The effect of human population growth on resources

The meat of gentle community maturement on resources homophile existence produce and the effect on natural resource consumptionIn the last 50 eld the world people has grown faster than ever before, and in some countries and regions of the world this state growth and the consumption of natural resources resulting from this growth is becoming a matter of great concern for governments and international maturement agencies (World Bank. 2004). National populations are expected to grow in every countries of East, southboundeast, and South and Central Asia except Japan and Kazakhstan, populations will double or to the highest degree double in Pakistan, Nepal, Bangladesh, Afghanistan, Cambodia, and Laos, growth calculates will likewise be particularly high in India, Indonesia, Iran, Malaysia, Mongolia, Myanmar, the Philippines, and Vietnam (Asia Population, 2013). This implies an enormous concern for the contend that population growth represents more consumption, depletion, contamination and affair of natural resources. This essay aims to debate the population growth crisis, specifically the relationship between population growth, environmental sustainability and ecological impacts due to benignant intervention on environment.In 1798, doubting Thomas Malthus studied the nature of population growth in Europe, he claimed that population was increasing faster than provender deed, and he feared that eventual global starving may become unsustainable on the years to come (Malthus, 1798). Several researchers let off debate this theory, neverthe slight, it is extend that the patterns of consumption and degradation of resources are treatly colligate to population growth and human being consumption of natural resources both in developing and developed countries. Some authors doing research about human population growth argue that a key component to achieve sustainable growth is to slow population growth by helping couples to furbish up their family size ( human beings Health Reports 1992). However, birth moderate and population management is non the only system required to crop population growth. Population growth cook is not only telling by introducing birth control mechanisms, is it besides important to recognize that the medical and scientific advances represents a grand and significant factor regarding population increase. To elaborate, there have been over the years enormous developments on the reduction of infant mortality rate, for instance, mortality rate has dropped significantly compared to fifty or sixty years ago and the control of diseases such(prenominal) as cholera, malaria and dengue are becoming more effective every twenty-four hours, adults rate expectancy is increasing and adults are extending their life expectancy by several years than they mathematical functiond to achieve decades ago. As a result, a greater production and consumption of resources is necessary to sustain the population, and it is undecipherable whether the food production is capable of growing as fast as population growth is able to grow in the modern world. environmental problems can be classified according to the nature of the vilify to human health (Holdren and Ehrlich, 1974), the authors argue that Environmental problems are usually a treat effect of wrong human interactions and resource exploitation. Common and every day diseases (lung disease due air pollution, lead poisoning and so many an(prenominal) more) are the direct consequence of human activities, the pollution of coastal waters, the speedup of erosion in agricultural soils are the result of human activities and global degradation on environment. One of the most important problems that requires observation is food production and soil fertility be incur this kind of degradation is a direct consequence of human activity. Soils increasingly lose their ability to store nutrients and be productive in their cycles, Water consumption for crops also becomes higher and less sustainable, and production is constantly decreasing, resulting in a threatening an irreversible damage to the environment. One example of this problem is the alteration of areas in the lush of the Tigris and Euphrates Valleys done erosion and salt accumulation, consequence of bad irrigation practises and systems (Thorkild and Adams, 1958 ), the Rajasthan desert in India is also a perfect example of the human pressure on the environment. another(prenominal) example is the pressure to expand agricultural areas, leading to damaging efforts to dress land that is unsuitable to cultivation, such as the expansion of cultivation on hillside in Indonesia, leading to serious erosion and new environmental problems (Ravenholt, 1973). illimitable examples of bad agricultural practises can be found around the globe, the techniques of temperate-zone agribusiness to the tropical soils of Brazil, leading to the loss of the soil nutrients and erosion can be found in S outh America (McNeil, 1972). Coastal regions are also affected by the human consumption and mismanagement of resources, impacts due the human activity are evident, the mismanagement of waste disposal, water mismanagement, metals and fertilizers residues and oil spills, bruising pollutants hurled to marine ecosystems, mining, CO2 emissions, greenhouse emissions, and many more harmful environmental practices can be found on different parts of the globe. The natural technologies, achievements and developments in the last hundred years concerning agriculture are not resolving these environmental conflicts in a small period of time, for this reason it is urgent to find creative solutions to address these issues and achieve sustainability in launch to create a consistent solution to the population growth concern. concord to naturalist Sir David Attenborough (BBC, 2010) there are three favourable ways to operate sustainable development first stop consuming so many resources, and one of the theories is that developed countries should stop using so many resources in order to allow developing countries to meet their necessary for resources, An example of this is the production methods of food that many developed countries have on countries like mainland China and Africa to meet their own needs and to export and sustain their own population, cause a enormous demand problem in production that bound this developing countries (Developing countries need to meet their own food supply requirements and at the same time they have to produce extra supplies to meet the demand from foreign countries using their land). The Second proposal by Attenborough, is the change of our engine room and production methodologies by using alternative methods of agriculture and energy production. It is a fact that the struggle to minimize the use of fossil fuels and promote the use of clean renewable energies is a difficult and constant effort, however an implant question comes to attentio n is the use of clean energy affordable to go through in developing countries? The cost and resources are not yet clear to respond that question. The third proposal presented is about reducing population growth, and to reduce population growth education is also essential. Education on birth control device methods and access to effective birth control systems are basic specially in developing countries where resources are scarce and population growth worsens the helping to access basic needs. It is evident that developing countries are more usually the ones to have more population growth worldwide (refer to table 1 and chart 1 appendices) and this increase in population is the direct cause of many of the numerous environmental problems in those countries.ConclusionIt is clear that population growth has a negative impact on the environment, the intensification of agriculture, the uncontrolled industrial enterprise and economic growth, the depletion of resources and the destructi on of natural habitats is evident and undeniable in our sure world. For this reason it is necessary to implement intelligent and concrete strategies to minimize the impacts and make of environmental degradation. There is an urgent need to look for real development solutions and sustainable policies to maximize the use of resources without degrading the environments capacity to restore it egotism and simultaneously obtain a balanced assessment for the impact that populace perform on the planet. human beings capacity for improvement and technology opens routine windows and doors to new sustainable solutions that can generate substantial changes in the levels of production, saving and renewal of ecosystems and resources. Governments are required to achieve improvements and find ways to be more involved in environmental issues, seeking to improve the feeling of life, health and livelihood of their populations through viable and sustainable solutions for the cover use of resourc es. It is the responsibility of governments, communities and every person on the planet whether living in a developed or developing country to find solutions and alternatives to derive not only current generations but also future generations to come. Human carrying capacity must not reach its limits before finding solutions to existing problems, human influence and positive technological advances and current developments on issues such as environment must be a permanent strategy to minimize the ecological footprint of humans on resources. Proper Education, correct land management, technological improvements, economic investment, proper resource management and awareness, and break out public policies regarding natural resource management are crucial and vital elements for the development of communities and poverty eradication around the world. AppendixTable 1TOP 20 LARGEST COUNTRIES BY POPULATION1China 1,399,913,213 2India 1,278,847,8043United States 324,475,111 4Indonesia 255,021 ,3095Brazil 203,283,249 6Pakistan 187,383,6827Nigeria 182,243,489 8Bangladesh 159,950,7539Russia 142,196,628 10Japan 126,893,22511Mexico 124,899,068 12Philippines 101,379,22413Ethiopia 98,330,593 14Vietnam 93,197,56315Egypt 84,387,897 16Germany 82,597,11117Iran 79,238,137 18Turkey 76,515,19119Congo 70,762,892 20Thailand 67,381,077Chart 1References.Public Health Reports 1992. Population Growth Threatens Natural Resources 107, p. 608.World Bank. 2004. World Population GrowthASIA POPULATION, R. 2013. Asia Population 2013 Online. Available http//www.worldpopulationstatistics.com/asia-population-2013/.BBC, H. S., EPISODE 7 2010. How Many battalion Can Live on Planet Earth? In ATTENBOROUGH, D. (ed.).HOLDREN, J. EHRLICH, P. 1974. Human Population and the Global Environment Population growth, rising per capita material consumption, and unquiet technologies have made civilization a global ecological force. American Scientist.MALTHUS, T. 1798. An Essay on the Principle of Population, L ondon, Printed for J. Johnson, in St. Pauls Church-Yard.MCNEIL, M. 1972. 32. LATERITIC SOILS IN DISTINCT TROPICAL ENVIRONMENTS Southern Sudan and Brazil.RAVENHOLT, A. 1973. Man-land-productivity Microdynamics in Rural Bali. Southeast Asia series, 21, 9.THORKILD, J. ADAMS, R. 1958 sodium chloride and silt in ancient Mesopotamian agriculture Vol. 128 no. 3334 pp. 1251-1258128 1251-58.

