Looks Can Be Deceiving Essays (1861 words) - Logic, Philosophy

Looks Can Be Deceiving Mysteries are once in a while made out of conflicting thoughts introduced together, at last prompting an unworkable circumstance. Conundrums, be that as it may, are definitely not essentially uncertain inquiries. Catch 22s are the pith of the characteristic multifaceted nature of frameworks (Internet 1). Every conundrum must be broke down and obviously comprehended before it tends to be clarified. Since arithmetic is, it could be said, an all inclusive language, certain oddities and logical inconsistencies have emerged that have grieved mathematicians, dating from old occasions to the present. Some are bogus Catch 22s; that is, they don't present real inconsistencies, and are simply smooth rationale stunts. Others have shaken the very establishments of science ? requiring splendid, inventive numerical speculation to determine. Others remain uncertain right up 'til today, however are thought to be feasible. One repeating subject concerning conundrums is that every one of them can be explained somewhat of fulfillment, yet are rarely totally convincing. At the end of the day, new replies will probably supplant more seasoned ones, trying to harden the appropriate response and explain the issue. A Catch 22 can be characterized as an unsatisfactory end inferred by clearly adequate thinking from evidently worthy premises. This paper gives a prologue to a scope of Catch 22s and their potential arrangements. What's more, a poll was created so as to show the degree of information that everyone has relating to mysteries. Catch 22s are helpful things, regardless of their astounding appearance. For the most part, be that as it may, most Catch 22s can be settled via looking for explicit properties that they may contain. Accordingly, on the off chance that you attempt to portray a circumstance and you end up with a Catch 22 (conflicting result), it for the most part implies that the hypothesis isn't right, or the hypothesis or the definitions separate en route. Likewise, it is conceivable that the circumstance can't in any way, shape or form happen, or the inquiry may essentially be futile for some other explanation. Any of these conceivable outcomes are pertinent, and on the off chance that you exhaust all the potential translations, one of them ought to end up being off base (Internet 1). The accompanying sort of mystery is called Simpson's Conundrum. This conundrum includes an obvious logical inconsistency, since when the information are introduced one way, one specific end is derived. Be that as it may, when the same information are introduced in another structure, the contrary end results. Mystery 1: Acceptance Percentages for College An and College Chart 1 Section A Area B Accepted Rejected Total Percent Accepted Rejected Total Percent Passing Women 400 250 650 61% 50 300 350 14% Men 50 25 75 67% 125 300 425 29% Total 450 275 725 175 600 775 As is clear in Chart 1, when the information are introduced in two separate tables, it looks as though men are acknowledged all the more regularly than ladies, in light of the fact that for each situation (College An and College B), men are acknowledged at a higher proportion than ladies. Nonetheless, when similar information are consolidated into one table (Chart 2), a negating result is inferred. Acknowledgment Percentage Totals for the University Chart 2 Accepted Rejected Total Percent Accepted Women 450 550 1000 45% Men 175 325 500 35% Total 625 875 1500 This table shows ladies in reality having a higher in general acknowledgment rate than men. This is a case of Simpson's Paradox since it includes misdirecting information. Clearly, the introduction of the information is significant, and can prompt wrong suppositions if the information are not utilized appropriately (Internet 2). Conundrum 2: An Arrow in Flight One can envision a bolt in flight, toward an objective. For the bolt to arrive at the objective, the bolt should initially travel half of the general good ways from the beginning stage to the objective. Next, the bolt should travel half of the remaining separation. For instance, if the beginning separation was 10m, the bolt first ventures 5m, at that point 2.5m. On the off chance that one broadens this idea further, one can envision the subsequent separations getting littler and littler. Will the bolt ever arrive at the objective? (Web 3) The appropriate response is, obviously, yes the bolt will arrive at the objective. Our good judgment lets us know so. Be that as it may, numerically, this reality can be demonstrated on the grounds that the aggregate of a limitless arrangement can be a limited number. The question contains a reason, which suggests that the unending arrangement will result in an interminable number. Consequently, 1/2 + 1/4 + 1/8 + ... = 1 and the bolt hits the target (Internet 3). Mystery 3: Two Equals One? Expect that a = b. (1) Duplicating the two sides by an, a? = abdominal muscle. (2) Subtracting b? from the two sides, a? - b? = abdominal muscle - b? . (3) Factoring the two sides, (a + b)(a - b) =

The Quintessential Rebel :: essays research papers

The Quintessential Rebel In Allan Sillitoe’s The Loneliness of a Long Distance Runner, we are acquainted with Smith, a man with his own norms, convictions, qualities, and fights. As we are taken through the account of a time of his live, we come to comprehend what Smith truly rely on. He is a diehard rebel that is bound to consistently adhere to his convictions, and is happy to forfeit all in a fight against his most prominent adversary and opressor, society.      Throughout the book Smith allows us to become acquainted with him. He energetically shares his musings with the peruser, and frequently his considerations create as he is recounting to his story surrendering us a nearby gander at the internal operations of Smith’s brain and character. Smith has a place with a gathering of individuals he gets the Out-Laws. It is the oppressed lower class poor road hoodlums. Wrongdoing runs in Smith’s family, and being naturally introduced to destitution he under observes, nor is in any event, ready to think about an existence without wrongdoing. At a point he indicates on having some socialist perspectives, and maybe recommends that his dad had socialist companions, on the off chance that he wasn’t one himself. Lethally perpetrated by malignant growth, Smith’s father passed on an excruciating demise. We later discover that it was Smith who discovered his dad short of breath in his very own pool blood, and right up 'til the present time has a lot of regard for him. The first run through Smith’s family experiences a monetarily agreeable life is the point at which the plant his dad worked in gave them a piece of money upon his father’s passing. â€Å"†¦a wad of fresh blue-back fivers ain’t a sight of good† (Sillitoe, 20) says Smith as the one break his family got was distinctly because of his father’s passing. Smith isn't cash hungry, he prepares essentially to get by. He knows precisely where he remains on the planet in direct restriction of the In-laws, the â€Å"pig-confronted nasty nosed dukes and ladies"†(Sillitoe, 8). He understands that he is a poor no one, a unimportant lawbreaker, an outsider of society.      Smith naturally is an agitator. He places himself and his individual Out-laws in direct resistance of the rest; for him it’s â€Å"us versus them†. As we are becoming more acquainted with Smith, he is investing his energy in a Borstal subsequent to having been gotten for a pastry shop theft. He has no second thoughts about doing what he did in the bread kitchen shop, and has a large enough heart to be glad for his associate, Mike for getting off.

