Otto Von Bismarck Essay Example for Free

Otto Von Bismarck Essay Otto Von Bismarck was made Prime Minister and Foreign Minister of Prussia by I in 1862. He stayed in power until 1890. His conduct of foreign policy between 1862 and 1871 is one of the most fascinating and complex parts of the nineteenth century. It ended with the unification of Germany on 18th January 1871, under Prussian dominance, with King William of Prussia being coroneted as Kaiser in Versailles. The German unification is possibly the most important and significant events in history, as it has had so many effects and consequences across the whole world, and still does to this day. One of the most widely debated topics of the nineteenth century is to what extent is Bismarck responsible for the unification. Basically, was Bismarck’s foreign policy more about conscious design, or a policy by default largely determined by other key personalities and events? Some people try and say that Bismarck was always heading towards German unification, and that he had been planning how to get there all along; but actually, Bismarck hardly planned a thing – he instead was just very good at taking things as they came. His main aim was to strengthen Prussia, and make it into a stronger country. An example of how Bismarck did not plan what he did is how he came to power. He was not elected, so he was not planning ways in which to gain votes etc. ; instead, he was suddenly catapulted from being ambassador to St. Petersburg, and then Paris, to being chancellor of Prussia. Bismarck was also known for his personality. It was this that initially got him to where he was. He was nicknamed ‘The Iron Chancellor†, and he fitted this name very well. In 1862, when William was refused money by liberals to pay for his army, he threatened to abdicate, but was persuaded to elect Bismarck as chancellor instead. Everybody who knew Bismarck knew him as being wild, and a bully, a conservative, an army man, and as being a ‘Machiavellian’. He was cunning, scheming, unscrupulous, vicious, manipulative, calculating, brutal, and devious, and also very good at improvising. It was these things that William liked about him, and Williams’s expectations of Bismarck were achieved. Immediately after being put in office, Bismarck suspended the constitution and gave the army the money it needed. Now he was in control of Prussia as it was maturing and reaching power. Another event that shows how Bismarck did not plan things is the Danish Crisis in Schleswig and Holstein in 1864. Some people say that Bismarck planned this, and did it to get Austria involved, and to be nice to her by giving her some land, but which he could take at any time as it was next to Prussia, and cause up rise. In reality, Denmark unexpectedly attempted to annex Schleswig and Holstein, and Bismarck just saw a chance to gain some land, respect, popularity, and a small advantage over Austria; he did not previously plan any of this, he just ‘played the cards he was dealt well’ e. g. e ended up doing it with Austria – this made him look good in front of everyone else, and also lulled Austria into a false sense of security. This was a first step towards Bismarck thinking cleverly about how he could get an upper hand over Austria. Although Bismarck did not necessarily plan all of the things that he did, he was very good at playing what came along well, and thinking about all of the consequences of his actions, and how he could use what he had to his best advantage; because of this, he was a great man who was clever and quick thinking, so we have not at all been deceived about him. It has often been said that Bismarck never meant for what most of what he did to happen, and that what he did was just mainly luck e. g. there was an extraordinary interlude of calmness during his time. This meant that he was able to many things that he should not have been able to do without risking international intervention. Britain is a good example of this international calmness. We were far more concerned with looking after ourselves, and keeping our empire strong and wealthy, than in events in Europe. The one thing that we did have a view on, and it was a strong view, was that we hated France, and this ended up being good for Bismarck anyway. Austria and France were also calm when Bismarck needed them to be – after Austria lost the war, it took her a reasonable amount of time to recover, and Bismarck used this time wisely; France had previously been hammered during Napoleon Bonaparte’s conquest of Europe, and was hated by many, and so was lying low for some time, and again, Bismarck used this greatly to his advantage. A handful people believe that Bismarck’s legacy is too big for his own good. As some people say that he caused German unification single-handedly, because this was a huge event which had enormous consequences and effects, people automatically think of Bismarck as being a greater and better person than he actually was, and that he shifted history his way more than he actually did. But, without Bismarck, luck and other things would not have been a big enough factor to cause German unification, and so he was needed, and he was a great man. Bismarck is said to have unified Germany, but there are several other people who contributed to it more than people think, who are often forgotten about, and not so well known. One of these people is Napoleon III of France. Napoleon III was a very weak, feeble, useless and pathetic ruler. When he was anxious to gain compensation and maintain France’s role as a great power, he was looking at Bismarck and Prussia for anything to grab onto and attack, but Bismarck gave him nothing to react to. This just angered Napoleon even more, and made it easy for Bismarck to use Napoleon when he wanted. Napoleon was such a weak and terrible ruler, that he automatically gave Bismarck an advantage, as Bismarck could easily control Napoleon, and trick him into doing things that he did not realize the consequences of. Bismarck very easily irritated Napoleon on purpose, but he did not go too far e. g. the Hohenzollem candidature, where Bismarck tried to put a Prussian prince in the Spanish throne. This would mean that Prussia would have a massive advantage, as France would be surrounded by Prussia, and could even face fighting on two fronts. Obviously Napoleon was furious when he heard about this, but Bismarck quickly withdrew the candidature, meaning that Napoleon did not act at all, and Bismarck looked good, as he had withdrawn it ‘to be nice to France’. Napoleon did not see what was happening, which meant that Bismarck could do almost what he wanted around him. Ludwig of Bavaria was an obstacle to Bismarck. He led the biggest German state (apart from Prussia). When Bismarck was making all of the head of the states agree to letting, acknowledging, and going to William’s coronation of becoming Kaiser of Germany, Ludwig was the only person to refuse, but Bismarck easily got around this problem by coming to an agreement with Ludwig, which was that Ludwig would accept the demands if Bismarck let him keep his ornate postboxes. This was a major victory for Bismarck, as it was the end of the very old state of Bavaria, which had lots of history, and patriotism, and was at one point a very strong power. Bismarck was controlled and told what to do mainly by William and also by the conservatives and the middle class taxpayers. William especially had absolute control over Bismarck. He had promoted him to