The Corn Laws in 1846 Essay Example for Free

The maize rectitudes in 1846 EssayPeels close to repeal the Corn Laws in 1846 was arguably influenced by the mass campaigning and debate aroused by the Anti-Corn Law league, however, it must be considered that there were a number of other all-important(prenominal) factors that contributed to Peels choice. It can be argued that it was rather more down to Peels free trade and other economic principles that the Corn Laws were change surfacetually repealed in 1846.The Anti-Corn Law league was certainly a major force in the years leading to repeal. It was the first National repeal movement, setting it apart from the numerous other Anti-Corn Law associations that had existed in the past. This national concept ensured that the movement had a very large following and was very well funded. Unlike the Chartist movement, the League was decidedly middle-class and in this gained a greater respectability however, it still faced considerable suspicion from the Aristocracy.They were from t he start suspected of wanting to destroy the Aristocracy, and this limited their political jar. Modern historians thrust suggested that despite outwards appearances of respectability, it was in fact an instrument of class war The league was very well funded at just one meeting in October 1842, they raised over 50,000 and this funding enabled a huge campaign of leafleting and supporting candidates who were sympathetic to their aims at election. Despite this, evidence of their success is limited at their flower in 1843, they had only managed to get four MPs into commons. This suggests that their influence on Peels decision to repeal the Corn Laws was not very great.However, there was an economic symmetry to their campaign, and it is this intellectual argument that could be considered as influential in Peels decision to repeal the Corn Laws. Many members of the Anti Corn Law League were brawny supporters of the new-fangled economic principles like free trade, and had reasoned tha t the Corn Laws were responsible for their low profits. The Corn Laws meant that the price of bread was relatively high, as it taxed the staple ingredient, wheat. As bread was a key part of the diet of the time, the factory owners had to pay higher wages to cover workers food costs, which meant that they were unable to maximise their profitability.A foster effect of the high food prices was the lack of disposable income people had to spend such a high proportion of their wages on food that they could not afford much else, so there was very little demand for consumer goods. This coupled with the damage that protection did to Britains export market, meant that the economy was slow, and was not developing and expanding into new areas a worry for Peel, who placed the economy very high on his list of priorities. However, many historians are of the opinion that so compelling was this argument that as yet without the league, the Corn Laws were already threatened.However, Peel had other influences that could have played a part on his decision to repeal the Corn Laws. The potato famine in Ireland caused a problem for Peel. He already faced opposition from many religious groups over the immorality of keeping prices high they cited the phrase he that witholdeth corn, the people shall annoyance him from the bible to illustrate their argument. For the government to be seen to be so openly keeping the price high whilst its people were starving was embarrassing for the government. Although the famine would not be affected by the repeal, so cannot be considered the cause, Evans suggests that it provided the occasion for it.There is also the argument that Peel was simply being pragmatic in his decision to repeal the Corn Laws. Although Boyd Hilton suggests that Peel had decided that the Corn Laws had to be repealed as early as 1828, there is no direct evidence to suggest that level before 1844 Peel had made the decision to repeal the Law. In the election of 1841, over ha lf of Tory candidates put forward the maintenance of agricultural protection as the main issue in their manifestos, and, as Evans wrote, the 1841 election was properly a victory for Protectionist Toryism, not Peelite Conservatism.In 1842, Peels public position remained that he was improving the Corn Laws, and was not intending to repeal them. It was not until 1843 that Peel mentioned reports of removing agricultural protection to close colleagues. Even then, it can be seen merely as a response to the unholy economic recovery of Britain following the success 1842 budget, which lead many to believe that complete free trade was the way forward. Following the 1845 budget in which even more tariffs were reduced and eliminated, the Corn Laws increasingly stood out as an anomaly that was unjustifiable. Therefore, we can consider that it was not Peels free trade principles that lead him to his decision.The evidence suggests that although the Anti-Corn Law league was a formidable force in terms of its vast resources and stirring up of argument, it did not in fact have much impact on Peels decision. Peel was more concerned with the economy, and whether it is argued that he was committed to free trade early on or decided that it was a good idea after the experimental 1842 budget we can conclude that it was this preoccupation with the economy that was the main spark for Peels decision to repeal the Corn Laws. However, the issue of Ireland must also be considered, and although repeal would not have an effect on the situation there, it provided an occasion for Peel to complete the development of Britain into a free trading nation.