Norepinephrines Role in Treating Mood Problems

Norepinephrines Role in Treating Mood Problems Bipolar Disorder Treatment Medications Print Norepinephrines Role in Treating Mood Problems By Marcia Purse Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing. Learn about our editorial policy Marcia Purse Medically reviewed by Medically reviewed by Steven Gans, MD on February 14, 2017 Steven Gans, MD is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital. Learn about our Medical Review Board Steven Gans, MD Updated on May 08, 2019 -Oxford-/ GettyImages More in Bipolar Disorder Treatment Medications Symptoms Diagnosis Norepinephrine, also known as noradrenaline, is both a hormone and a brain neurotransmitter, or chemical. Its mainly stored in the neurons (nerve cells) of the  sympathetic nervous system  with small amounts also stored in adrenal tissue, which  lay on top of your kidneys. As a hormone, norepinephrine is released into the bloodstream by the adrenal glands and works alongside adrenaline (also known as epinephrine) to give the body sudden energy in times of stress, known as the fight or flight response. As a neurotransmitter, norepinephrine passes nerve impulses from one neuron to the next. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Medications that inhibit the reuptake of norepinephrine and serotonin  (which is  another neurotransmitter) are called serotonin-norepinephrine reuptake inhibitors (SNRIs). By inhibiting the reuptake of these two neurotransmitters, SNRIs essential increase the levels of norepinephrine and serotonin in the brain. Serotonin makes a person feel good and norepinephrine improves energy and attentiveness. SNRIs have been found to be effective in treating mood disorders like depression, bipolar disorder, and anxiety disorders.  SNRIs are also sometimes prescribed for chronic pain and fibromyalgia. SNRIs for Treating Mood Disorders The SNRIs approved for use in major depression include Cymbalta (duloxetine), Effexor (venlafaxine) and Pristiq (desvenlafaxine), but there are others approved for other illnesses as well. Although no antidepressants, including SNRIs, have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bipolar disorder, they are sometimes prescribed as part of an individual treatment plan. Common Side Effects of SNRIs SNRIs may increase a persons blood pressure, so your doctor may want to monitor your blood pressure if he prescribes one. If you already have difficult to control blood pressure, an SNRI may not be a good option for you. These side effects often go away after a couple of weeks, but if they dont or they are particularly bothersome, be sure to contact your doctor. Some common side effects of SNRIs include: DizzinessDry mouthSweating more than usualUpset stomachFatigueHeadacheLosing your appetiteConstipationSexual difficultiesAnxietyDifficulty urinating The Family of Serotonin-Norepinephrine Reuptake Inhibitors Each of these SNRIs is a little bit chemically different from the others. Effexor (Venlafaxine) Effexor was the first SNRI to be approved in the United States in 1993. It has been approved by the FDA for depression, panic disorder, social phobia, and generalized anxiety disorder (GAD). Effexor inhibits the reabsorption of serotonin quite a bit more than it does norepinephrine. Cymbalta (Duloxetine) In 2004, Cymbalta was the second SNRI to be approved in the United States.  of the way it works, it has the highest number of FDA-approvals to treat illnesses, including diabetic peripheral neuropathy, depression, generalized anxiety disorder, fibromyalgia, osteoarthritis, and nerve pain. Like Effexor, Cymbalta also favors inhibiting the reabsorption of serotonin over norepinephrine, but to a lesser degree. Pristiq (Desvenlafaxine) Pristiq, the third SNRI to be approved. has only been approved to treat major depression so far. Chemically, Pristiq works very similarly to Cymbalta.   Savella (Milnacipran) This is the fourth SNRI to be approved in the U.S. to treat fibromyalgia. Savella works by inhibiting the reabsorption of both serotonin and norepinephrine equally and may even favor norepinephrine, according to some sources. Fetzima (Levomilnacipran) The most recent member introduced to the SNRI family, Fetzima was approved by the FDA in 2013 and has also only been FDA-approved for treating depression. Fetzima inhibits norepinephrine reabsorption twice as much as serotonin reabsorption, making it unique among the SNRIs.

Saying So-so; Mediocre in Mandarin Chinese

The rules of etiquette in Chinese culture state that compliments must be rejected. Therefore, if someone tells you that you speak Mandarin well, a good way of responding would be, â€Å"Not at all, my Mandarin is very poor.† One way of saying this is with the Mandarin Chinese phrase mÇŽmÇŽhÃ… «hÃ… «. This could be prefaced with nÇŽli nÇŽli, which means â€Å"where?†Ã¢â‚¬â€as in, â€Å"Where is my good Mandarin? I don’t see it.† MÇŽmÇŽhÃ… «hÃ… « is made up of four Chinese characters: é © ¬Ã© © ¬Ã¨â„¢Å½Ã¨â„¢Å½/é ¦ ¬Ã© ¦ ¬Ã¨â„¢Å½Ã¨â„¢Å½ (the second is traditional Chinese). The first two characters mean â€Å"horse† and the second two characters mean â€Å"tiger.† This makes the phrase very easy to remember, but why does â€Å"horse horse tiger tiger† mean â€Å"mediocre?† It’s neither one nor the other—it’s so-so, mediocre. Example of Mama Huhu Click on the links to hear the audio. NÇ  de guà ³yÇ” shuÃ…  de hÄ›n hÇŽo.ä ½  Ã§Å¡â€žÃ¥Å"‹è ªÅ¾Ã¨ ª ªÃ¥ ¾â€"Ã¥ ¾Ë†Ã¥ ¥ ½Ã¤ ½  Ã§Å¡â€žÃ¥â€º ½Ã¨ ¯ ­Ã¨ ¯ ´Ã¥ ¾â€"Ã¥ ¾Ë†Ã¥ ¥ ½Your Mandarin is very good.NÇŽli nÇŽli - mÇŽmÇŽ hÇ”hÇ”.å“ ªÃ¨ £ ¡Ã¥â€œ ªÃ¨ £ ¡ é ¦ ¬Ã© ¦ ¬Ã¨â„¢Å½Ã¨â„¢Å½Ã¥â€œ ªÃ©â€¡Å'å“ ªÃ©â€¡Å' é © ¬Ã© © ¬Ã¨â„¢Å½Ã¨â„¢Å½Not at all—it’s very bad. It should be noted that this phrase is very common in many beginner textbooks, but that few native speakers actually use it and it might come across as a bit strange or out-dated. Its a little bit similar to textbooks in English as a second language having its raining cats and dogs because its a cute expression that students like, but very few people actually say that. Its fine to use, of course, but dont be surprised if you dont hear other people saying it all the time.

