NMDA Receptor Pathways as Drug Targets in CNS Therapeutics

NMDA Receptor Pathways as Drug Targets in CNS Therapeutics 1. Introduction: Glutamate is the king of excitatory neurotransmission in the central nervous system (SNC) and acts on receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the brain and spinal cord (Ghasemi and Schachter, 2011). Although glutamate was known to have central nervous system effects for more than 75 years, it was not until 1984 that it was truly acknowledged as fulfilling the criteria of a neurotransmitter. (Niciu et al., 2012). Glutamate receptors are divided into two broad categorizations: ionotropic and metabotropic receptors. Ionotropic glutamate receptors are ion channels that flux cations (Ca2+, Na+) and open the channels in response to agonist binding. On the other hand, metabotropic receptors activate or inhibit second messenger systems via interactions with cognate G-proteins. (Niciu et al., 2012). Ionotropic glutamate receptors can be subdivided into three large families: AMPA receptors (AMPARs), kainate receptors and NMDA receptors (NMD ARs). Since three decades ago, the discovery NMDARs have kept fascinating neuroscientists while their dysfunctions are also involved in various neurological and psychiatric disorders, including stroke, pathological pain, neurodegenerative diseases and schizophrenia. (Paoletti et al., 2013) Fortunately, the NMDA receptor complex is composed with modulatory sites, and the late 1970s and 1980s saw the development of agonists, antagonists and modulators acting at different binding sites. In the last decade, the molecular biology of the NMDA receptors has been defined, and now it is known that these receptors are formed of an NR1 subunit in combination with one or more NR2 or less commonly an NR3 subunit. (Kemp and McKernan, 2002). 2. Molecular mechanisms NMDA receptors are named after their selective agonist N-methyl-D-aspartate. The receptors are multisubunit complexes associating NR1, NR2 and, more rarely, NR3 subunits. NR2 and NR3 subunits exist as four and two subtypes, respectively (NR2A-D and NR3A-B). NR1 exists as seven subtypes (NR1a–g) (Mony et al., 2009) The receptors are heterotetramers comprising a combination of NR1, NR2A-D and  NR3A-B subunits. The main agonists are glutamate and NMDA, with their binding site on NR2 subunits, while the binding site for the co-agonists D-serine and glycine is located on NR1 and NR3 subunits and the T most common composition of NMDA receptors includes two NR1 and two NR2 subunits, or two NR1, one NR2 and one NR3 subunits (Dzamba et al., 2013). A common structure for glutamate receptors contains an extracellular amino-terminal domain (ATD) for various modulatory functions, extracellular S1S2 domains for agonist binding, an ion channel domain with four transmembrane segments (M1â⠂¬â€œ4) for gating and ion permeation, and a carboxy-terminal domain for communicating with intracellular milieu Fig 1 (Majdi and Chen, 2009). Pharmacological regulation of the NMDAR depends on effects on unique combinations of subunit-specific binding sites. Once glycine coagonist attaches to its site, the glutamate can activate the ion channel and the Na+ and Ca2+ rush in. The Mg2+ blocks channel pore and the blockade is relieved by cellular depolarization, which has implications for synaptic plasticity, especially long-term potentiation (LTP). (Ghasemi and Schachter, 2011) Most compounds that act at NMDA receptors interact with one of 4 drug binding sites on the NMDA receptor complex, the glutamate or glycine binding sites, the ion channel pore, or a binding site on the regulatory NTD. The first compounds identified were agonists and antagonists of the glutamate like D-ÃŽ ±-aminoadipic acid and D-2-amino-5phosphonopentanoic  acid (D-AP5) then glycine competitive antagonists like 7-chloro-5-iodokynurenic acid and partial agonists were identified. It was also soon recognized that some dissociative anesthetics (e.g. ketam ine and phencyclidine) were NMDA receptor blockers and the widely used inhibitor MK-801 was shown to