chancellor. Prussia’s General (Moltke) was also very important. He was a superb General, and led Prussia’s army very well to its victories. Bismarck was not a military leader, and without Moltke could possibly not have done nearly as well as he did. Russia was massively important. She did not intervene during Prussia’s wars against Denmark and Austria in 1864 and 1866. If she had, Prussia would have probably lost, leading to a whole different outcome; the war with Austria led to the North German Confederation in 1867. Russia never once stopped the new central power from emerging, even though it was given plenty of opportunities. This may have been because of the Tsar. He always blamed Austria for his father’s death, and so refused to help her. Bismarck was helped on several occasions by certain countries not intervening in 1870 with the war with France, Britain did not intervene as she still hated France, neither would Italy, as she owed her acquisition of Venetia to Prussia’s victory over Austria in 1866 and also wanted to get the French out of Rome; and Austria was still recovering, and was held back by Russia, who threatened to send in 300,000 men if she got involved. This meant that Bismarck did not need to be scared of fighting on two fronts at all. Also, without the realignment of the great powers that resulted from the Crimean War, German Unification would probably not have happened. Bismarck himself even said: â€Å"It all began with the Crimean War†. Although all of these people and events were important, Bismarck was the fundamental key to the unification. Without him, it would not have happened, so we have not at all been deceived – he was a great man who was the key to the German Unification. When Bismarck came to power, Prussia was coming to its peak in almost every way. She had a brilliant General (Moltke), she was industrializing she had amazing railways and weapons and she had a thriving economy. Another help to Bismarck was the fact that Prussia was physically a large state. Some people believe that Bismarck did not need to do much, and he just did well, as it was a coincidence that he was in the right place at the right time. But, although Prussia was doing well at Bismarck’s time, it needed Bismarck to bring it all together, and make it happen! Many people say that German unification was inevitable, and would have happened even if Bismarck had never lived, because of certain preconditions. For example: nationalism had been growing for many years. This can be shown in the 1848 revolutions; also, it still kept on growing after the revolutions. Nationalism was now a talked about thing – people had written about it, and apart from the monarchs etc. who too were scared of it, people were discussing it among themselves. Also, gradually over the last few decades, there had been becoming less and less German states. Originally there were more than a hundred very small states, similar to the size of a large estate, or maybe a small county today; but as stronger states had engulfed other weaker states, fewer and larger states emerged. By the time Bismarck was around, there was not much more than twenty states. This gradual reduces in the number of states shows that eventually, there would have been a German unification without Bismarck anyway – he just sped the process up. The 1848 revolutions also showed that there was a want for change already there with the people, even before Bismarck, and so again, there would have been German unification without him. Another thing that shows that there would have been German unification without Bismarck anyway is that the Hapsburg Empire had slowly been on its downfall for many years, starting well before Bismarck’s time. At the height of its power, the Hapsburg Empire was enormous, and extremely powerful and very autocratic, but it had slowly been becoming less and less of a major power, and other countries were beginning to be able to almost rival it. Many people also say that the struggle between the German states and the struggle between Prussia and Austria had to be settled some time, and this would have happened regardless of whether Bismarck was there or not. By the time Bismarck came to power, there was as well a want for unification already there, which some say would have caused it anyway if Bismarck had not been there (liberals had wanted unification for a long time, but now there were also others who wanted it, like some of the working class, and some of the middle class – also, there were many who did not think about unification, but would have probably supported it if they could more easily). Also, in 1866, the southern states were becoming increasingly hostile to Prussia, and the other northern states. A war to resolve the hostility between France and Prussia, and to force the southern states into joining the North German Confederation seemed likely in 1869. This showed that even if Bismarck had not been there, then there would have been the unification anyway. People say that these points show that it was not Bismarck who caused the unification, but it was in fact going to happen anyway; but actually, it was Bismarck who brought all of these separate points together to make the unification happen. Without him these points would not have led to it, they need Bismarck! He brought these points together, and therefore it was Bismarck who made it possible. So we have not been deceived, as Bismarck was a great man, who shifted these points his way, leading to unification. Bismarck was a great man, and he had a great personality, and was always willing to do things. Bismarck was a great Machiavellian. He was brilliantly sly and cunning, and his truth was flexible. He was happy to put down anyone he needed to, even his friends. He always desired a stronger Prussia, and it was this desire that led to him unifying the German states. He was fundamentally a conservative, but he cleverly managed to get all different sorts of people to like him, and to be on his side – even many of the liberals. He was very gifted at making people believe something he wanted them to believe, or do what he wanted them to do e. g. he got William to agree to becoming the Kaiser, as he got all of the rulers of the other states to give him the crown. Bismarck was also very good at knowing when to stop – he would irritate someone a lot, but stop just before they exploded. He did this with Napoleon III. Bismarck also never took any risks that were too big. He always knew what he was doing, even though it often looked the opposite. He would only proceed with something if he was satisfied with his chance of success. This was his key strength – he was an unbelievable decision-maker. This meant that he was also very good at ‘playing things by ear’, which meant that he never had to plan things too far in advance, and he was very good at putting himself into other people’s shoes, and seeing what the consequences of all of his decisions could be. Bismarck was also very strong willed. He always did what he wanted, and never stopped or hesitated for anything. He was like a steam train going full speed, and having to make hundreds of decisions of what path to take – he was unstoppable. Proof of this is that when he came to power, the majority of people did not want unification, but he still managed to make it happen. William was also nearly useless without Bismarck. He was too weak and slow. Bismarck was a great man, and he certainly did shift history his way when he wanted to.