Women Venetian Societal Views - 1156 Words

Race. Women. Men. Class. Poor. Rich. Royalty. In Shakespeare’s play, Othello, many issues are explored through a tragedy. The rights of women are being put to the test. There are three women, Bianca, Desdemona, and Emilia that play a major role in Othello. In the Elizabethan Era women were neither very respected, nor considered to be intelligent. Yet, the women hold most of the power in the Tragedy of Othello. The women are also the only characters that are able to maintain the trust among themselves and with others in the play. From being submissive to standing up for them, Othello holds understanding for women’s abilities in England during the 16th century. Shakespeare introduces and explores the issues of women’s rights, for better understanding, through the art of acting. Many people think that Desdemona, a wife to a powerful man, should have had more say in her own decisions. Feminism is seen as a strong problem in this historical period. There was not a choice between what the husband and the wife said. Sadly, what the husband says; goes. Whether this is the case or not, Desdemona herself says, â€Å"I am obedient† (Shakespeare 3.3), as she obeys Othello’s orders when they had a happy relationship. Through the relationship changes, Othello goes off in jealousy rages. She answers everything with â€Å"I will, my lord† (Shakespeare 4.3), even when the going gets rough. She is acceptant of her role as a submissive and an obedient wife. Emilia is a stronger characterShow MoreRelatedWomen Of The Elizabethan Society1471 Words   |  6 Pages Women of the Elizabethan society, such as in Shakespeare’s Othello, are particularly not considered as equal. Women were more often seen as less of people who need to be helped and aided by man. This ideology was spread by both men and women of that time by them playing into the gender roles of male and female. Othello gives a relative example of the male and female ideology being accepted and spread throughout society in the Elizabethan age. With it only being three women in the play, DesdemonaRead More Mens Control in William Shakespeares The Merchant of Venice1437 Words   |  6 Pagescontrolled by men. Men, who live in the foreground of Venetian society, wield their power in business, government, and family life. In the background, women conduct their lives quietly. They are subservient to their husbands and fathers and are regarded as helpless and in need of male guidance in areas of decision making. Though in Shakespeare’s time such a societal structure was largely acceptable, the modern reader views the subjugation of women with aversion, and the ways in which Shakespeare presentsRead MoreThe Women in Othello Essay1080 Words   |  5 PagesThe women in Othello are synonymous with Venetian societal standards. Only three women are characters in Othello: Desdemona, Emilia and Bianca but the roles these women play give the reader an idea of how women were portrayed, not only in Shakespeares Othello but i n society in general. Women were viewed merely as possessions. After the Duke allows Desdemona to accompany Othello to Cyprus, Othello says To my conveyance I assign my wife (I.3.283), this statement implies that Desdemona and a possessionRead MoreWilliam Shakespeare s Othello, The Moor Of Venice Essay1251 Words   |  6 PagesMoor of Venice by William Shakespeare, the women take on various roles in this Venetian society. The roles include committing fraud, playing the part of the victim, and playing the part of the hero. In this Venetian society in the 1600s, the women served major purposes and were vital to keep the towns running. However, the women also faced being victimized and stereotyped in this man-run society. Women were inferior to men, treated unequally, and women were also viewed as sexual objects rather thanRead MoreWomen s Treatment Of Women837 Words   |  4 Pagesthroughout history. From times of severe incarceration to the near-equality of today, many valuable generalities can be drawn about societies from their treatment of women. Elizabethan Great Britain, heading the way of the medieval Renaissance, introduced previously unheard of customs of treating women. In Shakespeare’s â€Å"Othello†, women play integral roles in the outcome of the play yet are treated just as poorly, if not more so, than the racially and socially oppressed Othello, the â€Å"Moor of Venice†Read MoreTheories of Entrepreneurship1647 Words   |  7 Pageshow society affects the actions of male and female entrepreneurs in similar and varying ways. Societal norms and conditions, in many parts of the world, influence not only the actions of entrepreneurs but also their personalities and behavioural traits and mind set. Sociological Theory of Entrepreneurship The sociological theory of entrepreneurship examines the influence of cultural and ideological views, social relationships and networks and organisational and structural factors on entrepreneurialRead MoreA Comparative Study of Othello and O991 Words   |  4 Pagesuniversal themes such as race and gender through the use of literary techniques appropriate to audiences of the time. ‘Othello’ was written in the Elizabethan era. Its characters and their language reflected much of the white European society’s views of race and gender. People of colour in England at that time were exceedingly rare. Those that there were were an unfamiliar sight, and they provoked feelings of distrust, hostility and mystery. The idea of a baptised Moor, much esteemed by the senatorsRead MorePeople Who Dont Fit the Norm1468 Words   |  6 PagesMaurice Gee, and Shakespeares `Othello. This report discusses some common themes that I discovered amongst these texts, I outline how these texts represent a common idea that literature both New Zealand and European, is trying to portray societys views on people and what is considered `normal. How influential are main characters personas in portraying people who dont `fit the norm? In one of the opening scenes in the film `The Piano, the main character Adas appearance immediately makesRead MoreAnalysis Of Guy De Maupassant s `` The Necklace `` Essay1463 Words   |  6 Pagesbasis for â€Å"The Necklace†, wrote in 1884. In this short story, Maupassant uses third-person objective point of view with cleverly contrast and ironic setting but also figurative background accross the plot to paint a picture of a typical low-paid clerk’s family in 1880s French society. The protagonist, Madame Matilda Loisel, throughout the story has demonstrated a theme of disparage societal position based on money, fame and glamour. As said before, one of Maupassant’s signature style of writing isRead MoreWilliam Shakespeare s Othello - Reconsidering Loyalty And Honesty2431 Words   |  10 Pagesand calls Iago a betrayer. Shakespeare does not waste any time developing the manipulative character of Iago, as his Machiavellian actions are introduced in the first scene of Othello. Iago is a soldier in the Venetian army, who wanted the position of the lieutenant. When Othello, the Venetian army general, appoints Cassio to this position instead of Iago, he begins to portray a revengeful character with problematic actions. When Iago states, â€Å"I am not what I am† (1.1.64), this is the first notion

