debilitating if not treated promptly. Symptoms
include severe fatigue, joint pain, and heart trouble that can persist for years,
even if diagnosed and treated.

An ancient vector-borne disease is plague. The disease, which is caused by
the bacterium Yersinia pestis, is described in passages of the
Old Testament. Rodents harbor the bacterium. The vector that transmits the
bacterium from rodents to humans is another rat or, more commonly, a flea. Both
can feed on an infected rat and subsequently spread the infection to a human
through a bite. Several types of plague exist, depending on the site of the
infection. Infection of the lungs (pneumonic plague) is almost always fatal within
one week if not treated.

A final example of a vector-borne disease is yellow fever.
Also caused by a flavivirus, the disease is transferred from the host (a species
of monkey) to humans through a mosquito. Yellow fever has caused huge outbreaks in
tropical regions; one notable outbreak occurred during the original construction
of the Panama Canal. Each year, yellow fever sickens several hundred thousand
people and kills an estimated thirty thousand people.

Vector-borne diseases occur worldwide. While some diseases, such as malaria and
yellow fever, are concentrated in tropical equatorial regions of the globe, the
transmission of other diseases can occur in more temperate climates. An example is
mosquito-borne West Nile virus disease. The West Nile virus that causes the
disease also has spread to Canada, where it can be transmitted by mosquitoes
during warmer months and even during the cooler days of spring by mosquitoes that
have survived the cold Canadian winter.

Global warming has led to an increase in territory that is habitable for vectors such as the mosquito. The expanding geographic distribution of malaria has been documented. As global warming continues, vector-borne diseases are expected to continue to expand geographically.

Vector Control

Vector-borne diseases can be treated and even prevented by interrupting the vector-mediated transmission between the infected host and the susceptible person or animal. Treatment and prevention strategies for malaria focus on the mosquito vector. For example, spraying mosquito breeding grounds with insecticide can be an effective control. Indeed, mosquito control now involves the carefully controlled use of dichloro-diphenyl-trichloroethane (DDT).

Another efficient and environmentally friendly means of controlling the mosquito-borne spread of malarial protozoa is the use of mosquito netting (sleeping nets) to protect people at night. Organizations such as World Vision have patron-sponsored campaigns to supply villages in Africa with mosquito netting. Similarly, protective clothing with overlapping upper and lower layers minimizes exposed skin, which is susceptible to a bite from a vector.

A trial prevention program involved the release of laboratory-bred infertile male mosquitoes. Because malaria transmission requires female mosquitoes, it is hoped that the reduced reproductive success resulting from a greater population of infertile males will decrease the numbers of females.

Other treatment and prevention strategies include vaccine development and the use of genetic material (known as morpholino antisense oligonucleotides) to compete with viral genetic material for control of binding sites to host sites, which are critical to the formation of new virus particles.

Organizations including the World Health Organization are promoting
a vector-control program known as integrated vector management, which seeks to
prevent disease transmission and to optimize the environment. An example of this
approach is the rational design of drinking-water delivery systems to reduce the
harmful presence of stagnant water (which is a breeding ground for mosquitoes), to
minimize deforestation, and to optimize the protection of water quality.
Implemented solutions are relevant to a particular region.

Impact

That some infectious agents can be moved from one organism to another by means of another organism (a vector) is critical to disease transmission. Classic examples of this form of transmission are malaria, plague, and yellow fever, which have exacted a huge toll on human life. For example, the number of malaria infections each year is about 500 million, leading to approximately 3 million deaths. Infamously, plague led to millions of deaths worldwide in the fourteenth century. Yellow fever continues to infect hundreds of thousands of people in developing tropical countries each year, despite the existence of a vaccine capable of long-term protection.

Vector-borne diseases are difficult to treat. The vector is mobile and capable of movement over considerable distances. Additionally, as has been clear by the use of insecticides to kill mosquitoes in malaria prevention programs, one can see vector resistance to these compounds. Insects such as mosquitoes have been around for millennia, primarily because of their ready adaptation to change.