be a potent NMDA receptor channel blocker Fig 2 (Monaghan et al., 2012). Another important aspect of NMDA receptor pharmacology is modulation by posttranslational modifications, such as phosphorylation of the intracellular C-terminal of NR2 subunits. NMDA receptor-mediated calcium increases activate many downstream targets like protein kinase C (PKC) and the Modulation by protein kinase C (PKC) depends on NMDA receptor subunit composition; NR2A- and NR2B-containing receptors are potentiated by PKC activation, whereas NR2Cand NR2D containing receptors are unaffected or inhibited by PKC. PKC phosphorylates the NR1 subunit at serine 890 (S890) in the C1 cassette. The potentiatory effects of PKC are not dependent on phosphorylation of NR1, but inhibitory effects are blocked by mutation of S890 or removal of the C1 domain. The NMDA receptor function is also modulated by MAGUK protein fami ly which controls the NMDA receptor localization, the binding to the scaffolding proteins plays a major role in the control of downstream signals resulting from receptor activation. It thought that synaptic NMDA receptors are retained at the synapse by an attachment to PSD-95 through a PDZ interaction with the NR2 subunits.(Gardoni and Di Luca, 2006) 3. Therapeutics A high number of central nervous system disease states in which neuronal cell death is associated to glutamate induced excitotoxicity could be treated by blocking NMDA receptors such as neurological disorders including ischemia, epilepsy, brain trauma, dementia, and neurodegenerative disorders. à ¯Ã¢â‚¬Å¡Ã‚ · Ischemia : it has been shown that loss of calcium homeostasis may be an important mechanism of ischemic brain damage. Ischemia also resulted in a decrease in the size of protein complexes containing PSD-95. In addition, transient cerebral ischemia increases tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B. Recent studies suggested to treat stroke transducing neurons with peptides able to disrupt the interaction of NMDA receptor NR2B subunits with the postsynaptic density protein PSD-95. This procedure dissociated NMDA receptors from downstream neurotoxic signaling without blocking synaptic activity or calcium influx and protected cultured neurons from excitotoxi city. .( Gardoni and Di Luca, 2006). Many NR1/NR2B antagonists, including ifenprodil, eliprodil and the selective and potent congeners, Ro 25,6981 and CP-101,606, offer promise in preclinical models of ischaemia (Chazot, 2004) à ¯Ã¢â‚¬Å¡Ã‚ · Epilepsy: Recent work has suggested that hyper-phosphorylation of NR2B may results in hypersensitivity to the endogenous transmitter, and induction of neuronal hyperexcitability and epilepsy. Furthermore, kainic acid-induced alters tyrosine phosphorylation of NR2A and NR2B receptors. Interestingly, the high affinity NR2B compound, Ro 63-1908 was shown to be active versus acoustic-induced convulsions and NMDA-induced seizures at 4.5 mg/kg ip and 2.31 mg/kg iv, respectively and no adverse cardiovascular, motor deficits or other CNS sideeffects were observed at these active. (Chazot, 2004). à ¯Ã¢â‚¬Å¡Ã‚ · Huntingtons disease: The normal huntingtin binds to PSD-95 scaffold protein which inhibit the NMDA receptor Overexpression of the normal huntin gtin N terminus significantly attenuates neuronal toxicity induced by both NMDA receptors and the mutated huntingtin. This suggests that PSD-95 is a mediator of neuronal toxicity induced by NMDA receptors and mutated huntingtin. In addition, in a transgenic model of Huntington disease. Other studies show that expression of mutant htt (but not wild-type htt) in combination with NR1/NR2B increases cell death compared to  transfection of only NMDA receptor subunits, suggesting a role for NR1/NR2B NMDA receptors in cell death mediated by mutant htt .As NR2B antagonists block most of the NMDA receptor mediated currents in neuronal models of Huntington, the selective localization of NR2B in the striatum may also play a role in the efficacy of NR2B antagonists against cell death in models of Huntington.