Anti-tumour Immunity through GP-100-TLR Agonist Conjugation

Anti-tumour Immunity through GP-100-TLR Agonist Conjugation Enhancing anti-tumour immunity through gp-100-TLR agonist conjugation. Introduction Soluble cancer vaccines remain an area of high interest to researchers with the ability to enhance immune responses against present cancers and induce protective immunity against future cases. In developing new vaccines finding ways to increase the immunogenicity of cancer antigens is a major challenge(1-3). The addition of Toll-like receptor (TLR) agonists is one strategy which can successfully boost immune cell activation and response to cancer antigens. By stimulating TLRs, these agonists increase expression of several co-stimulatory molecules on antigen presenting cells (APCs) such as CD80/86 and CD40(4-6).They also increase tumour peptide loading onto type 1 2 Major histocompatibility complex (MHC) proteins. Together this leads to greater activation of tumour-specific effector immune cells such as CD4+ and CD8+ T-cells resulting in increased tumour clearance via their cytotoxic activity. Vaccine formulations which have included antigen and TLR agonists as a mixture have had pro mising results with many in clinical trials(4, 7, 8). Despite this, few have assessed the effect of chemically conjugating these constituents, a strategy which could increase efficiency of both TLR activation and peptide loading onto MHC(9-12). Many conjugation strategies that do exist today capitalise on the use of pH and redox sensitive linkers. Differences in pH and redox environments intracellularly enable triggerable release of these vaccines whilst protecting antigen and agonist from degradation extracellularly where they are administered. Research into the use of Glutathione-sensitive disulphide linkers has demonstrated that the immune response to model antigen Ovalbumin'(OVA) could be increased through linkage to the TLR agonist, CpG oligodeoxynucleotide (ODN)(10, 11). Our research aims to repeat this using both stable and reversible linkers as well as a more clinically relevant, tumour associated antigen (TAA) called gp-100 expressed on melanomas. In addition, we aim to ass ess the effectivity of different TLR agonists within conjugates including Polyinosinic polycytidylic acid (Poly I:C) and two different classes of CpG ODNs, B and C respectively. Each of these agonists activate different signalling pathways within antigen presenting cells leading to unique cytokine profiles and T-cell responses. Poly I:C for example, is a potent activator of TLR3 which activates the TRIF pathway inducing release of type 1 interferons such as IFN Beta(6, 13, 14). This increases MHC-I expression and stimulates a Th1 type immune response which favours cell-mediated immunity including CD8+ T-cell activation. In comparison, CpG class B and C stimulate TLR 9 activating the MYD88 pathway and release of proinflammatory cytokines IL-6 and IL-17. This results in enhanced CD4+ and CD8+ T-cell responses, B cell activation and antibody production(10, 11, 15). Both types of response have potential to give clinical benefit in different ways highlighting the potential of these conju gates in tumour treatment. Finally, we will also assess how the composition of the TAA effects its presentation on MHC. To assess this, a smaller Gp-100 peptide which does not require intracellular processing will be compared to a longer peptide requiring processing. This project will assess which conjugates enhance anti-tumour responses in mice and how they achieve this looking specifically at Dendritic cell activation and CD8+ T-cell proliferation and cytokine production. Hypotheses In terms of CD8+ responses, T cell proliferation and cytokine release, I hypothesize that Poly I:C reversibly linked to processed gp-100 will be the most effective inducing a strong Th1 response and IFN-B cytokine release. This is because Poly I:C stimulates several intracellular signals in addition to TLR3 including RIG-1 and MDA-5. This would lead to increased release of proinflammatory cytokines including IL-6, IL-12, IL-1B and IFN-B. Specifically the release of IFN-B would induce a strong anti-viral-like Th1 T cell response through increased expression of MHC-1 molecules on APCs and inducing release of IFN-Y, TNF-A and IL-2 from CD4+ T cells. As well as this factor, TLR3 is exclusively expressed on myeloid dendritic cells, the most effective dendritic cell subset in presenting antigen, and not expressed on plasmacytoid dendritic cells. Secondly, I Hypothesize that CpG class C will induce the most cytokine production in dendritic cells including the cytokines IL-6, IL-12, IFN-A and IL-1B. CpG molecules stimulate TLR9 which is expressed in the endolysosomal compartment of plasmacytoid dendritic cells exclusively. As a dendritic cell subset, plasmacytoid DCs are well known for their proinflammatory cytokine production at levels much higher than other DC subsets. CpG class C in particular stimulates the release of IFN-a in addition to IL-6, IL-12 etc. stimulating both a Th1 response and a B cell response. Aims and objectives Aims Produce gp-100-CpG ODN and gp-100-Poly I:C reversible and stable conjugates with either processed or non-processed Gp-100 peptides Measure dendritic cell subset activation through expression of MHC-II, CD40 and CD86 molecules and cytokine release (IL-12, IL-6, IL-1B, IFN-A and IFN-B ) Measure Tumour specific T cell activation (CD4+ and CD8+), proliferation using carboxyfluorecein succinimidyl ester (CSFE) and cytokine release (IFN-Y, IL-2,TNF-A) Methods The proposed project for the year