To lessen the effects of vector-borne disease, science needs to understand vector habitats, life cycles, and migratory patterns. Global climate change is another major concern in the study of vector-borne disease.

Bibliography

Brower, Vicki. “Vector-Borne Diseases and Global Warming: Are Both on an Upward Swing?” EMBO Reports 2 (2001): 755-757. Examines the medical and political controversy about whether or not warmer global temperatures are increasing the incidence of vector-borne diseases.

Gratz, Norman. Vector- and Rodent-Borne Diseases in Europe and North America: Distribution, Public Health Burden, and Control. New York: Cambridge University Press, 2006. Details diseases that are spread by vectors. Covers the costs to public health and the control and distribution of vector-borne diseases.

Marquardt, William C., ed. Biology of Disease Vectors. 2d ed. New York: Academic Press/Elsevier, 2005. An excellent reference for understanding the role of vectors in the transmission of infectious diseases. Discusses prevention and control strategies and future implications.

Tolle, Michael A. “Mosquito-Borne Diseases.” Current Problems in Pediatric and Adolescent Health Care 39 (2009): 97-140. A thorough review of the life cycles of insects as disease agents. Includes discussion of the diagnoses, treatments, and vaccines for several mosquito-borne diseases. Special focus on the impact of the diseases on pregnant women and on children.

Who was the leader of the French forces in The Last of the Mohicans?

The leader of the French forces in The Last of the Mohicans is the Marquis de Montcalm. Montcalm was a real-life historical figure in the French and Indian War, a general in the French army who accepted the surrender of the British under Colonel George Munro, also a real figure, at Fort William Henry in New York in 1757. In the book, after the surrender, Montcalm essentially allows his Huron allies to massacre the English troops who left the fort under flag of truce. In reality, this does not seem to have been his intent--he actually attempted to stop the massacre. The real-life Montcalm was a very successful and skillful military leader. He would win several more significant victories against the British before his death in the siege of Quebec in 1759. 

When was Homer's Iliad written?

This is a more complex problem than it might appear on the surface as the Iliad was originally an oral composition rather than a written text.

The war between Greece and Troy described in the epic took place roughly in the thirteenth century B.C. in an area of what would now be part of Turkey. The actual causes of the series of wars or skirmishes were probably trade disputes between the Mycenaeans (residents of the Greek mainland) and the Trojans over trade and areas of naval domination.

The Iliad includes many obviously fictional elements (such as the stories of Helen and the gods, the dialogues, the story of Achilles) but also some elements of historical fact, including descriptions of geography and of material culture. In terms of linguistic elements and cultural ones, it is a hybrid, with some elements deriving from Mycenaean language and culture (such as the term wanax for leader, the use of figure-eight shaped shields) and others from archaic Greek culture. 

The story was composed, revised, and handed down orally for many centuries. It probably took something approximating its current shape in the eighth century and was first written down in the seventh century. Our earliest extant papyrus fragments of the Iliad are from the Ptolemaic period (fourth and third century BC) and thus reflect some degree of editorial intervention by Alexandrian scholars. 

What were the social losses and economic gains that occurred when Newfoundland joined the Canadian Confederation?

Newfoundland had long fought to remain independent, first as self-governing from 1855-1934 and then as a British dominion from 1907-1949. In 1948, Newfoundland voted about whether to join the Canadian Confederation. Other groups in Newfoundland wanted the island to be self-governing or to join an economic union with the United States, which had placed several military installations on the island during World War II. The vote was about 52% in favor and about 48% opposed, and Newfoundland became part of the Canadian Confederation in 1949. 

The opposition to joining the confederation was fueled in part by the distinctive identity that many Newfoundlanders felt and that they developed as residents of an island that was separated from Canada. It could be argued that they lost some of this distinctive cultural identity when they joined the confederation, and the modernization that occurred with joining the confederation was detrimental to the culture of some of its outport, or isolated coastal, communities.

