Thursday, January 30, 2020

Great Expectations Essay Example for Free

Great Expectations Essay Task: How does the novel present Pips relationship with Magwitch, when he meets him in the graveyard and later when Magwitch returns form abroad to see Pip?  Great Expectations is a novel that is set in the late 1860s, in Victorian society, during the start up of the industrial revolution, which was speedily changing society. In chapter 1 of Great Expectations, the reader meets a young boy, Phillip Pirrip, although he is known as Pip, due to the reason that he cant pronounce his full name. The fact that this issue is introduced to the reader right at the beginning of the story, and that the story is narrated by Pip and his own voice, is attention grabbing; his youthful innocence and naivety is interesting, and immediately gets the reader close to the character. Dickens introduces Pip at a graveyard, where he sets the scene. Pip is visiting the graves of his deceased family, trying to find his identity as well as remind himself and imagine what his parents looked like. Pip is an image of vulnerability, and this is a target for ambiguity to come. Dickens does not state that Pip is an orphan; instead he allows his powerful use of words to demonstrate this. My first fancies regarding what they were like, were reasonably derived from their tombstones. The shape of the letters on my fathers, gave me an odd idea that he was a square, stout, dark man, with curly black hair Also Georgina wife of above, I drew a childish conclusion that my mother was freckled and sickly. Dickens introduces Pips childish imagination into the sequence. Dickens implies that Victorian life and society was like this; there were masses of orphans, like Pip, due to numerous epidemics sweeping the nation, diseases like cholera and smallpox which were rife, and regarded as a universal struggle, this resulted in high mortality rates. You were generally considered lucky if you survived the high mortality rates. The involvement of this fact early on shows that death, and poverty was an everyday occurrence; it wasnt an unusual nature, hence the matter of fact writing. The weather in this scene creates a solemn yet dramatic tone. A negative pattern exhibiting raging storms, adding to the bleak and cold winters day atmosphere is vividly painted. It is a gloomy Christmas Eves day. Pip ventures out into these eerie unknowns, which later on prove to be a symbol that his life is going to change drastically too, where peril and ambiguity await. This also reinforces Pips perception on his situation. While Pip is attempting to bring up recollections at the graveyard, he is surprised by an escaped convict who jumps out rather cynically, from a savage lair, among the looming mists and graves, scaring Pip. The opposite usage of some comedy, at the beginning, and a sharp dramatic twist is attention grabbing. A contrasting backdrop, on to which the messages of the tale can unfold, is created. The reader can tell that the mysterious man is a convict because of the way he is described. His condition is in disarray because of the poor living conditions in the hulks. They were overcrowded, leading to diseases that ended up killing many of the prisoners, and there was malnutrition from poor food. Hard labour was primed everyday too. He has escaped from prison and the hulks (old ships moored on the coast), whilst awaiting exile (to penal colonies in Australia) for 14 years hard labour. (Returning before the end of his term he will face execution). A fearful man, all in coarse grey, with a great iron on his leg. A man with no hat, and with broken shoes, and with an old rag tied round his head. This gives us an insight into the harsh conditions that were faced by prisoners during these times. This plight is shown further more; by the way this convict- Abel Magwitch is portrayed ferociously and pathetically. The harsh and unjust judicial system at the time was the cause of this. Forging banknotes (like Magwitch had done) carried the same penalty as murder! Criminals were brutalised. They were not given chances to reform, instead faced beatings, as forms of punishment. At least 10 hours of daily hard labour was forced on prisoners. Soaked in water, and smothered in mud, and lamed by stones, and cut by flints, and stung by nettles, and torn by briarsand glared and growled. Dickens gives Magwitch with animal like qualities, and so we are provided with a greater understanding that he is at the end of his tether. He is a human that has literally been weathered, like a mere object. A man with no hat and with broken shoessoaked in water, smothered by mud, and lamedlimped and shivered. Magwitch is desperate. This is shown by the way he speaks to Pip aggressively, and threatens him keep still you little devil, and also by the way he roughly handles Pip. The man, after looking at me for a moment, turned me upside down and emptied my pockets. When he tips Pip upside down a piece of bread falls out of his pockets. Magwitch scurries towards this. He ate the bread ravenously. The reader is reminded of his desperate, animal like status, and his plight. The tentative weather mirrors Magwitchs character-a vast wilderness in the vein of a storm, which rushes into Pips life, suddenly, causing an upheaval of ambiguity like disturbance. Dickens tries to connect the characters with a descriptive background, to create a realistic character, building up a reinforced feeling to the passage, which ties in with characters personalities. Upon discovering that Pip lives with Joe- who is a black smith, Magwitch continues to act aggressively towards Pip, as he is useful to him. He makes a threatening demand. You get me a fileYou get me wittlesYou bring them both to meor Ill have your heart and liver out. He continues to threaten Pip, telling him that he can even be hurt in his own home if he betrays the convict. He tells Pip that he is not alone, and if he gets caught then the man along side Magwitch will attack him. A boy may lock his door, may be warm in bed but that young man will softly creep and creep his way to him and tear him openin comparison with which I am a angel. Pip is petrified. The prospect of this occurring (made worse by his youthful innocence), has given way to the sensation of helplessness that clearly covers him. His eyes looked most powerfully into mine, and mine looked most powerfully up into his. This highlights a key detail of status/position that will be seen in depth throughout the story; its a running thread for which it is a major theme. This is the first landmark of Magwitch and Pips relationship. It is one of intimidation, and fear.