Carbohydrate and Peptide †Based Vaccines The Way Forward Free Essays

string(85) " being developed against certain types of pneumococci \(Francis and Tillett, 1930\)\." Abstract Existing treatments and therapies have supported a huge variety of diseases and infections, a significant example being antibiotics. However the increasing presence of multi-resistant bacteria, as well as increased changes observed in the mechanisms responsible for variation in viruses, involving accumulation of mutations within the genes that code for antibody-binding sites (known as antigenic drift), has resulted in these new strains not being inhibited as effectively by those treatments that originally targeted them (Reche, Fernandez-Caldas, Flower, Fridkis-Hareli and Hoshino, 2014). The knock-on effect has been that the bacteria or virus is able to spread more easily, and therapeutic treatments (used after a person contracts a disease), become less effective, unable to work by boosting the host’s own immune system. We will write a custom essay sample on Carbohydrate and Peptide – Based Vaccines: The Way Forward or any similar topic only for you Order Now As a result, it has been recognised that the vaccine offers the advantage of preventing the anticipation of disease occurrence, using advance action to counteract infection and chronic illness. Prophylactic, and to a lesser extent therapeutic, vaccines are the most cost-effective and efficient alternative to other treatments and prevention of infectious and chronic diseases. They work by causing changes to the T- and B-cells of the adaptive immune system to eliminate or prevent pathogen growth (Plotkin, Orenstein, and Offit, 2013). Going back to the introduction of vaccines more than 200 years ago, these were initially composed of killed pathogens, which although successful, also caused unacceptably high levels of adverse reactions. During the years of research that have since followed, as with the changes observed with antibiotics and other treatments becoming less effective, the need for safer and more effective vaccines has also been acknowledged. In addition, an improved underst anding of antigen presentation and subsequent recognition has supported the development of newer vaccine types (Flower, 2013). Equally, whilst many diseases and infections are controlled by vaccines, for some, no vaccines have been developed, including Streptococcus pyogenes, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) (Wang and Walfield, 2005; Barrett and Stanberry, 2009). Efforts to develop new vaccines are discussed in more details, with a focus on peptide-based and carbohydrate-based vaccines. Challenges are also discussed, leading to a summary of the potential direction of vaccination and research, which describes a promising future. Peptide-based vaccines An example of a newer category of vaccine is peptide-based vaccines. Peptides are short sequences of proteins, and diseases/infections use these proteins as part of their attack on the immune system. In many cases, the immune system has the ability to recognise the proteins associated with an attack by disease or infectious causing pathogens and can respond effectively. However as observed with many cancers, HIV, HCV and other conditions, an effective immune response is not triggered, hence the need for newer vaccine developments including those based on peptides, which encompass single proteins or synthetic peptides encompassing many antigenic determinants (B- and T-cell epitopes) (Flower, 2013). Peptide vaccines are a type of subunit vaccine, which presents an antigen to the immune system, using the peptide of the original pathogen, supporting immunity. Such peptide-based vaccines avoid the adverse effects described with traditional whole-organism vaccines (Moisa and Kolesanova, 20 12) with additional benefits also noted (Ben-Yedidia and Arnon, 1997), including: The absence of infectious material An immune response that is specific, focusing only on the targeted epitope, with the induction of site-specific antibodies No risk of an immune attack or cross-reactivity with the host tissues Flexibility, with an ability to modify products accordingly Improved effectiveness in relation to manufacturing on a large scale, and long-term storage where necessary e.g. a pandemic. However, a number of difficulties have been encountered during the development of such vaccines (Simerska, Moyle and Toth, 2011; Dudek, Perlmutter, Aguilar, Croft and Purcell, 2010) including: A short biological activity of peptides due to degradation by enzymes The trigger of a weak immune response when used alone i.e. single peptides Finding optimal delivery systems. As a result, and to overcome the difficulties mentioned above, synthetic peptide vaccines have been developed, on the basis that a greater more accurately targeted immune response will be achieved. Peptide antigens are not immunogenic by themselves, so this has led to investigations into co-administration of subunit peptide antigens with adjuvants (immunostimulants) to increase the peptide-induced responses to corresponding antigens. Appropriate delivery systems and often toxic adjuvants have demonstrated effective immunity, however, although many adjuvants are described in the literature, only a few have been approved for use with vaccines for delivery in humans due to their toxicity and include water/oil emulsions, liposomes, and bacterial lipophilic compounds to offer a few examples (Heegaard et. al., 2010). Incomplete Freund’s adjuvant (IFA) and Montanide ISA (both oil-based) have been used in clinical trials. Focusing on liposomes as another example, researchers have demo nstrated that use of lipid core peptide (LCP) technology (lipidation of peptides) improves the effectiveness of a self-adjuvanting vaccine delivery system, targeting a specific disease and triggering an effective immune response. This system provides a promising platform for human vaccine development (Zhong, Skwarczynski and Toth, 2009; Moyle and Toth, 2008). In animal models, peptide vaccines have been effective in generating the required immune response, and during recent years, peptide-based vaccines