Care Of The Patient In Recovery Inadvertent Hypothermia Case Nursing Essay

Care Of The Patient In Recovery Inadvertent Hypothermia Case Nursing Essay Before the author can discuss hypothermia in regards to the patient above they must first review how the body regulates heat control within the body. Many sources, give varying definitions of what normal body temperature or normothermia is. For example Marieb (2004) defines this as a core temperature range from 35.6 °c and 37.8 °C. Meanwhile Kiekkas and Karga (2005) defined the normal temperature range of adult patients as between 36.5 °C and 37.5 °C. National Institute for Health and Clinical Excellence (NICE) 2008 guideline for the management of inadvertent perioperative hypothermia agree with this definition. Core temperature, defined by Kiekkas and Karga (2005), is the blood temperature of the central circulatory system, which can be measured for example at the pulmonary artery, rectum or via the tympanic membrane, which occurs in recovery at Hospital x. The hypothalamus is the central organ that acts as the bodys heat promoting and heat loss centre, then brains thermoregulatory centre. Body temperature is kept stable and regulated with the help of blood. The neuronal centre in the posterior hypothalamus is triggered when there is a decrease in temperature in the blood or the external temperature is low. Mechanisms for heat conservation and heat production are triggered such as, shivering, which is the bodys natural response to cold, constriction of blood vessels in the skin and increased metabolic activity to produce energy (Hatfield and Tronson, 1996; Marieb, 2004). As with the varying definitions of normothermia, there are also differing definitions in hypothermia. NICE (2008) guideline defines hypothermia as a core temperature of less than 36 °C. Similarly several authors agree with this definition, Aikenhead et al (2007), American Society of Peri Anesthesia Nurses (ASPAN) (2009); Clarke and Clark , 1997). Meanwhile Kiekkas and Karga state, hypothermia as a core temperature of more than 1 (standard deviation) less than the mean value under resting conditions in a thermoneutral environment (Kiekkas 2005, p444) There are 4 ways in which the body loses heat; conduction, convection, evaporation and radiation. Talk about these briefly! There are patients who are more at risk of developing hypothermia these include; older and younger patients. The size of the patient: thin, due to the lack of tissue mass and obese, due to the large surface area. The type of procedure: open thoracic, abdominal, gynaecological or genitourinary. Patients having a combined general and spinal anaesthesia (Welch, 2002) Patient A falls into some of these categories, because of the type of surgery, age and anaesthesia she will be having. As part of the pre operative check in Patient A was asked the last time she had eaten, this was 12 hours before the procedure. Advice of fasting for 6 hours plus is given to patients to prevent nausea and vomiting during and after the induction of anaesthesia, as this along with the spinal causes the constriction of the abdomen and stomach. This in turn deprives the body of the metabolic system of energy it needs from food digestion (Cobbold Money 2010; McNeil, 1997). Following administration of Propofol and Remifentanil via a TIVA syringe pump, the patient was intubated with a size 7 endotracheal tube. Anaesthetic medications such as those given to Patient A; Propofol, depress the central nervous system which mean the hypodermic thermoregulatory centre function is decreased. This occurs as there is an increase in conduction and radiation to the peripheral points of the skin, where heat loss is at most, as the skin has a large surface area. This loss of heat is difficult to manage after anaesthesia has been administered as heat distribution, which is the increase in peripheral temperature and a decrease of core temperature has taken place (Kiekkas Karga, 2005; Sasad Smith, 2000). With her airway secured, Patient X was positioned for the administering of a spinal. Her back was exposed and sprayed with chlorhexidine gluconate solution, for pre operative skin disinfection (BNF, 2008), a cold solution thus further contributing to the decrease in Patient As body temperature, via evaporation (Bellamy, 2007). The effect of administering Diamorphine and Marcain Heavy ® is that it causes the sympathetic nervous system to be compromised as vasodilatation occurs (Fallacaro et al, 1986). Patient A was taken into theatre, where the ambient temperature as recorded by the author was 21 °C, reason for the temperature being so low is to minimise the growth of bacteria. However such a low temperature would affect Patient A as her body temperature will vary according to the environments conditions (Bellamy, 2007). McNeil (1998), advocates that the temperature in theatre should be raised from 21 °C to 24 °C to maintain Patient As core temperature, which unfortunately was not taken until the procedure in the operating had started. Whilst the author agrees with the later point so that the patients temperature is taken into consideration, they have to agree with Bellamys (2007) point on minimising bacteria production. Patient A was exposed for catheterisation and for the Bair Hugger ® to be positioned. This is a forced air system used in Hospital X, which several sources agree, is the best form of preventing inadvertent hypothermia (Hegarty et al, 2009; NICE Guidelines, 2008; Welch, 2002). This was however switched on at 36.5 °C after Patient A had been prepped and draped. Fluids were firstly administered to Patient A in the anaesthetic room at room temperature; they were then transferred into a warming coil at a temperature of 37 °C. Whilst the NICE (2008) guidelines recommend warm fluids are administered in the operating room at the temperature stated, the author feels that warm fluids should have been started in the