How To Make Macys More Competitive Business Essay

How To Make Macys More Competitive Business EssayA larger chunk of the total men is at Macys ar categorized as employees who are floor managers, supervisors, cashiers, handlers, and sales associates at Macys retail bloodlines. We piddle found that this form of employees have a really juicy turnover rate. There are several repercussions associated with a high turnover rate. If the turnover rate is high, the employees twist corrupt in their work duties which results in inadequate efficiency. Although, the high turnover is found amongst the lower level provide but still there is a humungous price associated with turnover. The equal to recruit, select, and train in the buff employees often exceed 100% of the annual salary of the position being filled (Allen, Bryant, Vardaman, 2010).Based on the exit interviews conducted by the management, it is found that most of the turnover is voluntary and controllable turnover. Voluntary turnover is when employees leave the company by t heir own choice whereas controllable turnover is when employees go down to leave for flat coats that are influenced by the employer. Therefore, it is evident that the high turnover rate has resulted due to lack of managerial effectiveness. Macys employs a diverse workforce of more than 167,000 employees beca drug abuse of which it is thorny to have a flat hierarchical structure. As a result the communication between lower level staff and high level staff is almost non-existent. Therefore, it is important for us to restructure the way we recruit our workforce especially for the positions that require managerial activities.The HR part along with the collaboration with the surgical incision of IT, Marketing, Finance, and Operations has realized that there is a need for an urgent strategy to shrink employee turnover because reducing this ratio is one of the ways to make Macys warlike again. The strategy depart be dual phased. The first phase of the strategy ordain focus on how t o effectively recruit individuals for managerial positions in the stores. For this pre-employment examination will be introduced in to the workplace which will test the managerial skills of the selected stooldidates for those positions. The first phase will too consist of conducting employee surveys every six months which will focus on employees feelings and attitudes nearly their descents and the organization. The second phase of the strategy will be the creation of a blog with collaboration with the IT department. The blog will accomplish a platform for the employees at all levels of management to communicate with each other and discuss their problems, job duties, problems at the workplace, and how they feel about the organization.The strategy to reduce turnover and increase Macys competiveness will be discussed further in detail in the Strategy Formulation and Strategy Implementation phase.Macys employee turnover rate is 3.726% compared to an diligence average of 3.1%. It is computed by dividing the upshot of employees in the beginning of the year (167,000) by the number of employees remaining at the end of the year (161,000). The resultant figure (1.03726) is then subtracted from one (0.03726) and multiplied by a hundred (3.726%) to determine the employee turnover in terms of percentage (Department of Labor, 2010).Although, the employee turnover rate is very close to the sedulousness average, a small difference in the percentages could translate into a signifi substructuret monetary amount. The cost of turnover is usually the cost to find, interview, train, and equip a new hire. Research shows that a minimum of $1,500 per employee is the cost of a turnover. While $1,500 may not be a huge amount of money for a store to cover that cost. Macys Inc. has a net profit margin of solo 1.49% which means that the company has to sell million dollars worth of items to cover that cost (Wolfe, 2010).Since most of the workforce at Macys comprises of lower mana gement staff such as floor managers, cashiers, supervisors, handlers, and sales associates, it is important to lower the employee turnover rate because otherwise the employees will become demoralized in their work duties which eventually results in decreased efficiency. In order to make Macys more competitive there are a number of strategies that need to be pursued specifically by the Human Resources department. The strategy consists of developing an internal blog for better communication, conducting exit interviews for valuable feedback, and hiring managers and supervisors effectively and efficiently.The reason to develop a blog is to give the lower management a platform where they can communicate freely with the upper management. This will not only result in increased communication between the two but also, a relationship between the two will be developed. In this blog, the employees will have liberty to write, comment, and share anything they would want coworkers and