APPLIED DECISION METHODS CLASS; MOD4; Regression Models discussion Essay

APPLIED DECISION METHODS CLASS; MOD4; Regression Models discussion - Essay Example Sales, and Price vs. Sales determined. Using computer software or excel, the coefficients can be generated and measures of goodness of fit determined hence assisting in drawing the scatter diagrams. Render et al. asserts that assessing the plots (measured and calculated values of the dependent variable) and can be used to determine the quality of the model (pg. 127). For a good and apposite model, the trends should not be very dissimilar, and if the difference between measured and calculated points is huge, an ostensible trend should exist. What’s more, in the residual plot, the residual values of the dependent variable should be arbitrarily scattered around the line err=0 and the mean should be zero (normality). For the model to be statistically valid and stable, the confidence intervals to be used should be significantly small. An awkward model yields inaccurate derivative values and impractical results for even smallest extrapolations. Additionally, for an appropriate model, the errors should have a constant variance that expedites the

The Prime Minister Essay Example for Free

The Prime Minister Essay The Prime Minister still didnt believe him so god ended up killing all mortal things, the prime minister is scared god tells him he can raise the dead and the prime minister asks god and begs him to bring everything back as it once was then god closes the lid on his coffin and says why? Who are you? Like the prime Minster once questioned god. So then all life was over. God did this in the story because that was his way or saying he does not want humans to interfere with how humans are created and it is not right for humans to be created by any other means other than the natural way. It is a kind of warning sign this story is sending the message across that creating humans in other ways is not right and shouldnt be done. But man really want to play with science and be like god once was because they would love to be responsible for a new human race and feel like a really powerful person like a leader, but these people often plan on doing this without thinking about the consequences, they are generally greedy money wanting people and only think about the facts that they will be rich and god like and a leader of a new human race, they totally ignore the fact that things could go wrong though. In Mary Shelleys story.. Frankenstein many things go wrong. The story is about a normal everyday human (Victor Frankenstein) a boy who grows up to be a doctor and study medicines and humans. In the story Victor Frankenstein creates a living thing much like a human but this creature was made from dead peoples body parts that Victor stole. Victor was being greedy and did not think about the bad points, just the good he did not think of the consequences. In the story Victor later admits this. Here is a quote form the story proving this: I did not think beyond putting my ideas into action all I wanted to do was to prove I could make life (pg 16) that quote also shows a reason why he wanted to do it. He wanted to prove he could make life. Again a greedy reason thinking of all the money he would get out of it. Again it tells us how desperate man is to be the creator and leader of a human race. They long for powerfulness over a new race. This is not good as it could get well out of hand. Victor Frankenstein was a man broken down by sorrow, hen he was younger his mother died during childbirth I think this is why victor was so desperate to create new life and make life last longer. He was very interested in science and wanted to be the BEST creating a human would make him the best. He felt the need to be a kind of god using his scientific powers. But then when the creature had been finished it turned out very ugly and ran away from Victor. Victor had already come across a problem as soon as the creature woke up! The monster started killing humans, he was angry because he was different to other living things. He felt he needed to be loved he realised he was different to others and got angry, he knew no-one would love him. Because people discriminated against him he turned very nasty. I think this is how Frankenstein his self (Victor) felt thats why he created this-to get attention. This is very worrying. I feel that is what may happen nowadays and there would be many problems if it did. Mary Shelley the author of Frankenstein had a bad life herself and a tough time growing up, I feel this is why she was so good at expressing her words while describing how the monster felt. Mary Shelley is concerned with ethnics and relationships with the human consequences of both the monster and Frankenstein and his loved ones of how we should live in times of rapid change and this is just as relevant to us now as it was for her then. I feel she is sending the message across that it will cause us lots of problems if we play god and change the rules of creation. I think Mary Shelley is just another person who has thought about the whole idea of manipulation and is scared it will get out of hand, although it is very hard to stop humans play god. I think she wrote Frankenstein to warn us things could go bad. Its very hard to stop all this though, humans are already starting to clone things one example is dolly the sheep. Doctors cloned a sheep and named it dolly the name dolly sounds very innocent to make it sound like a good thing. Many people think its a good idea because sheep arent exactly a very intelligent animal and the more sheep we have the more lamb there is to eat and wool to make things with, so it sounds like a good idea but there can be