anaesthetic room. The monitoring of Patient As temperature occurred after draping and prepping, it was measured using an oesophageal temperature probe as this measures the core temperature accurately and documented every 15 minutes (Al-Shaikh and Stacey, 2002; NICE, 2008). NICE (2008) recommends that temperature of a patient should be 36 °C before a procedure should proceed, the temperature of Patient A on arrival to the anaesthetic room was not taken and the first temperature in theatre was 35.6 °C increasing to 36.0 °c at the end of the procedure. After the procedure, which had no surgical complications and Patient A was extubated, she was transferred to recovery where the tympanic temperature; which is associated with the brain temperature therefore reflects the core temperature (Al-Shaikh and Stacey, 2002), was taken in recover 10 minutes after the patient arrived and was recorded to be 35.4 °C. Handover to the recovery personnel included patients name, date of birth, procedure, what drugs had been administered and the anaesthetist made an emphasis on the patients temperature which they wanted to make sure was up to at least 36.0 °c before the patient was transferred to the ward, part of the NICE (2008) guidelines. Standard recovery monitoring including Oxygen saturation, electrocardiogram and blood pressure results were constantly observed, with results being documented every 15 minutes. The effects of hypothermia are not known until the patient comes into recovery for some time as the effects are masked by the anaesthetic drugs given to Patient A. (Kiekkas et al, 2005). To prevent this a Bair Hugger was placed on Patient A to continue the warming cycle. There are many complications associated post operatively with hypothermia, the most common is post anaesthetic shivering, which is an involuntary muscular activity. This is bought on by the body returning to normal Delayed emergence, where the metabolism of drugs is decreased, as it makes it more difficult for the anaesthesia to be reversed due to the hepatic and renal functions being impaired. Add liver metabolism of drugs to this section Pressure sore development Blood clots clotting cascade, platelets do not work increased bleeding Discharge criteria Patient A woke up fully after 20 minutes in the PACU with no complaints of pain, sickness or nausea but thirst. Her temperature was taken again and this was found to be 35.8 °C, a marked improvement on her original recovery temperature. Before the patient is transferred to the ward what scale used observations etc? Urine output from catheter Sats BP

Ebola Virus Mechanism of Infection

Ebola Virus Mechanism of Infection The Ebola virus (EBOV) is an enveloped, non-segmented, negative-strand RNA virus, which  together with Marburg virus, makes up the filoviridae family. The virus causes severe  hemorrhagic fever associated with 50-90% human mortality1. Four species of the virus (Zaire,  Sudan, Cà ´te d’Ivoire, and Reston ebolavirus) have thus far been identified, with Zaire typically  associated with the highest human lethality2. A fifth EBOV species is confirmed in a 2007  outbreak in Bundibugyo, Uganda3,4. Infection with EBOV results in uncontrolled viral  replication and multiple organ failure with death occurring 6-9 days after onset of  symptoms5. Fatal cases are associated with high viremia and defective immune responses,  while survival is associated with early and vigorous humoral and cellular immune  responses6-9. Although preliminary vaccine trials in primates have been highly  successful10-13, no vaccines, specific immunotherapeutics, or post-exposure treatments are  currently approved for human use. Since 1994, EBOV outbreaks have increased more than  four-fold, thus necessitating the urgent development of vaccines and therapeutics for use in the  event of an intentional, accidental or natural EBOV release. The EBOV genome contains seven genes, which direct the synthesis of eight proteins. Transcriptional editing of the fourth gene (GP) results in expression of a 676-residue transmembrane-linked glycoprotein termed GP, as well as a 364-residue secreted glycoprotein  termed sGP14,15. EBOV GP is the main target for the design of vaccines and entry inhibitors. GP is post-translationally cleaved by furin16 to yield disulfide-linked GP1 and GP2  subunits17. GP1 effects attachment to host cells, while GP2 mediates fusion of viral and host  membranes16,18-20. EBOV is thought to enter host cells through receptor-mediated  endocytosis via clathrin-coated pits and caveolae21, followed by actin and microtubuledependent  transport to the endosome21, where GP is further processed by endosomal  cathepsins22-24. Essential cellular receptor(s) have not yet been identified, but DC-SIGN/LSIGN25,  hMGL26, ÃŽ ²-integrins27, folate receptor-ÃŽ ±28 and Tyro3 family receptors29 have all  been implicated as cellular factors in entry. Here, we report the crystal structure of EBOV GP,  at 3.4 Ã… resolution, in its trimeric, pre-fusion conformation in complex with neutralizing  antibody Fab KZ52. GP1 is responsible for cell surface attachment, which is probably mediated by a region  including residues 54-20132. GP1 is composed of a single d omain (∠¼65 Ã… Ãâ€" 30 Ã… Ãâ€" 30 Ã…),arranged in the topology shown in Fig. 2a, and can be further subdivided into the (I) base, (II)  head and (III) glycan cap regions (Fig. 2a and Supplemental Fig. S3). The base (I) subdomain  is composed of two sets of ÃŽ ² sheets, forming a semi-circular surface which clamps the internal  fusion loop and a helix of GP2 through hydrophobic interactions (Fig. 2b). Moreover, this  subdomain contains Cys53, which is proposed to form an intermolecular disulfide bridge to  Cys609 of the GP2 subunit17. Cys53 resides near GP2 in the ÃŽ ²2-ÃŽ ²3 loop at the viral membraneproximal  end of the base subdomain (Fig. 2a-b). Our EBOV GP contains an intact GP1-GP2  disulfide bridge, based on reducing and non-reducing SDS-PAGE analysis. However, the region containing the counterpart GP2 cysteine is disordered, which may reflect functionally  important mobility in the region. The head (II) is located between the base and glycan cap   regions towards the host membrane surface. Two intramolecular disulfide bonds stabilize the  head subdomain and confirm the biochemically determined disulfide bridge assignments17.   