will focus on three main objectives 1) Produce gp-100-CpG ODN and gp-100-Poly I:C reversible and stable conjugates with either processed or non-processed Gp-100 peptides. First, we will modify free amino groups on the lysine residues of each gp-100 peptide (processed amino acid sequence: KVPRNQDWL vs unprocessed: CAVGALKVPRNQDWLGVPRQL) and TLR agonists (suspended in a modification buffer ph. 8). Then we will link these together with either the stable linker (HYN) or the reversible linker (HYN-SS) in a ph. 6 conjugation buffer separately. Product concentration after each individual modification step will be measured using Nanodrop1000 at 280 m after desalting excess product using vivspin 500 filter. Final product conjugation will be confirmed using the reversed phase liquid chromatograph at the School of Pharmacy which will allow us to visualise each individual product according to their differing polarities, and quantify their ratio. Our second objective is to Measure dendritic cell subset activation through expression of MHC-II, CD40 and CD86 molecules and cytokine release (IL-12, IL-6, IL-1B, IFN-B, IFN-A). To achieve this, we will isolate bone marrow cells from C57BL/6 mice and treat with GM-CSF to produce CD11c+ dendritic cells. These will then be treated with either individual TLR agonists, TLR agonist-gp100 mixtures or TLR agonist-gp100 conjugates (reversible or non-reversible). After 24hrs of treatment these cells with be stained with fluorescent antibodies for CD80, CD40, CD11C, and MHC-II, viewed on the Gallios flow cytometer in Pathology and analysed using Kaluza software. This experiment will be repeated at least three times to enable statistical analysis, which will be performed using Graph Pad prism software. Cytokine release from these cells will be measured using an enzyme linked immunosorbent assay (ELISA) for IL-6, IL-12, IFN-B and IFN-a. Our third objective is to Measure Tumour specific CD3+ T cell: activation (CD8+), proliferation (CSFE) and cytokine release (IFN-Y, IL-2). This will be achieved through isolation of splenocytes from Pmel (T-cells specific to gp-100) transgenic mice and sorting of CD8+ cells using the Automacs machine at Pathology. These cells will then be stained using CSFE and co-cultured separately with C57BL/6 BMDCs treated according to objective 2. After 72hrs cells will be analysed using the Gallios flow cytometer to measure T-cell activation (CD3+) and proliferation (CSFE). To measure cytokine release, cell cultures will undergo an ELISA for IFN-Y and IL-2. Proposed Budget Mice C57BL/6 x 10 @ $50 each$500 PMEL x 10 @ $50 each$500 Antibodies CD86-PE$300 CD11c-APC$300 CD40-PECy7$300 CD8a-APC$300 CD3-PE$300 MHC-I$300 MHC-II FITC$300 Cell culture reagents IMDM Media$400 Foetal calf serum$500 Cytokine detection Cytokine detection kit$2000 Conjugation reagents S4FB Linker$450 S-SS-4FB Linker$350 S-HYNIC cross linker$850 2-Hydrazinopyradine.dihydrochloride$450 2-Sulphobenzaldehyde$450 CpG class B$500 CpG class C$500 Poly I:C$500 Vivspin filters$200 Total$9250 References 1.Obeid JM, Hu Y, Slingluff CL. Vaccines, adjuvants and dendritic cell activators Current Status and Future Challenges. Seminars in oncology. 2015;42(4):549-61. 2.Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang X-Y. Therapeutic Cancer Vaccines: Past, Present and Future. Advances in cancer research. 2013;119:421-75. 3.Schlom J. Therapeutic Cancer Vaccines: Current Status and Moving Forward. JNCI Journal of the National Cancer Institute. 2012;104(8):599-613. 4.Kaczanowska S, Joseph AM, Davila E. TLR agonists: our best frenemy in cancer immunotherapy. Journal of leukocyte biology. 2013;93(6):847-63. 5.Pradere J-P, Dapito DH, Schwabe RF. The Yin and Yang of Toll-like Receptors in Cancer. Oncogene. 2014;33(27):3485-95. 6.Maruyama K, Selmani Z, Ishii H, Yamaguchi K. Innate immunity and cancer therapy. International immunopharmacology. 2011;11(3):350-7. 7.Iribarren K, Bloy N, Buque A, Cremer I, Eggermont A, Fridman WH, et al. Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy. Oncoimmunology. 2016;5(3):e1088631. 8.Dowling JK, Mansell A. Toll-like receptors: the swiss army knife of immunity and vaccine development. Clinical Translational Immunology. 2016;5(5):e85. 9.Flanary S, Hoffman AS, Stayton PS. Antigen delivery with poly(propylacrylic acid) conjugation enhances MHC-1 presentation and T-cell activation. Bioconjugate chemistry. 2009;20(2):241-8. 10.Herbath M, Szekeres Z, Kovesdi D, Papp K, Erdei A, Prechl J. Coadministration of antigen-conjugated and free CpG: effects of in vitro and in vivo interactions in a murine model. Immunology letters. 2014;160(2):178-85. 11.Kramer K, Shields NJ, Poppe V, Young SL, Walker GF. Intracellular Cleavable CpG Oligodeoxynucleotide-Antigen Conjugate Enhances Anti-tumor Immunity. Molecular Therapy. 2017;25(1):62-70. 12.Slutter B, Soema PC, Ding Z, Verheul R, Hennink W, Jiskoot W. Conjugation of ovalbumin to trimethyl chitosan improves immunogenicity of the antigen. Journal of controlled release : official journal of the Controlled Release Society. 2010;143(2):207-14. 13.Ammi R, De Waele J, Willemen Y, Van Brussel I, Schrijvers DM, Lion E, et al. Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Pharmacology therapeutics. 2015;146:120-31. 14.Cho HI, Barrios K, Lee YR, Linowski AK, Celis E. BiVax: a peptide/poly-IC subunit vaccine that mimics an acute infection elicits vast and effective anti-tumor CD8 T-cell responses. Cancer immunology, immunotherapy : CII. 2013;62(4):787-99. 15.Scheiermann J, Klinman DM. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer. Vaccine. 2014;32(48):6377-89.