( Gardoni and Di Luca, 2006). à ¯Ã¢â‚¬Å¡Ã‚ · Alzheimers disease : In animal models, NR2B subunit expression decreases with age, which correlates well withreduced Long Term Potentiation (L TP) and inferior cognitive performance. The NR1/NR2B subtype decreases, in comparison to other subtypes, in the frontal cortex of aged humans while overexpression of the forebrain NR2B subunit in transgenic mice has been shown to have profound beneficial effects upon cognitive performance. Such information suggests that controlled potentiation of the NR2B may offer a novel strategy for treating cognitive disabilities. (Chazot, 2004). à ¯Ã¢â‚¬Å¡Ã‚ · Parkinsons disease: At the molecular level, alterations of NMDA receptor subunits localization in striatum have been described in Dopamine-denervated rats as well as in L-DOPA-treated dyskinetic monkeys. In particular, NR2B subcellular redistribution from synaptic to extrasynaptic sites represents the key element in the complex modifications of the glutamatergic synapse in L-DOPA-induced dyskinesia. On the other hand, recent studies in primates suggested that upregulation of NR2A abundance in synaptosomal membranesmay be an important pla yer in L-DOPA induced dyskinesias. And recently, two studies described results on the effects of NR2B selective NMDA receptor antagonist CP-101,606 on L-DOPA induced dyskinesia in two different models of experimental parkinsonism.( Gardoni and Di Luca, 2006). à ¯Ã¢â‚¬Å¡Ã‚ · Psychosis : Studies have suggested that the NR2B has role in psychotic disorders, including schizophrenia and bipolar disorder. The mRNA encoding the NR2B subunit and NR1/NR2B-type binding sites have been shown to be selectively increased in hippocampal and cortical regions, Recent work has identified a novel T200G variant located in the NR2B promoter, which endows dysfunction of the NR2B subunit. The frequency of this variant was significantly up-regulated in a schizophrenia group compared to a control group. The possible link between these observations is yet to be investigated. (Chazot, 2004). à ¯Ã¢â‚¬Å¡Ã‚ · Pain: Studies suggest that the NR2B subunit plays distinct roles in acute and chronic pain states, re cently NR2B antagonists were developped, including Ro 25,6981, CP -101,606, PD 174494 and PD 196860, are effective in a range of animal chronic pain models with a wide separation between anti-hyperalgesic and side-effect doses . . (Chazot, 2004). 4. References Chazot, P. L. (2004). The NMDA receptor NR2B subunit: A valid therapeutic target for  multiple CNS pathologies. Curr. Med. Chem. 11, 389-396. Dzamba, D., Honsa, P. and Anderova, M. (2013). NMDA receptors in glial cells: Pending  questions. Current Neuropharmacology 11, 250-262. Gardoni, F. and Di Luca, M. (2006). New targets for pharmacological intervention in the  glutamatergic synapse. Eur. J. Pharmacol. 545, 2-10. Ghasemi, M. and Schachter, S. C. (2011). The NMDA receptor complex as a therapeutic  target in epilepsy: A review. Epilepsy Behavior 22, 617-640. Kemp, J. A. and McKernan, R. M. (2002). NMDA receptor pathways as drug targets. Nat.  Neurosci. 5, 1039-1042. Majdi, M. and Chen, H. V. (2009). NMDA-gated ion channel research and its therapeutic  potentials in neurodegenerative diseases: A review. Journal of Receptor, Ligand and Channel Research 2, 59-73. Monaghan, D. T., Irvine, M. W., Costa, B. M., Fang, G. and Jane, D. E. (2012).  Pharmacological modulation of NMDA receptor activity and the advent of negative and  positive allosteric modulators. Neurochem. Int. 61, 581-592. Mony, L., Kew, J. N., Gunthorpe, M. J. and Paoletti, P. (2009). Allosteric modulators of  NR2Bà ¢Ã¢â€š ¬Ã‚ containing NMDA receptors: Molecular mechanisms and therapeutic potential. Br. J.  Pharmacol. 157, 1301-1317 Niciu, M. J., Kelmendi, B. and Sanacora, G. (2012). Overview of glutamatergic  neurotransmission in the nervous system. Pharmacology Biochemistry and Behavior 100,  656-664. Paoletti, P., Bellone, C. and Zhou, Q. (2013). NMDA receptor subunit diversity: Impact on  receptor properties, synaptic plasticity and disease. Nature Reviews Neuroscience 14, 383-400.