Cys108-Cys135 connects a surface-exposed loop (ÃŽ ²8-ÃŽ ²9 loop) to strand ÃŽ ²7, while Cys121-Cys147 bridges the ÃŽ ²8-ÃŽ ²9 and ÃŽ ²9-ÃŽ ²10 loops (Fig. 2a). The glycan cap (III) contains four  predicted N-linked glycans (at N228, N238, N257 and N268) in an ÃŽ ±/ÃŽ ² dome over the GP1  head subdomain (Fig. 1b and 2a). This subdomain does not form any monomer-monomer  contacts and is fully exposed on the upper and outer surface of the chalice. The central ÃŽ ² sheets  from the head and glycan cap together form a fairly flat surface and, in the context of the GP  trimer, form the three inner sides of the chalice bowl. Ebola virus GP2 GP2 is responsible for fusion of viral and host cell membranes and contains the internal fusion  loop and the heptad repeat regions, HR1 and HR2. Many viral glycoproteins have fusion  peptides, located at the N terminus of their fusion subunit, which are released upon cleavage  of the precursor glycoprotein. By contrast, class II and class III fusion proteins, as well as class  I glycoproteins from Ebola, Marburg, Lassa and avian sarcoma leukosis viruses, contain  internal fusion loops lacking a free N terminus. The crystal structure reveals that the EBOV  GP internal fusion loop, which encompasses residues 511-556, utilizes an antiparallel ÃŽ ²Ã‚  stranded scaffold to display a partially helical hydrophobic fusion peptide (L529, W531, I532,  P533, Y534 and F535) (Fig. 2c). The side chains of these hydrophobic residues pack into a  region on the GP1 head of a neighboring subunit in the trimer, reminiscent of the fusion peptide  packing in the pre-fusion parainfluenz a virus 5 F structure33. A disulfide bond between Cys511  at the base of ÃŽ ²19 and Cys556 in the HR1 helix covalently links the antiparallel ÃŽ ² sheet. This  disulfide bond between the internal fusion loop and HR1 is conserved among all filoviruses,  and is analogous to a pair of critical cysteines flanking the internal fusion loop in avian sarcoma  leukosis virus34,35. Interestingly, the EBOV internal fusion loop has features more similar to  those observed in class II and III viral glycoproteins (in particular to flaviviruses) than those  previously observed for class I glycoproteins (Supplemental Fig. S4). It thus appears that  regardless of viral protein class, internal fusion loops share a common architecture for their  fusion function. EBOV GP2 contains two heptad repeat regions (HR1 and HR2), connected by a 25-residue  linker containing a CX6CC motif and the internal fusion loop. The crystal structures of postfusion  GP2 fragments30,31 have revealed that the two heptad repeat regions form antiparallel  ÃŽ ± helices and that a CX6CC motif forms an intrasubunit disulfide bond between Cys601 and  Cys608 (Supplemental Fig. S5). In the pre-fusion EBOV GP, HR2 and the CX6CC motif are  disordered. By contrast, the HR1 region is well ordered and can be divided into four segments:  HR1A, HR1B, HR1C and HR1D (Fig. 2c), which together assemble the cradle encircling GP1. Similarly, heptad repeat regions in influenza and parainfluenza viruses also contain multiple  segments in their pre-fusion helices that substantially rearrange in their post-fusion  conformations33,36,37. The first two segments, HR1A and HR1B (residues 554-575), together form an ÃŽ ± helix with an  Ã¢Ë† ¼40 ° kink at T565, which delineates HR1A from HR1B. Interestingly, the bend between  HR1A and HR1B contains an unusual 3-4-4-3 stutter, which may act as a conformational  switch31, rather than the typical 3-4 periodicity of heptad repeats (Supplemental Fig. S6). A  similar stutter has also been noted in parainfluenza virus 5 F33. The Ebola virus HR1C (residues  576-582) forms an extended coil linking HR1B to the 14-residue ÃŽ ± helix of HR1D (residues  583-598). HR1D forms an amphipathic helix and the hydrophobic faces of each HR1D join to  form a three-helix bundle at the trimer interface. Although the breakpoint maps directly to a  Lee et al. Page 3 Nature. Author manuscript; available in PMC 2009 June 22. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript  chloride ion binding site in the post-fusion conformation of GP230,31 and at least two other  viruses38,39, no chloride ion is observed here as HR1 and HR2 do not come together to form  the six-helix bundle. Instead, the pre-fusion GP2 adopts a novel conformation, intimately  curled around GP1 (Fig. 1c). Ebola virus GP-KZ52 interface KZ52 is an antibody isolated from a human survivor of a 1995 outbreak in Kikwit, Democratic  Republic of the Congo (formerly Zaire)40. This antibody neutralizes Zaire ebolavirus in  vitro40 and offers protection from lethal EBOV challenge in rodent models41, but has minimal  effects on viral pathogenicity in non-human primates42. KZ52 is directed towards a vulnerable,  non-glycosylated epitope at the base of the GP chalice, where it engages three discontinuous  segments of EBOV GP: residues 42-43 at the N terminus of GP1, and 505-514 and 549-556  at the N terminus of GP2 (Fig. 3 and Supplemental Fig. S7). Although the majority of the GP  surface buried by KZ52 belongs to GP2, the presence of both GP1 and GP2 are critical for  KZ52 recognition43. It is likely that GP1 is required to maintain the proper pre-fusion  conformation of GP2 for KZ52 binding. Indeed, KZ52 is the only antibody known to bridge  both attachment (GP1) and fusion (GP2) subunits of any viral gly coprotein. Given that KZ52  requires a conformational epitope seen only in the GP2 pre-fusion conformation and that the  KZ52 epitope is distant