Coconut: the most economically important member of the great palm family Essay

CHAPTER 1 (BACKGROUND OF THE STUDY) In this modern world considered as the era of comforts, we also face poverty and scarcity of resources because of over population. So, people today are searching for some easier and better ways to save money through substituting commercialized products with improvised and homemade products, economizing, etc. In short people today are just being practical on what they will buy or what they will do to meet their needs. The coconut is the fruit of the most economically important member of the great palm family, Palmae. The genus Cocos are Southeast Asians and contain only one species, Cocos Nucifera.  Cultivated in tropical lowlands, almost always near the sea, the coconut has long been distributed throughout Southeast Asia and along the Tropical African and American coasts. The coconut is known for its great versatility as seen in the many uses of its different parts. For centuries, the coconut pal has supplied the people of the Pacific Islands with food, drink, shelter, and most of their needs. The durian is the fruit of several tree species belonging to the genus Durio. There are 30 recognised Durio species, at least nine of which produce edible fruit. Durio zibethinus is the only species available in the international market: other species are sold in their local regions. Regarded by many people in Southeast Asia as the â€Å"king of fruits†, the  durian is distinctive for its large size, strong odor, and formidable thorn-covered husk. The fruit can grow as large as 30 centimeters (12 in) long and 15 centimeters (6 in) in diameter, and it typically weighs one to three kilograms (2 to 7 lb.). Its shape ranges from oblong to round, the color of its husk green to brown, and its flesh pale yellow to red, depending on the species. Corn (Zea mays) has been grown in the northeast for generations, and is a demanding crop but one that is highly-valued for its use. Corn, Zea mays, is an annual grass in the family Poaceae and is a staple food crop grown all over the world. Corn is the second most important crop in the Philippines. About 14 million Filipinos prefer white corn as their main staple and yellow corn accounts for about 50% of livestock mixed feeds. Some 600,000 farm households depend on corn as a major source of livelihood, in addition to transport services, traders, processors and agricultural input suppliers who directly benefit from corn production, processing, marketing and distribution. Shoe shining is the process of applying an external substance to the surface of a shoe to improve the materials and make it shinier. Shoe shining has been a part of shoe care for hundreds of years. Adding a shine to a shoe brings polish to an outfit. Shoe polish products are low-value items are frequently purchased as a single but might last for several days. The researchers wanted to produce shoe polish out of the coconut husks, durian husks and corn cobs because we found another use for them. This leads to conduct an experiment using the ashes of coconut husk, durian husks and corn cobs for shoe polish. If these products would be successful, it can help in recycling coconut husks, durian husks and corn cobs and can lessen them to avoid them scattering all over our community. STATEMENT OF THE PROBLEM This study aims to make an effective shoe polish out of ashes from burned coconut husks, durian skins, and corn cobs. Specifically, the study would like to answer the following: * What are the components that are present in the ashes? * How effective is the shoe polish in terms of: – Shine that it could give – Life Span – Color of Polish compared to other brands * What is the difference between the commercial shoe polish from the shoe polish out of ashes from the coconut husks, durian skins, and corn cobs? ASSUMPTION The researchers believed that Coconut husks, Corn Cobs and Durian Skins are effective alternative shoe polish and can make it a source of income. HYPOTHESIS There was no significant difference between the efficiency of our product to the commercial shoe polish that was sold on the market. SIGNIFICANCE OF THE STUDY One of the main benefits of a shoe shine is that it helps preserve the material that shoes are made out of. Polishing products also provides the coating of wax on the leather that helps in keeping it waterproof and reduces the dirt accumulated on the leather. Shoe polish also gives a moisturizing effect to the leather and proper care may help in lasting the shoes for several years. Since coconut, durian, and corn is abundant in our country, people can make it a source of livelihood. SCOPE AND LIMITATION The study is focused on the effectiveness of the alternative shoe polish and aims to shine shoes at a long period of time. Furthermore, this study is only limited to the effectiveness, color, shine, duration, and the odor it can give. METHODOLOGY The purpose of this chapter is to present the experimental assumptions underpinning this research, as well as to introduce the research strategy and empirical techniques applied then the materials used in conducting this  study. The chapter defines the scope and limitations of the research design. Materials The researchers utilized the following materials in accomplishing the project: Coconut husks, Corn Cobs, Durian Skins, Coals, Matchsticks, Ashes, Tongs, Strainer, 3 Basins, Pitcher, Water, Measuring Cups, Detergent Bar Soap, Knife, Frying Pan, Spoon, Citric Acid, Glycerin, Dye, and Kerosene. The sun was used as the source of heat to dry the Coconut husks, Corn cobs and Durian skins. The coals and matchsticks are used to burn the three different fruit shells and tongs was used to protect our hands from getting burned. The strainer was used to remove big particles and for us to gather fine ashes. The 3 basins were used as containers of the ashes. The pitcher was used as a container for the water. The measuring cups were used to measure the quantity of the water, citric acid, glycerin, dye and kerosene needed. The knife was used to cut the bar soap. The frying pan and spoon were used in heating up the whole mixture. Procedure The researchers gathered (1) one sack coconut husk, (1) one sack corn cobs and (1) one sack durian skin. After collecting the three different fruit shells the researchers let them stay under the sun for three days to get totally dry. Then after three days the researchers prepared the materials for the burning process. The researchers burned the three different dried fruit shells separately and collected the ashes. Afterwards, they inspect the ashes and they remove the big particles using a strainer. 1.Burn the dried coconut husk, corn cob, and durian skin separately and collect the ashes. 2.Inspect the ashes and remove the big particles. 3.Measure a certain amount of water. 4.Cut the bar soap into small pieces and dissolve it on water. 5.Add the ashes. 6.Heat the mixture until it boils, then stir evenly. 7.After few minutes add the citric acid and the glycerin. 8.Pour into a container. The mixture needs to settle for a number of hours before used.

