PKR-eIF2α Signaling Mediated Spatial Memory Impairment

PKR-eIF2ÃŽ ± Signaling Mediated Spatial Memory Impairment SUPPLEMENTARY MATERIAL Activated PKR-eIF2ÃŽ ± signaling mediated spatial memory impairment, tau phosphorylation, AÃŽ ² pathology, oxidative stress, selectively synaptic protein loss in mice caused by low levels of Cu Mouse behavior analysis. Morris water maze test: MWM was performed as previously described (PMID:23402899) with minor modifications and the test was performed double blinded according to the standard operation protocol. The MWM consisted of a circular pool (120 cm diameter, wall depth 40 cm) in which all the mice were trained to escape from water by swimming to a hidden platform (2 cm beneath water surface) whose location only be identified by using the visual cures on the inner wall of the pool (Supplementary Fig. 3A). The water and the room temperature were kept at 23 ±1 à ¢Ã¢â‚¬Å¾Ã†â€™. The pool was divided into four quadrants by a computerized tracking software (Huaibei Zhenghua Biologic Apparatus Facilities Limited Company, Huaibei, Anhui, China). The platform was located half-way between the center and the wall in one quadrant and maintained at the same position during all the experiment. The navigation test consisted of 4 training trials per day and 5 consecutive training days. As can be seen in Table 1, mice were released with their heads facing the inner wall of the pool from the four quadrantal locations (N, E, SE, and NW) according the sequence as previous report (Supplementary Fig. 3B) (PMID:17406317), and not allowed to swim and search for the platform more than 60 s, after which they were guided to the platform and allowed to remain on it for 15 s. Each mouse was then returned to its cage for 30 min before its next trial. The latency to reach the hidden platform was recorded. One day or six days after the end of navigation test, mice received a probe test, in which the platform was removed. Mice were released from the NE location and allowed to a 120 s swim to find the previous location of the platform. The swimming path, the time spent in each quadrant, the distance traveled each quadrant, the probe time, the platform crossing number, the total distance traveled, and the average swimming speed was recorded by the computerized tracking software. Y-maze: In order to study the PKR role in exploratory behavior and spatial memory, we performed the Y-maze in the PKR+/+Tg+/- and PKR+/-Tg+/- mice as described previously (PMID: 8986335, 1393562). Response to novelty was tested in a Y-maze, adopting a two-trial procedure in this test. The apparatus was equipped with black materials with three identical arms each 50 cm long, 16 cm wide, and 32 cm high. Visual cues made from colored paper with different symbols and the floor of the maze was covered with soiled animal bedding (Beta wood chips). All the mice was performed with starvation treatment for 24h before Y-maze. In trial 1, one arm was blocked with black Plexiglas and referred to as the â€Å"novel† arm in Trial 2. The remaining two arms were designated as the ‘start’ arm and â€Å"other† arm respectively. Three arms were randomized between mice (but not for the same mouse) to reduce arm bias effects. At the start of testing, a mouse was placed in the start arm and was allowed to explore the start and other arms for 10 min (acquisition trial). At the end of Trial 1, the mouse was returned to its home cage and the bedding inside the maze was mixed to reduce the possibility of using odors as a cue. After an intertrial interval (ITI) of 1 h, the mouse was placed in the same start arm as in Trial 1. The previously blocked arm was opened in Trial 2 and the mouse was allowed to investigate all three arms for 5 min (recall trial). The dependent variables measured in Trial 2 were: (1) the amount of time spent in each arm for each minute; (2) the number of entries made into each arm for each minute (Entry). Those indexs reflect inquisitive behavior (i.e. response to novelty) and spatial recognition memory of the previously unvisited arm. Step-down test: This test was used to measure inhibitory avoidance and short-term memory, according to the previously described method (PMID: 24678498). The apparatus comprised a plastic chamber (12x12x18cm) with an elevated rubber platform (4.84.84.5cm) placed on the left side wall. The floor was made of caliber stainless steel bars (0.1cm in length) placed in parallel, 0.5cm apart. On the first training day, mice were exposed to a 5-min learning course, if the animals stepped down from the platform, they were exposed to an electric foot shock (36V, AC). After 24h, latency was reassessed and recorded as the learning grade (latency), which was taken as a measure of memory retention. Each acquisition trial was performed 5min in the PKR+/+Tg+/- and PKR+/-Tg+/- mice. Supplementary Table 1. Primary antibodies used for protein immunodetection in western blot analysis (WB), immunohistochemistry (IHC) and immunofluorescence (IF). Antigen Supplier Application PAGE (%) Species origin Incubation conditions Ab dilution 8-OhdG US Biological, H9076-02 IF N/A Goat 10% NGS, 12h, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:200 acetylated-ÃŽ ±-Tubulin Santa Cruz, sc- 23950 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:5000 APP Cell signaling, #2452 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 AT8 Thermo, MN1020B WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 ATF-4 Abcam, ab50546 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 ATF-4 Abcam, ab50546 IF N/A Mouse 10% NGS, 12h, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:100 AÃŽ ²42 Abcam, ab10148 IHC N/A Rabbit 10% NGS, 12h, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:100 BACE-1 Abcam, ab2077 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 CCS Abcam, ab16962 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:100 CHOP Cell signaling, #2895 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 CREB Cell signaling, #9197 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 complexin-1/2 Santa Cruz, sc-33603 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 Cp Abcam, ab48614 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 Drebrin Cell signaling, #12243 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 eIF2ÃŽ ± Cell signaling, #5324 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 GSK-3ÃŽ ² Cell signaling, #9315 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 JNK Cell signaling, ##9252 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 Nitro-Tyrosine Cell signaling, #9691 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 NR2A Molecular Probes, A-6473 WB 8 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:500 NR2B Molecular Probes, A-6474 WB 8 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:500 PKR (N-Term) GenWay Biotech, GWB-A4757E WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:500 p-PKR (Thr 451) Invitrogen, 44668G WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:500 p-eIF2ÃŽ ± (Ser51) Cell signaling, #3398 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 p-GSK-3ÃŽ ² (Ser9) Cell signaling, #9336 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 p-CREB (Ser133) Cell signaling, #9198 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 p-JNK Cell signaling, #4671 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 p-PP2A Epitomics, 1155-1 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PP2A C subunit Epitomics, 1512-1 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PS396 Invitrogen, 44752G WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PS404 Invitrogen, 44-758G WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PSD-93 Cell signaling, #9445 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PSD-95 Cell signaling, #2507 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 PSD-95 Cell signaling, #2507 IF N/A Rabbit 10% NGS, 12h, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:100 synapsin 1 Invitrogen, 51-5200 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 sAPPÃŽ ± Covance, SIG-39139 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 sAPPÃŽ ² Covance, SIG-39138 WB 10 Rabbit 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 Tau-1 Chemicon, MAB3420 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:1000 Tau-5 Abcam, ab80579 WB 10 Mouse 5% skim milk, 2h, O/N, 4à ¢Ã¢â‚¬Å¾Ã†â€™ 1:500 ÃŽ ±-tubulin Santa Cruz, sc-58667 WB 8-10 Mouse 5% skim milk, 2h, O/N, RT 1:1000 ÃŽ ²-actin Santa Cruz, sc-47778 WB 10 Mouse 5% skim milk, 2h, O/N, RT 1:1000 N/A, not applicable; NGS, normal-goat serum; O/N, over-night; RT, room temperature. SUPPLEMENTARY FIGURES Supplementary Figure 1. Content of Cu in Serum and brain. (A-D) Total iron, zinc, calcium, magnesium content in the serum respectively; (E-H) Total iron, zinc, calcium, magnesium content in the hippocampus respectively; (I-L) Total iron, zinc, calcium, magnesium content in the cortex respectively; *P