upper manage ment to consider. This could be complaints, recommendations, opinions, workplace ethics, job duties, or job descriptions.The reason to conduct exit interviews is to earlier get feedback from departing employees. Secondly, it gives the management an opportunity to retain the employee so as to overcome the cost of recruiting a new employee. The departing employees could be given a questionnaire which highlights job duties, management, job variety, work environment. This way the management can review the recommendation and opinion given by the departing employee and take necessary actions.Effectively recruiting managers and supervisors is also related to the high employee turnover rate. It is evident that the current managers were not effectively recruited because they lack the necessary knowledge, skills, and abilities to effectively manage and supervise a team of employees. During the hiring process, the HR department can develop a questionnaire which shall test the knowledge, skill s, and abilities of the candidates and determine if they have the key competencies to over achieve their job duties.In order to make Macys more competitive, the HR department has developed a three phased strategy. The first phase of the strategy deals with effective recruiting of managers and supervisors. This will require a development of new hiring techniques such as the use of latest technological instruments to filter the best candidates from job postings. Furthermore, online testing and questionnaires will be developed so as to test and hire the most fitted candidate.The second phase of the strategy deals with conducting exit interviews from the departing employees. This will require the HR representative to take notes while interviewing the departing employee because his/her comments, recommendations, and opinions will help in improving running(a) conditions and retaining employees. Sometimes, these interviews could save a company from being sued as some employees depart and later sue the company for reasons they were never aware of. The notes that the HR representative takes can become useful in the courtroom. Furthermore, in collaboration with the IT department, this phase will require a creation of a database to store and manage the feedback received from the questionnaires and interview.Phase three is the most important part of the strategy which is the creation of a blog which will be formed with collaboration from the IT department. The costs associated with creating the blog are negligible except the cost of time. Usually, the cost to create a blog is around $100 which includes a domain name, unlimited uploads and downloads, and unlimited backup of data uploaded on to secure servers.Effective recruiting, creation of a blog, and conducting exit interviews will serve as the basis to evaluate and control the high employee turnover. It can also be evaluated by checking the employee turnover rates at the end of first quarter of the year 2011. A low employee turnover would mean more cost savings from the HR department which could eventually be used to for higher profits and higher dividends to stockholders. Additionally, to evaluate the effectiveness of the strategy, the HR department will have to collaborate once again with the IT department to develop a database of the departing and departed employees. The reason for doing that would be, as these employees would be already trained and already knowledgeable about the company, it could help cut recruiting costs for the company.

Effect Of Arab Spring On Arab Countries

Effect Of Arab outpouring On Arab CountriesThe 18th and 19th century witnessed the colonisation of majority of Arab countries. The discovery of oil in Persia in 1908 subsequently in Saudi Arabia in 1938 has been one of the significant development in the Arab world. France, the United Kingdom, Spain and Italy. Though most of these states gained independence in the 1950s and 1960s, but the region has traditionally been characterized by dictators, hereditary monarchies, long serving military regimes and autocrats. These forms of rule deprived these countries from the winds of change .11. The Arab countries are mostly deprived of Human Rights,lack of freedom of public feeling and expression, fear of regimes, corruption, favouritism and nepotism. Transparency has receded giving way to all sorts of malpractices and misuse of tycoon. All this led to economic degradation and a fall in internal income in most of the Arab countries during the past 60 years.2 The main reasons for Arab Sprin g in mostly affected countries are as infra-(a) Tunisia. The revolution was sparked by a youth setting himself ablaze due to poverty and the resultant confrontation with security forces.(b) Egypt. The movement was a call for better economic conditions and antagonist to inheritance of power.(c) Libya It was against suppression and the rule of one man without any political institutions.(d) Yemen. it was against the dictatorship of one man and his tribe.