Wednesday, January 22, 2020

Loneliness in Steinbecks Of Mice and Men Essay -- essays research pap

How true is the statement "Guys like us are the loneliest guys in the world" Personally I believe that this statement is true in every aspect. Loneliness is a big part of the book "Of mice and men." The book shows loneliness in every ones life in the book. The quote says "Guys like us" George is talking about the ranch workers by saying "us" we know they are all lonely because they all show signs of loneliness, they try to fight this by making friends I think that in the book Steinbeck tries to show us that loneliness can be resolved by friendship. George blames Lennie for him being lonely ?I could get a girl, shoot some pool and stay at the cat house? George seems to be in denial as even if Lennie wasn?t there he wouldn?t be able to get all those things because of the depression 1929. Loneliness has made Crook's a very bitter and isolated man. He is truly not able to leave this situation because of his race. The other men at the ranch do not communicate with Crooks unless he is working because he is black. Other than when they are working, the other men ignore Crooks off all of their activities. Crooks is very isolated, and doesn?t seem to want any company. He has become bitter and known to lash out at people because of the loneliness that he has. Crooks's emotions are showed to the reader when he talks to Lennie in his room about having no one to relate to and communicate with. "Maybe you can see now. You got George. You know he's goin' to come back. S'pose you didn't have nobody. S'pose you couldn't go into the bunk house and play rummy `cuase you was black...A guy needs somebody--to be near him." Crooks has never been treated well by anyone because he is black. This has affected Crooks. Crooks's was shocked when... ..."I tried Aunt Clara, ma'am. I tried. I couldn't help it...I'll go right off in the hills an' I'll fin' a cave an' I'll live there so I won't be no more trouble to George." Lennie was basically in denial of his own loneliness. Loneliness has made Lennie want a better life for himself. This involves these soft items and the dream for his and George's farm. He believes at the farm he will not have to deal with all the problems that he has now. Lennie became unrealistic in many ways because of both his condition and his loneliness. Lennie most likely would have never got the farm or the soft items even if he wasn't killed, but his loneliness acts as motivation for these goals. In conclusion to this, yes I do think the statement ?Guys like us are the loneliest guys in the world? is true because loneliness is seen in all the ranch workers life?s, as I?ve just proved.