have advanced from animal models and pre-clinical studies, to human clinical trials (Yang et al., 2001). Although currently, all known peptide vaccines under development for humans remain at the stage of clinical trials, these trials should build on the promising evidence resulting from research to date of the potential application of vaccine candidates based on a LCP system, as well as other strategies. Prevention of not only many infectious diseases including hepatitis C virus, malaria, human immunodeficiency virus and group A streptococci), but also for cancer immunotherapy and improved allergen specific tolerance, remains an exciting, and very real possibility. Carbohydrate-based vaccines The development of vaccines based on carbohydrates not only has quite a history, but is also an area that is fast moving in the current research world. The literature provides evidence as far back as the early 1900s where researchers discovered a connection between type-specific polysaccharides and the induction of antibodies being developed against certain types of pneumococci (Francis and Tillett, 1930). You read "Carbohydrate and Peptide – Based Vaccines: The Way Forward" in category "Essay examples" This was confirmed by evidence of pneumococcal capsular polysaccharides being used as vaccines, providing effective and long lasting immunity (Heidelberger, Dilapi, Siegel and Walter, 1950). However despite these early findings, the discovery and success of other treatments such as antibiotics and chemotherapeutics led to this area of research being put on hold. As mentioned earlier however, due to increased resistance to existing treatments such as antibiotics, coupled with th e recognition for a need of newer treatments including improved vaccines, renewed interest into preventive vaccines has resulted in novel approaches, which include carbohydrate vaccines. Vaccines are commonly made from weakened pathogens, or, as we now know, other approaches also use immunogenic proteins or polysaccharides. Carbohydrates have been the centre of attention in the research field of vaccination because not only do they exhibit more stability than proteins, but they have roles in both physiology and pathophysiology, including cell interaction and signalling, inflammation, pathogen host adhesion/recognition, to name a few examples (Doshi, Shanbhag, Aggarwal, Shahare and Martis, 2011). During the last ten years or so, they have been used as adjuvants, as carriers for protein antigens to aid immunotherapy, and as targets for vaccines against bacteria. Additionally, as observed with DNA and proteins, carbohydrates are now recognised as biopolymers also, playing a role in many molecular and biological activities (Doshi et. al., 2011). These discoveries, partnered by an improved understanding of the immune system and the identification of specific and relevant carbohydrate structures, led to the development of glycoconjugates, which in turn led to carbohydrate vaccine development (Holemann and Seeberger, 2004). Glycoconjugates are present in the surfaces of cells, as well as in the surrounding extracellular matrices and connective tissue. Therefore both the identified structure and presence of glyconjugates, plus the role they play, means they are a suitable basis for the development of new vaccines. Induction of protective antibodies is key to an effective immune response as a result of a vaccine, and as with peptide vaccines, challenges have been evident in the research to develop effective carbohydrate vaccines, including the following: Glycans struggle to effectively induce protective antibodies Carbohydrates have a low immunogenic impact by themselves (as observed with peptides). There are two main carbohydrate vaccine types: 1. Natural carbohydrate vaccines: these include small amounts of impurities 2. Synthetic carbohydrate vaccines: these are produced with no contaminants, and are cost-effective due large-scale production. Synthetic carbohydrate antigens used to develop vaccines have triggered immune responses in clinical studies and are favourable given the risk of adverse effects with natural vaccines. Four crucial aspects need to be considered for the design of carbohydrate-based vaccines (Astronomo and Burton, 2010): The antigen source: glycan antigens are diverse, ranging from large polysaccharide capsules, to small monosaccharides, to oligosaccharides, all of which have been shown to be adequate for preparation of vaccines. The carrier: this is most often proteins, although other materials have been investigated, with the aim of ensuring that the link between the antigen and the carrier is specific. The method of conjugation (or ligation): protein conjugates, lipid conjugates and polyvalent scaffold conjugates have been developed. The success of a conjugate vaccine depends partly on the method of conjugation employed. This should be simple and efficient, as well as causing minimal distortion to the individual components involved, with many differing techniques used (Zou Jennings, 2009; Ada and Isaacs, 2003). The choice of adjuvant: required to improve immunogenicity of the carbohydrate antigens being targeted, with a limited choice approved for use in humans. Examples of diseases targeted by carbohydrate-based vaccines The discussion will now move on to the use of carbohydrate-based vaccines in three disease areas: Group A Streptococcus (GAS), HIV/AIDS and Haemophilus influenza type b. GAS The need for a safe, effective, affordable and practical vaccine against GAS (also known as Streptococcus pyogenes), has been recognised for many years, as has the research into a vaccine against this disease, given the global burden on health that this disease causes in particular in less developed countries. More than 500,000 deaths result from the GAS each year, with the bacteria causing a range of both less complicated and life-threatening illnesses (Carapetis, Steer, Mulholland and Weber, 2005). The diversity of GAS strains is the major challenge for the development of an anti-GAS vaccine, with more than 100 different strains identified, of which the genetic sequence for several different strains have been determined (Johnson and Pinto, 2002). Research has identified that GAS bacteria contain a surface polysaccharide made up of long, repetitive polysaccharide chains. The conserved and constant arrangement of these chains suggests conjugate vaccines to be an attractive and achiev able option, with animal models supporting this theory (Cunningham, 2000). Synthetic carbohydrate vaccines, although only studied in a limited set of GAS infections, have demonstrated a protective immune response (Robbins et al., 2009). In addition, some areas of research have focused