Polycystic Kidney Disease Causes and Treatment

Poly cystic Kidney Disease Ca calls and TreatmentIntroductionPolycystic kidney illness effectuate roughly 10 million people worldwide. Even though this indisposition is so prominent it wants research in the field of therapeutics from biopharmaceutical companies as they give their resources into fields which argon seen to be more than profitable i.e. give the gatecer research. This lack of research is what enticed us to carry out our design on polycystic kidney distemper.This project get out first of allly outline the history of the polycystic kidney sickness, how it effects diligents, the ca physical exercise of the complaint and the menses therapeutic treatment available to combat polycystic kidney malady in section 1.Section 2 will look at the current diagnostic order acting actings employed by a physician to see if a affected role is suffering from polycystic kidney illness. Diagnostic methods such as imaging and ancestral test will be dealt with here.Lastly section 3 will look at a potential new diagnostic proficiency which has been varianceed victimisation proteomic techniques to identify the difference between a brawny polycystin-1 protein comp ard to a mutated polycystin-1 protein.The first record of Polycystic Kidney Disease (PKD) is from the 16th century. In 1586, the index of Poland died from cysts on his kidneys. The cysts were described by his surgeon as large comparable those of a bull, with an uneven and bumpy surface. At the time of his death he was diagnosed with meningeal abscesses. It wasnt until a group of physicians re-examined the records of the Kings death over 300 nose shagdy old age later that his cause of death was agreed to be PKD. The destination polycystic kidney infirmity was first used by Flix Lejars in 1888, although the fashion of getance of this malady wasnt understood for almost an other wiz one hundred years. In the 1990s, the composition of cysts was understood at a molecular(a) level. This helped in the disco precise(prenominal) of the divisors that cause PKD (Ayse, 2016).Figure.1 A visual representation of the trans weave paper layer proteins Polycystin-1 and Polycystin-2. in any case seen is the Polycystin-1 receptor located in extracellularly.(Gallagher, Germino and Somlo, 2010)PKD is a contractable disease in which the renal wind in spite of appearance the outer cortex and internal light bulb is replaced with quiet filled sacs (or cysts). These cysts enlarge the kidneys and crucify kidney function. Hypertension, hematuria and continuing pain ar the most common symptoms associated with PKD (Seeger-Nukpezah et al., 2015). PKD has twain forms autosomal prevailing (ADPKD) and autosomal Recessive (ARPKD). ADPKD is the result of the inheritance of one mutant PKD1 or PKD2 gene, which affects 1750 people worldwide. 85% of ADPKD cases are caused by noveltys in PKD1. Mutations in this gene conduct to earlier disease onset. The other 15% of cases are attributed to a mutation in PKD2.All ADPKD forbearings inherit one normal allele and one mutant allele. Cases where both alleles know the superior mutation lead to embryonic lethality. ARPKD is caused by the inheritance of two recessive mutated PKHD1 genes. ARPKD is turn overably less common with an incidence of 120,000. ARPKD progresses at a much faster rate than ADPKD. It usually causes death at birth or requires transplantation in other(a) childhood. Multiple varied types of mutations in PKD1, PKD2, and PKHD1 have been researched, including frameshifts, deletions, and premature stop codon insertions (Wilson, 2015).In the dominant form of PKD there is only one mutated gene inherited. This mutated gene is otiose to produce the proteins PC-1 or PC-2. However, the non-mutated allele mint still function as normal and earth-closet produce enough of the polycystin proteins to maintain kidney function. It is only when a somatic mutation occurs cavictimization the normal allele t o become inactivated that symptoms of the disease will occur. (Torres and Harris, 2010)PKD-1 is located on the short arm of chromosome 16 (16p13.3). PKD-2 gene is located on the long arm of chromosome 4 (4q21) ( promptlyak et al., 2016). Polycystin-1 and 2 are large transmembrane proteins which are encoded by PKD1 and 2. Both proteins affect multiple gloomyriver signalling proteins (Seeger-Nukpezah et al., 2015).In a normally functioning nephron as the urinary filtrate flows by and causes the primary cilia to bend polycystin 1 and 2 serve by allowing atomic number 20 influx which activate pathways in the cell which inhibit cell proliferation. PC1 has the ability to sense when the primary cilia bends which activates PC2 calcium channels. If each PC1 or PC2 is absent the signal to inhibit cell growth is non received (Chebib et al., 2015).PKD1 or PKD2 mutations cause a reduction in intracellular calcium. This triggers a swop in the response of the cell to cyclic adenosine monoph osphate (cAMP) from inhibition to proliferation. The concentration of cAMP directly affects the activity of Protein Kinase A. Four cAMP molecules are required to activate one PKA enzyme. The increased toil of cAMP via adenylyl cyclase 6 is dependent on vasopressin (Chebib et al., 2015).Despite the m both breakthroughs in research allowing for a greater understanding of the disease, there is currently no recover for PKD. However, there are drugs which can suppress symptoms brought on by the disease. of import blockers such as, Tenormin, can be used to treat hypertension and hematuria can be treated with antibiotics. Understanding the effect of PC1 and PC2 mutations on the vasopressin receptor in the cell lead to the development of Tolvaptan. This drug slows down the shaping of cysts in the kidneys. Tolvaptan blocks the vasopressin receptor, which will stop the signalling pathway. Therefore, cAMP production will be reduced. (Ema.europa.eu, 2017)The current diagnostic methods for polycystic kidney disease include contagious testing, pre-natal testing and imaging studies in the form of ultrasounds, CT (Computed Tomography) scans and MRI (Magnetic sonority resourcefulness) scansThe imaging studies take a scan of the kidneys to identify the presence of any abnormalities in the form of renal cysts. An ultrasound mechanism uses high frequence sound waves to capture and jut out images that cant be seen with the naked eye. The CT scan combines many x-ray images with the aid of a computer to picture cross sectional views and/or collar-dimensional images of the kidneys and the MRI scan uses a magnetic field and pulses of radio wave energy to from pictures of the kidneys.The appearance of three or more renal cysts, either unilateral or bilateral, on the image is enough to diagnose a patient between the ages of 15 and 39 with polycystic kidney disease. In patients aged 40 59, the presence of two or more cysts in each kidney fulfils the criteria to diagnose the patient with polycystic kidney disease. The presence of intravenous feeding or more cysts in each kidney is used to diagnose sometime(a) patients (F. Belibi et al., 2008). The kidneys on an image w knock againstethorn appear enlarged but apply their normal reniform shape in the case of a patient presenting with possible polycystic kidney disease. The medullary pyramids in the centre of the kidney may be more visible on an image in contrast to the cortex which can give a peripheral halo on the image obtained. heights resolution imaging studies allows the visualisation of numerous cylindrical cysts inside the medulla and the cortex which represent ectatic collecting ducts within the kidney (F. Gaillard, 2015).Genetic testing for polycystic kidney disease is for those who have a family history of polycystic kidney disease who has no symptoms and may consider being screened for the disease. Genetic tests can be make to screen for both PKD1 or PKD2 mutations. A method of PCR cogni se as PCR- SSCP (Polymerase Chain answer Single Strand Conformation Polymorphism) is used to view mutations, if any, in the patients genomic desoxyribonucleic acid. In SSCP analysis, a mutated DNA sequence is detected as a change of mobility in polyacrylamide gel electrophoresis caused by the altered folded structure of single-stranded DNA (K. Hayashi, 1991). The genomic DNA of the white blood cells in patients with the possible polycystic kidney disease gene are isolated. These smacks of genomic DNA are past amplified by PCR utilise two primers to amplify the potential polycystic kidney disease genes (R. Jas et al., 2012) The PCR product is then analysed using the SSCP method. This method involves loading the PCR product types onto the acryl amide gel and gel electrophoresis occurs. afterwards completion of the gel electrophoresis step, the gel is subjected to silver staining to visualise the SSCP band patterns (B. Yadav et al., 2009). The silver stained gel is kept on a tra nsilluminator and the SSCP variants are recorded. DNA samples from the abnormal bands seen on the transilluminator are sequenced to see what potpourri of mutation and where the location of the mutation is on the polycystic kidney disease gene (Z. Dian-Yong et al., 2002). In PCR-SSCP analysis, changes in several hundred base pairs are detected in contrast with other techniques in which changes in relatively short sequences can be detected. Because of this, PCR-SSCP analysis is much more sensitive to the replication errors that can occur during the PCR process (K. Hayashi, 1991).Diagnosis of polycystic kidney disease can also be done prenatally. If the parents agree, a prenatal diagnosis can be done on the developing fetus if there is a history of polycystic kidney disease in either the parents or extended family . A DNA sample is taken from both parents and a sample of tissue is taken from the fetus. The tissue sample is obtained from the fetus by a procedure called aminocentesis w hich involves passing a needle into the mothers lower abdomen and into the amniotic cavity inside the uterus. The sample is then amplified by PCR to detect any mutations in the DNA that could lead to the fetus developing polycystic kidney disease in the future (K. MacDermot et al., 1998).The imaging studies, genetic testing and prenatal testing for polycystic kidney disease have proceedss and disadvantages. One advantage of the imaging studies is that they are reliable, inexpensive and a non-invasive way to diagnose polycystic kidney disease (A.Khan, 2015). A disadvantage of imaging studies is that while they are sensitive in the detection of polycystic kidney disease, problems may arise with smaller cysts. Smaller cysts on scans may not be easily differentiated from small, solid bay windowes within the kidneys (A.Khan, 2015). An advantage of CT scans when compared to MRI scans is that the cysts on the kidney will enhance on the image when dye is administered into the patient intr avenously (A. Khan, 2015) (F. Gaillard, 2015). MRI scans of the kidneys are bonnie a useful technique in diagnosing more confused cysts and can be used in addition to or rather of CT scans (A. Khan, 2015).The advantage of genetic testing as a method of diagnosing polycystic kidney disease is that it can determine if a person who has a relative with polycystic kidney disease will in the future start book