(e) Syria. It was against family and sectarian dictatorship.3. Though this revolution was triggered by incompatible factors specific to their own unique socio-economic and political structures but they engage one unifying factor that they mystify been all youth-led movements.2. However the roots of the Arab Spring commit in the fol belittleding factors-(a) An entrenched dictatorship/autocracy/monarchy vs the peoples desire for freedom and body politic.(b) Widespread corruption on the part of the ruling elite.Frequent violation of homosexual rights and brutal repression by the national security force.The rich poor divide getting wider.High cost of living that was constantly on the rise and low income.Lack of adequate job opportunities and the high rate of unemployment among the educated youth.Rejection of the idea of the inheritance of presidency.Social network media namely, facebook and twitter ,which served to rally the youth.3. There has been a monarchal exception in the Arab Spring which makes one believe that monarchies could be more resilient during popular unrest. With the exception of Bahrain to an extent , separate monarchies were not seriously affected. Arab Spring has brought to fore the role of monarchy in regime stability also.2. The Arab Spring has altered the politics in the Arab world by bringing saucy political forces. The Islamists live with emerged as political parties in Egypt and Tunisia. It can concluded that Islamists have been the real gainers of the undergoing socio-political translation.Tunisia2. In Tunisia, the formulation of a new constitution is by now under way aft(prenominal) the termination of preference for the Constituent Assembly in October 2011. Tunisia also witnessed the arrival of the Islamists in the power struggle after decades of alienation by Ben Ali. Tunisia was the first rural to observe regime change when the Muslim An-Nahda party won the majority of votes. Hamadi Jebali, Secretary General of An-Nahda, is the new Prime Minister and the Islamic party is presently working in close alliance with Progressive Democratic Party. Though at present their roadmap is devoid of any Islamic rhetoric, it is concentrating more on the model of civic governance. The biggest challenge to Tunisian democracy is likely to be from the Salfists who represent the Islamic fundamentalists.Egypt2. The Freedom and Justice Party, a political encircle of Muslim Brotherhood ,has made a clean sweep in the Parliamentary elections,but the liberals failed to make a n impact in the first ever fair election. The going of the army from the helm of the affairs also brings to an end to the era of ruler-army nexus in Egypt. It is not only Muslim Brotherhood which gained ground, but there other Islamic hosts like the Salafists have also risen to a considerable position and are dominating national politics. So far, the Islamists have adopted the schema of adjustment . The surfacing of several(prenominal) liberal parties like Third Current, Free Egyptian Party, Egyptian Social Democratic Party and the Tagammu Party is a despotic sign and signals evolution of a multi-party system which had been absent for decades. Presently Mohamed Morsi has been elected as the new president in June 2012 but he has grabbed uncurbed power for himself , which has led to violent outburst from the masses in the country.Libya2. The departure of Colonel Gaddafi after the involvement of the NATO set the stage for democratic practice in the country. In July, 2012, the elect ion was held for the General National Congress, the first democratic election in Libya in half a century. In contrast to Egypt and Tunisia, in the Libyan election, liberal forces won the elections. The poor show of the Islamists may be accredited to the time-honored Sufi character of Libyan Islam and peoples non- proclivity to struggleds Islamic brand of politics. In addition, during Gaddafis regime, most of Islamist never surfaced and were aslo not organised like Muslim Brotherhood of Egypt or An-Nahda of Tunisia.3. The democratic process in Libya has been unsuccessful in bringing about the political solidity such as the one in Egypt or Tunisia. The country has turned out to be more delicate and vulnerable. It is also the tribal character of party in Libya that is causing disintegration and disorder of the social fabrics. Libyan society is now both horizontally and vertically disjointed and neo-tribalism has replaced the old national uniqueness and loyalty.Morocco3. Political co ncessions approved by King Mohammed VI led to referendum on constitutional reforms. In dissimilarity with protesters in other countries, the Moroccans who initiated the Feb 20 movement for transformation have not voiced for the kings overthrow. Instead, their focal point has been on significant constitutional reforms, which restricts the powers of the king and consolidates the theory of separation of powers. The demonstrations right through the country