Crucible essay Essay

The Crucible takes place in Salem Massachusetts during 1692. It takes place during the tragic time of the so called Salem witch hunts when many innocent people were accused of being a witch or dealing with the devil. As a result of these convictions many people confessed to save their lives, others who would not confess to a lie were hung or executed by other methods such as being pressed. The play the Crucible was wrote by Arthur Miller during the â€Å"Red Scare†, which was almost parallel with the Salem witch hunts in that many innocent people were accused of actions of communism and espionage that they did not take part in. The Crucible is not so much about a witch hunt as it is an illumination of human weakness, hypocrisy, and vindictiveness. In the Crucible there is quite a bit of human weakness. This can easily be seen through all of the people in the story who admitted to being a witch or dealing with the devil instead of being strong and denying the fact that were not a witch and be put to death. When this all begins, Abigail, the reverends own niece, blames Tituba, the reverends slave from Barbados of being a witch. When she is accused on page 847 she first denies it, â€Å"I don’t compact with no devil,† later on after Mr. Putnam says â€Å"this woman must be hanged†, Tituba gives into her natural human weakness and cries out â€Å"†¦ I tell him I don’t desire to work for him(the devil) sir.† That is just one of the many cases where human weakness is illuminated in the play, it is also the most common, many people gave in to the pressure so they wouldn’t be hung. Another way human weakness was illuminated in the Crucible is that John Proctor will not admit his affair with Abigail because he is afraid he will lose his farm and ruin his name. Mary Warren also gives into human weakness when John Proctor asks her to go to the court and tell that the girls are all faking there so called sickness caused by the accused witches. When she tries to tell Judge Danforth Abigail interferes and Mary pretends to go crazy again. Amongst all the human weakness there was a lot of hypocrisy mostly amongst the people who seemed strong and pure. The Crucible may take place during the Salem witch trials of 1692, however the illumination of weakness, hypocrisy, and vindictiveness are what the  play is actually about. Just like what was going on during the Red Scare during Arthur Miller’s time.

Workers of the Progressive Era - 1047 Words

Progressive Era: Working Class Workers during the gilded age were marginalized by their working conditions, low income, and limited working hours. To overcome the marginalization for the working class, they created labor movements and went on strikes. Although the workers had created many strikes and labor unions, they were at the least successful. Workers were marginalized by the poor working conditions they had. A lot of the time the workers feared going to their workshops because they knew what they were getting themselves into. In 1906, Upton Sinclair, a writer during the gilded age, wrote a novel, The Jungle, in which took place inside work factories. He expressed the fact that the work was†¦show more content†¦They would have no nails,-they had worn them off pulling hides; their knuckles were swollen so that their fingers spread out like a fan.†(Sinclair, 1906) He stated this to point out that the workers had horrible conditions in the workshops and they needed to be justified in that state. Similarly, a recent article ,Labor in Progressive Era Politics, expressed an event of deaths in a workshop located in New York in 1911; this event is well known by the name The Triangle Fire. In the article it states that the â€Å"Triangle Shirtwaist Company in New York killed 146 garment workers in 1911, public outrage prompted the creation of a state commission to study the origins of the fire and the conditions of industrial workplace.†(Unknown) This event was not only tragic, but also a huge spark of the idea that the marginalization shall be no more. They were going to do what they needed to overcome the working conditions. To overcome the harsh and terrible working conditions, workers decided to go on strikes to catch the attention of the â€Å"big guys† so they can make improvements in the workshops. Many of the strikes were unsuccessful, stopped, or ignored. The strikes went on for about twenty years, a few of them were: The Great Strike,1877; Haymarket Riot,1886; Homestead Strike, 1892; Pullman Strike, 1894. In a Speech given by Eugene Debs he had said â€Å"To realize this great social ideal is a work of education, and organization. The working classesShow MoreRelatedThe Progressive Era And The New Deal1103 Words   |  5 Pagestraditions of the Progressive Era. When examining the New Deal, Progressive influence is evident based first off of the social and political issues addressed by reforms. Second, the reforms from the two times themselves are uncannily similar, again due to the focus on the same problems existing in the United States. In addition to this, the icing on the cake is foun d when examining President Roosevelt’s administration during the New Deal, a majority of which were intelligent Progressive reformers duringRead MoreDealing with the Class Gap During the Progressive Era830 Words   |  3 Pagespolitics and society as a whole. While there were a plethora of issues to be dealt with within the Progressive Era, one of the most noteworthy issues to discuss would be that of the working class and the businessmen of the first quarter of the 1900s. The reason why these two portions of society within the Progressive Era are the most relevant to discuss stems from the fact that during the Progressive Era there was a great gap between the upper-class (businessmen) and the lower-class (working class)Read MoreThe Progressive Era And Its Impact On American History1279 Words   |  6 PagesThe Progressive Era was a period of broad and varied movement which changed American values and life styles by having everlasting impact on American History. Most of the people during the progressive eras, lives changed through. During the Progressive Era Women wanted the right to vote and work outside their homes. Workers wanted better wages, hours, and safe condition while they are working. Coming with people who had race, which means all people wo were not white, they wanted a freedom, place toRead MoreThe Case Of Jesse Washington1247 Words   |  5 Pagespictures of the hanging, the children and their parents looked intently at the camera without remorse, Their fixed expressions suggested they were convinced that killing blacks was the right thing to do. Thus, even the lynch mobs represented the progressive mindset. Outside of organizations, individuals led social reform as well. Jane Addams built Hull House in Chicago to educate poor immigrants. There, she offered free education to the poor. She believed that one’s environment shapes his or her lifeRead MoreAnalysis Of The Gilded Age And Progressive Era1108 Words   |  5 Pagesthe Gilded Age and Progressive Era Throughout the history of time, people named certain time periods based on the events that occurred. 