binding symptoms of the disease. Some disadvantages of genetic testing as a method of diagnosing polycystic kidney disease is that they are extremely costly tests to carry out and sometimes they cant pick up on certain gene mutations that could in conclusion lead to the person having polycystic kidney disease ( subject area Kidney Foundation, 2016).The major advantage of prenatal testing for polycystic kidney disease is the fact that treatment using cyst suppressing drugs can be used early in the diseased patients life meaning the formation of renal damaging cysts will be slowe d down drastically compared to a patient who was not on the cyst supressing treatment early in their life time. The negative of prenatal testing is of course the invasive temper of extracting tissue from the foetus which many parents would not agree with however the benefits of early diagnosis of this disease will lead to a better fictional character of life for the child in their later years.As discussed in the foregoing section the current diagnostic methods for diagnosing polycystic kidney disease is through the use of various scans and genetic testing. The genetic testing is carried out by analysing the DNA sequence in sight to identify any mutations which may be present.As a new method of diagnosing this disease a study of the protein polycystin-1 which when mutated is responsible for polycystic kidney disease, will be analysed by using proteomic methods.Firstly, the polycystin-1 protein mustiness be extracted from a patient who wishes to obtain diagnosis of the disease. S ince polycystin-1 is a membrane protein and is located in the kidney it will be necessary to extract kidney tissue from the patient by carrying out a quick and simple biopsy procedure. The biopsy removes kidney tissue by inserting a thin biopsy needle through the skin and into the kidney whilst the patient is under local anaesthetic.Now that tissue containing the polycystin-1 or its mutated form is extracted from the patient it must be treated in hunting lodge to release the proteins contained within the tissue. The tissue will firstly be homogenized and lysed in order to release the proteins into solution. The sample will then be centrifuged at 14,000 rpm at 4C for 15 min. This centrifugation step removes any insoluble material and the supernatant will contain the proteins from the tissue sample including the protein of hobby polycystin-1. This method was carried out by Malhas, Abuknesha, and Price 2001 whilst trying to crystalize the polycystin-1 protein.Now that polycystin-1 i s in solution it can be separated from the other proteins by means of 2D gel electrophoresis. This technique will separate the polycystin-1 protein from other proteins based firstly on their isoelectric points (pIs) and secondly by their molecular cargo. later on carrying out this two-dimensional separation the gel is stained with stains such as coo busie brilliant blue (CBB) or silver staining in order to visualize the spots on the gel. By carrying out bioinformatical analysis the molecular weight and pI of polycystin-1 can easily be obtained (Mishra 2010).The molecular weight of polycystin-1 is 460.3 kDa and it has a pI of 6.27. With this information, the band which corresponds to the molecular weight and pI of polycystin-1 can be easily identified and excised from the gel.Before excising the polycystin-1 protein from the gel it must first be fragmented into peptides using trypsin cleavage.By fragmenting the protein with trypsin, peptide molecules are formed which are now suitab le to be sequenced using MALDI-TOF mass spectrometry. These peptides must then be suspended in a matrix suitable for MALDI-TOF MS. An archetype of such a matrix is -cyano-4-hydroxycinnamic acid which was used in the change by reversal carried out by Malhas, Abuknesha, and Price, when they crystallized the polycystin-1 protein using the MALDI-TOF technique. This matrix is suitable as the peptides are below 5 kDa.The matrix and peptide mixture is then flush onto the metal plate of the MALDI-TOF MS analyser where it will be hit by a pulsing UV laser. The matrix molecules absorb the UV light causing the matrix molecules to enter the gas phase along with their coupled vaporised peptides which then become ionized. The TOF MS then measures the time it takes the ions to aerify as lighter ions travel faster. The ions will then hit the ion demodulator and the on board computer will produce the plot of the mass spectrum (Kraj and Silberring 2008).MALDI-TOF MS is the ideal method to analys e the polycystin-1 protein as like ESI, it is a soft ionization technique meaning there will be little or no fragmentation of the compounds being analysed. Once the mass spectrum is obtained it is then compared to the mass spectrum of the normally functioning polycystin-1 protein which can theoretically be fragmented by trypsin in the online databases. Any differences between the sample and the known mass spectrum of the normal protein will signal a mutation has occurred.This method of protein analysis is a very effective and efficient way of screening for the mutated proteins. The study carried out by Brioude et al 2016 proves this as they looked at using MALDI-TOF MS to test for mutated proteins leading to lung tumours. In this study, they concluded that the method is very promising and it should be used in several surgical settings where rapid evaluation of abnormal tissue is required. This highlights how this new method of analysing polycystin-1 for a mutation could prove very effective in diagnosing polycystic kidney disease.This method holds a distinct advantage over the imaging methods currently in use as diagnosis can be made early in a patients life before they show symptoms or the formation of cyst on their kidneys which are associated with polycystic kidney disease. Early diagnosis of this disease means that drugs for the streak of cyst formation such as Jinarc which contains the API Tolvaptan can prolong a patients kidney function by slowing down the rate at which the fluid filled cysts on the kidneys are formed.This method is used to identify a mutation of the polycystin-1 protein which attributes to 85% of autosomal dominant polycystic kidney disease cases. The other 15% is made up of mutations of the protein polycystin-2. Fibrocystin is the mutated protein responsible for autosomal recessive polycystic kidney disease. Both the dominant and recessive forms of this disease can be diagnosed using the above method in order to identify a mutation i n either polycystin-2 or fibrocystin proteins if there is no mutation of polycystin-1 observed.From the above sections, it can be seen how sever and prominent polycystic kidney disease is worldwide. Although this disease is genetically inherited from or both parents, symptoms of the disease are slow progressing. In 85% of cases the disease will not advance to renal failure until the patient is 50-60 years of age.The current diagnostic techniques currently used by doctors such as imaging and genetic testing have their benefits however they are also flawed. The major disadvantage seen in this project regarding the current diagnostic techniques is the diagnosis of polycystic kidney disease in a patient where uncontrolled cyst formation has already occurred and serious renal problems have begun.With the use of our new proteomic technique earlier diagnosis will be possible before the disease has progressed to renal failure. Early diagnosis means that the use of drugs such as Tolvaptan ca n be used to significantly slow down cyst formation which will ultimately increase the length of time a patient suffering with polycystic kidney disease has before renal failure occurs.A.Khan (2015) Imaging in Autosomal Dominant Polycystic Kidney Disease, Medscape ledger , 01(1).Ayse, B. (2016). Tear drops of kidney a historic overview of Polycystic Kidney Disease. Giornale Italiano di Nefrologia, 1.B. Yadav D. Kale (2009) Single Strand Conformation Polymorphism (SSCP) Analysis by Nondenaturing PAGE Journal of Biological Methods, 01 (1).Brioude, G., Brgeon, F., Trousse, D., Flaudrops, C., Secq, V., De Dominicis, F., Chabrires, E., Djourno, X.-B., Raoult, D. and Thomas, P.-A. (2016) Rapid diagnosis of lung tumors, a Feasability study using Maldi-Tof mass Spectrometry, PLOS ONE, 11(5). doi 10.1371/journal.pone.0155449.Chebib, F., Sussman, C., Wang, X., Harris, P. and Torres, V. (2015). Vasopressin and disruption of calcium signalling in polycystic kidney disease. Nature Reviews Neph rology, 11(8), pp.451-464.Ema.europa.eu. (2017). European Medicines Agency Human medicines EU/3/13/1175. online Available at http//www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2013/09/human_orphan_001257.jspmid=WC0b01ac058001d12bsource=homeMedSearch Accessed 4 Mar. 2017.F. Gaillard (2015) Autosomal Recessive Polycystic Kidney Disease Radiopaedia Journal, 01(1).F.Belibi C. Edelstein (2008) Unified Ultrasonic Diagnostic Criteria for Polycystic Kidney Disease Journal of the American Society of Nephrology, 20 (1).Gallagher, A., Germino, G. and Somlo, S. (2010). Molecular Advances in Autosomal Dominant Polycystic Kidney Disease. Advances in Chronic Kidney Disease, 17(2), pp.118-130.K.Hayashi (1991) PCR-SSCP A Simple and Sensitive Method for spotting of Mutations in the Genomic DNA Genome Research, 01 (1).Kraj, A. and Silberring, J. (eds.) (2008) Proteomics Introduction to methods and applications. Chichester, United Kingdom John Wiley Sons.MacDermot, K., Saggar -Malik, A., Economides, D. and Jeffery, S. (1998). antenatal diagnosis of autosomal dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease. Journal of Medical Genetics, 35(1), pp.13-16.Malhas, A.N., Abuknesha, R.A. and Price, R.G. (2001) Polycystin-1 Immunoaffinity isolation and characterisation by mass spectrometry, FEBS Letters, 505(2), pp. 313-316. doi 10.1016/s0014-5793(01)02842-3.Mishra, N.C. (2010) Introduction to proteomics Principles and applications. United Kingdom John Wiley Sons.National Kidney Foundation (2016) Polycystic Kidney Disease online, available https//www.kidney.org/atoz/content/polycystic/ accessed 26 February 2017.Nowak, M., Huras, H., Wieche, M., Jach, R., Rado-Pokracka, M. and Grecka, J. (2016). Autosomal dominant polycystic kidney disease diagnosed in utero. Review. Ginekologia Polska, 87(8), pp.605-608.Rusni Mohd, Jas (2012) Amplification of Real Time graduate(prenominal) Resolution Melting Analysis PCR Method for Polycystic Kidney Disease (PKD) Gene Mutations in Autosomal Dominant Polycystic Kidney Disease Patients African Journal of Biotechnology, 11(25).Seeger-Nukpezah, T., Geynisman, D., Nikonova, A., Benzing, T. and Golemis, E. (2015). The hallmarks of cancer relevance to the pathogenesis of polycystic kidney disease. Nature Reviews Nephrology, 11(9), pp.515-534.Torres, V. and Harris, P. (2010). Comprehensive Clinical Nephrology. 4th ed. Elsevier Saunders, pp.529-542.Wilson, P. (2015). Therapeutic targets for polycystic kidney disease. Expert thinking on Therapeutic Targets, 20(1), pp.35-45.Z. Dian-Yong, Z. Shu-Zhong, T. Bing, Z. Wei-Li, D. Bing, S. Mao, S. Tian-Mei M. Chang-Lin (2002) Detection of Polycystic Kidney Disease Gene 2 Mutations in the Hans by PCR-SSCP Academic Journal of Second Military Medical University, 01 (1).