have been generally peaceful and free of violent expression.2. Similarly, in the recent elections too, the Islamist won the majority of seats and the King designated Abdelilah Benkirane, an Islamist figure, as Prime Minister. The delicate balance is to be seen between the monarchy and the new Islamists forces, and how they are adjusted in national politics. The King has by now initiated a major political reform capable of sanction of the people.Syria4. The Syrian National Council an opposition administration formed in exile has not been recognized by the Western Arab nations due to the councils internal divisions. Syria was expelled from the Arab League after it agreed to a peace plan only to step up attacks on protesters. In late 2011 and early 2012, Syria agreed to allow league observers into the country but their presence did nothing to slow the violence. In February 2012, the United Nations General Assembly voted overwhelmingly to approve a resolution condemning President Assads unbridled crackdown on the uprising, but China and Russia, Syrias traditional patrons, blocked all efforts for stronger Security Council action. Iran, Syrias closest ally in the region, also doubled down on its mount for Mr. Assad. The conflict is becoming more radicalized, homegrown Muslim jihadists, as well as small groups of fighters from Al Qaeda, have been taking a more spectacular role and demanding a say in running the resistance. Recent months have witnessed the emergence of larger, more organized and better armed Syrian militant organizations move an agenda based on jihad. As the conflict has continued without resolution, the Assad regime has lost many key players, as growing numbers of high-ranking government and military officials have defected. In early August 2012, President Assad fired his primal minister, RiyadFarid Hijab who defected to neighboring Jordan. Days after Mr Hijabs defection, Mr Assad appointed a new prime minister, Wael Nader al-Halqi.2. Except for Syria, nearly each country affected by the Arab Spring is steadily moving towards some sort of stability. The bloodiest upshot of the Arab Spring has been the incessant war in Syria. Syria is subject to Sunni-Alawite conflict but the Arab Spring has aggravated the crisis. The inveterate courtly war between Free Syrian Army, the main umbrella group for fighters the Syrian Army has resulted in the death of more than 30,000 people. By September 2012, 2,34,000 Syrian refugees had registered in neighboring countries about half of who m left during August.The end of continuing unrest is nowhere in sight1.The violent clashes between the regime and the rebels reflect the deep hatred between the Sunni majority and the ruling Alwite nonage. Syrian civil war has all the potential to become the scene of an international conflict. So far, no endeavor, including the U.N.-Arab League Mission led by Kofi Annan, could contain this strife. Even the new U.N.-Arab League envoy to Syria, Lakhdar Brahimi confessed that he was not certain that he would be able to end the conflict.Yemen5. President Saleh signed the GCC sponsored peace process on 23 Nov 11, in which he agreed to step down and set the stage for transfer of power to his vice president.A presidential election was held on 21 Feb 12 in which AbdRabbuh Mansur Al-Hadi (the only candidate) won 99.8% of vote. The new president has been mandated to lead a two year political transition process including a fully inclusive National Dialogue, constitutional electoral reforms en ding with full Presidential Parliamentary elections in 20142.In addition monetary assistance has been received from World Bank to mend the economic condition. The developments as of now put an end to more than 12 months of violence civil unrest across Yemen.2. After the Gulf Cooperation Council (GCC) mediated an understanding between the opposition groups and President Abdullah Saleh to leave the Presidentship, Yemen underwent the Presidential election in February 2012 and acting President Abd Rabbuh Mansur al-Hadi won 99.8% of vote and was was elected as the President. But the elections have failed to amalgamate a society that is divided by cultural and tribal loyalties. The Houthis, an insurgent Shiite group, boycotted the elections which reflects the political division in Yemen and leaves enough room for trouble in future. In addition new governance could not rein in the new resurgent groups operating in the name of north-south and sectarian entity.Bahrain5. Bahrains politica l order of affair has been unable to keep tempo with demands for representation for the majority Shia population and has almost responded to unrest with an iron fist3. King Hamad did attempt to provide some measuring stick of economic concession by giving out financial relief to each Bahraini family also initiated judicial, security economic measures. However as per acquittal report, these reforms appear to have scratched the surface as human rights crisis still continue4.During