The Tragic Impermanence of Youth in Robert Frosts Nothing Gold Can Sta

The Tragic Impermanence of Youth in Robert Frost's Nothing Gold Can Stay In his poem "Nothing Gold can Stay", Robert Frost names youth and its attributes as invaluable. Using nature as an example, Frost relates the earliest green of a newborn plant to gold; its first leaves are equated with flowers. However, to hold something as fleeting as youth in the highest of esteems is to set one's self up for tragedy. The laws of the Universe cast the glories of youth into an unquestionable state of impermanence. It is an inescapable fact that all that is born, pure and clean, will be polluted with age and die. The aging process that Frost describes is meant to be taken literally as well as metaphorically. Literally, the plants that Frost describes are an example of this nonexclusive law of aging. This prooving through common natural phenomenom the tangible and scientific merit of the poem. There is also a spiritual understanding. Frost uses a religious allusion to further enforce the objective of the poem.Whether Frost's argument is proven in a religious or scient ific forum, it is nonetheless true. In directly citing these natural occurrences from inanimate, organic things such as plants, he also indirectly addresses the phenomena of aging in humans, in both physical and spiritual respects. Literally, this is a poem discribing the seasons. Frosts interpertation of the seasons is original in the fact that it is not only autumn that causes him grief, but summer. Spring is portrayed as painfully quick in its retirement; "Her early leaf's a flower,/ But only so an hour.". Most would associate summer as a season brimming with life, perhaps the realization of what was began in spring. As Frost preceives it however, from the moment spring... ...f impurity. In Christianity it is called sin. The fact that pollution of the soul is a concept in religion the world over is a testament to the Universal nature of Frosts argument. Frost's poem addresses the tragic transitory nature of living things; from the moment of conception, we are ever-striding towards death. Frost offers no remedy for the universal illness of aging; no solution to the fact that the glory of youth lasts only a moment. He merely commits to writing a deliberation of what he understands to be a reality, however tragic. The affliction of dissatisfaction that Frost suffers from cannot be treated in any tangible way. Frost's response is to refuse to silently buckle to the seemingly sadistic ways of the world. He attacks the culprit of aging the only way one can attack the enigmatic forces of the universe, by naming it as the tragedy that it is.