Abortion Essay -- essays research papers

According to Webster’s dictionary, abortion is the termination of pregnancy after, accompanied by resulting in, or closely followed by death of the embryo or fetus. I believe that abortion should be illegal. Our world today is full of unsolved, devising and controversial issues. Most of them relate to our morals, ethics, and religion, thus creating a very strong ‘Yes’ and ‘No’. If you were to come to any kind of conclusion on abortion, there would still be a downside to it, and that is primarily why the world cannot agree on this sensitive and emotional issue.   Ã‚  Ã‚  Ã‚  Ã‚  Make no mistake-that from the moment of conception, a new human life has been created. Only those who allow their emotional passion to override their knowledge can deny it: only those who are irrational or ignorant of science doubt that when a human sperm fertilizes a human ovum a new human being is created. Do you consider something with a beating heart a living creature? A baby’s heart forms and starts beating in the fifth week of pregnancy: therefore, that would make abortion murder. Most people consider it murder to kill a baby the day after it is born. Then why would it not be murder to kill it before it is born?   Ã‚  Ã‚  Ã‚  Ã‚  Abortions are often considered â€Å"the easy way out.† I feel that abortions are just selfish. There is no easy way out. I could not imagine living with the guilt of taking Maker 2 another’s life. Especially the life of something I created, and that ...

Arm Holdings Strategic Swot Analysis

This paper evaluates the strategic position and activities of the microchip producer ARM by means of a PESLE analysis and a Porter's six forces analysis to review the company's internal and external environment. Using these analytical tools, the author deems how well ARM's strategy fits within the constraints of the external environment, the distinctive elements of ARM's products and services that distinguish it from its competitors and the sustainability of this strategy in the long-term.The paper concludes that, while presently the semi-conductor industry is significantly challenging, ARM has developed a differentiated strategy, which is capable of competing with large rivals, such as Intel, and which is sustainable over the long-term sustainability. Table of Contents: Executive Summary Introduction Environmental Analysis PESTLE Analysis Competitive Stance Porter's Six Forces Analysis Scale and Scope Analysis of Strategy Evaluation of Sustainability Description From the Paper Sampl e of Sources UsedRelated Papers Cite this Analytical Essay Comment & Share From the Paper: â€Å"Overall it would appear that ARM is making use of a differentiated generic strategy. Here while in general terms the industry for microchips may be seen as one which has become increasingly commoditised in recent years with large incumbent suppliers such as Intel focusing upon producing large volumes at low costs (Roca and Sills, 2011). ARM would seem to have adopted an alternative approach in attempting to develop a niche product hich outperforms cheaper micro chip products in terms of energy efficiency and size. In other words, it may be seen as ARM has built its differentiated generic strategy based upon re-evaluating the needs of its customers and potential customers who have show a clear desire to purchase a generation of microchips which are suitable for inclusion in a range of communications products such as smart phones and tablet computers (hence need to be smaller).In addition , ARM may also be seen as attempting to tap into the growing market for energy efficient products which give numerous benefits to the consumer including cost savings, a feel good factor and in the case of industrial buyers, the ability to market their own products within increased environmental credentials†. Sample of Sources Used: BBC News. 2010. The ups and downs of social networks. Available online at: http://www. bbc. co. k/news/technology-10719042 [Accessed on 22/03/12]. Butterton, G, R. 1996. Pirates, dragons and the US. Intellectual property rights in China. Ariz legal review. 1081. Begg, D, Fischer, S, Dornbusch, R. 2008. Economics. 9th ed. London: McGraw-Hill. Economist. 2012. Space invaders. Available online at: http://www. economist. com/node/21542402 [Accessed on 22/03/12]. Grant, R, M. 2008. Contemporary strategy analysis. 6th ed. Oxford: Blackwell Publishing.