However, the island had been suffering economically, particularly during the Great Depression of the 1930s. The island's economy was dependent mainly on fish exports, which provided a poor living a great deal of the time, and the population lacked services such as sufficient medical care. In addition, poverty and malnutrition affected the population because the growing season is short on the island and many types of food need to be imported. During the Great Depression, many people relied on government help when the fish export business declined, and Newfoundland was forced to go from being a dominion to being a colony of Great Britain so that the island could get help. Joining the confederation offered Newfoundland a more secure economic future with generous social programs. Canadian programs played a role in improving medical care and reducing poverty on the island. 

How are each of the Seven Commandments broken?

In Animal Farm, the Seven Commandments represent the animals' utopian dreams after they overthrow Mr Jones in Chapter Two. It does not take long, however, before the commandments are broken by the power-hungry and corrupt pigs. Here is a glimpse of how this happens:

1. "Whatever goes upon two legs is an enemy." This commandment is broken when Napoleon begins trading with the neighbouring humans, Mr Pilkington and Mr Frederick. In addition, by the closing scene of the novel, Napoleon has adopted human dress and walks around on his hind legs.


2. "Whatever goes upon four legs, or has wings, is a friend." Napoleon breaks this rule when he runs Snowball off the farm in Chapter Five and later portrays him as an enemy of Animal Farm. 


3. "No animal shall wear clothes." By the final chapter of the novel, all of the pigs can be seen in human clothing which they have taken from Mr Jones' wardrobe.


4. "No animal shall sleep in a bed." The pigs break this commandment in Chapter Six when they move into the farmhouse to be more comfortable.


5. "No animal shall drink alcohol." Napoleon changes this commandment to include the words "to excess" in Chapter Eight after he drinks whiskey for the first time and suffers from a terrible hangover.


6. "No animal shall kill any other animal." Napoleon breaks this commandment when he brutally slaughters the hens who rebel against him in Chapter Seven.  


7. "All animals are equal." This commandment is famously changed in the final chapter of the book when Napoleon declares that some animals are "more equal than others." This sums up the divide between the pigs, the ruling class, and the other animals on the farm.  

Explain how modern-day values might coincide or not with the Greek values or traditions represented in the Odyssey.

Certainly, one of the biggest values presented by the Odyssey is loyalty. Penelope is extremely loyal to Odysseus, never doubting that he is still alive, and refusing to choose another husband from among her very persistent and aggressive suitors. Odysseus is somewhat less loyal, by our standards, because he does sleep with a few goddesses while he is away from his wife; however, one could make the argument that he could hardly reject the advances of immortal women without dire consequences. We also very much value loyalty today, especially marital fidelity.

Another important value from the Odyssey is the ancient Greek concept of xenia. Xenia refers to the importance of offering hospitality to travelers, a group believed to be under the especial protection of Zeus; it also includes the reciprocity of the guest-host relationship: the host is supposed to offer what he has freely, and the guest is supposed to behave gratefully and not take advantage of what is offered. Today, we don't seem to place the same level of importance on hospitality; in fact, we would likely see it as foolhardy to welcome a stranger into our homes.  For them, it was a religious imperative as well as a necessity in a world that lacked hotels, ATMs and restaurants. Now, if we travel far from our home, we have resources available to us to sustain ourselves; they did not have these resources, rendering hospitality to strangers a great deal more necessary.

In "The Brook" by Alfred Lord Tennyson, how does the brook lose its identity?

I would actually encourage you to see the poem as presenting the opposite idea: that the brook in this poem maintains its identity, asserting itself again and again as something permanent: "For men may come and men may go, / But I go on for ever."

While it's true that the brook shows itself as often changing, sometimes chattering and other times murmuring, sometimes winding and sometimes leaping forward in "a sudden sally," the often-repeated refrain of the poem seems like a very clear insistence of the notion of the brook as a constant, steady entity with a clear and lasting identity. 

If you wanted to argue that the brook does lose its identity, you might focus on the fact that it goes to join the river over and over, and yet it stays a brook. You might interpret this repeated confluence with the larger body of water as multiple endings of the brook's particular journeys. However, this argument is rather untenable. You'll find yourself trying to answer the question of whether the brook is an abstract notion of a brook or whether it is actually the individual set of water molecules that flow from a starting point ("haunts of coot and hern") to an end point ("the brimming river"). That question is a bit tangential to the poem's purpose, which is to explore how the permanent identity and character of the brook provides a humbling juxtaposition to the brevity of human life.