Calcium In Contraction Of The Heart

atomic number 20 In Contr performance Of The HeartIn cardiac muscle, excitation-contr do coupling is mediated by atomic number 20- spawn atomic number 20 pass from the sarcoplasmic reticulum end ryanodine sensory receptors that argon activated by atomic number 20 gate d one and only(a) L-type atomic number 20 wrinkles on the sarcolemmal membrane. Although Ca2+ factor sponsore Ca2+ bend start outed by the L-typed atomic number 20 online is the primary pamphlet for triggering Ca2+ from the sarcoplasmic reticulum, thither argon some some early(a) implements that rout out a wish well activate Ca2 + reconcile from the sarcoplasmic reticulum such(prenominal)(prenominal) as atomic number 20 induce atomic number 20 rid (CICR) induced by T-typed atomic number 20 received, CICR triggered by atomic number 20 inflow with with(predicate) Na+/Ca2+ exchange, and CICR mediated by calcium through tetrodotoxin (TTX)-sensitive Ca2+ up-to-date(ICa,TTX). As calcium is an central second base messenger which is essential in regulating cardiac electrical activity as well as being the chief(prenominal) activator of the myofilaments to which ca pneumonic tuberculosis cardiac muscular comp execution. Mishandling of calcium is thought to top many an opposite(prenominal) pathophysiologic conditions. Knowledge of the mechanisms involved in regulating intra cellular telephoneular telephoneular calcium and therefore muscle abbreviation of the nerve, whitethorn attend to to prevent and/or treat pathological conditions such as cardiac grow, arrhythmias or subject matter failure by using therapeutic agents targeted at modulating intracellular calcium.ACKNOWLEDGEMENTFirstly, I would like to show my deepest gratitude to my supervisor, Dr. Munir Hussain, who is a elderly Lecturer in Biomedical Sciences in University of Bradford for his innovative, supportive, expert, professional, kind and sustainmentful supervision, ever changeless guidanc e and, academic support. Without his advice and guidance, my dissertation will non be finished with great success.I would also like to show my sincere thank to all the lecturers from Management Development Institute of Singapore (MDIS) and teachers in my savant life for letting me gain strong knowledge in biomedical science field and essential knowledge to be in this be and my student coordinator and stuffs from Student Service Unit (SSU) for their kind arrangement, support, encouragement and c be.I would like to thank to all my friends who supported me both physically and mentally during my preparation for the dissertation.Last b arely not least, I would like to mother my special deep thank to my p arents who al ways give me tender love, care and all supports all the time. Without their guidance, support and love, nothing give the axe be achieved by me.LIST OF FIGURES insert 1 Calcium transport in ventricular myocytes 3Figure 2 Six potential mechanism of cardiac excitation-co ntraction coupling 9LIST OF ABBREVIATIONSLTCC = L-type calcium takeCICR = Calcium induced calcium releaseerror correction code = Excitation-contraction couplingNCX = Sodium-Calcium Exchangeelder= Sarcoplasmic RecticulumICa = Calcium currentICa,T = T-type calcium currentICa,L = L-type calcium currentICa,TTX = Tetrodotoxin-sensitive calcium currentRyRs = Ryanodine ReceptorCa2+i = Intracellular calcium concentrationCa2+Tot = Total concentration of CalciumPKA = Protein Kinase ALVH = Left Ventricular HypertrophyHOCM = Hypertrophic obstructive cardiomyopathy chip inIn breast muscle cell, the depolarization of action emf is ascribable to the entering of Na+ ions via voltage gated Na+ line and it is called fast inbound current. The immediate repolarization is not possible due to rapidly in energizing of Na+ blood and initial depolarization allow the entering of calcium through voltage-grated Ca2+ impart and it is called second or the slow inward current. The rate of atomic number 11 carry in energizing is more rapid than that of calcium transmit so that Ca2+ enters into the cell providing the membrane potential to close to 0mV for some part of action potential of philia muscle (Reuter, 1984).Excitation-contraction coupling (ECC) is the process in which an action potential triggers a myocyte to contract. In excitable muscle cells, the excitation predict causes rapid depolarization that produces the physiological response of contraction. Calcium is a omnipresent second messenger, historic in both, regulating the electrical activity of the intent as well as elating the myofilaments promptly to cause contraction (Bers, 2001). In mammalian cardiac myocytes, the process of ECC is mediated by Ca2+ influx from the extracellular space that triggers Ca2+ Calcium induced Calcium release (CICR) from the sarcoplasmic reticulum (SR) (Bers, 1991 Stern Lakatta, 1992).When action potential reaches the myocyte, causing it to undergo depolarization, which causes ca lcium ions to enter the cell through L type calcium channel hardened on the sarcolemma and thereby trigger calcium release from the SR. Calcium influx and the intracellular calcium concentration trigger the contraction of heart due to binding of Ca2+ to cardiac muscle fiber protein, troponin C. For activation of SR calcium release, the L-type calcium current is the most widely true mechanism thought to be responsible for CICR. still, SR calcium release can also be triggered by calcium influx through sodium-calcium exchange, calcium influx via T-type Ca2+ current or through tetrodotoxin-sensitive Ca2+ current, or Inositol (1,4,5)-triphosphate ( besides not so much in cardiac muscle). Declining of calcium level in the cells cause the detachment of calcium from myofilament and resulting in relaxation of the heart. in that location are four main pathways for Ca2+ transport out of the cytosol including SR Ca2+ ATPase, sarcolemmal Ca2+-ATPase or mitochondrial Ca2+ uniport and sarcolem mal Na+/Ca2+ exchange. (Bers, 2002).Since CICR is a positive-feed fend for mechanism, it has to be terminated which is essential for diastolic replenish of the heart. in that location are three main pathways for termination of calcium release such as local anaesthetic depletion of SR Ca2+, Ryanodine ( RyR) defusing (or accommodation), and stochastic attrition. (Lukyanenko et al., 1998). Mutation in calcium take can lead to wicked arrhythmias. The improper contractile function and abnormal heart rate associated with cardiac grow and heart failure is due to the mishandling of calcium in heart muscle cell (Pogwizd et al., 2001). In this dissertation, here I discuss some the key mechanism of how Ca2+ transport in cardiac ventricular myocytes. Moreover, I also discuss about how they are modulated and learnd as well as how they interact specifically. In addition, by knowing the subcellular mechanism of E-C coupling, here I discuss about how calcium is altering and getting muta ted so as to cause cardiovascular diseases. The important molecular directing pathways in contraction of heart will also be addressed.Figure 1. Calcium transport in ventricular myocytes. (Adapted from Bers, 2002) The figure shows the time consort of an action potential, Ca2+ transient and contraction in rat ventricular myocytes, NCX, and other protein involved in contraction.Calcium channels in contraction of the heartIn cardiac muscle, calcium has a fictional character for the ability to thrust the cardiac cell to contract. There are five types of calcium channels L, T, N, P/Q and R types. Among them, L-type and T-type calcium channels are two major(ip) types of calcium channels in the cells of cardiac tissues (Bean, 1989). L-type Ca2+ channels return many subunits in the heart such as 1, 2, and subunits. The 1 subunit is the dihydropyridine (DHP) receptors which are important for calcium entry into the cells (Liu et al., 2000). L-type calcium channels (long-lasting) can activates at more positive membrane potential (Em), at greater than -40mV and generate peak inward current at 0mV and slowly inactivated, and is sensitive to dihydropyridines (Tsien et al., 1987). Thus, the L-type Ca2+ channels are the majority of calcium channels responsible for entering of Ca2+ into the cardiac cell during phase 2 (plateau phase) of the action potential. On the other hand, T-type (tiny or transient) Ca2+ channels cause the activation and inactivation at more detrimental membrane potential (Em) and dihydropyridines cannot immobilise pieceively (Nowycky et al., 1985). However T-type Ca2+ channels prepare instant(prenominal) kinetics than compared to L-type Ca2+ channels. During information and hypertrophy, T type calcium current is more prominent and the T-type current is typically small or thoughtless in ventricular myocytes. The entering of Ca2+ into the cell by passing through I Ca,T is only responsible for smaller substance of Ca2+ than that passing thr ough ICa,L. In most ventricular myocytes, T-type calcium current is almost negligible. It shows that the let go and refilling is mainly provided by Ica,L. The amount of L-type calcium current and T-type calcium current is versatile among cardiac myocytes. L-types calcium current is present in all cardiac myocytes whereas T-type calcium current have larger cistron in the canine Purkinje fiber (Zhou, 1998). Depolarization during the action potential causes activation of calcium current. During an action potential, the amount of calcium entry is limited by calcium subordinate inactivation at the cytosolic side. L-type calcium channel is located at the sarcolemmal-SR junction where ryanodine receptors exist (Scriven et al., 2000). There is a negative feedback effect on Ca2+ influx and SR Ca2+ release during excitation-contraction mechanism. When there is increase Ca2+ influx or release, further release of Ca2+ is move off.There are many isoforms of ryanodine receptors, (RyR1, RyR2 , RyR3), among them, RYR2 is the cardiac isoform. RyR2 mediated release of Ca2+ from sarcoplasmic recticulum is an important step in cardiac E-C coupling in the heart. RyR2 is a Ca2+-gated channel (Nabauer et al, 1989). RyR2 is activated by Ca2+ influx through L-type Ca2+ channel or dihydropyridine receptor (Adachi-Akahane, 1996). Cytosolic Ca2+ is increased by the RyR2 opening and bind with contractile protein (troponin C) that trigger the contraction of heart. In ventricular myocytes, there are much more ryanodine receptors than dihydropyridine receptors. Therefore, four or ten RyRs can be associated with a single L-type Ca2+ channel (Bers et al., 1991). Defection in excitation- contraction coupling can occur due to either if RyRs channels predisposition is altered for activation/inactivation or if the SR Ca2+ is depleted. There has been demo in animal dashl of cardiomyopathy (Gomez et al, 1997).Ca2+i and Ca2+ start outsCa2+i and total Ca2+ determine the development of contract ion which produces both isometric specialty and rapid shortening (Moss, 2001). The persuasiveness of cardiac contraction can be changed by two ways (1) by changing the extent and amplitude of the Ca2+ transient, (2) by altering the myofilament predisposition to Ca2+. The esthesia of myofilament calcium is increased by contracting the myofilament when the heart fills with parentage resulting the contraction to be stronger. Caffeine and certain inotropic agents can enhance the myofilament sensitivity whereas the increased concentrations of phosphate and Mg2+ and acidosis reduce myofilament Ca2+ sensitivity. Ca2+ stumbles is the process of spontaneous release of SR Ca2+ and it was described by using confocal fluorescence microscopy (Cheng et al., 1993). The release of SR Ca2+ via single L-type Ca2+ channel or RyRs openings generates Ca2+ sparks (Song et al., 1997). Ca2+ spark is activated by the Ca2+ entery through ICa (Cannell et al, 1995). Ca2+ spark is triggered by the opening of single channel opening. There have been reported that spark fortune can be depend on binding of two Ca2+ ions to the RyR (Santana et al., 1996). Thus, local cytosolic Ca2+i is important in the frequency of Ca2+ sparks and SR Ca2+ release. Moreover, the frequency of Ca2+ spark depends on the SR Ca2+ blame (Cheng et al, 1993). When there is increased SR Ca2+ load, this may lead to increase the amplitude of Ca2+ spark. Therefore SR Ca2+ load is an important factor for Ca2+ release from SR.Role of Sarcoplamic RecticulumECC and intracellular Ca2+ homeostasis are primarily regulated by sarcoplasmic recticulum (Bers, 1991). Once stimulation, calcium enters the cell, thereby stimulating the release of larger amount of calcium from SR resulting in activation of contractile protein and contraction of the heart. During cardiac relaxation, Ca2+ is taken up by SR by SR Ca2+ ATPase pump and Na+/Ca2+ exchange pump. The key SR Ca2+ release channel involved in cardiac contraction is RyRs and RyR2 is the cardiac isoform. The amount and fraction of Ca2+ release that depends on the level of SR Ca2+ load can release for a given ICa trigger (Shannon et al., 2000). Sensitivity of RyRs receptor to Ca2+i at high load of SR Ca2+ leads to increase spontaneous SR Ca2+ release. On the other hand, decrease in SR Ca2+ release (which is induced by ICa ) can be due to low SRCa2+ content. The cast down the amount of the SR Ca2+ release, the more amount of Ca2+ enter the cells through Na+/Ca2+ exchange. When there is low concentration in SR Ca2+, Ca2+ release from SR is turned off during E-C coupling. Furthermore, SR Ca2+ content depends on the heart rate and season of action potential. Ca2+ concentration release from SR can be increased by more mount of Ca2+ enter into the cell, by decreasing Ca2+ evasion or increase SR Ca2+ inlet. Phospholamben, an endogenous inhibitor of SR Ca2+ ATPase, is triggered by activation of summer camp-dependent or calmodulin-dependent protein kinase. When this phospholamben becomes phosphorylated, Ca2+ uptake by SR is increased and allows faster cardiac relaxation and declining of Ca2+i. Targeted knockout of phospholamben leads to hyperdynamic hearts with negative effects (Brittsan Kranias, 2000). Interestingly, lower SR Ca2+ uptake, reduced SR Ca2+ATPase gene and protein expression were seen in weakness forgiving heart (Pieske et al., 1995). On the other hand, there has been demonstrated that increased gene expression of sarcolemmal Na+/Ca2+ money changer was seen in human failing heart (Reinecke et al., 1996).Regulation of Calcium currentIca can be variable physiologically and pharmacologically. During physiological sympathetic stimulation of heart, catecholamine stimulate beta-adrenegic receptors, which improve the military capability of contraction (inotropic effects) and relaxation (lusitorpic effects) and declining of Ca2+i. In addition, stimulation of -adrenergic receptor stimulates a GTP-binding protein that acceler ates adenylyl cyclase for the cAMP mathematical product. cAMP activates PKA, which phospharylates severe protein such as phospholamban, RyR, L-types Ca2+ channels, myocin binding protein C and troponin I ( which are related to ECC). Activation and phosphorylation of L-type Ca2+ channels will cause Ca2+ release from SR causing contraction of the heart. Phosphorylation of troponin I and phospholamban stimulate the reuptake of Ca2+ release from SR and Ca2+ is dissociated from the myofilament and develops to cardiac relaxation (Lusitropic effect). The inotrophic effect of PKA (protein kinase A) activation is triggered by the junto greater availability of SR Ca2+ and increased calcium current. Open probability of RyR channels can also be modulated by protein kinase A. RyRs receptors are hyperphosphorylated in heart failure causing a diastolic leak of SR Ca2+. However, whether PKA-dependent phosphorylation will alter during excitation-contraction or not still delay controversial. Moreo ver, phosphorylation of L-type Ca2+ channels, phospholamban and troponin I are analogueed with activation of 1-adrenergic receptors in ventricular myocytes that produce inotrophic and lusitropic effects. On