What Is AP Capstone Should You Do It

What Is AP Capstone Should You Do It SAT / ACT Prep Online Guides and Tips Have you heard about the AP program's new diploma program, AP Capstone? Is this just an IB clone or something more interesting? And will completing AP Capstone get you into college? We’ll explore those questions here. Read on for a complete guide to AP Capstone! What Is AP Capstone? AP Capstone is the AP program’s new diploma program. A diploma program is a program that signifies you completed a certain set of requirements in high school to earn an advanced diploma. (This is in addition to your basic high school diploma.) Probably the most well-known advanced diploma program is the International Baccalaureate (IB) program. Perhaps to compete with IB, the AP program launched its own diploma program, AP Capstone, in fall 2014. While the regular AP program allows students to choose whichever AP classes they want to take and doesn’t have any overarching structure, AP Capstone requires you take a certain number of AP classes and meet certain requirements to earn the AP Capstone advanced diploma. You have to take skills-based and subject-based AP classes to earn the Capstone diploma. Specifically, AP Capstone includes two foundation courses – AP Seminar and AP Research – to enhance four subject-specific AP courses (in any subject) for a total of six AP courses. Diagram via College Board. College Board says of the program: â€Å"[AP Capstone] cultivates curious, independent, and collaborative scholars and prepares them to make logical, evidence-based decisions.† In other words, AP Capstone is working to bring some thematic unity to the AP program. Typically, students will choose AP classes that are interesting to them and treat them as totally separate entities. They don’t have to make connections between their AP classes or the skills they require. By including AP Seminar and AP Research, the Capstone program aims to make AP a more cohesive high school program. AP Capstone also includes a 5,000 word research paper, which is quite similar to IB’s extended essay. Additionally, some of the curriculum aligns with new common core standards – a bid to make AP Capstone competitive and desirable to schools in today’s changing education world. How AP Capstone Works To get the AP Capstone diploma, you take two special AP courses. You’ll take AP Seminar in 10th or 11th grade, followed by AP Research in the 11th or 12th grade. (You can’t take both in the same grade; AP Seminar has to come before AP Research!) In addition to AP Seminar and AP Research, you have to take four AP classes of your choosing at any point in high school. This means you could simply take one AP course each year (freshmen, sophomore, junior, senior) or pack them into your last two years of high school. If you receive a 3 or higher on all these exams, you will receive the AP Capstone Diploma. (Of course, there is nothing preventing you from taking more than four AP classes if that's what you want to do. You just need a minimum of four to get the AP Capstone diploma.) If you receive scores of 3 or higher in AP Research and AP Seminar, but don’t take four other AP classes or don’t get high enough AP scores in them, you’ll get the AP Seminar and Research Certificate, which shows you gained college-level academic and research skills. The Two Capstone Courses – AP Seminar and AP Research Both AP Seminar and AP Research aim to create a college-like academic experience right in your high school classroom. The AP Seminar and AP Research classes are the main distinguishing features of AP Capstone. These courses give students additional skills to use in other AP classes and college, but aren’t based in specific subjects (e.g. math, language arts, science, or social studies). They aim to help students do the following: Analyze topics through different lenses for greater meaning or understanding Plan and conduct a study/investigation Propose solutions to real world problems Collaborate to solve a problem Plan and produce communication Integrate, synthesize and make cross-cultural connections Let's take a look at each class to learn more. AP Seminar Overview In Seminar, you'll develop analytic and inquiry skills, exploring two to four issues chosen by you or your teacher, depending on how your teacher runs the class. The class focuses on themes based on student interests, local and/or civic issues, global or international topics, and concepts from other AP courses. For example, you might explore the question of whether national security is more important than a citizen’s right to privacy; or whether genetic engineering is a benefit to society. Both topics would draw from multiple subjects (social studies, science, ethics) and allow you to look at issues through many different lenses. During the course, you also complete a team project, an individual paper and presentation, and take a final AP exam. The AP Seminar Exam score is based on all three components and is reported on the standard 1–5 AP scoring scale. AP Research Overview You have to take AP Seminar before you can take AP Research. While Seminar introduces you to discussion, research, and presentation skills, AP Research allows you to design, plan, and conduct a year-long research-based investigation on a topic that interests you. You'll build on skills from AP Seminar by learning about research methodology, using ethical research practices, and analyzing the information you find to write and defend your argument. Get ready to spend a lot of time in the library! For your research paper, you can dig into a topic you