downsides to this the sheep are like zombies and there can be sheep that go wrong and are formed wrong. It is cruelty to animals and shouldnt be done, again its all down to selfishness thats what it all boils down to. People who want to be rich they are greedy and dont even consider how cruel it is they just think about how much money they will have. Cloning sheep is not for the benefit for mankind, neither is cloning humans it is just peoples desires to be god like it is wrong and selfish people just crave to be leaders of new races thats all. The doctor who created dolly the sheep wants permission to clone humans but I think thats going to far, it would not be successful there would be too many difficulties and there would be a lot of racism going on, so cloning is not very successful. Frankenstein is very relevant to the stories we hear in the newspaper thats why it is such a good story! Its about a man getting greedy trying to prove a point that life can be created in different ways, but why does it have to be put into action? We know it shouldnt be done!!! Man is getting to clever for their own good. I think Mary Shelley wrote Frankenstein as a warning to us that making new life using science is wrong and dangerous. And that there is only one god, n nature should be let to run its own course, I think the articles in the newspapers are trying to tell us whats going on and we should put a stop to it. Making all these new races is not a good thing it is dangerous and very unsuccessful. Victor Frankenstein in the story is like god in the story of genesis but the thing is what Frankenstein done was very dangerous. This should be a very clear warning that it should not be done. Also I think dolly the sheep was created so they thought if they could successful clone a sheep they could do bigger and better things! But thankfully there are many articles telling people it is wrong so hopefully it will put more people off. Frankenstein probably was the best story to show us what can happen and Im sure Mary Shelley intended to do that. It is a very good book and sends across a very strong point. I believe that it is always men because people think that the word men or man seems more powerful and stronger I myself dont believe this and I think especially in this day and age woman have the same right as men. Show preview only The above preview is unformatted text This student written piece of work is one of many that can be found in our GCSE Mary Shelley section.

Polycystic Kidney Disease Causes and Treatment

Polycystic Kidney Disease Causes and Treatment   Introduction: Polycystic kidney disease effects roughly 10 million people worldwide. Even though this disease is so prominent it lacks research in the field of therapeutics from biopharmaceutical companies as they invest their resources into fields which are seen to be more profitable i.e. cancer research. This lack of research is what enticed us to carry out our project on polycystic kidney disease. This project will firstly outline the history of the polycystic kidney disease, how it effects patients, the cause of the disease and the current therapeutic treatment available to combat polycystic kidney disease in section 1. Section 2 will look at the current diagnostic methods employed by a physician to see if a patient is suffering from polycystic kidney disease. Diagnostic methods such as imaging and genetic testing will be dealt with here. Lastly section 3 will look at a potential new diagnostic technique which has been formed using proteomic techniques to identify the difference between a healthy polycystin-1 protein compared to a mutated polycystin-1 protein. The first record of Polycystic Kidney Disease (PKD) is from the 16th century. In 1586, the King of Poland died from cysts on his kidneys. The cysts were described by his surgeon as large like 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 hundred years later that his cause of death was agreed to be PKD. The term polycystic kidney disease was first used by Fà ©lix Lejars in 1888, although the mode of inheritance of this disease wasnt understood for almost another one hundred years. In the 1990s, the formation of cysts was understood at a molecular level. This helped in the discovery of the genes that cause PKD (Ayse, 2016). Figure.1 A visual representation of the transmembrane proteins Polycystin-1 and Polycystin-2. Also seen is the Polycystin-1 receptor located in extracellularly. (Gallagher, Germino and Somlo, 2010) PKD is a genetic disease in which the renal tissue within the outer cortex and inner medulla is replaced with fluid filled sacs (or cysts). These cysts enlarge the kidneys and inhibit kidney function. Hypertension, hematuria and chronic pain are the most common symptoms associated with PKD (Seeger-Nukpezah et al., 2015). PKD has two forms; Autosomal Dominant (ADPKD) and Autosomal Recessive (ARPKD). ADPKD is the result of the inheritance of one mutant PKD1 or PKD2 gene, which affects ~1:750 people worldwide. 