the other hand, 2-adrenergic receptors activation can give more restricted to the sweetener of ICa (Kushel et al., 1999). cAMP production can also be stimulated by the G-protein-coupled receptors such as prostaglandin E and histamine that will lead to little or no effect of inotropic effects (Vila Petroff et al, 2001). Other receptors will also regulate the signaling pathway. For instance, M2-muscarinic receptors activation can decrease cAMP and activation of PKA thereby decreasing Ca2+ entry and release. In addition, this pathway also enhances repolarization. The pharmacological effects of L-type Ca2+ channels are in which calcium sensitivity to dihydropyridines (nephedipine, amlodipine, nitrendine, nimodipine, nisoldipine). Ica is inhibited by most of DHPs and they are called C a2+-channel blockers. In DHPs, there are two other types of specific L-type Ca2+ channel blockers (1) phenyalkylamines (eg. verapamil, D600) and (2) benzothiazepines (eg, diltiazem), and those agents can act together directly with the Ca2+ channel (Glossmann et al., 1985). Verapamil can inhibit the calcium channel in the open state only if it select depolarization pulse) and this is called use dependent. The neutral ligands such as nitrendipine and nisoldipine inhibit ICa depend on the calcium channel whether they are in the opening state or inactivated state , and does not require depolarization pulse as they are voltage dependent than use dependent.Figure 2. Six possible mechanism of cardiac excitation-contraction coupling. (Adapted from Bers, 1999)The figure shows Ca2+ influx via ICa,L, Ca2+ influx via ICa,T,Ca2+influx through NCX, Ca2+ influx via IP3 ,Ca2+ influx via ICa,TTX and depolarization dependent Ca2+ influx.Calcium induced calcium release during E-C couplingThere have been demonstrated that CICR in skinned ventricular myocytes (Fabiato and Fabiato, 1975). There was been proved that main pathway of E-C coupling in cardiac myocytes is by Ca entry through L-type Ca2+ channels and triggers SR Ca2+ release (Bers, 1991). When calcium channel becomes deactivates, forward calcium channels close, calcium transient is induced by a large and short-lived ICa causing contraction. Moreover, Ca2+ channel activation in the absence seizure of Ca2+ influx also cannot induce calcium release from the SR (Nabauer et al., 1989). There is supported that ICa activate SR Ca2+ release channel when there is a high concentration of Ca2+ buffer in the cell (Adachi-Akahane et al., 1996). Ca2+ release from SR is most commonly activated by L-type Ca2+ channels and this pathway is called Ca2+ induced Ca2+ release (CICR). There has been little doubt that E-C coupling occurs physiologically but there are other mechanisms which can exit in parallel and give rise to the functional effects.Ca influx via ICa,TIn ventricular myocytes, T-type calcium channels is relatively small or absent but it is more prominent in the development and hypertrophy of the heart. Because of T-type calcium current is relatively small and rapidly inactivated, the total amount of calcium influx through T-type calcium current is absolutely small compared to calcium influx via ICa,L (Zhou, 1998). Moreover, T-type calcium current is negligible in most of ventricular myocytes. T-type Ca2+channels are not located at the SR junction, therefore the durability of ICa,T as a trigger for Ca2+ release from SR is not in effect(p) as ICa,L. Furthermore, SR Ca2+ release by ICa,T is delayed on trespass and slower than ICa,L. However, it can be significant in other cardiac cells such as some atrial cells and Purkinje fibers (Zhou and January, 1998). Since T-type calcium channel is non-functional in most of the myocytes of ventricle, it does not play a major social occasion for ECC although it may function like ICa,L. So, ICa,T only plays a minor role in triggering Ca2+ release from SR during action potential. Ca influx via Na+/Ca2+ exchangeAlthough L-type Ca2+ current is a major role of CICR in contraction of the heart, some argued that the L-type Ca2+ channels could not be the only way to trigger the calcium release from SR. There is an alternative trigger of calcium release in mammalian cardiac myocytes (Chunlei Han et al., 2002). The result of Ca2+ release by Na+/Ca2+ exchanger has been proved by examination on rats (Wasserstorm and Vites, 1996), rock dassie (Litwin et al., 1998) and guinea pig (Sipida et al., 1997). Immunofluorescence labeling shows that the exchanger current is present in the cardiac T-tubules system (Scriven et al, 2000). There are two ways of triggering Ca2+ release from SR by Na+/ Ca2+ exchanger. The first mechanism is Na+ current by increasing local Na+sm, increasing Ca2+ entry through Na+/Ca2+ exchanger and causing SR Ca2+ release (Levesque et al.,1994 ). The second one is that depolarization directly stimulates outward INa/Ca and Ca2+ release and contraction when L-type Ca2+ channel become stop or at high positive Em (Levi et al.,1994 and Litwin et al.,1998 ). Increased intracellular sodium stimulate the Na+/Ca+ exchanger (Evans and Cannell, 1997 ) and, if INa is low (Na+i=10nM) or lower, the reverse current of the Na+/Ca2+ exchange could trigger Ca2+ release mark for 25%. When Na+i=30nM, the contribution of Na+/Ca2+ exchanger increase up to carbon%. Additionally, the exchanger current is more dependent on the temperature and changes in the intracellular sodium and calcium concentrations than compared to L-type calcium current. Furthermore, these changes are larger in the microdomain or subspace (interaction between RyR receptors and L-type Ca2+ channels occurs) than compared to the rest of the cytoplasm (Vornanen et al., 1994). Although LTCC are faster than the exchanger current in triggering of Ca2+ release from SR, Ca2+ entry through the exchanger into the subspace is faster in beginning than L-type Ca2+ current when there is action potential stimulations because the action potentials upstroke and sodium (inward) current is associated with rapid increase in Na+i. Therefore, any physiological stimulation or medication that alters the intracellular sodium becomes the governor of calcium release from sarcoplasmic reticulum. foreplay via hormone, such as activation of endothelin-1 (ET-1) receptor (Alvarez et al., 1999), and increasing frequency of action potential (Simor et al., 1997) will increase the intracellular sodium concentration, causing calcium release triggering via the Na+/Ca2+ exchanger by contend to via the L-type calcium current. Ca2+ release from SR is slower via Ca2+ influx through Na+/Ca2+ exchanger than through L-type calcium channel (Spido et al., 1997) .Ca influx via TTX sensitive-Na channelsAggarwal and co-worker reported voltage-gated, calcium carrying sodium channel, (ICa ,TTX), calcium entry via tetrodotoxin-sentive Na+ channels can also mediates CICR. This channel activates at membrane potential of -60mV and has faster kinetics than L-type Ca2+ channels. It can alter selectivity of cardiac Na+ channels triggers by either activation of agonist effects -adrenergic receptor or cardioactive steroids or cardiac glycosides, resulting Na+ channel prefer Ca2+ than Na channels and it is called slip mode or altered selectivity mode. The tetrodotoxin-sensitive Ca2+ influx can also trigger the SR Ca2+ release. The inotrophic effects of cardiac glycosides and -adrenergic agonists could be a bracing mechanism. These effects could be triggered by SR Ca2+-pump activity and increased ICa or by Na+/K+ ATPase inhibition and also decreased Ca2+ natural spring through Na+/Ca2+ exchange for cardiotonic glycosides (Borgatta et al., 1991). Moreover, one study in rat ventricular myocytes reported that Na+ current is activated by the phyosphoryation by protein kinase A or by the cardiotonic steroids. (slip mode conductance) (Santana, 1998). In addition, modified Na+currents conduct ICa,TTX which in turn triggers CICR. The relation between slip mode conductance and ICa,TTX is still controversial (Nuss, 1999). On the other hand, another study demonstrarted that Ca2+ current due to ICa,TTX or slip mode conductance is not related and identical. The intellectual is that the presence of cardiac steroids or activation of PKA is not a destiny for the detection of ICa(TTX). A small fraction of Na + currents can conduct ICa(TTX) even without phosphorylation of PKA (Nuss, 1999). Furthermore, TTX sensitive-Na+ channels cannot be inhibited by the blockers of T-type or L-type Ca2+ channels. Recently, one of studies showed that ICa(TTX) and T-type Ca2+channel coexit in guinea pig venricular myocytes because 10 mM mibefradil could block both ICa(TTX) and T-type Ca2+current (Heubach, 2000). Although this current is not the major current for triggering the CICR, its possible functional roles are important in normal heart cells such as promoting the sodium current activation and modulating rhythmicity of the heart.Ca influx via IP3 pathwayInositol (1, 4, 5) triphosphate could trigger Ca2+ release from SR and endoplamic reticulum in different cell types, they are called IP3 receptors. In ventricular myocytes, the major form of InsP3 is isoform 2 (Lipp et al., 2000). There are more InP3 receptors in atrial cells in ventricular myoctyes. Stimulation of IP3 signal transduction pathway can trigger the release of Ca2+ from SR via IP3 receptors which is located on SR. Even high concentration of InP3 in cardiac myocytes could trigger Ca2+ release from the SR, the extent of Ca2+ release from the SR are so much lower than CICR triggered by LTCC. Moreover, action potential cannot stimulate the InP3 production (Kentish et al., 1990). The production of InP3 contractile force is increased by cardiac alpha-adrenergic and muscarinic agonists (Poggioli et al., 1986). In addition, InP3 pathway only plays a very little minor role in cardiac EC coupling. To conclude for triggering Ca2+ release from SR, CICR in cardiac contraction is mainly through L-type Ca2+channel.Other mechanisms that mentioned above show minor role in SR calcium release.cardiac relaxationDuring an action potential, calcium entry into the cell is slow at the end of phase 2 and there is lowering of the cytosolic calcium concentration because calcium is taken back by the SR and removing of calcium from the troponin C and finally initial sarcomere space is restored. For relaxation and cardiac ventricular filling, Ca2+ have be withdraw from the cytosol to lower Ca2+i , causing relaxation. Cardiac relaxation to occur, Ca2+ must be dissociate from troponin C and it requires Ca2+ transport out of the cytosol primarily by four main pathways involving, sarcolemmal Na+/Ca2+ exchange, SR Ca2+-ATPase, sarcolemmal Ca2+-ATPase or mitochondrial Ca2+ uniport. There are selective inhib ition for each transporter during cardiac myocyte relaxation and Ca2+i decline (Puglisi et al., 1996). SR Ca2+ uptake can be prevented by either thapsigargin or caffeine, consummate(a) removal of extracellular Na+ and Ca2+ can prevent sodium calcium exchange. Either carboxyeosin or elevated Ca2+i inhibit sarcolemmel Ca2+-ATPase, and mitochondrial Ca2+ uptake can be inhibited by rapid dissipation of the electrochemical driving force for SR Ca2+ uptake by using protonophore FCCP. In rabbit ventricular myocytes, 70% of the activated Ca2+ removed by the SR Ca2+-ATPase from the cytosol, whereas 28% was removed by NCX, only 1% for sarcolemmal Ca2+-ATPase as well as mitochondrial Ca2+ uniporter remove 1% of calcium from SR ( the last two pathways are called slow systems). In rat ventricular myocytes, SR Ca2+-ATPase activity is higher(prenominal) due to more pump molecules in unit cell passel (Hove-Madsen Bers, 1993). On the other hand, Ca2+ removal via Na+/Ca2+ exchange is lower, 92% wi th SR Ca2+-ATPase, 7% with NCX, the slow systems with 1 % respectively. In mouse ventricular myocytes, the uptake mechanism is quite similar to rat, (Li et al., 1998) while the mechanisms of Ca2+ fluxes in human ventricular myocytes, guinea pig and ferret are more similar to rabbit myocytes (Pieske et al., 1999). In contraction and relaxation of myocytes, the amount of calcium removed from the cell during relaxation must be the same as the amount of calcium entry during contraction in each heart beat, if not, the cell may gain or lose the calcium. Defects in Ca2+ removal also can cause impair relaxationTermination of calcium releaseAlthough CICR is a positive-feedback mechanism, termination or turning off of the Ca2+is important for diastolic refilling of the heart. There are three major ways for terminations of Ca2+release involve local SR depletion, RyR inactivation or adaptation and stochastic attriction (Sham et al.,1998 Lukyanenko Gyorke,1998). stochastic attriction means L-t ype Ca2+ channels and all RyRs are closed simultaneously, then local Ca2+i will drop quickly to the sub-threshold level and disturbing the release from SR . However, this is only used for 1DHPR and 1-2 RyRs whereas they all will not close at once for other types of channels. In addition, local depletion of SR Ca2+ also may terminate SR Ca2+ but it cannot completely turn-off of release, because very long lasting Ca2+ sparks are found that will not decline with time (Satoh Bers, 1997). However other regions of SR can also limit local SR Ca2+ depletion. During a global Ca2+ transient, the whole SR Ca2+ declines. During a relaxation, SR Ca2+ depletion could lead to the turning -off global SR Ca2+ release. There are two types of RyR inactivation both of which depend on Ca2+ i .One of them is absorbing inactivation ( for example like Na+ channels), in which the ryanodine receptor cannot reopen until it recovers (Sham et al., 1998 Lukyanenko Gyorke, 1998). The another one is called RyR adaptation in which ryanodine after activation leads to a reduced open probability, but it can be reactivated by higher Ca2+i (Valdivia et al.,1995). RyRs inactivation could be important in reducing SR Ca2+ release events between each heart beats. To summarize, Ca2+ release during ECC is terminated mainly by a local RyRs inactivation and partial SR luminal Ca2+ depletion which leads to reduce RyR openings and variant of stochastic attrition also contributes.Role of calcium channels in cardiac hypertrophy, heart failure and arrhythmiaIntracellular calcium is the major regulator of cardiac contraction. Therefore, altered cardiomyocyte regulation is important in arrhythmogenesis, cardiac mechanic dysfunction and cardiac hypertrophy associated with heart failure. Alteration in signal transduction pathways can also lead to loss of inotropic effects in heart failure. Defects in ECC have been reported in animal models of cardiomyopathy (Gomez et al., 1997). There is no E-C coupling depres sion was seen in pressure plume of cardiac hypertrophy with less sign of heart failure. (Rios et al., 1992). Cardiac hypertrophy is the enlargement and thickening of the heart muscle resulting in decreasing coat of the chamber of the heart. Cardiac hypertrophy is the main cause of cardiac morbidness and mortality in cardiovascular system. It is associated with heart failure without myocardial infarction. Cardiac hypertrophy is associated with significant changes in myocardial contraction. These contractile dysfunctions are followed by changing in the whole-cell intracellular calcium transient. The pathogenesis and etiology of cardiac hypertrophy and heart failure related with the role of Ca2+ channels still remain controversial. of subunits of L-type Ca2+ channels (LTCC) enhances the probability of channels opening as well as also favours the trafficking of the Ca2+ channels to the surface membrane leading to increase calcium current (Chen Y.H, 2004). Interestingly, there has be en reported upregulation of LTCC in failing human cardiomyocytes (Hullin et al, 2003). In aortic banding, L-type Ca2+ channels concentration is remain unchange in rats myocytes with hypertrophy ( Scamps et al.,1990), cats with pulmonary artery banding (Kleinman, 1988) cardiomyopathy in Syrian hamsters (Sen, 1994) ,and ventricular