Biography of Franklin Delano Roosevelt Essay

The 32nd president of the United States, Franklin Delano Roosevelt, accomplished many things during his three terms in office. Being the only president ever elected to more than two terms, it is easy to suppose that he was a well-rounded president. His leadership, success in getting programs passed, management of economic and domestic policy, foreign policy, and role as Chief Party Leader all contribute to an overall grade of an A for his presidency. First off, as the symbol of the country and the presidency, Franklin Delano Roosevelt gets an A. He showed great character and leadership with his thirty â€Å"fireside chats† on the radio. With these, he was able to soothe the thirty five million people listening. It was successful too, in that, after his first in which he assured the safety of keeping money in a reopened bank, confidence was restored and the banks began to open up. His ability to master the press contributed strongly to his overall public opinion and showed he had good character. Also, in WWII conferences such as Casablanca and Teheran, Roosevelt represented the country well in his efforts with the Allies to stop Nazi Germany. His leadership of the country and his character are the reason that he was the only president ever to be elected to four consecutive terms as the leader of the country. Particularly with the New Deal, FDR was rather successful as a policy and legislative leader. With the nation in the midst of the Great Depression, there was a lot of pressure on the president to take immediate action. Beginning with â€Å"the first hundred days,† Roosevelt shut down the banks and met with Congress. He was able to get 15 major bills approved regarding the economy in attempts to get it back on track. With such turmoil happening in the country, FDR was very efficient in getting bills passed by Congress, which is why he deserves an A. Though the actual success of each program may be questioned, his quick action and role as a policy and legislative leader was executed well. The same is true for when the United States became involved in WWII. This situation again demanded quick action and Roosevelt pulled through by passing various acts such as the Lend Lease Act and Neutrality Acts. Though again these may not have always had the best outcomes, his initiative and f air thinking are what gets him an A for this category. FDR’s most noted domestic policies while in office were those of the New Deal. With a nation pressuring the president for change, Roosevelt developed a plan called the New Deal. The principal acts were done during his first hundred days, as mentioned earlier, in attempts to achieve his goals of relief, recovery, and reform. Regarding the economy, Congressed passed the Glass-Stegall Banking Act which established the FDIC, a very important act after the crises leading up to the Great Depression. By stopping the bank runs, he was able to steer the economy in the right direction, creating a corporation that is still used today. In addition, under his presidency, the Civilian Conservation Corps (CCC) was established, giving jobs to young men while at the same time conserving both human and natural resources. With the young men being able to send the money back to their families, it was a way to decrease unemployment and boost the economy. Another important issue was his repeal of t he Prohibition through the 21st amendment. This gave much needed revenue to the country and provided employment. Despite these successful acts of domestic policy, Roosevelt was not always so brilliant. The Agricultural Adjustment Administration, one of the New Deal agencies, increased unemployment, frustrated farmers, and was eventually deemed unconstitutional by the Supreme Court. His intentions and theories to end overproduction were good, just not executed well. Another of Roosevelt’s reforms is Social Security. This is perhaps one of the most controversial of his policies. Some loved it and some hated it. In fact, the benefits of this administration are still debated over today with people calling into question the longevity of its existence. One problem that Roosevelt seemed to face was his long-running battle with the Supreme Court. Consisting of older aged, ultraconservative men whom Roosevelt had not appointed, the Supreme Court was something the president wanted to change. To fix it, he asked Congress to permit him to add up to 15 justices to the Supreme Court. This attempt to â€Å"pack† the court cost Roosevelt severely in the eyes of the public. It was his away of going around the Constitution in order to be able to keep more of his programs and agencies from the New Deal. In total, despite also several failures, many of FDR’s domestic policies were good. They helped relieve some of the stress set on by the depression. However, that’s all they did – relieve. His policies and the New Deal did not cure the country of the Great Depression, only temporarily masked the problems with only of his agencies still existing after his presidency. For these reasons, I give Roosevelt a B for his domestic policy. In the beginnings of a second world war, Roosevelt had important foreign