already studied in a different AP course, or come up with your own topic that combines different subjects. At the end of the research investigation, you’ll write a paper of about 5,000 words, then present and defend it. The AP Research Exam score is based on the paper, presentation, and defense, and is reported on the standard 1–5 AP scoring scale. So note that, unlike AP Seminar, there is not a formal AP Research exam. Your paper and presentation will be the exam! How Popular Is AP Capstone? The AP Capstone program is quite new, as it only debuted in 2014. Currently, about 300 American schools, 15 Canadian schools, and 30 other international schools have the program. Considering 894 schools in the US alone have IB, AP Capstone is pretty small in comparison. That said, the program will likely grow and expand quite a bit in the next few years as more schools choose to implement it. Some states don’t have any AP Capstone schools yet.several (like Missouri and Utah) have just one participating school, while others have quite a few. (Florida has almost 100!) It will be interesting to see if the state representation evens out in the coming years or if Capstone becomes very popular in certain states and rare in others. How Capstone Differs From â€Å"Regular AP† The basic AP program is more flexible than AP Capstone. The regular AP program is an â€Å"a la carte† program – you can choose which AP classes to take and how intense you want your schedule to be. Some students might just take 1 or 2 AP classes in high school, others could take over 10. It all depends on how much you want to challenge yourself, how many AP courses your school offers, and which subjects you're interested in. The success of a student is judged by how they do on each exam – students aren’t expected to take a certain number of AP classes or get a certain average score. In short, the basic AP program is quite flexible and can fit the needs of many students. In contrast, AP Capstone is a diploma program with stricter requirements. If you don't take the right AP classes or get high enough AP exam scores, you won't earn the Capstone diploma. How Similar Is AP Capstone to the IB Program? You may be wondering how similar AP Capstone is to the IB program, since they are both advanced diploma programs. We’ll run through some of the main similarities and differences since many students considering IB might also consider AP Capstone, and vice-versa. Similarities Both programs function pretty similarly. Students take advanced classes in high school (marked as either AP or IB), and then take an exam for each class at the end of the year. For both AP Capstone and IB, you have to obtain a minimum score on your exams to earn the diploma. For IB you have to earn at least 24 points total on your exams (IB exams are scored from 1 to 7), for Capstone you need a 3 or higher on each exam. Each program also requires a long piece of writing, though AP Capstone’s 5,000 word research paper is longer than IB's 4,000 word extended essay. Finally, both programs include subject-based and skills-based courses – though IB has one skills-based course, Theory of Knowledge, while AP Capstone has two – Seminar and Research. Differences The IB program requires some of your courses be more difficult, while there’s no distinction between standard level and higher level courses in AP Capstone. To earn an IB diploma, 3 of your 6 courses have to be designated "higher level," while three can be "standard level." For the AP Capstone diploma, you can choose the four additional AP courses you want to take, even if they are known as easier exams. Also, AP Capstone does not have any extracurricular requirements whereas IB has the Creativity, Action, Service program, which essentially requires extracurricular activities. Another major difference between the programs is that AP Capstone has no requirements as to the four additional AP classes you take, whereas in IB you need to take courses from six specific subject areas. So while you could get the AP Capstone diploma with all humanities or all sciences classes if you wanted, IB requires courses taken from across the board. For this reason, the IB Diploma is arguably more comprehensive. Finally, the IB program is more established, since it's a much older program. While many colleges are likely familiar with IB, you may have to explain AP Capstone a bit more on your applications so colleges know what it is and how it's different from regular AP. Should You Take AP Capstone? So now, the big question: if your school (or a school nearby) is offering AP Capstone, should you take it? Before deciding, consider the cost – you’re committing to taking at least 6 exams to earn the diploma. At $91 per exam, that’s significant! Whereas by taking regular AP classes you can decide each year how many AP classes to take and whether you can afford them, for AP Capstone you're committing to a set number. Speaking of which, are you up for six classes? With regular AP you can drop out of any one class at any point, but with Capstone you need 6 courses to finish the diploma. Think hard about whether that’s a commitment you’re willing to take on. Also, who at your school is teaching AP Research and/or AP Seminar? Those courses are a big part of the Capstone experience, so if the teacher isn’t great you might want to skip Capstone and just take regular AP courses. Since this is a new program, expect some kinks and growing pains in the first few years. Be especially cautious if you’re a current sophomore or junior looking to jump into AP Capstone. Talk to your guidance counselor and