What are two similes from Chapter 7 of the book The Magician's Nephew?

A simile is a means of comparison using the words "like" or "as"; for example, saying, "She hovered like a helicopter." In Chapter 7 of The Magician's Nephew, as Digory tries to sort out what to do about the Witch, who has come into his world, there are more than two similes. I will share a few.

Digory must keep an eye on the front door, to try to stop the Witch before she enters the house. He "must watch the front door like a cat watching a mouse's hole" (90). Next, when the Witch appears, standing on the roof of a hansom, "her eyes shone like fire, and her long hair streamed out behind her like a comet's tail" (93). She whispers to the horse in a way that stirs it up, and "its neigh was like a scream" (93).

Similes are quite important in literature, allowing us to experience something more concretely and at the same time more imaginatively. As we imagine Digory watching over the front door, we get that image of a cat waiting to pounce, and as we think about the Witch, we get a sharper image than if the writer had simply said her eyes shone and her hair blew out behind her.  As we read, these concrete comparisons contribute a great deal to our enjoyment of a story.

What do Tom Sawyer's musings, thoughts, self-analysis, book choices, and decisions show us about what kind of person he is?

Tom Sawyer is a person with a need for fun, but most importantly he is a very compassionate and caring individual.  Tom shows his compassion in his dealings with Becky, Huck, and Aunt Polly.  

When Becky gets in trouble at school for ripping the teacher's book, Tom takes the blame for her and gets in trouble with Mr. Dobbins.  He does this because he is very caring and sensitive.  Simply put, Tom can't stand to see Becky in trouble.  He would rather take the lashes set forth by Mr. Dobbins than allow Becky to get in any trouble at all. 

Tom also shows his compassionate side in his dealings with Huck.  Tom in Huck get in many adventures together, but in the end Tom really is compassionate when he looks out for Huck's well being.  When Huck says he no longer wants to live with Widow Douglass, where he is being cared for well for the first time in his life, Tom convinces Huck to stay with her, as he knows it is best for Huck.  Tom does this through the unconventional method of telling Huck that in order to be in his gang,  he has to be a proper robber, and this means he needs to stay living with the widow.

Tom shows his very compassionate side in his relationship  with Aunt Polly.  When Aunt Polly was sad after Tom disappeared to play pirates, Tom couldn't stand to see her in pain.  This hurt him terribly and he couldn't leave his spying post without giving her a kiss goodbye.  Tom knew that he caused Aunt Polly's pain by disappearing, and this was more pain than the sensitive young man could handle.  

Tom is a very sensitive and compassionate person.  He wants everyone to be happy.  He can't stand to see his friends and family in pain.  He seems to know what is best for them and he uses his compassion to help out his favorite people.

What is syndrome of inappropriate antidiuretic hormone production (SIADH)?

Related conditions:

Dehydration, water intoxication (hyponatremia), electrolyte abnormalities

Definition:
Syndrome of inappropriate antidiuretic hormone (SIADH) was first described by Frederic C. Bartter and William B. Schwartz in 1957 when their patient, diagnosed with oat cell carcinoma, was experiencing symptoms related to a low sodium level. Sodium is an electrolyte that is important for the function of many cells within the body. SIADH occurs when there is an excessive release of antidiuretic hormones (ADH, or vasopressin), which causes an increase in fluid retention by the kidneys.

Risk factors: Patients who have small-cell lung cancer are at high risk for developing SIADH. Other cancers that may place the patient at high risk for developing this syndrome are pancreatic cancer, colon adenocarcinoma, olfactory neuroblastoma, lymphoma, and leukemia. Chemotherapy drugs, pain medications, tricyclic antidepressants, general anesthesia, and other drugs used to treat cancer side effects can also cause SIADH.