85% of ADPKD cases are caused by mutations in PKD1. Mutations in this gene lead to earlier disease onset. The other 15% of cases are attributed to a mutation in PKD2. All ADPKD patients inherit one normal allele and one mutant allele. Cases where both alleles have the dominant mutation lead to embryonic lethality. ARPKD is caused by the inheritance of two recessive mutated PKHD1 genes. ARPKD is considerably less common with an incidence of 1:20,000. ARPKD progresses at a much faster rate than ADPKD. It usually causes death at birth or requires transplantation in early childhood. Multiple different 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 unable to produce the proteins PC-1 or PC-2. However, the non-mutated allele can still function as normal and can produce enough of the polycystin proteins to maintain kidney function. It is only when a somatic mutation occurs causing the normal allele to 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) (Nowak et al., 2016). Polycystin-1 and 2 are large transmembrane proteins which are encoded by PKD1 and 2. Both proteins affect multiple downstream 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 respond by allowing calcium 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 either PC1 or PC2 is absent the signal to inhibit cell growth is not received (Chebib et al., 2015). PKD1 or PKD2 mutations cause a reduction in intracellular calcium. This triggers a change in the response of the cell to cyclic adenosine monophosphate (cAMP) from suppression 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 production of cAMP via adenylyl cyclase 6 is dependent on vasopressin (Chebib et al., 2015). Despite the many breakthroughs in research allowing for a greater understanding of the disease, there is currently no cure for PKD. However, there are drugs which can suppress symptoms brought on by the disease. Beta blockers such as, Tenormin, can be used to treat hypertension and haematuria 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 formation 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 genetic testing, pre-natal testing and imaging studies in the form of ultrasounds, CT (Computed Tomography) scans and MRI (Magnetic Resonance Imaging) scans The 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 frequency sound waves to capture and visualise images that cant be seen with the naked eye. The CT scan combines many x-ray images with the aid of a computer to generate cross sectional views and/or three-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 four or more cysts in each kidney is used to diagnose older patients (F. Belibi et al., 2008). The kidneys on an image may appear enlarged but retain 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. High resolution imaging studies allows the visualisation of numerous cylindrical cysts within 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 done to screen for both PKD1 or PKD2 mutations. A method of PCR known as PCR- SSCP (Polymerase Chain Reaction Single Strand Conformation Polymorphism) is used to view mutations, if any, in the patients genomic DNA. 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 samples of genomic DNA are then amplified by PCR using 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 samples onto the acryl amide gel and gel electrophoresis occurs. After 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 transilluminator and the SSCP variants are recorded. DNA samples from the abnormal bands seen on the transilluminator are sequenced to see what kind 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 which 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 advantages 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 masses 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 intravenously (A. Khan, 2015) (F. Gaillard, 2015). MRI scans of the kidneys are becoming a useful technique in diagnosing more complicated cysts and can be used in addition to or instead 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 showing 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 eventually lead to the person having polycystic kidney disease (National 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 slowed 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 nature 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 quality of life for the child in their later years. As discussed in the previous 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 order 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 must be extracted from a patient who wishes to obtain diagnosis of the disease. Since 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 order 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 4ÃÅ'Ã…  C 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 interest 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 is 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 weight. After carrying out this two-dimensional separation the gel is stained with stains such as coomassie 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 suitable to be sequenced using MALDI-TOF mass spectrometry. These peptides must then be suspended in a matrix suitable for MALDI-TOF MS. An example of such a matrix is ÃŽÂ ±-cyano-4-hydroxycinnamic acid which was used in the work 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 loaded 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 fly as lighter ions travel faster. The ions will then hit the ion detector 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 analyse 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 prevention 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 in 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 © can 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 Journal , 01(1). Ayse, B. (2016). Tear drops of kidney: a historical 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., Brà ©geon, F., Trousse, D., Flaudrops, C., Secq, V., De Dominicis, F., Chabrià ¨res, 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 Nephrology, 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 Detection 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). Prenatal 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., WiecheĆ¡, M., Jach, R., RadoÅ„-Pokracka, M. and Gà ³recka, 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 High 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 Opinion 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).