the Seminar and/or Research teachers to get a sense of what AP Capstone will be like at your school and if you want to do it. If you’re a freshman or younger, you have more time to wait and see how well the program does at your school and at the national level. Will Colleges Care? Similar to IB, since AP Capstone is only offered at a select few schools, colleges won’t be specifically looking for AP Capstone or favoring it, since not all students have access to it. Still, if you take Capstone, aspects of the program – especially the long research paper – will likely look desirable to most colleges. The independent reseach AP Capstone requires could be the topic of a college essay or at least something substantial to talk about in an interview. However, like we mentioned earlier, since AP Capstone is new, make sure you explain what it is on your college applications, so colleges realize that you undertook an advanced diploma program. Odds are, that will look pretty good to them! Also, remember that colleges will look at your schedule in the context of your school, so as long as your schedule is as challenging as possible – whether you’re in Capstone or not – you are setting yourself up for success. It may be that taking AP Capstone will push you to take more AP classes, making your schedule look more challenging in the context of your school. If your school does have Capstone and you opt to not take it, make sure you are taking a challenging mix of AP and honors courses so it doesn't look like you slacked off. What’s Next? If you decide to take AP Capstone, you’ll have to choose 4 AP courses on your own. Read about the hardest and easiest AP classes to help you decide on your schedule. Learn about another popular diploma program – the IB program, and whether or not you should take it or AP. If you’re applying to top colleges, you also need to think about your SAT/ACT score. Come up with a target SAT score based on your dream schools (ACT version here). Want to improve your SAT score by 160 points or your ACT score by 4 points?We've written a guide for each test about the top 5 strategies you must be using to have a shot at improving your score. Download it for free now:

Taoism Essays - Taoism, Tao Te Ching, Tao, Laozi, Wu Wei

Taoism Essays - Taoism, Tao Te Ching, Tao, Laozi, Wu Wei Taoism Throughout history, Taoism has been one of the most influential religions of Eastern culture. This is certainly one of the most unique of all religions. Many Taoists, in fact, do not even consider it a religion; and in many ways it is not. Taoists make no claim that the Tao exists.1 That is what essentially separates Taoism from the rest of the world religions: there is no heated debate or battle over Taoist doctrine; there have been no crusades to spread the religion. The very essence of Taoism is quite the opposite. Taoism?s uniqueness and open-endedness have allowed the religion to flourish almost undisturbed and unchanged for over two thousand years. The founder of Taoism was a man named Lao Tzu, who lived around the year 604 B.C.E. According to Chinese legend, Lao Tzu was an archivist in the imperial library at Lo Yang was known for his knowledge, although he never taught.2 When Lao Tzu left his position at the library, he went to the Chinese province of Chou. At the border, however, he was stopped and forced to write down his teachings. During this time, he wrote the Tao Te Ching, the major scripture of Taoism.3 After Lao Tzu?s death, a man named Yang Chu (440-366 B.C.E.) took up his teachings.4 A naturalist and philosopher, Yang Chu believed highly in self-regard and survival as the core of human nature and direction. His ideals were personal integrity and self-protection, and said that he was unwilling to pluck one hair from his head even if all humanity were to benefit from it.5 The next influential Taoist philosopher was Chang Tzu, who lived from 350-275 B.C.E. He defined existence using Lao Tzu?s teachings.6 He wrote fifty-two books in response to the Tao Te Ching, thirty-three of which still survive today.7 Using exaggeration and fantasy, he illustrated Lao Tzu?s teachings and how the Tao acted in nature. His theories spoke of a cosmic unity which encompasses all reality and guides it naturally, without force, to its proper end.8 The Yin and Yang theory became part of Taoist philosophy around 300 B.C.E. when they were mentioned in the Hsi tz?u, an appendix to the I Ching.9 Yin and Yang are defined as the two forces in nature. They are often called the two ?breaths? or ch?i.10 Yin is the feminine principle, representing darkness, coolness, and dampness; Yang is the masculine principle, representing brightness, warmth, and dryness.11 Neither principle is good or bad; they are not opposites, but each is needed to maintain stability in the universe.12 This belief holds that everything is defined through opposition; consequently, the virtues of balance and understanding are highly valued.13 Taoism became an official religion between 100 and 200 C.E.14 Due to competition from Buddhism, Taoists adopted many Buddhist beliefs. During this pivotal point in the religion?s history, searching for self-knowledge and wisdom were replaced by searching for solutions to sorrows and other physical problems.15 Alchemy and superstition became highly popular during this period of time, as Taoists tried to escape reality rather than to control the artificial and unnatural. Many Taoists used magic and the concept of Tao to try to extend the physical life rather than to focus on the afterlife.16 Gradually the religion becomes more complicated, with a