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This era also had complications such as racial tension between immigrants, poor working and living conditions amongstRead MoreEffects Of The Progressive Era1577 Words   |  7 Pages The Progressive Era was the solution to many different problems that were caused by the fast pace of industrialization and city growth within the United States after the Civil War. Problems during this time included poverty, cheap labor, corruption within government and within big industries, and political organizations that broke down the integrity of the government. During this time, many Americans saw the United States as non-traditional. They felt that government being corrupted by the richRead MoreThe During The Progressive Era989 Words   |  4 PagesDuring the Progressive Era, various groups responded to the political, social, and economic woes that resulted from the rapid industrialization and urbanization of America during the 19th Century. The mass immigration of foreigners and the northern migration of Africa-Americans l ed to urban overcrowding and competition for wage-paying jobs. Electric lighting allowed factories to expand the working hours and increase the output of manufactured goods. There was little regulation for employee welfareRead MoreProgressivism Between The Ideals Of Social Justice And The Urge For Social Control1130 Words   |  5 Pages1. Discuss the tensions within progressivism between the ideals of social justice and the urge for social control. What concrete achievements are associated with each wing of the movement? What were the driving forces behind them? Progressives not only focused on improving quality of life for its citizens, but also on controlling certain aspects of the legal system. For instance, educated middle class women fought for better recognitions of women’s achievement, and they focused on improving healthRead MoreAnalysis Of Uptons Sinclairs The Jungle1084 Words   |  5 PagesPrimary Source Paper Uptons Sinclairs The Jungle from 1906 is a fictional book from the progressive era. Even though The Jungle is a fictional novel, it described conditions that were real during the progressive era, such as working class poverty and harsh working conditions. The novel was written as a way to exploit the real lives of working citizens at home and at work. In chapter nine of The Jungle, Upton Sinclair talks about the lives that the working-class experiences at work. They are horrible

Theme Of Sin In Hamlet - 1956 Words

When King Hamlet’s ghost tells Prince Hamlet that he was murdered by his ruthless brother, Claudius, he commands the prince to avenge â€Å"his foul and most unnatural murder† (1.5.25). Hamlet chooses to obey the ghost and seek vengeance, rather than justice. William Shakespeare uses Hamlet (appx. 1599) as an example of the nature and consequences of sin in the world, which is highlighted by five specific themes; one per each act. The first act’s theme is the actual â€Å"Fall† itself, while the second’s is acting and spying. The third act’s theme is guilt, the fourth’s is deception and madness, and lastly, the fifth and final act’s theme is death. The theme, of sin, is â€Å"fully absorbed into the aesthetic DNA of imagery, language, and character.†¦show more content†¦Ã¢â‚¬Å"If thou didst ever thy dear father love†¦ Revenge his foul and most unnatural murder† (1.5.23-25). From the Fall grows a new sin; obsession. Hamlet begins to obsess over what to do, if the ghost is even real, and if revenge is even his to take. â€Å"What buckles under the pressure of the apparition is the notion of likeness†¦ that underwrites Hamlet’s recollection of his father, or, rather, the ratio or likeness and difference threatens to collapse.† (Greenblatt 192) Because of the original sin and the Fall, Hamlet is trapped. Claudius has â€Å"covered his tracks so well that he is vulnerable only to a secret revenge† and Hamlet believes that he must take it (Gilles 418) The second act of the play’s theme is repercussions of the Fall and broken trust. Prince Hamlet has devoted himself to plotting his father’s revenge, but after spending so much time on such difficult and contemplative issues, he has gone a bit â€Å"mad† (both literally and also, for show). His mother, Gertrude, and the new King, Claudius, begin to worry about his behavior. During this time, Polonius, a Lord, suggests that Hamlet is perhaps acting insane because he secretly desires his daughter, Ophelia, and is deeply in love with her. Claudius agrees to spy in on Hamlet and Ophelia as they are conversing to see if what Polonius has said is true and he deduces that Hamlet is mad, alright, but not with love for Ophelia; he orders her to a nunnery and even declares thatShow MoreRelatedAnalysis Of William Shakespeare s Hamlet 903 Words   |  4 Pagesbeing wrong for something that he or she didn’t commit. It is based on the old saying ‘an eye for an eye principle’ and isn’t the best way to deal with conflicts, especially when it involves family members. In William Shakespeare’s play â€Å"Hamlet†, Laertes, Hamlet, and the younger Fortinbras all had thoughts of vengeance for the deaths of their fathers. Although they acted on their emotions, but their methods of doing so was entirely different. Because of this, only one out of the three rose toRead MoreThe Theme of Appearance vs. Reality in William Shakespeares Works729 Words   |  3 PagesThe Theme of Appearance vs. Reality in William Shakespeares Works Characters within one of William Shakespeares greatest tragic plays, Hamlet, appear to be true and honest but in reality are infested with many falsehoods and deceptions. Characters such as Polonius, Claudius, and Hamlet give an impression of a person who is sincere and genuine, but behind their masks are plagued with lies and evil. AsRead MoreHamlet As A Tragic Hero1305 Words   |  6 Pagesunderstanding of someone else’s misfortune. Hamlet, in this case, is the tragic hero due to many different sources that cause the reader to have an immense amount of sympathy for him. A series of events such as murder, failed relationships, and all the madness, created the feeling of sympathy from the audience. These specific sources cause the reader to see the development of the overall themes of deceit, justice, and revenge. Deceit is one of the main themes presented throughout the play startingRead MoreEssay on Suicide in Hamlet1624 Words   |  7 PagesWilliam Shakespeares Hamlet, suicide is an important and continuous theme throughout the play. Hamlet is the main character who contemplates the thought of suicide many different times throughout the play, since the murder of his father. Hamlet weighs the advantages