on the molecular analysis of a surface protein labelled the M protein, which is encoded by the emm gene. This particular gene has been found to be the major cause of GAS related clinical manifestations (Smeesters, McMillan and Sriprakash, 2010). These findings have allowed a greater understanding of the functioning of specific proteins responsible for the virulence of the disease, which in turn, supports the development of potential GAS vaccines. Vaccine prevention of GAS and the resulting symptoms and complications has been a goal of researchers for many years. A number of vaccines have been in research development to offer protection against GAS, with the research vaccine strategies focusing on eithe r M protein, or non-M protein antigens (Smeesters, 2014). However only those vaccines that use the M protein as the antigen have progressed to clinical trials (McNeil et. al., 2005), and have included conserved antigens coverage across the many strains of GAS, a type-specific vaccine based on the N-terminal portion of the M protein, and a recombinant vaccine that reached phase II clinical trials (Pandey, Wykes, Hartas, Good and Batzloff, 2013; Bauer, 2012). However no vaccine has currently reached licensing and so the diseases caused remain uncontrolled in many areas, with reviews covering the research suggesting that even those vaccines developed with the aim of providing large coverage of GAS strains, these vaccine might achieve acceptable coverage in developed countries, but in less developed countries where the disease burden is much greater, the positive impact of the vaccines would be much lower due to a greater strain diversity (Smeesters, McMillan, Sriprakash, and Georgousak is, 2009; Steer, Law, Matatolu, Beall and Carapetis, 2009; McMillan and Sanderson, 2013). Equally, antibiotic treatment is either impractical with regards to implementation (specifically in less developed countries) or ineffective. One research group targeted the bacteria by synthesising a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, resulting in successful synthesis and characterisation of the vaccine candidate. This may contribute to the identification of a safe and effective vaccine against GAS in the future (Simerska et. al., 2008; Simerska, Lu and Toth, 2009). HIV/AIDS One of the main challenges researchers have faced within the field of vaccine development against HIV/AIDS, is that the virus surface is covered with layers of glycans, which conceal underlying viral antigens that are potential good targets in the production of vaccines (Scanlan, Offer, Zitzmann, and Dwek, 2007). They are produced by the host cell, which makes the virus appear as â€Å"self† resulting in no attack being triggered by the host immune system. The layers of carbohydrate also contain mannose residues, making these another potential target for a vaccine aimed at preventing HIV infection, whereby lectins preferentially bind to ? 1-2 linked mannose residues. Such lectins are being investigated as possible therapeutic tools (Tsai et al., 2004) although the fact that lectins are often toxic needs to be researched further to avoid the host immune system damaging host cells. Indeed, other drugs that are known to inhibit synthesis of carbohydrates only have this effect at often toxic concentrations to cause antiviral activity. Another strategy based on the same principle of developing a carbohydrate vaccine, is the identification of antibodies that again recognise and bind to glycans. (Scanlan et al., 2002, Scanlan et al., 2007). The antibody appears to recognize these glycans because although they belong to the host, they are arranged in a â€Å"non-self† manner (Scanlan et al., 2002; Scanlan et al., 2007), making the production of effective ant-HIV vaccines a real possibility, in addition to vaccines for other diseases such as cancer (Galonic and Gin, 2007). Studies have also been described using immune enhancing adjuvants, carrier peptides such as keyhole limpet hemocyanin and altered glycan structure constructs that support immune recognition in the development of vaccines against cancer (Galonic and Gin, 2007). These same strategies are being used in development of possible HIV vaccines, where antibodies target self-carbohydrates arranged slightly differently on cancer cells and HIV-infected cells, in comparison to healthy cells. (Galonic and Gin, 2007). These approaches have not as yet led to clinically effective vaccines, but it is clear that antibodies that strongly bind to carbohydrate antigens on, for example, prostate cancer cells, have been generated (Slovin et al., 2003) and this appears to be a highly promising approach. Further exploration is required based on the carbohydrate coat of the virus, which may lead to improved prevention treatment of HIV. Haemophilus influenza type b The first synthetic vaccine for human application was developed in 2003 for protection against Haemophilus influenza type b vaccine, not only providing protection against this bacterium, but also against all the associated diseases it causes ranging from meningitis, septicaemia, pneumonia and arthritis (Doshi, Shanbhag, Aggarwal, Shahare and Martis, 2011). Indeed this bacterium is the leading cause of serious illnesses in children under 5 years worldwide. The majority of strains of Haemophilus influenza are non-encapsulated, and are lacking in any carbohydrate polysaccharide protective structure, as opposed to the GAS bacteria and HIV virus described earlier. This structural information armed researchers with the knowledge that carbohydrate polysaccharide conjugate vaccines would be required to ensure the development of an effective vaccine (Verez-Bencomo et. al., 2004). As a result, carbohydrate-based vaccines have been licensed for protection in humans against haemophilus influenza type b, using oligomerization and a carrier protein (Doshi et. al., 2011). Evidence of progress To end this section of the discussion, several conjugate polysaccharide carbohydrate vaccines are now well into pre-clinical/clinical development, or have been licensed and are now commercially available. Examples of licensed vaccines include the following (Astronomo and Burton, 2010): Haemophilus influenza type b (Hib) – 4 carbohydrate-based vaccines are licensed via 3 different pharmaceutical companies: ActHIB and Hiberix; Pentacel; PedvaxHIB; and Comvax Neisseria meningitides A, C, Y and W-135 – 2 carbohydrate-based vaccines are licensed via the same pharmaceutical company: Menactra; and Menomune-A/C/Y/W-135 Salmonella typhi – 1 carbohydrate- based vaccine is licensed: TYPHIM Vi Streptococcus pneumonia variants – 2 carbohydrate-based vaccines are licensed via 2 different pharmaceutical companies: Prevnar; and Pneumovax 23. Examples of carbohydrate-based vaccines in development include the following, where the disease is described in addition to the phase of development (Astronomo and Burton, 2010): Breast cancer – with 1 vaccine at the preclinical phase and a second at phase I Prostate cancer – 4 vaccines are in development at the preclinical, phase I and phase II stages HIV-1 – 1 vaccine at the preclinical phase Group A streptococcus – 1 vaccine at the preclinical phase Group B streptococcus – 1 vaccine at phase II. Conclusion It is fact that vaccines have had a major role to play in the success of preventing and treating many diseases, however many challenges remain. Diseases exist for which no effective vaccines have yet been discovered, including HIV/AIDs. In addition, diseases that have been controlled by vaccines in some parts of the world continue to affect the lives of people adversely in other areas where infrastructures for vaccination are poor/non-existent. Continued research is necessary to develop vaccines not only for those diseases with no vaccine available, but also to improve the effectiveness of existing vaccines. In addition to research focusing on novel and promising approaches such as carbohydrate and peptide based vaccines, efforts also need to concentrate on areas such as lower cost, more convenient delivery of vaccines, and longer-term protection. The future direction of research in this field has become focused with the help of new evidence-based information and promising data. The advent of synthetic peptide-based and carbohydrate-based vaccines signified a new era for vaccines, over-taking traditional treatments and vaccines which have become either ineffective or only offer short term protection. As the discussion demonstrates, a number of vaccines are already successfully protecting humans against some pathogens and disease, with the potential for further vaccines to follow. Finally, and perhaps most importantly, it should be remembered that unlike drug-based medicines, vaccines primarily offer a cure, a goal all aim to achieve. Word count: 3130 (excluding references) References Ada, G. Isaacs, D. (2003). Carbohydrate-protein conjugate vaccines. Clinical Microbiology and Infection. 9(2): p. 79-85. Astronomo, R.D. Burton, D.R. (2010). Carbohydrate vaccines: developing sweet solutions to sticky situationsNature Reviews: Drug Discovery. 9: p. 30-324. Barrett, A.D.T. Stanberry, L.R. (Eds.). (2009). Vaccines for Biodefense and Emerging and Neglected Diseases. Elsevier Inc., ISBN 978-0-3-69408-9. Bauer M.J., Georgousakis M.M., Vu T., Henningham A., Hofmann A., Rettel M., Hafner L.M., Sriprakash K.S. McMillan D.J. (2012). Evaluation of novel streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein. Vaccine. 30(12): p. 2197-2205. Ben-Yedidia, T. Arnon, R. (1997). Design of Peptide and Polypeptide Vaccines. Curr. Opin. Biotech. 8(4): p. 442-448). Carapetis, J.R., Steer, A.C., Mulholland E.K. Weber, M. (2005). The global burden of group A streptococcal diseases. Lancet Infect Dis. 5(11): p. 685-694. Cunningham M. (2000). Pathogenesis of group A streptococcal infections. Clin Microbiol Rev. 13: p. 470-511. Doshi, G.M., Shanbhag, P.P., Aggarwal, G.V., Shahare, M.D. Martis, E.A. Carbohydrate Vaccines- A burgeoning field of Glycomics. Journal of Applied Pharmaceutical Science 1(02): p. 17-22. Dudek, N.L., Perlmutter, P., Aguilar, M.I., Croft, N.P. Purcell, A.W. (2010). Epitope discovery and their use in peptide based vaccines. Curr Pharm Des. 16: p. 3149-3157. Flower, D.R. (2013). Designing immunogenic peptides. Nature Chemical Biology. 9(12): p. 749–753. Francis Jr, T. Tillett, W.S. (1930). Cutaneous reactions in pneumonia. The development of antibodies following the intradermal injection of type-specific polysaccharide. J. Exp. Med. 52: p. 573–585. Galonic, D.P. Gin, D.Y. (2007). Chemical glycosylation in the synthesis of glycoconjugate antitumour vaccines. Nature. 446: p. 1000–7. Heegaard, P.M.H., Dedieu, L., Johnson, N., Le Potier, M-F., Mockey, M., Mutinelli, F., Vahlenkamp, T., Vascellari, M. Sorensen, N.S. (2010). Adjuvants and delivery systems in veterinary vaccinology: current state and future developments. Arch Virol. 156(2):p. 183-202. Heidelberger, M., Dilapi, M.M, Siegel, Walter, A.W. (1950). Persistence of antibodies in human subjects injected with pneumococcal polysaccharides. J. Immunol. 65l: pp. 535–541. Holemann, A. Seeberger, P. (2004). Carbohydrate diversity: Synthesis of glycoconjugates and complex carbohydrates. Curr Opin In Biotech. 15(1): p. 615-622. Johnson, M.A. Pinto, B.M. (2002). Saturation transfer difference 1D-TOCSY experiments to map the topography of oligosacchraides recognised by a monoclonal antibody directed against the cell-wall polysaccharide group A streptococcus. J Am Chem Soc. 124: p. 15368-15374. McMillan, D.J., Sanderson-Smith, M.L., Smeesters, P.R. Sriprakash, K.S. (2013). Molecular markers for the study of streptococcal epidemiology. Current topics in microbiology and immunology. 368: p. 29-48. McNeil, S.A., Halperin, S.A., Langley, J.M., Smith, B., Warren, A., Sharratt, G.P., Baxendale, D.M., Reddish, M.A., Hu, M.C., Stroop, S.D., Linden, J., Fries, L.F., Vink, P.E. Dale, J.B. (2005). Safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adult volunteers. Clin Infect Dis. 41(8): p. 1114-22. Moisa, A.A. Kolesanova, E.F. (2012). Synthetic Peptide Vaccines, Insight and Control of Infectious Disease in Global Scenario. Dr. Roy Priti (Ed.), ISBN: 978-953-51-0319-6. Moyle, P.M. Toth, I. (2008). Self-adjuvanting lipopeptide vaccines. Current Medicinal Chemistry. 15: p. 506–516. Pandey, M., Wykes, M.N., Hartas, J., Good, M.F. Batzloff M.R. (2013). Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help. Journal of immunology. 190(6): p. 2692-701. Plotkin, S.A., Orenstein, W.A. Offit, P,A. Eds (2013). Vaccines. 6th ed. Edinburgh: Elsevier/Saunders. Reche, P.A., Fernandez-Caldas, E., Flower, D.R., Fridkis-Hareli, M. Hoshino, Y. (2014). Peptide-Based Immunotherapeutics and Vaccines. Journal of Immunology Research. Editorial. 2014: 2 pages. Robbins, J.B., Kubler-Kielb, E., Vinogradov, E., Mocca, C., Pozsgay, V., Shiloach, J. Scheerson, R. (2009). Synthesis, characterisation, and immunogenicity in mice of Shigella sonnei O-specific, oligosaccharide-core-protein conjugates. Proc Natl Acad Sci USA. 106: p. 7974-7978. Scanlan, C.N., Pantophlet, R., Wormald, M.R., Ollmann Saphire, E., Stanfield, R., Wilson, I.A., Katinger, H., Dwek, R.A., Rudd, P.M. Burton, D.R. (2002). The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha12 mannose residues on the outer face of gp120. J Virol. 76: p. 7306–21. Scanlan, C.N., Offer, J., Zitzmann, N. Dwek, RA. (2007). Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature. 446: p. 1038–45. Simerska, P.,Abdel-Aal, A.B.M, Fujita, Y., Batzloff, Good, M.F. Toth, I. (2008). Synthesis and in vivo studies of carbohydrate-based vaccines against group A Streptococcus. Peptide Science. 90(5): p. 611-616. Simerska, P., Lu, H. Toth, I. (2009). Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein PL1 epitope. Bioorganic Medicinal Chemistry Letters. 19(3): p. 821-824. Simerska, P., Moyle, P.M. Toth, I. (2011). Modern lipid-, carbohydrate-, and peptide-based delivery systems for peptide, vaccine, and gene products. Med Res Rev. 31: p. 520-47. Slovin, S.F., Ragupathi, G., Musselli, C., Olkiewic,z K., Verbel,D., Kuduk, S.D., Schwarz, J.B., Sames, D., Danishefsky, S., Livingston, P.O. Scher, H.I. (2003). Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with alpha-N-acetylgalactosamine-O-serine/threonine conjugate vaccine. J Clin Oncol. 21:p. 4292–8. Smeesters, P.R., McMillan, D.J. and Sriprakash, K.S. (2010). The streptococcal M protein: a highly versatile molecule. Trends Microbiol. 18: p. 275-282. Smeesters, P.R., McMillan, D.J., Sriprakash, K.S. Georgousakis, M.M. (2009). Differences among group A streptococcus epidemiological landscapes: consequences for M protein-based vaccinesExpert Rev Vaccines. 8(12): p. 1705-20. Smeesters, P.R. (2014). Immunity and vaccine development against Streptococcus pyogenes: is emm-typing enoughProc Belgian Roy Acad Med. 3: p. 89-98. Steer, A.C., Batzloff, M.R., Mulholland, K. Carapetis, J.R. (2009). Group A streptococcal vaccines: facts versus fantasy. Current Opinion in Infectious Diseases. 22(6): p. 544-552. Steer, A.C., Law, I., Matatolu, L., Beall, B.W. Carapetis, J.R. (2009). Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis. 9(10): p. 611-6. Tsai, C.C., Emau, P., Jiang, Y., Agy, M.B., Shattock, R.J., Schmidt, A., Morton, W.R., Gustafson, K.R., Boyd M.R. (2004). Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses. 20(1): p. 11–18. Verez-Bencomo, V., Fernandez-Santana, V., Hardy, E., Toledo, M.E., Rodriguez, M.C., Heynngnezz, L., Rodriguez, A., Baly, A., Herrera, L., Izquierdo, M., Villar, A., Valdes, Y., Cosme, K., Deler, M.L., Montane, M., Garcia, E., Ramos, A., Aguilar, A., Medina, E., Torano, G., Sosa, I., Hernandez, I., Martinez, R., Muzachio, A., Carmenates, A., Costa, L., Cardoso, F., Campa, C., Diaz, M. Roy, R. (2004). A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science. 305(5683): p. 552-555. Wang, C.Y. Walfield, A.M. (2005). Site-specific peptide vaccines for immunotherapy and immunization against chronic diseases, cancer, infectious diseases, and for veterinary applications. Vaccine. 23(17-18): p. 2049–2056. Yang, D., Holt, G.E., Rudolf, M.P., Velders, M.P., Brandt, R.M.P., Kwon, E.D. Kast, W.M. (2001). Peptide Vaccines. In: New Vaccine Technologies. Chapter 12: p. 214-226. Zhong, W., Skwarczynski, M. Toth, I. (2009) Lipid Core Peptide System for Gene, Drug, and Vaccine Delivery. Australian Journal of Chemistry. 62: p. 956–967. Zou, W.. Jennings, H.J. (2009). Preparation of glycoconjugate vaccines. In: Carbohydrate-Based Vaccines and Immunotherapies. Chapter 2. How to cite Carbohydrate and Peptide – Based Vaccines: The Way Forward, Essay examples

The Chosen Essays (585 words) - The Chosen, Rabbi, Talmud

The Chosen Zycer Book Report Title : The Chosen Author : Chaim Potok Number of pages : 271 pages Date published : 1967 What is your book about? The story, set in New York during the Second World War, is basically about the friendship between two boys. It begins with a baseball game between Reuvens team and Dannys team. During the game, when Reuven is pitcher, Danny, the batter, hits the baseball in the pitchers direction which Reuven tries to block with his glove but it strikes him and shatters his glasses and Reuven is forced to be hospitalised. While Reuven is in the hospital Danny comes to visit him. They have quite a few conversations throughout Reuvens stay in hospital and become friends. After Reuven goes back home, the rest of the book is about the friendship evolving as the two boys grow up and go through high school. There are few events of great importance that take place during the remainder of the story, with most of them having a marginal impact. The Chosen is more about the development of the characters and their relationship than the individual actions. It describes a place where the worlds of very religious Judaism and not so religious Judaism meet, which is hard to imagine for an outsider. It shows how, even though two groups of people are Jewish, there are many differences between them. Describe an intersting character Reb Saunders is Dannys father, the rabbi of an Hasidic synagogue near Reuven's house. Close to the end of the novel, he gives a lengthy explanation to Danny and Reuven of the reasons that he brought up his son in silence. The justification given is that he received a son who had a tremendous mind, but no soul. He was forced to educate him in this manner in order to prevent Danny from becoming like his own brother, who also had a great mind but was insensitive towards others that were not as intelligent as him which prevented him from becoming a wise man. Reb Saunders' father also brought up Danny's father in silence so that he would not always ask questions, but instead look inside himself for answers ; and that is also what Reb Saunders did with Danny. He is very interesting because, sometimes he seems nice and gentle and other times cruel and mean, especially in the way he brought up his son. But he always has a reason for every act he performs. What did you particularily like or dislike about this book? This book was extremely interesting because it taught me a lot about the Hasidic movement but most importantly, the contrast between the two different Jewish communities. It is ironic that Reuven, brought up in a more secular society, decides to become a rabbi, while Danny, the religious one, wants to become a psychologist. I found the last part, when Reb Saunders explains his silence with Danny very thought-provoking. It tells us to have understanding and compassion for others. Find three new or interesting words in the book 1- brooding 2- ordination 3- Talmud Define them and put them in a sentance showing its meaning 1- brooding : to think deeply or worry anxiously He was brooding endlessly after I told him the news. 2- ordination : the act or ceremony of ordaining ordaining : to install as a minister, priest or rabbi Finally, after many years of work, the rabbi received his ordination. 3- Talmud : the collection of ancient Rabbinic writings constituting the base of religious authority in Orthodox Judaism The rabbis often study Talmud for great lengths of time.