Tuesday, January 14, 2020

Pseudomonas Aeruginosa and Nosocomial Infections

Bielecki et al. Research Paper Pseudomonas aeruginosa is a Gram-negative bacteria, particularly known for causing nosocomial infections (1). As a pathogen, it effectively causes disease by acquiring resistance to antibiotics that would otherwise inhibit growth (2). Reported rates of infection range from 0. 6 to 32% across various clinical environments because Pseudomonas aeruginosa has gained multi-drug resistance (2). Certain strains of Pseudomonas aeruginosa treated with gamma rays can break down the hydrocarbons in crude oil and are thus useful in cleaning up oil spills (3).The genome of Pseudomonas aeruginosa is 6. 3 million base pairs long, which is the largest bacterial genome to be sequenced (4). It contains about 5,570 open reading frames (4). Argyrin is a naturally synthesized antibiotic peptide extracted from myxobacteria (1). It has cytotoxic properties, suppresses the immune system, and is a highly active antibiotic used against Pseudomonas strains (1). Figure 1. Argyrin A structure. Bielecki et al chose to isolate these resistant clones in order to observe the mechanisms by which the P. eruoginosa acquires resistance to Argyrin A within the fusA1 gene (1). They isolated these clones by growing Pseudomonas aeruginosa strains on agar that contained Argyrin A (1). After incubation, the colonies that formed were able to grow in the presence of argyrin; these colonies were then streaked onto plates with Argyrin A again to ensure accuracy of obtaining resistant strains (1). A point mutation is an alteration of one base pair within a DNA sequence (5). The point mutations, which caused changes in the amino acid sequence within the fusA1 gene, were different among the six isolates (1).They might have conferred resistance because the mutations caused the same impact on the resulting protein (1). The gene was identified by sequencing the whole genome of Pseudomonas aeruginosa strains with the bacterial target of Argyrin A, which showed mutations within fusA1 that encode for the elongation factor EF-G in resistant strains of Pseudomonas aeruginosa (1). The diagram below illustrates the process of elongation during the translational phase in EF-G along with EF-Tu (12). Figure 2. Elongation during ribosome-catalyzed translation (12). Bielecki et al confirmed the identity of the gene by using genetic maps. This required sequencing the resistant strain a second time to make a reference strain to compare the genes at a specific loci (1). Adding a mutation into the sensitive Pseudomonas aeruginosa strain demonstrated a resistance phenotype (1). Surface plasmon resonance is a lab technique that involves aiming a beam of light at a thin metal sheet, which catalyzes a reaction by causing movement in the molecules behind the metal sheet (6).SPR was useful in this experiment because it confirmed that fusA1 is the target gene for Argyrin A, rather than fusidic acid, the antibiotic previously recognized (1). A heterologous protein, or a heterologue, is a protein that differs in structure and function relative to a given protein; not all proteins with different amino acid sequence necessarily differ in function (7). N-terminal His6-tags were fused to the fusA1 genes before undergoing the SPR experiments, causing the production of heterologous proteins in relation to the original fusA1 (1).According to Bielecki et al, the SPR procedures supported that Argyrin A binds to fusA1 by the resulting KD value (1). This shows that Argyrin A has a target on the heterologous protein (1). It is important to compare the variations made in the mutations because the other bacteria may have a different sequence that can still achieve resistance (1). It cannot be assumed that all bacterial strains will be identically resistant or sensitive because they all contain differences in their genomes (1). By mapping the mutated genes, the authors found the locations of the mutations in different domains (1).They deduced that the mutations exhibiting resi stance to Argyrin A in Pseudomonas aeruginosa are found on opposite sides of the domain, despite the fact that most mutations involving fusidic acid and Argyrin A are located on the same side of the