of leaving his miserable life with the living, for possibly a better but unknown life with the dead. Hamlet seriously contemplates suicide, but decides against it, mainly because it is a mortal sin against God. Hamlet continues to sayRead MoreThe Great Flood Of Gilgamesh, The Canterbury Tales, And Hamlet1311 Words   |  6 Pages A theme is the underlying message or overall meaning of a story. Authors use this literary device in stories to convey a critical belief about life. A theme of a book is usually seen as a universal in nature because when a theme is universal, it touches on human experience. Sometimes there are multiple themes to a story and they may or may not be stated directly. Religion is a theme found throughout the stories of Gilgamesh, Beowulf, The Canterbury Tales, and Hamlet. The theme of religion isRead MoreAppearence vs. Reality in William Shakespeares Hamlet Essay1671 Words   |  7 Pages amp;#65279;Appearance vs. Reality nbsp;nbsp;nbsp;nbsp;nbsp; In Shakespeare’s tragedy, Hamlet, there is a dominant and overwhelming theme that is concurrent throughout the play. Throughout the play, all the characters appear as one thing on the outside, yet on the inside they are completely different. The theme of appearance versus reality surrounds Hamlet due to the fact that the characters portray themselves as one person on the outside, and one different on the inside. 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Ophelia is also driven to madness at the mercy of Hamlet, taking her own life. Shakespeare uses the few women in Hamlet, who are portrayed as sinful and weak-willed by being manipulated by men, toRead MoreEssay about Appearance vs. Reality in William Shakespeares Hamlet1007 Words   |  5 PagesAppearance vs. Reality in William Shakespeares Hamlet In Hamlet, one of Shakespeares greatest tragedies, there is a prevailing theme that is concurrent throughout the play. Throughout the play, all the characters appear to be one thing on the outside, yet on the inside they are completely different. The theme of appearance versus reality is prominent in Hamlet because of the fact that the characters portray themselves different from what they really are. In the playRead More Revenge in Shakespeares Hamlet Essay1124 Words   |  5 PagesRevenge in Shakespeares Hamlet Revenge. Revenge causes one to act blindly through anger, rather than through reason. 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Gay Rights Essay - 1291 Words

Gay Rights Two men are walking down the street very peacefully until they decide to kiss one another right out in the open. Some people look upon this as weird and others look upon it in disgust. Some even get angry about it. Is there a problem with what these men just did? Should they be left alone or reprimanded for what they have done? The issue of gay rights is very cloudy in our great nation. Most of this is due to the problems with the issue, the reasons for controversy, and pros and cons of the issue. nbsp;nbsp;nbsp;nbsp;nbsp;First of all, both sides have too many problems with gay rights for there to be a common ground on the issue. The biggest problem I find with the whole thing is the problem is not just fought by words,†¦show more content†¦All who oppose state that marriage is the holy joining of a man and a woman, not a man and a man. Secondly, the question of whether gays should be able to adopt children is also a problem. According to the American Academy of Pediatrics â€Å"†¦gay couples can provide the loving, stable and emotionally healthy family lives that children need† (Adoption). But, â€Å"Family values advocates have attacked the policy, accusing doctors’ group of using faulty science to advance a gay agenda† (Adoption). The third issue is whether or not gays are born the way they are or if it is genetic. This of all the issues would help to shape the decisions of both sides of the issue. Tony, a gay student at Valencia Community College states, â€Å"I know many gay people, sometimes it depends on the individual person, I personally think that I was born gay† (Tony). nbsp;nbsp;nbsp;nbsp;nbsp;Lastly, each one of these issues of controversy has its good and bad points. To get a better view on both sides of the issue I interviewed two homosexual males who have differing opinions on the issue. On the issue of gay marriage, Brian had this to say: â€Å"Since gay people tend not to stay together as long, I see no reason for them to be married in the first place† (Brian). The second interviewee, Brandon, responded with: â€Å"I believe gays should have the right to marry, because if a man and a woman love one another just as a man and a man love one another, you should notShow MoreRelatedGay Rights1419 Words   |  6 Pagessimply, they are in love. The gay rights movement is a continuing procession that fights for their rights. The gay rights movement actually begins on November 11, 1950 when gay rights activist Harry Hay founds America’s first national gay rights organization by the name of Mattachine Society, according to the  "Timeline: Milestones in the American Gay Rights Movement†. Their leaders or people who advanced their purpose are Harvey Milk, Harry Hay, LGBT, or lesbian, gay, bisexual, and transsexual groupsRead MoreGay Rights, Gay, Lesbian, And Society1202 Words   |  5 PagesOver the past decades, being gay was something no one talked about. It was a subject that was very taboo and society didn’t accept. People saw it as a stage one goes through and something unnatural. Thanks to the media, more and more celebrities have come out of the closet over the years. Soon people became accepting of the gay community and their life style. Being openly gay, lesbian, transgender, or bisexual in the workforce can lead to discrimination. Gay mirages are also frowned upon by societyRead MoreThe Rights Of Gay And Lesbian Couples Essay1536 Words   |  7 Pagesthe majority believe that they deserve the rights they are granted with the aid of the government. 