Fall of Man Depicted in Atwoods Backdrop Addresses Cowboy Essay

Fall of Man Depicted in Atwood's Backdrop Addresses Cowboy The sexual politics of the man-woman relationship, or more specifically the sexual exploitation of women by men, is a clear concern in Margaret Atwood's "Backdrop Addresses Cowboy." Although the oppressor-as-male theme is by no means an original source of poetic inspiration, Atwood's distinction is that she views the destructive man-woman relationship as a metaphor for, symptom and symbol of, bigger things. From the vantage-point of feminine consciousness, Margaret Atwood empahsizes the "backdrop" as being not only the woman, but also the land and the spiritual life of the universe; the "cowboy" is both a man bent on personal gain (possibly an American based on Atwood's strong anti-American sentiments in her novel, Surfacing) and an emissary of technological progress. The structure of the poem logically supports the theme of conflict and "imperialism" in that it is clearly divided into two sections or "camps." The first four stanzas offer a description of "you", the "righteous and heroic" cowboy who brutalizes life without creating new life. The perspective shifts then from predator to prey in the final five stanzas as "I", presented as victimized woman and exploited nature, "addresses" her antagonist. The tone or mood of "Backdrop Addresses Cowboy" also undergoes a change after the first four stanzas when the reader enters the tragic, joyless experience of one who is paying the price of "slaughter and desecration." At this point in the poem, it seems futile to consider whether or not the price should be paid and the metaphoric man-woman tension remains distrubingly unresolved. In terms of form, "Backdrop Addresses Cowboy" is written in open (org... ...esecrate", the emphatically placed word of the climactic line in "Backdrop Addresses Cowboy", emphasizes again the "backdrop" as being not only the woman, but also the land and the spiritual life of the universe. As an emissary of technological progress, man has committed a sacreligious act against nature and humanity and his "fall" embodies the fall of the spiritual, the historical and the rational. In Margaret Atwood's poem, then, the troubled man-woman relationship is symptom and symbol of a greater alienation within humanity. Man's past and present curelties to human, natural and spiritual life are expressesed metaphoricall in terms of a cowboy "winning the West" on a movie set, against a backdrop "supporting" his heroism. "Backdrop Addresses Cowboy" offers a vision that is both desolate and conscious-expanding but it does not present answers.