from the putative receptor-binding site (RBS), KZ52 likely neutralizes  by preventing rearrangement of the GP2 HR1A/HR1B segments and blocking host membrane  insertion of the internal fusion loop. Alternatively, IgG KZ52 may sterically hinder access to  the RBS or to a separate binding site of another cellular factor, especially if multiple attachment  events are required for entry. The KZ52 epitope of GP is convex and does not have a high shape complementarity to the  antibody (Sc index of 0.63), although ∠¼1600 Ã…2 of each GP monomer are occluded upon KZ52  binding. The antibody contacts a total of 15 GP residues by van der Waals interactions and 8  direct hydrogen bonds (Supplemental Fig. S7). Ten out of 15 residues in the structurally defined  KZ52 epitope are unique to Zaire ebolavirus (Supplemental Fig. S6), thus explaining the Zaire  specificity of KZ52. Ebola virus GP glycosylation We generated a fully glycosylated molecular model of EBOV GP to illustrate the native GP  trimer as it exists on the viral surface (Fig. 4). The majority of N-linked glycosylation sites are  concentrated in the mucin-like domain and glycan cap of GP1. Given that the mucin-like  domain is ∠¼75 kDa in mass (protein and oligosaccharide), the volume of this domain is  predicted to be similar to each GP monomer observed here. The crystal structure suggests that  the mucin-like domain is linked to the side of each monomer and may further build up the walls  of the chalice, forming a deeper bowl (Fig. 4). Although a mixture of complex, oligomannose  and hybrid-type glycans are found on intact, mucin-containing GP144, those glycans outside  the mucin-like domain are likely to be complex in nature: the mucin-deleted GP used for  crystallization is sensitive to PNGaseF, but not to EndoH treatment (Supplemental Fig. S8).   Modeling of complex-type oligosaccharides on the EBOV GP indicates that the majority of  the GP trimer is cloaked by a thick layer of oligosaccharide, even without the mucin-like  domain (Fig. 4). The ∠¼19 additional oligosaccharides on the full-length GP (17 on the mucinlike  domain and 2 more on GP1, disordered here) further conceal the sides and top of the  chalice. The KZ52 binding site and, presumably, the flexible regions of HR2 and the  membrane-proximal external region (MPER) remain exposed and perhaps vulnerable to  binding of antibodies and inhibitors. Lee The development of neutralizing antibodies is limited in natural Ebola virus infection. Many  survivors have low or insignificant titres1,7, and those antibodies that are elicited preferentially  recognize a secreted version of the viral glycoprotein that features an alternate quaternary  structure and lacks the mucin-like domain43. The glycocalyx surrounding EBOV GP likely  forms a shield that protects it from humoral immune responses and/or confers stability insideor outside a host. The mucin-like domain and glycan cap sit together as an external domain to  the viral attachment and fusion subunits, reminiscent of the glycan shields of HIV-1  gp12045,46   and Epstein-Barr virus gp35047, perhaps pointing to a common theme for immune  evasion. Alignment of filoviral sequences indicate that regions involved in immune evasion  have a low degree of sequence conservation [i.e. GP1 glycan cap (∠¼5%) and mucin-like domain  (0%)], but the N-glycosylation sites in the glycan cap are mostly conserved among all EBOV  subtypes (Supplemental Fig. S6), indicating the functional importance of these posttranslational  modifications. Sites of receptor binding and cathepsin cleavage Although a definitive receptor for EBOV remains to be identified, previous studies32,48,49  have determined that residues 54-201, which map to the base and head subdomains of GP1,  form a putative receptor-binding site (RBS) for attachment to host cells. Additional  experimental studies have identified at least 19 GP1 residues, assigned into four groups based  on the location in the structure, that are critical for viral entry48-50 (Fig. 5). Many of these  residues are apolar or aromatic and are involved in maintaining the structural integrity of GP1  for receptor binding or fusion. However, six residues (K114, K115, K140, G143, P146 and  C147) cluster within a ∠¼20 Ãâ€" 15 Ã… surface in the inner bowl of the chalice and may thus  represent important receptor contact sites. All residues in the putative RBS are highly conserved  among Ebola virus species (Supplemental Fig. S6). Importantly, this putative RBS is recessed beneath the glycan cap and perhaps further masked  by the mucin-like domain (Fig. 4), suggesting that additional conformational change or removalof the mucin-like domain could reveal additional surfaces required for receptor or cofactor  binding. It has been demonstrated that endosomal proteolysis of EBOV GP by cathepsin L  and/or B removes the mucin-like domain to produce a stable ∠¼18 kDa GP1 intermediate which  has enhanced viral binding and infectivity22-24. The precise site of cathepsin cleavage is  unknown and the role of cathepsins in natural infection is as yet unclear. However, formation  of an ∠¼18 kDa GP1 fragment implies that cathepsin may cleave near the GP1 ÃŽ ²13-ÃŽ ²14 loop  (residues 190-213). Indeed, this loop is unresolved in the pre-fusion structure, suggesting  enhanced mobility and accessibility to enzymatic cleavage. Cleavage within this loop would  remove the entire mucin-like domain and glyc an cap region (Fig. 5). As a result, ÃŽ ²7 to ÃŽ ²9  strands and their associated loops would become exposed. These regions of GP are in proximity  to the previously identified residues critical for viral entry. The fold, location and  physicochemical properties of this site should now provide new leads in the search for the  elusive filoviral receptor(s). A summary of the Ebola virus mechanism of infection, including the events of cathepsin  cleavage and conformational changes to GP2 during fusion, is presented.