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There have been multiple incidents LGBT individuals have beenRead MoreEssay on Effects of Gay Rights in America943 Words   |  4 PagesMatthew Shepard. He was given a life sentence. States must inflict a harsher punishment for people who commit gay violence crimes because over the years hate crimes based on sexual orientation have become the third highest category reported. Many people claim that the violence happenes not because of sexual orientation, but because it is just an act to be committed. According to the Human Rights Campaign, crimes against homosexual people resulted in four deaths in 1998 alone. James Ward, a thirty-sevenRead MoreThe Struggle Of Gay Rights1893 Words   |  8 Pages The struggle between Edward and Bella in the â€Å"Twilight Saga† can be closely related to the struggle of gay right’s in today’s society. During the whole entire saga Edward and Bella have to fight to keep their relationship with one another. This is similar to what the LGBT community has been doing for many years now. In the â€Å"Twilight Saga† some of the characters do not believe that Edward and Bella should be with one another because he is a vampire and she is a human. Similarly in today’s societyRead MoreThe Rights Of Gays And The Homosexual Agenda1743 Words   |  7 Pagesdelivered a speech that was to have a drasti c effect on the human rights of gays and lesbians in Uganda. The speech, given at an anti-gay conference titled â€Å"Exposing the Truth behind Homosexuality and the Homosexual Agenda†, linked homosexuality with child molestation and the destruction of African families and laid the foundation for what was to become a virulently homophobic movement in Uganda. This religious crusade against the rights of gays and lesbians culminated in an oppressive law, passed in 2014Read MoreGay Rights And The Lgbt Community1542 Words   |  7 Pagesmass shooting in U.S. history occurred not to far from UCF. Patrons of Pulse nightclub, a gay nightclub in Orlando where massacred by Omar Mateen, Mateen took the lives of forty-nine individuals all because of their presence in a gay establishment. This tragic incident wasn’t the first attack on the LGBT community, but it’s massive fatalities put Congress under even more pressure to reform gun laws, gay rights, and suspected terrori st legislation. As a political Science major, I take a special interestRead MoreThe Fight for Gay Rights Essay1515 Words   |  7 PagesThe Fight for Gay Rights Restrictions have been put in place on homosexuals’ basic human rights because of individuals’ opinions and lack of tolerance. America is a country where all people should have the same rights, regardless of sexual preference. Gay marriage is illegal in more than thirty states even yet today (ProQuest). Homosexual people have been struggling with their rights for over a hundred years now, but the issue still hasn’t been resolved. Gay marriage and rights didn’t become aRead MoreThe Fight For Gay Rights Movement1155 Words   |  5 PagesToday, the fight for homosexual right is at the forefront of society, which yields a greater thrust towards full equality to heterosexuals with every passing day. This campaign for equality is known as the Modern Gay Rights Movement. The modern struggle for gay rights started as early as The Civil Rights Movement in 1954, and still continues today (Britannica). The Civil Rights Movement, from 1954-1968, sparked oppressed people to fight for their rights. In this period, shockwaves from blacks’ gaining

Learning Psychological Theories to Motivate Oneself

Question: Write about theLearning for Psychological Theories to Motivate Oneself. Answer: Learning is the gaining of knowledge and skills by training, experience or practice. Learning results in the change of behavior. However, learning faces challenges that originate from the learner or as a consequence of an unaccommodating environment. Though the study of factors contributing to learning has eliminated external obstacles, for people, internal motivation plays a major factor. Besides, people have different abilities regarding memory thus requiring some to take longer time and effort than others. For effective learning, an individual has to understand his/her internal obstacles and work around them to achieve the desired results from a learning process (Swets, 2014). Today, education has been diversified to accommodate the differences in individuals by incorporating audio-visual devices, rewards or punishment and other motivating factors. This paper seeks to explore the psychology theories of learning, thought and language, and motivation and emotion. It also examines ho w these approaches may be used in improving education and the use of memory techniques. Achieving the benefits of learning depends on the memory capacity of the learner. Nonetheless, people have different aptitudes in remembering things or knowledge learned. Due to these variations, different memory techniques were introduced to enable trainees to improve their abilities to remember what was taught. Each of the techniques has different efficiency and works differently for individuals. In schools, the most effective memory used by teachers and trainers in practice testing and distributed practices. The two approaches are believed to have the highest levels of efficiency compared to other methods. Practice testing involves challenging oneself with questions and answering them. It is not necessary that the person is in a testing environment (Jerome, 2013). Practice testing, however, works efficiently if a time lapse is allowed between the time of training and the time of testing. Otherwise, immediate retesting is less efficient. Practice testing enables a trainee to retain information and retrieve it from their long-term memory. Secondly, it allows the learners to organize their information and knowledge thus facilitating fast retrieval. They do so by encoding mediators through targets and cues (Barkley, Major 2014). Secondly, distributed practice is a process where the learner divides their training time by incorporating time intervals. This technique eliminates chunky learning sessions and splits them to shorter time periods. This approach increases both retention and absorption of information. It reduces the options of cramming and unproductive studying. The mind of the learner absorbs the information through interchanging periods of focused learning and diffused method of thinking. It allows the student to remember what was taught by processing small portions of information rather than large ones. Apart from this two, other procedures exist but have less efficiency (Neisser, 2014). Elaborative Interrogation includes creating a clarification for why an unequivocally expressed truth or idea is valid. A sizeable collection of confirmation backings the energy of illustrative addressing for advancing adapting, particularly "Why?" questions. The impacts are biggest when elaborations are exact as op posed to general; when earlier information is higher prior learning centers memory on particular preparing; and when elaborations are self-created instead of gave. Most reviews have concentrated on signaled coordinated, and certainty acknowledgment, with blended outcomes for studies concentrating on free review tests. Be that as it may, a current review including elaborative strategies in an undergrad initial Biology course demonstrated a 7% expansion in understudy execution (Barkley, Major 2014). Self-clarification includes understudies conveying in their particular words how new data is identified with known data or clarifying strides taken amid critical thinking. It upgrades learning by incorporating new information with prior information. It works best when no clarifications are given before or amid the understudy era of self-clarification. Likewise, self-clarification shown improvement