the unrest, the old sectarian fault lines between Shiites and Sunnis surfaced. To soothe anti-government protestors, the King dismissed several cabinet ministers and pardoned political prisoners, including the Shia opposition leader Hassan Mushaimaa, who had been in exile in Lebanon.2. The condition in Bahrain can be seen in similarity to that in Syria where minority Sunnis rule over majority Shiites. It was GCC under the direction of Saudi Arabia which suppressed the revolt in Bahrain. Besides, Bahrai n has also turned out to be a battle ground of power between Iran and Saudi Arabia..2. The situation at hand appears to be calm but one cannot rule out the likelihood of repeating in the near future because of the unpredictable nature of the region. Furthermore, Iran may endeavor to capitalise on the amplified sectarian tension.Jordan5. Subsequent to the initial protest the government retrousse the rise in fuel prices, but protestors still persisted with their demands for reforms. The King in an attempt to soothe the masses have dismissed three prime ministers from the time when the of Arab Spring started, finally paving way for Fayez al- Tarawneh to head the cabinet to deliver reform agenda5. Frequent and small scale protests and turmoil still continues in Jordan to keep the system off balance.Saudi Arabia5. Saudi Arabia is also transiting through low level sectarian conflict. The Shiite minority in the eastern part is do recurrent protests seeking rights and freedom. The king d olled out economic concessions in the form of US $ 130 billion. Subsequently Municipal elections were held in Sep 2011. Reforms were also initiated for womens alliance in municipal election in 2015 and for their nomination to informative Assembly.Oman6. Political reforms were announced in reaction to the spate of protests. The most noteworthy reforms include the granting of Consultative Council (Majilis) of Oman ample legislative and audit powers6. Sultan Qaboos reorganized the Council of Ministers and replaced three top administration officials. A new body was also shaped to manage the countrys providence while Sultan Qaboos promised extra 50,000 jobs7. The generally affirmative Omani views of Sultan Qaboos, attached with the economic and supplementary political reform measures caused the unrest to subside.Kuwait5. As a consequence of the protests that demanded political transparency and a clamp down on corruption within the government, the Prime Minister Sheikh Nasser Al Mohamm ed Al-Ahmed Al-Sabah, resigned on 29 Nov 2011. The government used financial generosity like budgets laden with subsidies and salary increases as well as used oppressive measures in wrong of imprisonment which kept the public display of dissent relatively restricted. As Kuwait is a relatively wealthy society where it appears that most citizens do not want to risk their economic wellbeing to bring the downfall of Al Sabah rule8.2. From the events as it unfolds in Arab world ,it can be generalized that the historical phenomenon of Arab Spring reflects the following which has wide implications for non- Arab countries also -(a) The deep structural malisie of Arab society in general.(b) The democratic aspiration of the marginalised section of Arab society, particularly the youth, for a dignified livelihood, a kind of social, economic and political reform that ensures respect for individual identity, dignity and social equity.(c) The inspiration for this movement is deeply Arab-Islamic, rather than tradition of western democracy and therefore eventhough the movement aspires for democratic space but it does not necessarity imagine this democractic space in terms of western democratic values and principles.(d) It is the rainbow of multiple ideological currents vis islamism, nationalism, tribalism, sectarism and localism with each competing with each other for representation in future power-arrangement but also uniting for loosely defined national purpose against extraneous challanges.(e) The movement is likely to have long term implication for the stability and security of the region.(f) The relatively peaceful, leaderless, unorganised but having mass element only reienforces the purpose that people remains the motor of wider social and political changes and in the process totally delegitimise the violence-prone politics and discourses of radical/militant Islamic organisations in the name of Moslem transformation of Muslim societies.

Ebola Virus Mechanism of Infection