Compare and Contrast the Ways in Which Two Poets Create Sympathy for Their Characters †‘on a Portrait of a Deaf Man’ and ‘the River God’. Essay

The poems ‘On a Portrait of a Deaf Man’, written by John Betjeman and ‘The River God’, written by Stevie Smith appear as two very different poems; one in monologue form and the other in a regular form; but they are in fact two very similar poems. ‘On a Portrait of a Deaf Man’ presents a character mourning the death of a deaf man who was very close to him/her, and ‘The River God’ presents a lonely God who is abused by people and resorts to murdering women to keep himself company. Both characters are lonely and the portrayal of this loneliness causes you – the reader – to feel sympathetic towards them. The ‘River God’ is lonely because he is only used by others, no one stays to be with him, they leave – ‘and I like the people who bathe in me . . . or will she go away?’ suggesting that he enjoys their company but doesn’t want them to go as he get’s lonely. In ‘On a Portrait of a Deaf Man’ the mourner feels lonely because he/she has lost someone very close to them – ‘the kind old face . . . he took me on long silent walks . . . when young’ implying they were close as they have known each other since a young age. Both blame others for the situations that they have found themselves in. The ‘River God’ blames the women who ‘bathe in [him]’ for his loneliness, meaning that out of desperation he tries to keep the women with him but by doing so ends up killing them ‘she lies in my beautiful deep river bed with many a weed’. I believe he understands though that he has killed them and that is why he keeps them in the ‘beautiful deep river bed’; this causes you to feel some sympathy for him as he accidentally kills them but then out of love keeps them in his ‘beautiful deep river bed’. The mourner blames God for the death of the ‘deaf man’: ‘You, God, who treat him thus and thus, /Say ‘Save his soul and pray.’/You ask me to believe You and / I only see decay’ describing how God should be, but then the reality of asking God for things which aren’t achieved. This causes you to feel sympathetic because you see someone who asked God to save him yet he still died – ‘see decay’. The poems both begin with descriptions of characters. ‘The River God’ begins ‘the kind old face, the egg-shaped head’ and ‘On a Portrait of a Deaf Man’ begins ‘I may be smelly and I may be old’; the first description makes you feel sad that someone kind and good has died and the second makes you feel pitiful for the river, it’s not the river’s fault that it’s that way as it’s reflective of old age and the abuse it has had by mankind, all of which you would be distraught if you found yourself in so you can feel sympathetic towards them. The poets use the death of a person to draw sympathy from you. In ‘The River God’ a woman dies, one that he was fond of and he was against her dying; in ‘On a Portrait of a Deaf Man’ a friendly deaf man dies, presumably suddenly; these draw your sympathy because it suggests that they are lonely, in a state of mourning and vulnerable – all of which are states in which you would not want to find yourself and when you see someone else in such a state, you will feel sympathetic and be able to relate to the emotions they are feeling. The poets use the deaths of characters in their poems to create side-personas for the characters through the persona of the main-speaking character. ‘The River God’ uses the dead woman to give another perspective of what’s going on, ‘This beautiful lady, or will she go away?’ shows this perfectly. The questioning gives her perspective that she wants to leave but she is being held, leading you to feel sympathetic for her as this large ‘River’ is holding her captive and she cannot leave. However, it shows the misunderstanding of the ‘River God’ as she is drowned, ‘Oh who would guess what a beautiful white face lies there’, ‘white face’ implying she is dead, leading you to feel sympathetic again towards him as he is totally ignorant of everything going on around him. ‘On a Portrait of a Deaf Man’, the writer uses the deaf man to display what exactly he/she has lost through his death, Ã¢â‚¬Ë œHe knew the names of ev’ry bird’. This shows how caring he was and this would presumably translate to how he acts to people – kind and caring – and lead to sympathy as you would never want to lose a person so good to die. The poem also describes what further potential to do good he had if he knew what was coming, ‘He would have liked to say good-bye/Shake hands with many friends.’ This causes a sympathetic response from the reader because again even though he was dying he would have wanted to show respect to his friends rather than just leaving. It also creates sympathy because the person who has lost this ‘kind’ man would be very upset about his/her death. We see this when he/she blames God for his death as he didn’t save him/her, ‘’Save his soul and pray.’/ You ask me to believe You and/ I only see decay.’ – this shows a stage of mourning in which you blame others for the death you have experienced. In conclusion, the poets create sympathy for their characters very effectively through: descriptions, meanings and powers out of the characters control; all of which attract the reader to feel some understanding, pity or empathy towards them. The poets both use the deaths of characters to contrast the feeling of the characters and the feelings of the dead to create sympathy.