policies that were crucial to the United States’ welfare. With an attempt to end the Depression, Roosevelt was initially going to send a delegate to take part in the London Conference. However, upon a second look, he decided that international agreements about the value of the dollar might restrict him in domestic recovery. This begins a trend toward increased nationalism and eventually to the United States’ views on isolationism. Though we are unable to tell what might have come out of the conference, it seems like a poor decision for Roosevelt to leave America totally on its own from other countries. Along with this idea of isolationism, through the Tydings-McDuffie Act, the United States freed the Philippines (after 12 years). This act was more beneficial for the United States than the actual freed country because of less foreign competition for sugar, as well as fewer people competing for jobs. Overall, it did help the U.S.; however, it also kind of abandoned the Philippines with not-so-nice economic terms. In contrast to these inward-looking acts, Roosevelt also created the Good Neighbor Policy with Latin America. He focused on consultation and nonintervention in hopes to unite the Western Hemisphere against any powers on the other side of the world. This was a smart move after withdrawing ties from Europe and Asia. It was a good idea that ended up being very successful for him and Roosevelt ended up with the title of â€Å"traveling salesman for peace.† In such fear of war, Congress passed the Neutrality Acts so as not to be brought into the violence like had been done in WWI. However, Roosevelt later changed these Acts to mean that an arms embargo be established for both Loyalists and rebels. As far as Roosevelt’s foreign policies go, this one was really bad. So scared of war, they basically aided in Franco’s taking over of the republican government of Spain. This in turn led to the strengthening of the European dictators, leading to the second world war. For this reason, Roosevelt’s grade goes down. Then, in 1941, neutrality had its meaning changed again. Really, it was thrown out the window with passing of Lend-Lease Act. The reasoning behind it was very understandable. Arm the other fighting democracies with weapons to defend against Hitler, or allow them to fall and have the U.S. face them alone. Knowing the risk, and after many debates, it was finally approved. It also set up the United States for war production when they did fight. However, the Lend-Lease Act ultimately was what brought them into the war once they had to start using armed Destroyer ships to take them to Britain. Roosevelt’s idea was good, however the consequences were bad. Later in the war, Roosevelt met with Churchill and Stalin for the Teheran Conference. Here, the three agreed upon a plan to attack Germany from the East as well as from the West. This was an incredibly important part of Roosevelt’s foreign policy since it was the beginning of the end for Nazi Germany. The Allies were able to recover France from the Nazis and continue their fight with Germany. Though Roosevelt died a month before V-E Day, his position as Commander in Chief for the past twelve years caused the United States and the Allies to defeat Germany. Though nobody is perfect, Roosevelt was able – through all decisions, good and bad – to stop the Nazis and ultimately save Europe. For these reasons, Roosevelt gets an A as Commander in Chief. Franklin Delano Roosevelt was strong in communicating with the public was well as dictating foreign and domestic policy. For this reason, his party grew during his presidency and so he deserves an A as Chief Party Leader. He started the â€Å"FDR Coalition† for his first term to get votes. Throughout his successes in the beginning, he was able to change many Republicans into Democrats, strengthening the Democratic Party for years to come. In addition, he also aided more Democratic candidates in all areas of government into office. With Roosevelt in office, the party grew both in voters as well as representation in Congress and other branches of government. His role as Chief Party Leader was done well and that is why he gets an A. Franklin Delano Roosevelt came into office at first having to deal with the struggles of the Great Depression. He was then later faced with the challenges of World War II, attempting to protect the United States as well as all Democratic countries from Nazi takeover. Anyone faced with these difficult challenges would have their ups and downs. FDR, on balance, was a good president and gets and overall A for his role as a country symbol, legislative leader, manager of the economy, Global leader, Commander in Chief, and Chief Party Leader. Works Cited Bailey, Thomas Andrew, David M. Kennedy, and Lizabeth Cohen. The American Pageant. Boston: Houghton Mifflin, 1998. Print. Hughes, L. P. â€Å"†FDR AS NATIONAL LEADER†Ã¢â‚¬  Austin Community College – Start Here. Get There. 1999. Web. 06 Apr. 2011. . Mintz, S. â€Å"The First 100 Days.† Digital History. 2007. Web. 01 Apr. 2011. . http://www.digitalhistory.uh.edu/database/article_display.cfm?HHID=468 (80%) http://www.austincc.edu/lpatrick/his2341/fdr.html (shrink 90%, page 4)