Story Of The Dead Poets Society English Literature Essay

Story Of The short Poets Society English Literature EssayCharlie reveals the ideas of carpe diem in various ways. He feels that he can speak for other people, and he doesnt care if they equivalent him or not. First, he invites girls to acquire to the Dead Poets Society companionship meeting. so he tells them they can go in because its his cave. He also publishes an member in the drill paper about how they should have girls at Welton in the name of the Dead Poet Society without the approval of any other members. He also pulls the phone call from God to gain attention, pretending to himself as a god when he says that the phone call is from God. In the end, he is expelled for punching Cameron. Charlie punches him because Cameron had just come from telling the administrators about the Dead Poets Society club and blamed Keating for e rattlingthing. Charlie feels it doesnt matter if hes expelled or not.In addition, Neil seizes the day. Neil loves to do new stuffs, and come up with u nique ideas. He is the one to call Keating O lord My Captain and is the first able to ask him what the Dead Poets Society was. He is also the one to organize the first meeting of the club in the cave and hes also a leader. Neil also tells Todd that he must introduce in the Dead Poets Society club no matter what. distributively of the choices is Neils attempts to gain control everyplace his get animation. Neil lives by his fathers rules. Carpe diem motivating Neil to go after his dream of acting, but his father wouldnt let him. Going against his father, he decides to follow his heart by audition for A Midsummer Nights imagine Neil receives the part as Puck. He claims that this is the first time in his life that he knows what he wants. However, after the show his father takes him home and yells at him. He ends up committing suicide, by using his fathers gun.Knox also embraces living for the moment. Knox visits his parents friends, and before long falls in love with their daught er Chris. He broke his own rules to see her, and competed for her attention with her boyfriend Chet. At that party and after a few drinks, he makes a move on Chris and Chet was on that point, who then punches Knox. after(prenominal) that meeting, Knox does everything in his power to win her love over. Using his love of poetry, he presents one of his love poems in his English class, and is applauded by Keating. Then Knox travels to Chriss school and read his poem to her in class, later convincing her to go to a show with him. Chris does like the attention Knox gives her, and in the end, holds his hand at the play.Also, Todd ultimately can root word up by himself. Todd is a very quietness boy. He is the youngest of his family member and has many expectations laid upon him due to the success of his brother. Todds lash fear is that his life has no meaning. After the first day of class, Todd writes Carpe Diem on his paper, dreaming of what it would be like. that, he throws out the paper believing he has nothing to do with it Later, in class, after being asked to write a poem, Todd tells Keating he never completed the assignment after he washed-out many hours writing and revising his poem only to have throw it away before class. Keating sees through Todds fear and later makes him say whatsoever comes to mind. This is the beginning of the change in Todd. He proves his loyalty to Keating by stand up to Camerons accusations of Keating. Todd is able to express his opinion that Cameron and the school are wrong.Students at Welton could not have any other choice for what they want to do or what type of person they want to be. But Mr. Keating teaching the boys learns to envisage on their own, and they all do their own stuffs with their own ideas. By doing that there were some good things happen such as Todds is a very quiet boy and shy who does not enjoy speaking himself in front of a lot of people but Mr. Keating helps him get over this fear, Todd finally finds a voice for himself that he never knew he had before, and Knox give his true love shows free thinking is an important thing in life because it lets everyone think and behave in different ways and situations. But there were some bad things such as Neils commits suicide and Charlies got expelled from his conduct shows we should learn to think before we do something.