Aquinas vs. Augustine on Their Varying Views of Women

St Thomas Aquinas and St Augustine of Hippo are considered to be two of the greatest Christian theologians in the history of Christianity. Both of these men are apart of the same organization, the Church. Just by this fact it would be easy to assume that they agree on all major issues of the day but this is not the case. They have completely differing views with respect to women in secular and religious life corresponding with the idea of original sin, human sexuality, and social roles. Even in the modern Catholic Church they are still regarded as two of the most important doctors of the church despite their different teachings on key important aspects of leading a Christian life. This shows the variability within the institution of the Catholic Church and some degrees of disagreement within a major faith organization. St Augustine of Hippo termed the idea of original sin. Nowhere in the history of the church had any such concept been taught. He was a man who lived a life of sin and promiscuity until he had an extreme conversion. After this conversion he needed a way to justify all his bad decisions. He did so by terming original sin as the first sin made by Eve that doomed all of mankind for the rest of days. Augustine blames Eve for all the bad experiences in his life, even for all the bad decisions that he has made. He uses original sin and reveals the idea in such a way that no one has to take responsibility for his or her actions because it is innate in us to be bad. Original sin gives people an ‘easy out’ to excuse all previous bad behavior. Never before had the term ‘original sin’ been placed on the sin’s of Adam and Eve in the Garden of Eden. Augustine’s example of an ideal woman, his mother, is even faulted by this original sin caused by Eve. â€Å"†¦the torments which she suffered were proof that she had inherited the legacy of Eve, seeking in sorrow what with sorrow she had brought into the world† (Confessions, 101). It is as if woman cannot help but be lesser than man. Even his mother, who he has a high regard for, is as good as she can be—for a woman, â€Å"It is not of her gifts that I shall speak, but of the gifts you gave to her† (Confessions, 192). Original sin is possessed by all humankind and cannot be avoided, this makes it easy for people to remain blameless for sins they have committed. St Thomas Aquinas did not believe in the idea of original sin. He believed that you make choices in life and that original sin was a way to get out of taking responsibility for all the actions that you make, â€Å"†¦so original sin is not the sin of this person except insofar as this person receives his nature from his first parent† (The Summa, 44). He notices that in Genesis that man and woman are created by God before sin and by this interpretation it would be impossible for original sin to exist if it is inherent in mankind. â€Å"What is natural to man was neither taken away nor added to him by sin† (The Summa, 40). Inadvertently by stating this, he is not blaming women for the fall of man. He didn’t believe that woman should be blamed for every evil thing in the world. In fact, he agues that woman was made to perfect man and that without her he would not be whole and able to procreate. †¦it was necessary for woman to be made as a ‘helpmate’ to man† (The Summa, 37). Woman is not condemned to be below man. Aquinas does not explicitly state this however; he does omit mentioning woman as separate from man in his section of the order among man and other things. He states, â€Å"Those of superior intellect are the natural rulers while those who are less intelligent but have stronger bodies s eem to be made by nature to serve†¦Ã¢â‚¬  (The Summa, 11). He is not gender specific. In fact, one could read into this that most men are to be the servants because they have a stronger physique for working. Aquinas is much more for the idea of actual sin where †¦Ã¢â‚¬ the sin that is the result of [the action of] the soul upon the parts of the body†¦Ã¢â‚¬  (The Summa, 44). This means that each person’s sin is based upon the choices that they make in their life, not from something that is passed down from the original man. In a different aspect, Augustine believes that human sexuality is dirty. His writing is in favor of rejecting his own sexual nature to live a life away from woman altogether. In his writing he always uses negative language to talk about sexuality. He writes about a dream. He sees Continence and she says to him a quote from the Psalms â€Å"Close your ears to the unclean whispers of your body, so that it may be mortified. It tells you of things that delight you, but not such things as the law of the Lord your God has to tell† (Confessions, 176). These sexual temptations are impure, and disordered. He has to turn away from all things sexual. Through all his giving in to temptation in life he pulls a 180-degree turn once he converts and believes that he should never be with another woman again. He runs away