Etiology and the disease process: Antidiuretic hormone (ADH) is normally produced in the hypothalamus and stored in the posterior pituitary, which are both located in the brain. ADH is released by the pituitary gland but also can be released from a few cancer tumors. It works with the kidneys to regulate the amount of fluid that either remains in the body or is released in the urine. An increase in ADH can cause the kidney to retain fluid, which in turn causes fluid volume overload and dilutes the sodium as well as other electrolytes in the body.

Incidence: SIADH is the most common cause of euvolemic hyponatremia, which affects up to 30 percent of patients in hospitals. It occurs more frequently in females and older patients.

Symptoms: Symptoms are related more to the sudden changes in the sodium level than to the sodium level itself. Early signs and symptoms of SIADH include weakness and lethargy, confusion, irritability, altered mental status, nausea, vomiting, increased thirst, abdominal cramping, decreased urine output, and weight gain. Unresponsiveness, muscle cramping, and seizures are symptoms of progressively greater sodium deficiency. Normal blood sodium levels are 135 to 145 milliequivalents of solute per liter of solvent (mEq/l). Symptoms usually start occurring when the sodium level in the blood decreases to 120 to 125 mEq/l.

Screening and diagnosis: Initial blood tests should be taken to evaluate sodium levels. The blood test of a patient with SIADH will commonly reveal low serum (blood) sodium levels. Urine levels will show an increase in sodium levels and an increase in osmolarity. Patients will typically show no edema or volume depletion (dehydration). The patient will have normal renal, adrenal, and cardiac function. The decrease in sodium levels can be a slow gradual process or may have rapid onset.

Additional blood tests include a complete blood count, electrolytes, urea, creatinine clearance, glucose, and serum (blood) osmolarity. Urine can also be tested for electrolytes.

Tests that may also be considered are thyroid-stimulating hormone (TSH) levels, cortisol level, and liver function tests (LFTs). A chest X ray and a computed tomography (CT) scan of the head may also be completed to assist with diagnosis.

Treatment and therapy: SIADH will need to be corrected slowly. Sodium levels that rise too quickly can cause central pontine myelinolysis (CPM), a type of nerve damage caused by the destruction of the layer covering the nerve cells in the brain stem. Symptoms of CPM are mental status changes, weak muscles, and cranial nerve abnormalities. There is no known cure.

Patients with SIADH will be assessed by medical personnel to evaluate for any signs of swelling, increase in thirst, intake and output, urine concentration, daily weights, and what they are currently consuming.

Asymptomatic cases are treated by treating the underlying cause. Symptomatic patients will be initially treated by being placed on fluid restrictions that allow for one half to one liter of fluid every twenty-four hours. Patients may also be placed on a high-protein, high-salt diet. Loop diuretics, such as furosemide (Lasix), may be given to help the body excrete more urine while retaining the sodium. Demeclocycline, a form of tetracycline antibiotic, may also be used to increase urine output. Demeclocycline is a pill that stops the kidneys from responding to the increased ADH, allowing the body to excrete large amounts of urine. For more severe cases, hypertonic saline (3 percent saline) is given intravenously to increase sodium levels within the serum. Furosemide can also be given with the hypertonic saline to help balance the fluid levels.

Prognosis, prevention, and outcomes: Outcomes for SIADH are related to the underlying disease. Prompt treatment of the underlying condition may improve the outcomes for the patient. The more rapid the increase of the sodium levels, the higher the risk of mortality. Patients may have to limit fluid intake for an extended period to ensure that the SIADH does not return if the underlying condition does not improve.

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What decisions did Bruno's father make throughout the novel that came with consequences?

Bruno's father makes several important decisions throughout the novel that have dire consequences. The first fateful decision Bruno's father makes is to join the Nazi regime. His decision to join the Third Reich negatively impacts his relationship with his mother. His mother opposes his decision to join such a ruthless regime and support Hitler's extremist views. The last conversation they have ends in an argument with his mother yelling that she is ashamed of him.

Another decision that Bruno's father makes that has disastrous consequences is when he decides to invite Adolf Hitler over for dinner. Adolf assigns him the position of Commandant of the Auschwitz concentration camp. Bruno's father has no choice but to accept Hitler's assignment.