wide pantheon of gods and a ruling hierarchy.17 The leader Chang Ling took the title ?Heavenly Teacher? in 200 C.E. He created a dynasty of high priests who manipulated Taoism to support a superstitious doctrine of magic and mysticism.18 Seizing higher power as a religious leader, he pioneered a merging of Taoism and Zoroastrianism into a system called Five Bushels of Rice Taoism. Eventually this developed into a society based on Mazdaism, a Zoroastrian sect, where every believer was charged five bushels of rice.19 Although the believers followed the basic Zoroastrian worship format, they worshipped different gods: the Tao instead of Ahura-Mazda, and the various Chinese folk gods in place of the Persian Angels.20 Three hundred years later, the philosopher Honen moved away from Mazdaism and combined Taoism with Buddhism. This simplified religion he created became known as the Pure Land School, or Amidaism. Gradually, however, Taoism again became tied to magic, and it failed as a religion.21 Today, only its original philosophies survive and there are very few followers of Taoism, mostly found in Taiwan.22 Although Taoism?s religious practices deteriorated with advancing Western influence, its philosophical aspects have outlasted those of Confucianism and Zen Buddhism.23 For centuries, Taoism has been known as the Way of Harmony.24 This is because Taoists believe that the Tao leads all nature toward a natural balance. The Tao, however, is not

Analyzing a key business leader Essay Example | Topics and Well Written Essays - 1250 words

Analyzing a key business leader - Essay Example Leadership plays a key role in the success of any business and can determine the success or failure of a business venture. Around the world, there are many notable leaders who have managed to steer their companies from small local enterprises to large multinational companies. Richard Branson is one such notable leader. An article entitled The importance of being Richard Branson (Knowledge@Wharton 1-3) reveals that Branson is the founder and owner of the Virgin Group – an empire of 350 companies with ventures in the airline, telecommunication, trains, cosmetic, credit card and several other industries. His empire is worth over 7 billion dollars and it employs over 9,000 people in 28 countries (Morris, par. He has also been recognized as one the 25 most influential leaders in the last 25 years. He is a leader who has mastered the ability to build successful brands and the ability to create a common purpose among his followers. At the core of Branson’s leadership style, is his belief that people, or more specifically his employees, are the foundation of his company success. A Wall Street Journal poll carried out in 2004 reported the following five characteristics as strengths that make a good leader; integrity, ability to get along with others, industriousness, intelligence, business knowledge and education (Ebersohn, 11). Branson’s integrity is perhaps best exemplified by his open and honest attitude to his employees. He believes that it is important that employees are aware at all times about the successes and the problems that the company is going through. He encourages the celebration of company successes and on the other hand also encourages his employees to suggest solutions and innovation to grow the company and solve any problems the company might be going through. Branson is known as a hard worker. His industriousness nature is often described as workaholic. His intelligence is manifested in his ability to identify good business

Religion Essay Example | Topics and Well Written Essays - 750 words - 9

Religion - Essay Example According the Durkheim, the Orthodox Church is more likely to stress on the importance of conserving old traditions, while the teachings of the Protestant used to emphasize freedom and autonomy as the greater priority. The Protestant Church separated from the Roman Catholics on Reformation, and tends to view change and an occasional deviation from traditions as a positive change (Huismans, & Schwartz, 1995). There are a few distinctive differences in the teachings of Roman Catholics, Orthodox and the Protestant Church, but they revolve mostly around the different values and belief that each of these sects prioritize (Huismans, & Schwartz, 1995). For example, as the Protestants view development and success over stagnancy. While Roman Catholics and Orthodox Church both give more importance to not letting go of the old traditions, through which humankind initially learned about and sustained Christianity. These facts may point out the blatant differences, which can be found for each, bu t meanwhile also show that each has its own value-based teachings, none of which can be objectively proved more correct than any other. The understanding that Orthodox Church, as the name suggests, promotes the adherence to traditional ceremonies and worship, while the Protestant Church encourages change, is correct. While these two sects operate on polar beliefs as far as the importance of conservatism is concerned, it is important to note that religious leaders preach the importance of some values while perhaps shunning the value of other beliefs. This shunning is not, perhaps done voluntarily, but does result in the matter of the teachings of Christianity turning from objective to subjective, as each sect is taught to emphasize a difference belief by their leaders. As Weber pointed out, â€Å"Calvinist Protestantism promoted and supported industrialization in western Europe by influencing believers to emphasize wealth, success, ambition, and