domain (1). This shows that the binding sites for fusidic acid and Argyrin A must be independent of each other (1). Both fusA1 and the second gene, fusA2, encode for the elongation factor EF-G (1). The fusA2 gene was expressed 30 times less in the strains of Pseudomonas aeruginosa than in the fusA1 gene, as shown by RNA sequencing (1).Homology modeling uses the model of a target protein to produce an estimated structure of a homologous template protein (8). After creating a homology model of Argyrin A’s protein structure, Bielecki et al concluded that it â€Å"most likely binds to a site distinct from that of fusidic acid, indicating a new mode of protein biosynthesis inhibition by Argyrin A† (11). Multi-drug resistant pathogens pose a very big risk on the world because the y can easily mutate their genomes to adopt resistance to a given antibiotic and persist in causing harmful diseases (1).The authors used MDR clinic isolates in order to observe the mechanisms by which these pathogens mutate to build resistance to Argyrin. The fact that eleven of the twelve isolates showed sensitivity to Argyrin suggests that Argyrin is a useful antibiotic in preventing infections by Pseudomonas aeruginosa (1). There are other factors besides the uptake and export of Argyrin that affect Pseudomonas aeruginosa’s sensitivity to Argyrin, such as efflux pumps (1); however, the uptake and export of Argyrin in other bacteria does play a role in its sensitivity (9).A proteasome is a hollow protein complex with active sites that break down proteins by proteolysis (10). The degraded peptides that are produced can be used for other functions in the cell (10). Argyrin A is a factor used to inhibit proteasome function, yet there is no distinct evidence that Argyrin A bind s to the site on the proteasome (1). This paper is important because it analyzes the resistance and sensitivity to Argyrin A in various strains of Pseudomonas aeruginosa.This bacteria has been a leading cause in nosocomial infections, so it is important to determine which antibiotics best work to stop the spread of disease (1). About ten percent of patients in hospitals across the United States obtain a significant nosocomial infection (13). Although there are effective methods to prevent the spread of pathogens in clinical environments (13), it is important to study how bacteria acquire resistance, so that scientists can develop ways to inhibit the spread of nosocomial infections by multi-drug resistant pathogens.Bibliography Bielecki, P. , Lukat, P. , Husecken, K. , Dotsch, A. , Steinmetz, H. , Hartmann, R. W. , Muller, R. , and Houssler, S. (2012) Mutation in elongation factor G confers resistance to the antibiotic Argyrin in the opportunistic pathogen Pseudomonas aeruginosa. Che mbiochem. 13, 2339-2345. Obritsch, M. 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Accessed 1 8 Oct. 2012 http://www. astbury. leeds. ac. uk/facil/SPR/spr_intro2004. htm Jackson, J. H. (1999) Terminologies for gene and protein similarity. Michigan State Univ. , Dept. of Microbiology. Accessed 19 Oct. 2012 https://www. msu. edu/~jhjacksn/Reports/similarity. htm Bevan, D. R. (2003) Homology modeling. Virginia Tech, Dept. of Biochemistry. Accessed on 19 Oct. 012 http://www. biochem. vt. edu/modeling/homology. html Sasse, F. , Steinmetz, H. , Schupp, T. , Petersen, F. , Memmert, K. , Hofmann, H. , Heusser, C. , Brinkmann, V. , von Matt, P. , Hofle, G. , and Reichenbach, H. (2002) Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological properties. J. Antiobiot. 55, 543-551. Rape, M. , and Jentsch, S. (2002) Taking a bite: proteasomal protein processing. Nat. Cell Biol. 4, 113-116. Bielecki, P. , Lukat, P. , Husecken, K. , Dotsch, A. Steinmetz, H. , Hartmann, R. W. , Muller, R. , and Houssler, S. (2012) Mutation in e longation factor G confers resistance to the antibiotic Argyrin in the opportunistic pathogen Pseudomonas aeruginosa. Chembiochem. 13, 2340. Simonovic, M. and Steitz, T. A. (2009) A structural view on the mechanism of the ribosome-catalyzed peptide bond formation. BBA Gene Reg. Mech. 1789, 612-623. Abedon, S. T. (2009) Nosocomial infections. Ohio State University. Accessed on 27 Oct. 2012 http://www. mansfield. ohio-state. edu/~sabedon/biol2053. htm