The Commandant's decision to move his family from Berlin to Auschwitz has fatal consequences. His marriage falls apart after his wife begins having an affair with Lieutenant Kotler. Bruno sneaks off into the concentration camp to search for Shmuel's father and tragically loses his life in a gas chamber. Bruno's family moves back to Berlin, and Bruno's father loses his mind and his job by the end of the novel.

When does Westerberg encounter McCandless again?

This question is not as straightforward as it appears.  The reason for that is because Chris McCandless and Wayne Westerberg interact with each other on more than two occasions.  So I can't know exactly which "again" that the question is referring to.  I am going to assume that the "again" is referring to the second time that Westerberg and McCandless see each other.  

Wayne Westerberg owned a grain elevator in Carthage, South Dakota, but every summer he operated a custom combine.  He would follow the harvest north from Texas all the way to the Canadian border.  

In the early fall of 1990, he was wrapping up the season and preparing to return to Carthage.  On September 10, in northern Montana, Westerberg picked up a hitchhiker.  That hitchhiker was none other than Chris "Supertramp" McCandless.  

The two of them drove together into a small town, had a beer together, and chatted for a bit.  McCandless told Westerberg that he was heading for a place several hundred miles down the highway.  Westerberg told him that he could take him part of the way.  When it was time to drop McCandless off, it was raining hard, and Westerberg felt guilty.  Westerberg offered to shelter McCandless for the night, and McCandless agreed.  McCandless ended up staying with Westerberg for three days.  At the end of the three days, McCandless said that he was moving on.  Westerberg told McCandless that he owned a grain elevator in South Dakota and that he would give him work if he ever showed up in Carthage.  

To Westerberg's surprise, McCandless showed up a couple of weeks later.  That, I believe, is the "when" that your question is referring to.  

“Was only a couple of weeks that went by before Alex showed up in town,” Westerberg remembers. He gave McCandless employment at the grain elevator and rented him a cheap room in one of the two houses he owned.

What happens when the children trespass on the Radley property in Harper Lee's To Kill a Mockingbird?

In Chapter 6 of Harper Lee's To Kill a Mockingbird, one of the most important events that occurs during the children's escapade of trespassing on the Radleys' property is that they are heard and pursued by Mr. Nathan Radley.

When they first make it inside of the grounds, they try peering through a window on the side of the house with a broken shutter. Jem and Scout give Dill a boost up to the window sill so he can take a peek inside, but all he can report seeing are curtains and a "little teeny light way off somewhere." Dill then gets the notion to try one of the back windows that they must mount the back porch to see into, and, unfortunately, the steps of the back porch squeak. Jem makes it all the way onto the porch when Scout sees a "shadow of a man with a hat on," moving toward Jem across the porch. The shadow retreats around the side of the house, and the three children make a run for it through the garden to the back of the Radley lot where they came in. Scout narrates that "halfway through the collards [she] tripped; as [she] tripped the roar of a shotgun shattered the neighborhood."

They make it to the fence separating the Radley lot from the schoolyard, and Scout and Dill make it safely under the fence. However, Jem gets his pants caught on the fence and must kick them off to escape the fence. The children then make it safely back into the Finches' back yard, but Jem has no pants. When they walk into the front yard, they see that all of their neighbors are gathered in front of the Radleys' gate, and Jem argues it will look suspicious if they don't join the neighbors to see what the commotion is all about. When Jem is discovered pantless by Miss Stephanie Crawford, the children must think of an excuse. They believe they have gotten away with their excuse of playing strip poker.

Later that night, Jem decides he must go back to try and retrieve his pants to keep Atticus from discovering the truth of what they had been doing. Later, in Chapter 7, we learn that Jem had discovered his pants laying neatly folded on the fence, and the rips had been mended. The tidy condition of Jem's pants gives us our first clue into the true benevolent nature of their neighbor, Arthur Radley, whom the children call Boo Radley.