The Crucible By Arthur Lee Miller - 788 Words

Doing the right thing can be hard, but when it comes down to life or death situations, the decision is that much more challenging. In Arthur Lee Miller s drama The Crucible, he tells the story of John Proctor, the troubled land owner, who changes over time to help his wife and his town. John proctor starts off as a selfish, sinful man, but as the play progresses he fights for what is right and becomes a pure man again. John Proctor starts off the play being selfish. Miller shows this when Proctor says, â€Å"My lumber. From out my forest by the riverside, and Putnam replies, Why, we are surely gone wild this year. What anarchy is this? That tract is in my bounds, it’s in my bounds, Mr. Proctor (15). They cannot agree on who s lumber is who s. Even though John is rich, he still insists on having more land rather than sharing with Mr.Putnam. John proctor is also sinful. Miller shows this when Mr.hale says, â€Å"In the book of record that Mr. Parris keeps, I note that you are rarely in the church on Sabbath Day. Proctor replies, No, sir, you are mistaken. Mr.Hale says, Twenty-six time in seventeen month, sir. I must call that rare,†(33). Mr.Hale is questioning John about why he does not spend much time in church, as a man in his town should. Not coming to church on Sabbath day (Sunday) is a sin, and he rarely went, making him a sinful man. John Proctor also started out as a lier. He says â€Å"Wipe it out of mind. We never touched, Abby (11). John is not admitting to have sleptShow MoreRelated McCarthyism versus The Crucible by Arthur Miller Essay example1174 Words   |  5 PagesScare (Brinkley). One writer that used this era as a basis for his play, The Crucible, was Arthur Miller. He was able to capture the panic and mere insanity of many Americans in an allegorical way. 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Love in the Time of Cholera Essay - 1296 Words

Love is a powerful emotion that can cause people to act in abnormal ways. In the novel, Love in the Time of Cholera, the main character Florentino Ariza falls passionately in love with Fermina Daza. He immediately spends hours composing poetic love letters to Fermina as his entire life becomes dedicated to loving her. Fermina’s father, who greatly disapproves of the relationship between the two, decides to take his daughter to travel throughout the Caribbean. After many years of separation, when Fermina finally sees Florentino for the first time since she had been back in Hispaniola, all of her love immediately disappears after realizing she does not actually love Florentio. From that day on, Florentino would live for over a century in†¦show more content†¦Devastated by the loss of Fermina, Florentino spends months sick and unable to go on with his life. As the years go by since his rejection by Fermina, he finds himself in a web of love affairs with women from all w alks of life. Although he goes against his rule that he must remain a virgin until he can finally be with Fermina, he never marries or has children. The scars of losing his first and only love makes it impossible for Florentino to ever settle down, get married, have a family, or even a stable job. In comparison, David Lambert, the main character of the novel A Scientific Romance , also fails to progress in life after the loss of his true love. David’s life seems to deteriorate when he loses his lover Anita. He later spends years searching for her around the globe. It becomes clear that David has never moved on from loving Anita as he says, â€Å"†¦ sail back to Anita, to my parents; restore truncated lives, rebuild my own.† (Wright 62). His only hope to ever return to being happy will only happen if he can go to the past and be with Anita and his family. David, much like Florentino, spends his life consumed with thoughts of Anita. He never marries or has childre n and lives life lonely and miserable. The loss of both Florentino and David’s only true loves prevent them from developing as individuals. Secondly, the authors of these novels use the motif of misery caused by lost love. After Florentino is rejected by Fermina and then later finds out she is soonShow MoreRelatedLove in the Time of Cholera Essay651 Words   |  3 PagesGabriel Garcia Marquez, the novel Love in the Time of Cholera deals with a passionate mans unfulfilled love and his quest of more than 50 years to win the heart of his true love. Its without question one of the most emotional depictions of love, but what separates it from similar novels is its suggestion that lovesickness is a literal disease, a plague comparable to cholera. 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Levering Business to Customer Business Value through Internet Research Proposal