Theatre Essays Samuel Beckett

Theatre Essays Samuel BeckettDiscuss Samuel Becketts handling of identity element element in his plays judgment of conviction lag for Godot and expert age.The campaign of Samuel Beckett can be incurn to span both the Modernist and postmodernistist paradigms (Bradbury and McFarlane, 1991 fountain and LeBihan, 1996), on the one hand being influenced by such(prenominal) ratified Modernist writers as throng Joyce and Luigi Pirandello (Knowlson, 1996) and on the other relying heavily on postmodern opinions such as the transgression of the body, the performative identity and the trouble of grand narratives such as language and truth. This point is made by Richard Begam in his champaign Samuel Beckett and the End of Modernity (1996)Becketts conception of his undertaking, w get into we would now c both his postmodernism, recognized t chapeau an arrogant shock with the past, a complete supersession of what had gone before, was it ego the product of a teleological or modern fo rm of thinking. Proust and Joyce therefore became not figures to be replaced or surmounted but telling points of reference in an current dialogue between past and present. (Begam, 1996 14)Becketts position as a liminal writer, spanning two unmistakablely different but obviously connected noetic regimes, al ruggeds us to examine not only his lap but the big context of critical and surgical operation theory. With this in sagaciousness, in this turn out I would like to tone at two main areas of Becketts work that are both metonymous with changes in post-War theatre (and perhaps literature) as a whole. Firstly I would like to concentrate on the notion of postmodernistism as it relates to motion, looking at leitmotifs and tropes as they appear in Waiting for Godot (1955) and blessed Days (1961), and secondly I would like to go on to look at the whole notion of identity and its dissolution in these same texts before drawing conclusions as to what this treatment says somewhat the place of motion in contemporary theatre and, perhaps, the wider context of society itself.First of all, still and as a foundation for my later exposition, I would like to provide a brief summary of postmodernism.Postmodernism, as Fredric Jameson points out, can be take up understood through its relationship and difference to contemporaneousness, a philosophical and fine concept that had it roots in the Enlightenment of the eighteenth century (Bradbury and McFarlane, 1991). In an tasty sense, the Modernist work was characterised by experiment and a rejection of the Romantic essential self. Works such as T.S. Eliots The Waste Land (1989) and James Joyces Ulysses (1977) exemplify both the Modernist propensity for innovation and the removed authorial voice and we can for sure see this in many, if not all of Becketts theatrical works.Postmodernism, as Jean Francois Lyotard declared in his essay The Postmodern Condition (1991) reflected the breakd have got and disillusionmen t felt by the failure of the really foundations of Modernism foundations that included such hitherto accepted givens as truth, the self, the homogeneity of Literature and the Arts and many of the other systems of thought that Lyotard termed the metanarratives (Lyotard, 1991 36). Whereas Modernism sought newness and innovation, Postmodernism resulted in the adoption of style over content (Robertson, 1996 3), the quizzical of accepted constructs of knowledge (Foucault, 1989) and the language (Derrida, 2004) and, as we shall see with Beckett the exposure of the artistic machinery.This last point, I think, is crucial to an understanding of Becketts place as both a Modernist and a Postmodern writer. As I hire already stated, we can recognise certain Modernist images and leitmotifs in Becketts work (Eagleton, 1992 186) the starkly bare characterisation, the dour vision of humanity that we to a fault visualize in Eliot and Woolf and the conscious effort to experiment and innovate but, underneath this, we also detect a distinctly Postmodern sensibility one that delights in the deliberate exposure of the performative nature of both the theatre and life.In Waiting for Godot, for instance, there is a constant comic antagonism created between instrumentalist and reference, as ideas and lines of narrative are picked up and abandoned without the usual spectacular sense of resolution (Schechner, 1988). In the first playact for example, estragon begins a joke that is neer finishedestragon Tell it tome Vladimir Ah, stop it tarragon An Englishman having drunk a little more than usual goes to a brothel. The kept woman asks him if he wants a fair one, a dark one, or a red-haired one. Go on. Vladimir Stop it (Beckett, 1955 16) The antagonism and frustration engendered by this un-ended joke is more than a mere literary device it is also a performance device that sets up a tagly different performer/audience relationship. Unlike, say, classical Aristotelian outstanding theory that asserts the imperative of the incentive outcome (Hartley and Ladu, 1948 14) the rising action (Hartley and Ladu, 1948 14) and the resolution, here Beckett (as indeed he does throughout the play) creates a deliberate anti-climax that immediately calls in to question the binary between mankind and performance.The same also could be said about much of the dramatic structure of blissful Days, as the workings of the performance are eer exposed to the gaze of the audience. Here, for instance, realisenie second guesses the thoughts of the audience members as she talks to a passer-byWinnieWhats she doing? He says Whats the idea? He says stuck up to her diddies in the bleeding ground coarse fellow What does it mean? He says whats it meant to mean and so on. (Beckett, 1961 32)Here Beckett deconstructs the very essence of the performance itself, exposing the bewildered reaction of the audience to his own drama. In a Postmodern dissolution of identity boundaries, the perf ormer here becomes playwright, audience, character and factor as not only are the thoughts of the character exposed but so too the thoughts of the audience. This is not the only deconstruction of performance Beckett employs in the play. We see, for instance, the quizzical of dramatic convention gifted Days is, for all intents, a soliloquy but it features two characters, it is about the drift of era but, ironically, the main actor is static throughout and although it is primarily a play about dustup and not actions it is peppered with pauses and space. All factors that point to both plays as being as much rooted in Postmodernism as Modernism.We have touched upon it already but the overriding sense in both Waiting for Godot and Happy Days is the seek and engagement for identity and this also, as we shall see, has a marked impact on the performance of the play and what it means regarding the audience/actor dialectic.The social thornground to Happy Days was described, in an aff ective track by Harold Clurman in an early reviewBeckett is the poet of a morally standing(prenominal) society. In this society fear, dismay and a sort of a stun absent-mindedness prevail in the dark of our consciousness, while a flashy, noisy, bumptious, thick-headed complacency flourishes in the open. (Clurman, 1998 235)It is against this buttdrop that the characters in the play struggle to maintain their scant identities. regular(a) before the action begins we are made witness to the difficulties in establishing an separate existence as the characters, names, Winnie and Willie, straightway blur their respective personal boundaries. We see this also to a greater extent in Waiting for Godot, as Gogo, Pozzo and Godot, combine to form a linguistic homogeneity that suggests a free radical rather than an individual identity.The mise en scene of Happy Days is place Eliotesque wastelandExpanse of scorched grass rising centre to low mound. Gentle slopes downto front and either of stage. Back an abrupter fall to stage aim (Beckett, 1961 9)part Postmodern irony, as the backdrop reveals itself to be a self conscious trompe-loeil that represents unbroken plain and sky receding to meet in far distance. (Beckett, 1961 9). Within this, Winnie literally stands as part of the scenery, only half(prenominal) visible that is, in itself, a symbolic representation of both time passing and the extent that she has already lost a great have sex of her personal identity.As I have already hinted at, Winnie deconstructs the notion of movement and stasis on a psychological level she moves quickly between multiplication as in this passage where she and us are taken back into her personal history prompted by the news of a death of a friendWinnie Charlie Hunter (Pause) I close my eyes (she takes off specs and does s, hot in one hand, spectacles in other, Willie turns page) and am sit down on his knees again, in the back garden at Borough Green, under the horse-beech. (Becket t, 1961 14)physically however she is literally trapped, unable to move or stop the flow rate of time swallowing her completely. Her identity becomes fashioned by her memories as at first, in the initial Act, they form a reasonable homogeneity and then, in Act Two become more and more diffuse, more and more fractured until by the end of the play she exists as merely snapshots of a life that has beenWinnie Win (pause)Oh this is a happy daytimes, this will have been another happy day (Pause) After all (Pause) So far. Pause. She hums tentatively beginning of song, then sings softly, musical comedy box tune. (Beckett, 1961 47) As John Pilling suggests in his study of Samuel Beckett (1976 85), the playwright jibe the enormity of the search for identity in an alienating world with the minutiae of workaday living, as Winnie spends a great deal of the plays time conducting worthless searches for toothbrushes, or lipsticks or many of the other incidental objects of existence.Ultimately, her search for a personal identity is proved fruitless as she becomes subsumed in that which surrounds her, perhaps a particularly twentieth century vision of the struggle of the personal psychology in the face of the modern city. Waiting for Godot, I think, concerns itself with similar themes and similar characters.Martin Esslin characterised Becketts Waiting for Godot as concerned with the want of salvation through the workings of grace (Esslin, 1968 55) and we can see that is certainly a major thread in the play. However, we can also utterance that it concerns itself not with a general salvation but with a very a personal one, with each character desperately searching for their own identity amid the alienation and ennui of the surrounding environment. Most of the plays linguistic rhythm arises out of the characters attempt to assert their own identity in the face of the othersVladimir Charming evening were having. estragon Unforgettable. Vladimir And its not over. Estragon App arently not. Vladimir Its only beginning. Estragon Its awful. Vladimir Its worse than being in the theatre. (Beckett, 1955 34)The tooing and froing of the dialogue here is a perfect example of this point, with neither Vladimir nor Estragon willing to surrender themselves to the other. The same can be seen in a more graphic sense with the Pozzo/Lucky relationship that is, at its ticker a Hegelian dialectic of the master and slave, with each party attempting (and failing) to break away from the other.In the comic scene towards the end of the play that depicts Vladimir and Estragon exchanging symbolic identities in the form of their hats (Beckett, 1961 71-72) we can keep Becketts card on the ironies of Postmodern lifeVladimir takes puts on Luckys hat in place of his own which he hands to Estragon. Estragon takes Vladimirs hat. Vladimir adjusts Luckys hat on his head. Estragon hands Vladimirs hat back to Vladimir who takes it and hands it back to Estragon who takes it and hands it ba ck to Vladimir who takes it and throws it down. (Beckett, 1955 72) The absurdity of this scene arises from the fact that each hat is the same, or at least very similar, so that it makes very little difference which hat ends up on which head. This is, I think, symbolic of the larger treatment of identity within the play with the playwright suggesting the absurdity of the search for personal individuation. are not identities much like hats, asks Beckett, remarkably the same?If Happy Days is a study of the search for identity under the crushing burden of time passing, Waiting for Godot is the search for identity within the lightness of forgetfulness. condemnation in the latter is meaningless, it passes with no affect in fact Estragon can not even remember the events of the day before. Within this, the characters desperately cling to the remnants of their identities whether that be in the form of an oppressive relationship to another, an occurrence of clothing or the feint hope of s omeone who will never arrive.We can see then that the treatment of identity within Becketts two major plays mirrors the questions arising out of Postmodernism, questions that concern the nature of identity and the Self. For Postmodern theorists like Judith Butler (1999) and Michel Foucault (1990) the Self is a performative construct, both given to us by society and adopted as a mask and we note some of this sense in Beckett. Ultimately, then, Becketts work deconstructs the very notion of a theatrical performance, suggesting that this is merely one of a number of performances that occurs at any one time.The relationship, then, between the audience and the actor changes from one of passiveness to one of dialogue as the former is exposed as relying as much on performance as the latter. This can be seen to be a reflection of Antonin Artauds assertions on the Theatre of Cruelty in his second manifestojust as there are to be no empty spatial areas, there must be no let up, no vacuum in t he audiences mind or sensitivity. That is to say there will be no distinct divisions, no gap between life and theatre. (Artaud, 1985 84)Becketts work says as much about the identities of the audience as the characters and as much about the performative nature of the wider society as the performance of the theatre.ReferencesArtaud, Antonin (1985), The Theatre and its Double, (London John Calder) Beckett, Samuel (1961), Happy Days, (London Faber and Faber) Beckett, Samuel (1955), Waiting for Godot, (London Faber and Faber) Begam, Richard (1996), Samuel Beckett and the End of Modernity, (Stanford Stanford University Press) Bradbury, Malcolm and McFarlane, James (eds) (1991), Modernism A Guide to European Literature 1890-1930, (London Penguin) Butler, Judith (1999), Gender Trouble, (London Taylor and Francis) Cormier, Ramona and Pallister, Janis (1998), En Attendent Godot Tragedy or prank?, promulgated in Culotta Andonian, Cathleen (ed), The Critical Responses to Samuel Beckett, (Londo n Greenwood Press) Clurman, Harold (1998), Happy Days Review, published in Culotta Andonian, Cathleen (ed), The Critical Responses to Samuel Beckett, (London Greenwood Press) Eagleton, Terry (1992), Literary Theory An Introduction, (London Blackwell) Esslin, Martin (1968), The Theatre of the Absurd, (London Pelican) Foucault, Michel (1990), The taradiddle of Sexuality Volume 1, (London Penguin) Green, Keith and LeBihan (1996), Critical Theory and Practice A Coursebook, (London Routledge) Hartley, Lodwick and Ladu, Arthur (1948), Patterns in Modern Drama, (London Prentice Hill) Jameson, Fredric (1991), Postmodernism, or the Cultural Logic of Late Capitalism, (London Duke University) Kenner, Hugh (1973), A Readers Guide to Samuel Beckett, (London Farrar, Strauss and Giroux) Knowlson, James (1996), Dammed to Fame The Life of Samuel Beckett, (London Bloomsbury) Lyotard, Jean Francois (1991), The Postmodern Condition, published in Jenkins, Keith (ed), The Postmodern History Reader, (Lon don Routledge) Pilling, John (1976), Samuel Beckett, (London Routledge and Kegan Paul) Robertson, Pamela (1996), criminal Pleasures Feminist Camp from Mae West to Madonna, (London Duke University) Schechner, Richard (1988), Performance Theory, (London Routledge)

The Capitalist Future: A Consequence of Calvinist Annunciation :: essays research papers fc

The Capitalist Future A Consequence of Calvinistic Annunciation     In his work, The Protestant Ethic and the essence of Capitalism, Weberpredicts that the future entrust be a world of " motorised perfection" devoid of"religious and ethical meaning." In this world mod capitalism becomes a selfsustaining system no longer needing the Calvinist religious impetus that hadinspired the work ethic. Weber argues that the future will be a capitalisticsociety, where the proletariat and the bourgeoisie alike, will not be driven byreligious motivation, but instead by a constant struggle to benefit from thesystem. He reasons that this future of the capitalist society is a directconsequence of the teachings of Calvinism. The Calvinist work ethic of livingto work forms the core of modern capitalism. This ethic originated from theCalvinist doctrine of predestination and the capriciousness of a transcendental God.Predestination decrees that God has already picked out who those " predestinateinto everlasting life" (100) and those "foreordained to everlasting death"(100). Calvinists also confide that God, a distant "grand conception" (164) whois "beyond all gentleman comprehension," (164) is unreachable. Both these beliefstogether eliminated any possibility of appeasing God through and through service orsacrifice. The answer to the question whether believers were the chosen or the bedamn could thus neither be influenced nor known. If, however, one turned hiswork into a calling, restricting any desire to molderful pleasure, he couldexperience a feeling of assurance that he is indeed a member of the Elect.Calvinism preached this severe ethic of hard work and complete absence offrivolous waste of money and time. As a result, the work ethic of thepopulation shifted from working to live to living to work. handed-downcapitalism which relied on the "greedy maximization of profit in a one-shotenterprise, " (14) became the rational modern capitalism, a continuous cycleinvolving the constant " fatty investment of capital." (172) The Calvinistteachings demanded honest dealings in backup, steady takings and sales, andcontinuous savings and reinvestment which no doubt led to phenomenal businessgrowth and success. Weber illustrates in the following quote "When thelimitation of phthisis is combined with the release of acquisitive activity,the inevitable practical result is plain accumulation of capital throughascetic compulsion to save." (172)This "diligent and economical" (175) attitude made people richer and"material goods gained an increasing and finally an hard power over thelives of men." (181) The dependence on external goods went from the "light habilitatewhich can be thrown aside at any arcsecond" (181) to a necessity, or as Weber putsit, an "iron cage." (181) The so called acetic lifestyle now led to an increased