Ebola Virus Mechanism of InfectionThe Ebola virus (EBOV) is an enveloped, non-segmented, negative- mountain range RNA virus, whichtogether with Marburg virus, makes up the filoviridae family. The virus causes severehemorrhagic fever associated with 50-90% human mortality1. Four species of the virus (Zaire,Sudan, Cte dIvoire, and Reston ebolavirus) cod thus far been place, with Zaire typic whollyyassociated with the highest human lethality2. A fifth part EBOV species is confirmed in a 2007 forbiddenbreak in Bundibugyo, Uganda3,4. Infection with EBOV results in uncontrolled viralreplication and multiple organ failure with death occurring 6-9 old age after onset ofsymptoms5. Fatal cases are associated with high viremia and defective insubordinate responses,while survival is associated with early and vigorous humoral and cellular immuneresponses6-9. Although preliminary vaccine trials in primates have been highlysuccessful10-13, no vaccines, specific immunotherapeutics, or post-exposu re treatments arecurrently approved for human use. Since 1994, EBOV outbreaks have change magnitude more than quaternion-fold, thus necessitating the urgent development of vaccines and therapeutics for use in theevent of an intentional, accidental or natural EBOV release.The EBOV genome contains seven genes, which direct the synthesis of eight proteins.Transcriptional modify of the fourth gene (GP) results in expression of a 676-residue transmembrane- think glycoprotein termed GP, as well as a 364-residue secreted glycoproteintermed 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 GP2subunits17. GP1 effects supplement to host cells, while GP2 mediates fusion of viral and hostmembranes16,18-20. EBOV is thought to enter host cells through receptor-mediatedendocytosis via clathrin-coated pits and caveolae21, followed by actin and microtubuledependent convey to the endo some21, where GP is further processed by endosomalcathepsins22-24. Essential cellular receptor(s) have not yet been identified, but DC-SIGN/LSIGN25,hMGL26, -integrins27, folate receptor-28 and Tyro3 family receptors29 have allbeen involve as cellular factors in entry. Here, we report the crystal structure of EBOV GP,at 3.4 resolution, in its trimeric, pre-fusion conformation in complex with neutralizingantibody Fab KZ52. GP1 is responsible for cell rebel attachment, which is probably mediated by a regionincluding residues 54-20132. GP1 is composed of a single farming (65 30 30 ),arranged in the topology shown in Fig. 2a, and can be further subdivided into the (I) pedestal, (II)head and (III) glycan cap regions (Fig. 2a and Supplemental Fig. S3). The imbruted (I) subdomainis composed of two sets of sheets, forming a semi-circular fold up which clamps the internalfusion kink and a helix of GP2 through hydrophobic interactions (Fig. 2b). Moreover, thissubdomain contains Cy s53, which is proposed to form an intermolecular disulfide bridge toCys609 of the GP2 subunit17. Cys53 resides near GP2 in the 2-3 loop at the viral membraneproximalend of the miserly subdomain (Fig. 2a-b). Our EBOV GP contains an intact GP1-GP2disulfide bridge, based on reducing and non-reducing SDS-PAGE analysis. However, the region containing the counterpart GP2 cysteine is disordered, which may reflect functionallyimportant mobility in the region. The head (II) is located between the base and glycan capregions towards the host membrane surface. Two intramolecular disulfide bonds stabilize thehead subdomain and confirm the biochemically determined disulfide bridge assignments17.Cys108-Cys135 connects a surface- unfastened loop (8-9 loop) to strand 7, while Cys121-Cys147 bridges the 8-9 and 9-10 loops (Fig. 2a). The glycan cap (III) contains fourpredicted N-linked glycans (at N228, N238, N257 and N268) in an / dome over the GP1head subdomain (Fig. 1b and 2a). This subdomain does not form any monomer-monomercontacts and is fully exposed on the upper and outer surface of the chalice. The central sheetsfrom the head and glycan cap together form a fairly flat surface and, in the scope of the GPtrimer, form the three inner sides of the chalice field.Ebola virus GP2GP2 is responsible for fusion of viral and host cell membranes and contains the internal fusionloop and the seven repeat regions, HR1 and HR2. Many viral glycoproteins have fusionpeptides, located at the N terminus of their fusion subunit, which are released upon cleavageof the precursor glycoprotein. By contrast, pattern II and class III fusion proteins, as well as classI glycoproteins from Ebola, Marburg, Lassa and avian sarcoma leukosis viruses, containinternal fusion loops deficient a free N terminus. The crystal structure reveals that the EBOVGP internal fusion loop, which encompasses residues 511-556, utilizes an antiparallel stranded scaffold to display a partially turbinate hydrophobic f usion peptide (L529, W531, I532,P533, Y534 and F535) (Fig. 2c). The side chains of these hydrophobic residues pack into aregion on the GP1 head of a neighboring subunit in the trimer, resonating of the fusion peptidepacking in the pre-fusion parainfluenza virus 5 F structure33. A disulfide bond between Cys511at the base of 19 and Cys556 in the HR1 helix covalently link the antiparallel sheet. Thisdisulfide 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 sarcomaleukosis virus34,35. Interestingly, the EBOV internal fusion loop has features more similar tothose 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 thatregardless of