Essays on Levering Business to Customer Business Value through Internet Marketing Research Proposal The paper "Levering Business to Customer Business Value through Internet Marketing" is an excellent example of a research proposal on e-commerce. This report proposes research to assess the levering of B2C business models through internet marketing. The proposed research strategy is a case study of Tesco. The choice of this firm is justified by indications of its business model and its marketing and advertising strategies. Past studies have shown how e-marketing adds business levers to businesses. The literature review will guide this study through the identification of variables, parameters, scope and data sets. Primary data shall be collected via emailed questionnaires. The data obtained will be tabulated and analyzed using qualitative data analysis techniques. Grounded theory or analytic approach will be used to analyze the data through the former option is more preferable. The data shall then be used to test the hypothesis. The findings of the research will be important to Tesco and other B2C firms as it will inform them about the effectiveness of internet marketing.IntroductionE-commerce has grown tremendously in the past few years in the UK and globally more so in the developed world. This has been facilitated by increased access to internet connection especially broadband, technology growth, increased awareness of the benefits of e-commerce and a change in lifestyles. The e-commerce industry has been segmented into a number of sections with the main ones being groceries, clothing and apparel, electronics and hospitality and travel. The grocery segment, dominated by supermarkets, faces numerous challenges as opposed to the other segments due to the short shelf life of the majority of the items on offer. For this reason, online groceries shoppers account for only 6% of total grocery sales in the UK (Online grocery shopping 2011). However, the industry is expected to grow further to 5.4% of the retail market by 2015.A report carried out by the Guardian in O ctober last year put the UK’s internet industry at  £100 billion worth accounting for over 7% of the GDP. This growth of the internet is powered by growth in online shopping. In fact, the UK has the biggest e-commerce market globally by the amount spent per capita. This has also fueled online marketing and advertising. The online advertising industry generates  £3.5bn per year. Projections indicate that the industry is poised for greater growth spurred by increased online retailing and online marketing.Business BackgroundTesco is a brand name for one of the largest supermarket chains in the UK that is publicly traded on the London Stock Exchange. Established in 1919, the supermarket introduced online retailing in December 2009 on some of its items. As of May 2011, it was the third biggest online retailer in the country after only a brief presence (Tesco, 2012). Online shopping has grown in popularity as it allows more convenience especially for working mothers who have li ttle time to go shopping. Thus the creation of an online store was a response to a market need.

English schools free essay sample

English kids must travel to school when they are five. First they go to infant schools, where they learn the first stairss in reading, composing and utilizing Numberss. When kids leave the infant school, at the age of seven, they go to junior schools until they are about 11 old ages of age. Their school topics are English, arithmetic, history, geographics, nature survey, swimming, music, art, spiritual direction and organized games. Towards the terminal of their 4th twelvemonth in the junior school English schoolchildren have to compose their Eleven Plus Examinations, on the consequence of which they will travel the undermentioned September to a secondary school of a certain type. About 40 % of simple school departers in Britain go to secondary modem schools. Modem schools are the most popular secondary schools, but they do non supply complete secondary instruction, because survey programmes are instead limited in comparing with other secondary schools. The secondary proficient school, in malice of its name, is non a specialized school. We will write a custom essay sample on English schools or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page It teaches many general topics. The gm mar school is a secondary school which offers a full theoretical secondary education including foreign languages, and students can choose which subjects and languages they wish to study. They leave the school after taking a five-year course. Then they may take the General Certificate of Education at the ordinary level. The others continue their studies for another two or three years to obtain the General Certificate of Education at the advanced level, which allows them to enter university. The comprehensive school combines in one school the courses of all types of secondary schools. There are many schools in Britain which are not controlled financially by the state. They are private schools, separate for boys and girls, and the biggest and the most important of them are public schools. They charge high fees and train young people for political, diplomatic, military and religious service. Other non-state schools which charge fees are independent and preparatory schools. Many of the independent schools belong to the churches. Schools of this type prepare their pupils for public schools.