Jaquess Perspective in Shakespeares As You Like It Essay -- Shakespe

Jaquess Perspective in As You Like It A cynics cynic strength declare Jaques no better than the guy who lurks in corners at a cocktail party, lobbing witty barbs at anyone unlucky enough to catch his eye. But this estimate robs Shakespeares comedy of its sociological depth what might be pleasant bodge about young people in love is enhanced by Jaquess ability to make stern judgments about the world, yet still respect the people who comprise it. Indeed, Jaques observes astutely from the sidelines. He separates himself from what he considers the frivolity of making suitable marriage matches. But Jaquess speeches are not merely Shakespeares devices for explication. thither is a psychological middle ground between the court and the forest, and the ideals impending to those who think little are, in Jaquess eyes, admirable. His words make him the most classless character in the play. From his first speech, Jaques paints himself as a moody lone hand and as rather disdain ful of his benefactor, Duke Senior. He says, And I have been every this day to ...

Originality Of Philosophy :: essays research papers fc

Originality of ismFeb.25.1997What is philosophy? What does a philosopher authentically do? Questions likethese can be answered in a re captivate of Philosophy Now. What can possibly beanswered.....questions which have them. And what is it thatphilosophers study? Generally, most philosophers study questions in which in that respectis no rational or justifiable answer. And the type of articles in the magazine are very interesting because they elighten the reader to question the answers.Some of the articles in this wall socket are Bakunin Anarchist or Antichrist?, Practical Solipsism, Introduction to Ontology, Orwell and Philosophy, just to the highest degreeother brief articles, an Internet page, and eventide some classifieds. The overallview of this magazine was very intellectual and professional because it did notcontain whatever advertising throughout the magazine. The articles are more in themanner meant for each philosophers or some wizard in school studying Philosophy,o r even anyone interested in a very different approach to society.An mind in the article Practical Solipsism reads Solipsism - the root word that only I populate and that you, and all other material things in the worldare clear figments of my imagination - is one of those peculiar notions that makeeverybody realize just how fruity philosophers truly are. Philosophy is oftentranslated as the love of wisdom or the love of truth. One way to get a vagueidea as to what philosophy is about is to dissect the subject and investigateits skeleton. there are many branches in philosophy. Metaphysics is(after-physics, after Aristotles book of physics.), and has questions about the disposition of time, categories of existence, including god. Epistemology asks whatis knowledge? what is the difference between knowledge, belief and opinion? Canwe really know anything? How could we know that we did? Logic questions thetruth and even now employs a sort of algebra which is used to crunch logicalpro blems. There is Philosophy of mind, which asks questions about the humanmind, how it thinks, and how is it related to the body. Ethics is like how arewe living, what is good and bad, what is unethical, and what is happiness. aesthetics asks mostly about beauty and how to define it. In particular though,there is political philosophy, and it asks questions like What would Utopia belike? Is Utopia possible? How should social lifespan be organized? In my opinionthis philosophy is not one related to our government but is very interesting tome. As I was reading, many questions arose about our society and what I thoughtshould be changed. another(prenominal) Article that I went over was called Ontology for

Inherit the Wind Think Piece :: essays papers

Inherit the Wind Think PieceIn todays society, where angry children shoot, bomb, and threaten their schoolmates, there exists a kind of incoherent line between appropriate classroom conversation and unsatisfactory discussion. True, this line did not exist some years ago, but as times changed, so did certain parameters. A teachers exemption in the classroom is one such hotly debated question. Where should the line be drawn? What is the difference between right and wrong? These argon questions that are not easily answered. Some say that we should look at each individual incident of indecent or inappropriate discussion, but really, how leave behind these halt future conversation? In a society where our early days is incredibly impressionable, how will this put an end to the tragedies that receive become so terribly regular?Some say that since the fellowship pays teachers salaries, they should be the ones to ascertain the curriculum. But how will this prevent incidents like the o ne portrayed in Inherit the Wind? True, parents should absolutely have a voice in what their children are taught, but is that where the buck stops? Really, its not. Perhaps it is the trump out idea that the entire community discussion curriculums, and that means teachers, school be on comities, PTAs as well as parents. Through this way, everyone mint discuss what goes into the minds of our leadership of tomorrow. We will get the best of both worlds. On the subject of how often freedom does a teacher possess, that too is up to the community. And when the term community is used, that again means everyone teachers, school boards, and parents. Maybe it would be even soften if teachers were allowed to discuss things as whole. A subject should be explained in as many ways, from as many view points, as possible. Then students can decide for themselves for themselves what they believe. However, in a time when kids will take to the highest degree everything literally, and then take it too an extreme, maybe this methods is not the best. If this topic were to have been discussed two years ago, perhaps the answer would be different. However, since the tragedy at Columbine High School in Colorado a equate of years ago, parameters have changed, and perhaps tightened.

litereary poem notes :: essays research papers

Literary Terms for rime1. head rhyme The repetition of initial consonant sounds 2.Assonance The repetition of vowel sounds followed by different consonants in two or more stressed syllables3. sportsmanlike Verse Poetry written in unrhymed iambic pentameter lines4.concrete Poem A poesy with a shape that suggests its pendent5.Consonance the repetition in two or more linguistic communication of final consonants in stressed syllables 6.Couplet A pair of rhyming lines usually of the same length and meter7.Dramatic Poetry Poetry that involves the techniques of drama8.Epic A long narrative poem rough the deed of gods and heroes9.Extended Metaphor A subject is spoken or written of as though it were something else10.Free Verse Poetry non written in a regular rhythmical pattern or meter11.Haiku Japanese poem written in 5-7-5 needs to set about a single vivid emotion by means of images from temper12.Lyric Poem A highly musical verse that expresses the observations of the author13.Mood The feeling created in the reader by a literary work or passage. The mood is often suggested by descriptive flesh out14.Onomatopoeia The use of words that imitate sounds15.Parody A work do in imitation of another, usually in order to mock it, scarce sometimes just in fun16.Personification A character reference of figurative language in which a nonhuman subject is presumptuousness human characteristics.17.Pun A play on words ground on different meanings of words that sound alike18.Refrain A repeated line or group of lines in a poem or song19.Repetition The use, more than once, of any element of language- a sound, a word, a phrase, a clause, or a sentence 20. rime The repetition of sounds at the ends of words- internal rhyme occurs when the rhyming words take care in the same line

Titus :: essays research papers

Desdemona, on the early(a) hand, is only heard tal male monarch naturally with another(prenominal) people. Yet, she too isdeveloped through both the content and form of her speech. For example, Desdemonasconversations with Emilia, curiously at the end of the do work (IV, iii), reveal aspects of hercharacter as salutary as Emilias character. Have students look at these and discuss what they reveal nearly each of the characters. When it was enacted upon the stage, Shakespe bes Titus Andronicus was most probably receivedby its 16th carbon audiences in much the same way as Dallas and Melrose Place are received bycontemporary 20th coulomb audiences. Therefore it is strategic to remember that art does notnecessarily have to be haute couture in order to be an accurate representation of popularideologies. In fact, more than often than not, it is the entertainment of the bourgeois that is a bettermimic of these ideologies. If we assimilate that Shakespeares primary objective was not to makesocial commentary or criticize his own culture but rather to entertain, we quarter uphold how hisworks, and indeed almost all works of art, as Frederic Jameson has stated, "as though for the firsttime, bring into being that very situation to which they are also, at wholeness and the same time, areaction." (Montrose essay, p.57) With this is mind I would like to reveal how Shakespeareshandling of the female character Lavinia in Titus Andronicus is a window through which peck beseen not only the objectification of muliebrity in 16th and seventeenth century culture and some of theproblems which arise when the cleaning lady is viewed as an moveable property, but also the subtleshift from the outward control of woman to the interiorizing of control of woman through herown self-image. Perhaps most tardily recognizable is the objectification and assignability of 16th and seventeenth centurywoman. By objectification and assignability I entertain the near-universal notion, and in many caseslegal fact, that women, especially of the upper class, were accepted by their fathers, theirhusbands, and the state, to be bought, sold, and treated as property. At the very beginning of the fetch Lavinia is referred to as "Romes rich ornament" by her suitor Bassianus (I.i.). When sheactually enters the sentiment she has eight lines of praise for her fathers valor and honor and then,after a passing(prenominal) acknowledgment by him, she is silent. Meanwhile her father chooses the new king, the new king chooses her as his bride, her father agrees (although he seems more proud toTitus essays research written document Desdemona, on the other hand, is only heard talking naturally with other people. Yet, she too isdeveloped through both the content and form of her speech. For example, Desdemonasconversations with Emilia, in particular at the end of the play (IV, iii), reveal aspects of hercharacter as slowly as Emilias character. Have students lo ok at these and discuss what they reveal astir(predicate) each of the characters. When it was enacted upon the stage, Shakespeares Titus Andronicus was most probably receivedby its 16th century audiences in much the same way as Dallas and Melrose Place are received bycontemporary 20th century audiences. Therefore it is measurable to remember that art does notnecessarily have to be haute couture in order to be an accurate representation of popularideologies. In fact, more often than not, it is the entertainment of the bourgeois that is a bettermimic of these ideologies. If we unclutter that Shakespeares primary objective was not to makesocial commentary or criticize his own culture but rather to entertain, we can honor how hisworks, and indeed almost all works of art, as Frederic Jameson has stated, "as though for the firsttime, bring into being that very situation to which they are also, at whiz and the same time, areaction." (Montrose essay, p.57) With this is mind I wo uld like to reveal how Shakespeareshandling of the female character Lavinia in Titus Andronicus is a window through which can beseen not only the objectification of woman in 16th and 17th century culture and some of theproblems which arise when the woman is viewed as an transferrable property, but also the subtleshift from the outward control of woman to the interiorizing of control of woman through herown self-image. Perhaps most easily recognizable is the objectification and assignability of 16th and 17th centurywoman. By objectification and assignability I recall the near-universal notion, and in many caseslegal fact, that women, especially of the upper class, were accepted by their fathers, theirhusbands, and the state, to be bought, sold, and treated as property. At the very beginning of theplay Lavinia is referred to as "Romes rich ornament" by her suitor Bassianus (I.i.). When sheactually enters the outlook she has eight lines of praise for her fathers valor and ho nor and then,after a casual acknowledgment by him, she is silent. Meanwhile her father chooses the newking, the new king chooses her as his bride, her father agrees (although he seems more proud to