from the general population and hides away in a monastery for the rest of his life. He changes from not being able to wait two years for a wife to have sex, to giving up sex forever. He feels like he had been greedy in the first part of his life and that the latter part should be given up to God. â€Å"†¦no bodily pleasure, however great it might be and whatever earthly light might shed luster upon it, was worthy of comparison†¦beside the happiness of the life of the saints† (Confessions, 197). Aquinas believes that human sexuality is innocent. He argues against the popular belief that woman is a ‘ misbegotten man’ by stating that â€Å"†¦woman is not something misbegotten but intended by nature to be directed to the work of procreation† (The Summa, 38). He goes on to say in that paragraph that because God is the creator of all things, and he created male and female, it is obvious that God intended for man and woman to exist with each other equally in nature. Human sexuality is necessary for procreation. Sin does not define whether or not human nature would procreate. â€Å"What is natural to man was neither taken away nor added to him by sin† (The Summa, 40). Sex is not a dirty act, quite the contrary; it is a perfection of God’s creation. â€Å"†¦by nature there is a union of the male and female for the purpose of procreation† (The Summa, 40). If the human race had never sinned and the world was in complete innocence we would still have the need to procreate and sex would be the necessary means to such. â€Å"In the state of innocence, however, reproduction would have taken place without lust† (The Summa, 40). Augustine had ideas for woman’s social roles as well. He had his mother as an example of an ideal woman and described how the ideal woman would be. Woman should behave a certain way. There is no circumstance where a woman would be over a man in any situation. He uses the example of his mother who he praises as possessing â€Å"†¦modesty and temperance†¦obey[ing] her parents†¦Ã¢â‚¬  (Confessions, 194) as well as serving her husband as her lord (Confessions, 194). With her husband she â€Å"†¦knew better than to say or do anything to resist him when he was angry (Confessions, 195) and encouraged other women to â€Å"†¦not defy their masters† (Confessions, 195), in speaking about spousal relationships. In other words, woman should know their place and serve their husband without regard for self. He believed that the man was always to be placed first in every situation and that all women should be like his mother. Service should be a woman’s strong suit and it seems that Augustine believed that in this woman would be fulfilled. Aquinas believed that woman had worth and uses reason to prove this. Throughout his writings he uses non-gendered terms to describe most things, which is a sign to the reader that he believes in equality amongst men and women. He does say that woman was not made to be subjective to man in that she is a slave to him. He points out the two different meanings of subjection. The one kind is a product of the result of sin. The other kind is â€Å"†¦that of the household or the citizen in which the superior makes us of his subjects for their benefit or good† (The Summa, 38). He further specifies this to women when he says â€Å"woman is naturally subject to man in this kind of subjection because by nature man possesses more discernment of the reason† (The Summa, 38). In this, he is stating that there is a natural order to things. Not that woman is below the man in equality, but that there is simply a difference. This introduces the idea, separate but equal in a way. Man and woman are different, but also man and man are different. There are many cases in existence where a leader is needed to take charge. This is not because the one man is highly superior to all other men or that all other men should be slaves to the one, but that someone is needed to be a leader; â€Å"†¦someone can have dominion over another person as a free man, when he directs him to his own good or to the good of the community† (The Summa, 39). He also introduces an idea that if a woman is raped, she has committed no sin. Previously, when a woman was raped she was unworthy of marriage and was termed ‘dirty’. Aquinas finds worth in woman, and introduces the voice of reason in non-gendered terms in order to have his philosophies available to both man and woman. In their writings, St. Thomas Aquinas and St Augustine of Hippo have presented significantly differing views on women and the roles that they should have in the world. These three areas are some of the most important aspects of leading a good Christian life. Even today, these two men are regarded as doctors of the church and their ideals and philosophies are taught, with little regard for the fact that some of the things they teach are completely opposite of each other. Through these varying ideas about original sin, human sexuality, and social roles of man and woman they have set the stage for diversity within the Catholic Church.