over intelligent self-clarification after the issue has been explained. Examine shows self-clarification works for a wide age scope of learners and subjects. Across the board utilization of this system is tedious. Interleaved Practice will be the practice that blends various types of issues or studies material inside a solitary review session (Dunlosky, et al. 2013). The regular approach is to take in all parts of one idea, then refine issues or exercises applying that idea, then proceed onward to the following one in a direct manner. A case of this is to take in the ideas and equation on f inding the volume of a particular sort of healthy, then taking care of a few issues where you discover the amount of that strong. From that point onward, understudies proceed onward to the ideas and recipe for finding the volume of an alternate healthy and do a few practice issues for that sort. Following the learning techniques, operant conditioning theory by B.F. Skinner depends on the rate of chance under which knowledge forms a great component for progress in a plain conduct. The consequences of personal reaction to different occasions that occur in nature depend on one's ability to amend his or her conduct. Individual reaction delivers different results under different environments (Slavin Davis, 2006). For instance, the ability to characterize a word, solving a mathematical challenge, or even hitting a ball. Under conditions whereby specific stimulus-response gets compensated, the person concerned is mold to react on the same. The particular behavior of an individual to get molded operant operates in respect to the past experiences that a person has undergone in his life. Further, the reactions different people have on particular activities originate from their indented reactions and thus evoking a different reaction due to external jolts. The key element of Skinner's S-R hypothesis is supported. A coveted reaction is fortified by a support trainer. This support may be acclaimed in verbal terms, based on a descent evaluation and sentiments diversified to realize the set fulfillment goals. Further, the S-R hypothesis explains about the negative rewards that tend to boost the outcomes in an expanded reaction recurrence if this is drawn back into a distinguishable relationship so as to aversive the decreased results and reactions (Byrne, 2014). The calendars of fortification were given a significant consideration and these established positive impacts on strengthening people's conduct. The most negative aspect of the Skinner's hypothesis is that the hypothesis endeavors to offer behavioral clarifications of individuals based on an expensive scope of intellectual capabilities (Melton, 2014). The theories of language and thought, on the other hand, show that understanding the meaning and the different forms of a word would help in learning. The visualization of information and attaching it to a certain meaning by encoding targets and cues helps in learning. Relativity is anything but difficult to illustrate. To talk any dialect, you need to focus on the implications that are linguistically set apart in that dialect. Advocates of semantic determinism contend that such contrasts between dialects impact the ways individuals thinkmaybe the routes in which entire societies are sorted out Lastly is the theory of motivation and emotion. Motivation is a key element in learning. It is the driving force towards achieving behavioral changes. Maslow's Hierarchy of Needs has regularly been spoken to in a various leveled pyramid with five levels (Cherry, 2015). The first four pyramid levels form humans physiological needs while the highest level of self actualization gets viewed as a d evelopment need for an individual. The lowest needs must get met or satisfied first before one aspires to address the higher range needs as long as far as the pyramid is concerned. The levels are as per the following. First, Self-actualization entails one's ability to invent new ideas, think critically, show great charisma, and ability to conduct intense research among others. Self-esteem needs involve confidence, accomplishment, the certainty of progress, and regard for other people (Jerome, 2013). Belongingness incorporates love, fellowship, closeness, family, and so forth. Security integrates security of condition, work, assets, well-being, property, and so forth. Physiological incorporates air, sustenance, water, sex, rest, different elements towards homeostasis, and so forth. In learning, however, only the highest dual levels act as significant motivators (Lester, 2013). They are the growth needs. The most elevated amount is self-completion or the self-satisfaction. Conduct for this situation is not driven or inspired by lacks but instead one's yearning for self-awareness and the need to wind up noticeably every one of the things that a man is equipped for getting to be. Learning is challenging where obstacles faced are recurrent. However, psychology has developed theories that relate to learning, motivation and improving retention of information. Practice testing and distributed methods use employ the operant conditioning theory of learning. They allow a learner to retain information and retrieve the relevant knowledge in a testing environment. Additionally, including visualization and encoding of knowledge according to linguistic relativism enables learners to absorb information at a faster rate. Finally, motivation is a key driving force, and the desire to achieve the benefits of a learning process is the intrinsic motivator. References Barkley, E. F., Cross, K. P., Major, C. H. (2014). Collaborative learning techniques: A handbook for college faculty. John Wiley Sons. Byrne, J. H., LaBar, K. S., LeDoux, J. E., Schafe, G. E., Thompson, R. F. (2014). Learning and memory. In From Molecules to Networks. Elsevier Inc.. Cherry, K. (2015). Hierarchy of needs.The Five Levels of Maslow's Hierarchy of Needs. About.com Guide. Link. Dunlosky, J., Rawson, K. A., Marsh, E. J., Nathan, M. J., Willingham, D. T. (2013). Improving students learning with effective learning techniques: Promising directions from cognitive and educational psychology. Psychological Science in the Public Interest, 14(1), 4-58. Jerome, N. (2013). Application of the Maslows hierarchy of need theory; impacts and implications on organizational culture, human resource and employees performance. International Journal of Business and Management Invention, 2(3), 39-45. Lester, D. (2013). Measuring Maslow's hierarchy of needs.Psychological Reports,113(1), 15- 17. Melton, A. W. (Ed.). (2014). Categories of human learning. Academic Press. Neisser, U. (2014).Cognitive psychology: Classic edition. Psychology Press. Slavin, R. E., Davis, N. (2006). Educational psychology: Theory and practice. Swets, J. A. (2014).Signal detection theory and ROC analysis in psychology and diagnostics: Collected papers. Psychology Press.