Biotechnology- food :: essays research papers fc

Bibliography 1.  Ã‚  Ã‚  Ã‚  Ã‚  http://scope.educ.washington.edu/gmfood Copyright 2000-2004 by the SCOPE Research Group (UC Berkeley, UW, AAAS), all rights reserved. 2.  Ã‚  Ã‚  Ã‚  Ã‚  http://www.safe-food.org 3.  Ã‚  Ã‚  Ã‚  Ã‚   http://www.englishnature.org.uk/news/story.asp?ID=230  © 1998 - 2004 English Nature, Northminster House, Peterborough PE1 1UA England 4. http://www.fda.gov 5. http://pewagbiotech.org/resources/factsheets/display.php3?FactsheetID=2 Copyright  © 2004 The Pew Initiative on Food and Biotechnology Agricultural biotechnology is a collection of scientific techniques, including genetic engineering, that are used to create, improve, or modify plants, animals, and microorganisms. Using conventional techniques, such as selective breeding, scientists have been working to improve plants and animals for human benefit for hundreds of years. Modern techniques now enable scientists to move genes (and therefore desirable traits) in ways they could not before - and with greater ease and precision (scope.educ.washington.edu). Biotech food, which is genetically modified or genetically engineered, is grown from seeds that carry specific genes to produce desired characteristics. In the early 1990s, the first biotech food on the market was a tomato that ripened on the vine and could be transported without bruising. The products of agricultural biotechnology today include plants that are protected from insects or are tolerant to herbicides. Biotech foods have now made their way onto our tables. More than a third of the corn and more than half of the soybeans in the 1999 U.S. harvest were grown from seeds produced using biotechnology. As biotechnology crops and foods have proliferated, so have questions and concerns. European consumers, perhaps because of unrelated food scares about diseased beef and contaminated soda, are arguing to label biotech food or keep it out of stores. Consumers in the United States are starting to pay more attention to these issues. Concerns range from food safety to environmental impact. Also framing the debate are ethical questions, including whether it is right to change the genetic makeup of a plant. Some objections that activists raise also apply to conventional crops grown with modern high-intensity agriculture. Increasing acreage given over to GA crops is one of the most frightening aspects. The pollen from these plants can travel miles from their host via wind and insects and fertilize other non-GA crops or related weed species growing nearby. This has already happened with canola and sugar beet. Furthermore, the genes inserted by the alteration process are more biologically vigorous and may be up to 30 times more likely to escape than the plant's own genes. We have already seen this process take place with disastrous results with other 'exotic' and invasive species such as kudzu in the south, and zebra mussels in our waterways( http://www.

My Life is a Cluttered Drawer :: essays research papers

My life is a cluttered drawer if you looked inside you would see a variety of pictures. Pictures of places far and near. Pictures of friends, family and loved ones. In the back of the drawer tools for the tinkering that everything seems to need at one time or another. Different types of music would be scattered throughout the drawer on tapes and CD’s for the good times and the bad.   Ã‚  Ã‚  Ã‚  Ã‚  Often I sit in my room and look back at all the pictures of the interesting places I have been, the unusual sights I have seen and the people I meet doing it all. A picture I often look at is a picture of Time Square New York. This particular picture I took myself. I look at this for motivation, motivation that one day I will be in the city of opportunity. The picture I keep right beside my new York picture is an army photo. A photo of one of my buddies out in the field gun by his side. This picture gives me a completely different feeling. A feeling of appreciation for the solders that are fighting for our country at this point in time. Every parent or friend with a picture like mine I’m sure, knows the feeling of wondering will they be sent, or asks the question will they come back.   Ã‚  Ã‚  Ã‚  Ã‚  As the drawer slides more than half way open now the stacks of CD’s and tapes begin to come into view. The tapes mostly of childhood music that got lost or out grown. The lessons or sharing, and good attitude all waiting to be passed down to a cousin or niece in dire need. The CD’s in the drawer I am sure have been pulled out, and again returned depending on the mood, or the company. As for the artists of these CD’s, mostly String Cheese, a semi blue grass band with a song for every mood.   Ã‚  Ã‚  Ã‚  Ã‚  At the far back of my cluttered drawer there are several tools. The tools you would find in my drawer are common tools. The tools needed just for the basic workshop. Both kinds of screw drivers, Phillips head and a flat head. A hammer, and last but not least needle nose pliers. With this set of tools I feel I can fix, or â€Å"rig† almost anything I own to a certain extent. This set of tool would also cure the boredom of everyday life. Scratch up some nails and grab my trusty hammer with a cuple of planks of

Leadership Essay -- Leader essays research papers

Everyone has probably played the game â€Å"Follow the Leader† back in elementary school. It is a game where the leader stands in front of the line. He or she can say or do anything, and her followers (standing in a straight line behind her) must repeat exactly the same thing he or she does or says. Whoever was picked to be the leader must have loved the experience because one had the freedom to do whatever they please, while others followed miserably or happily depending on what the leader is saying or doing. However, if one was the follower, one would wait anxiously to be the next chosen leader. At the same time, one must somehow express his or her self in a fashion that will make them stand out from the rest of the students. Whether he or she is perfectly imitating the leader or behaving really respectfully of others. Nonetheless, who determines who should be the leader? What kind of characteristics must a leader possessed? What makes a great leader (Robbins, 2005)? Is the re only one kind leadership? These questions will be answered as you continue to read on. In addition, you will come across case studies, real life experiences, and my own observation on how leaders in my work setting exhibit leadership behavior and how followers respond to it.   