What is the best synonym for the word "incredulous" as it is used in Doris Lessing’s short story “Through the Tunnel"?

Lessing uses the word "incredulous" just once in her story. Let's look at it in context:

"He sat by the clock in the villa, when his mother was not near, and checked his time. He was incredulous and then proud to find he could hold his breath without strain for two minutes. The words 'two minutes,' authorized by the clock, brought close the adventure that was so necessary to him."

We can tell that, at first, the narrator can't even believe how long he'd held his breath. And then when he realized that his timing was correct--when he did believe his results, since the clock "authorized" them--then he was proud of what he'd accomplished. This is how we can tell from the context that "incredulous" means "unbelieving" or "not believing."

Even outside of this context, the best, simplest synonym for "incredulous" is "disbelieving," "unbelieving," "doubtful," or "skeptical."

By definition, people who are incredulous, or people who show an incredulous reaction or speak incredulously, cannot believe what they are seeing or being told. For example, if you read the first Harry Potter book, Harry is constantly incredulous when he sees magical items for the first time. He can't believe what he's seeing. And if your friend told you that she just won a billion dollars in the lottery, you'd be incredulous: you'd have an incredulous look on your face, or you'd shout "No way!" incredulously.

Here are a couple of good ways to remember the meaning of "incredulous."

First, look at how the roots ("in" + "cred") mean "not" + "believing." This "cred" is the same one you see in "credo," "credit," "credibility," "credential," "street cred," and so on. Any time you see "cred," you know it has to do with belief or trust.

Second, compare and contrast "incredulous" with the much more familiar "incredible." This will help you anchor the word "incredulous" in your mind to something that you already know. What does "incredible" literally mean, besides "amazing"? It means "unbelievable." Incredible things are so awesome or so wacky or so terrible that you can't believe them. So, while "incredible" means "unbelievable," "incredulous" means "unbelieving." Notice how "incredible" usually describes things and events, while "incredulous" usually describes people and their reactions. In other words, you talk about incredible accomplishments, incredible deeds, and incredible facts, but in contrast, you talk about incredulous speakers, incredulous stares, and incredulous silence.

What are some struggles that happen in the story "Through the Tunnel"?

"Through the Tunnel" is not a story for anyone who's claustrophobic or afraid of drowning! It's an intense tale full of danger that's made all the more frightening by its peaceful, happy backdrop. Let's take a look at the individual struggles:

1. Jerry and his mom try to get along well with each other. This is an interpersonal struggle, a struggle to maintain a good relationship. It's a bit awkward. Here's his mom worrying about how she doesn't understand what he wants to do, followed by Jerry feeling guilty about how anxious she is:

"'Why, darling, would you rather not come with me? Would you rather---' She frowned, conscientiously worrying over what amusements he might secretly be longing for, which she had been too busy or too careless to imagine. He was very familiar with that anxious, apologetic smile. Contrition sent him running after her."

2. Jerry struggles to fit in with the older boys who are also swimming at the beach. He desperately wants to be acknowledged and accepted by them:

"To be with them, of them, was a craving that filled his whole body. He swam a little closer; they turned and watched him with narrowed, alert dark eyes. Then one smiled and waved. It was enough. In a minute, he had swum in and was on the rocks beside them, smiling with a desperate, nervous supplication."

3. There's also a struggle to communicate with the other kids. Jerry speaks both French and English, and he struggles to speak meaningfully with the other boys:

"[The other boys] were of that coast; all of them were burned smooth dark brown and speaking a language he did not understand."

4. The main struggle is Jerry's desire to copy the other boys' behavior by swimming down underwater through a tunnel in the rock. This is an extremely dangerous thing to do, and it becomes Jerry's obsessive quest throughout the rest of the story. He succeeds, but it takes a lot out of him mentally and physically--his nose bleeds, his lungs ache. Here he is as the struggle finally ends:

"He lay face down, gasping. He could see nothing but a red-veined, clotted dark. His eyes must have burst, he thought; they were full of blood. He tore off his goggles and a gout of blood went into the sea. His nose was bleeding, and the blood had filled the goggles."