Ã‚  Ã‚  Ã‚  Ã‚  Leadership is the capability to influence a person or a group to achieve many goals (Robbins, 2005). To elaborate, leadership is a complex process by which a person influences others to accomplish a mission, task, or objectives and directs the organization in a way that makes it more cohesive and coherent by applying their leadership attributes such as values, ethics, knowledge, skills, and belief (Clark, 2000). Most importantly, not all leaders happen to be managers, and not all managers are leaders (Robbins, 2005). Even though one is positioned as a manager or a supervisor (he has the power to accomplish certain tasks within the organization) it does not necessarily mean he is a leader unless he makes people want to achieve high goals and objectives. He has the authority to tell his subordinates to do the task and they will do it just to complete it but is not interested in achieving higher goals. However, â€Å"leaders can emerge from within a group as well as being formally appointed [manager]† (Robbins, 2005).   Ã‚  Ã‚  Ã‚  Ã‚  What is great leadership? According to the trait theories, some personality traits may lead pe... ... be technically proficient; one must know his job and the duties of his employees. A leader should always look for new ways to guild your organization to new heights. And if it does not work, re-evaluate, take corrective action and move on to the next challenge. However, do not look for someone to blame. A good leader is not an authoritarian leader. A good leader sets good examples (employees should also see and hear what they are expected to do) and work as a team. A good leader always look out for the well being of their people and always keep them informed. (Clark, 1999). Leadership is like an ART! REFERENCE Ballentine, k., George, A., and Hamburg, D. (1999). Preventing deadly conflict: the critical role of leadership. Archieves of General Psychiatry; 56, 971-976. Clark, D. (2000). Big dog’s leadership page-concept of leadership. Retrieved on December 02, 2004 from http://www.nwlink.com/~donclark/leader/leadcon.html. In Brief; do women make better leaders? (2004). Harvard Mental Health Letter, pNA. Pree, M.D (1992). Leadership jazz. New York: A Dell Trade Paperback. Robbins, S. (2005). Essentials of organizational behavior. New Jersey: Pearson Prentice Hall.

Anth Final

Veronica Kim Final Exam –Anth101 Kohistani Violence Thull, is an area where the violence of Kohistani was studied by R. Lincoln Keiser. In this region, the Kohistani, initially did not believe in bloodshed in order to solve conflicts. As elements in their traditional lives changed, Kohistani violence became more and more prevalent in their culture. Three specific changes were the main reasons for the growth in violence. One change led to another change, which then led to a third change. These changes to the traditional culture of the Kohistani were the reason for increased violence among the Kohistani in Thull.The Kohistani were originally pastoralists. Their subsistence methods consisted of a balance of farming and herding. The Kohistani of Thull had permanent residences in the river valleys throughout the seasons. Traditionally, women would continue to stay in these river valleys during the winter to farm, while the men moved to higher altitudes during the summer to find lan d for the animals. Eventually, men took over much of the subsistence efforts and took part in both farming and herding.The culture of herding meant that the Kohistani had to build relationships with other herders in order to maintain peace and decrease violence within groups. Thull is a region that was difficult to travel in and out of without developed roads. Once roads were constructed and transportation was introduced, the Kohistani were able to travel to other regions to trade. This change introduced the Kohistani to the market economy, which disturbed the balance of herding and farming. As they became less dependent on herding, they were able to use the land for more farming.Thus, cultivating potatoes became the main source of income for the Kohistani. The entrance into the market economy enabled the people of Thull to increase their wealth. Through the road systems and the increased inflow of cash, Kohistani were introduced to another cultural change. Initially, the Kohistani were not a group of people who resolved conflicts with bloodshed. In this culture, with a system of hierarchy, leaders were chosen to mediate when disputes arose. However, when the Kohistani entered the market economy through the development of roads, they were able to purchase firearms.In the past, they protected themselves against enemies with other weapons such as knives and spears. As a result, when conflicts surfaced, the men of Thull were required to come into close proximity to their enemies. This was not a reasonable form of conflict resolution for the people of Thull. Therefore, violence was not the primary means of resolving disagreements. Once firearms were introduced, there was a new form of protection for the Kohistani. There was no longer a reason for the Kohistani to resolve issues through negotiations.Instead, there was an increase in violence and blood feuding because they were able to fight and easily murder their enemies from afar. The construction of roads not on ly exposed the people of Thull to firearms and the market economy, but also to different influences and religions from other regions. One specific religion that influenced the Kohistani of Thull was fundamentalist Islam. The major beliefs of fundamentalist Islam were the protection of women’s purity and one’s honor. A man’s honor was directly related to a woman’s purity. For this reason, men of a family needed to protect the women in the family.A male member of the woman’s family avenged any type of insult or action that was believed to be a threat to that woman. For example, if it were perceived that someone had threatened a woman, that person would be killed. The family of the murdered victim would want revenge upon the murderer and more killings would occur. The idea of honor was so important to the Kohistani men, that they would act in any way to protect their honor. This influence of fundamental Islam, on the Kohistani, led to greater actions of violence within and between communities.Traditional Kohistani culture developed into what it is today through modernization. Change in one element of culture inflicted a transformation in traditional ways of conflict resolution. There is evidence of this integrated change in the culture of the Kohistani. Through the development of roads, the Kohistani adjusted their subsistence methods, how they resolved conflicts and influenced their beliefs. All of these shifts in culture eventually contributed to increased violence in the Kohistani communities of Thull.