viral protein class, internal fusion loops share a common architecture for theirfusion function.EBOV GP2 con tains two heptad repeat regions (HR1 and HR2), connected by a 25-residuelinker containing a CX6CC motif and the internal fusion loop. The crystal structures of postfusionGP2 dispels30,31 have revealed that the two heptad repeat regions form antiparallel helices and that a CX6CC motif forms an intrasubunit disulfide bond between Cys601 andCys608 (Supplemental Fig. S5). In the pre-fusion EBOV GP, HR2 and the CX6CC motif aredisordered. By contrast, the HR1 region is well ordered and can be divided into four segmentsHR1A, HR1B, HR1C and HR1D (Fig. 2c), which together assemble the cradle encircling GP1.Similarly, heptad repeat regions in influenza and parainfluenza viruses also contain multiplesegments in their pre-fusion helices that substantially rearrange in their post-fusionconformations33,36,37.The first two segments, HR1A and HR1B (residues 554-575), together form an helix with an40 kink at T565, which delineates HR1A from HR1B. Interestingly, the bend betweenHR1A and HR1B conta ins an unusual 3-4-4-3 stutter, which may act as a conformationalswitch31, rather than the typical 3-4 periodicity of heptad repeats (Supplemental Fig. S6). Asimilar stutter has also been noted in parainfluenza virus 5 F33. The Ebola virus HR1C (residues576-582) forms an extended lock linking HR1B to the 14-residue helix of HR1D (residues583-598). HR1D forms an amphipathic helix and the hydrophobic faces of each HR1D join toform a three-helix bundle at the trimer interface. Although the breakpoint maps directly to aLee et al. Page 3Nature. causality manuscript available in PMC 2009 June 22.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscriptchloride ion binding site in the post-fusion conformation of GP230,31 and at least two otherviruses38,39, no chloride ion is observed here as HR1 and HR2 do not come together to formthe six-helix bundle. Instead, the pre-fusion GP2 adopts a novel conformation, intimately curling around GP1 (Fig. 1c).Ebola virus GP-KZ52 int erfaceKZ52 is an antibody isolated from a human survivor of a 1995 outbreak in Kikwit, DemocraticRepublic of the Congo (formerly Zaire)40. This antibody neutralizes Zaire ebolavirus invitro40 and offers protection from lethal EBOV challenge in rodent sit downs41, but has minimaleffects 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 discontinuoussegments of EBOV GP residues 42-43 at the N terminus of GP1, and 505-514 and 549-556at the N terminus of GP2 (Fig. 3 and Supplemental Fig. S7). Although the majority of the GPsurface buried by KZ52 belongs to GP2, the presence of some(prenominal) GP1 and GP2 are critical forKZ52 recognition43. It is likely that GP1 is needed to maintain the proper pre-fusionconformation of GP2 for KZ52 binding. Indeed, KZ52 is the only antibody known to bridgeboth attachment (GP1) and fusion (GP2) subunits of any viral glycoprotein. dispos ed(p) that KZ52requires a conformational epitope seen only in the GP2 pre-fusion conformation and that theKZ52 epitope is distant from the putative(prenominal) receptor-binding site (RBS), KZ52 likely neutralizesby preventing rearrangement of the GP2 HR1A/HR1B segments and pulley host membraneinsertion of the internal fusion loop. Alternatively, IgG KZ52 may sterically hinder access tothe RBS or to a separate binding site of another(prenominal) cellular factor, especially if multiple attachmentevents are required for entry.The KZ52 epitope of GP is convex and does not have a high shape complementarity to theantibody (Sc index of 0.63), although 1600 2 of each GP monomer are occluded upon KZ52binding. The antibody contacts a total of 15 GP residues by van der Waals interactions and 8direct hydrogen bonds (Supplemental Fig. S7). Ten out of 15 residues in the structurally definedKZ52 epitope are unique to Zaire ebolavirus (Supplemental Fig. S6), thus explaining the Zairespecificity of KZ52.Ebola virus GP glycosylationWe generated a fully glycosylated molecular model of EBOV GP to illustrate the native GPtrimer as it exists on the viral surface (Fig. 4). The majority of N-linked glycosylation sites areconcentrated in the mucin-like domain and glycan cap of GP1. Given that the mucin-likedomain is 75 kDa in mass (protein and oligosaccharide), the volume of this domain ispredicted to be similar to each GP monomer observed here. The crystal structure suggests thatthe mucin-like domain is linked to the side of each monomer and may further build up the wallsof the chalice, forming a deeper bowl (Fig. 4). Although a mixture of complex, oligomannoseand hybrid-type glycans are found on intact, mucin-containing GP144, those glycans outsidethe mucin-like domain are likely to be complex in nature the mucin-deleted GP used forcrystallization is sensitive to PNGaseF, but not to EndoH treatment (Supplemental Fig. S8).Modeling of complex-type oligosaccharides on the EBOV GP indi cates that the majority ofthe GP trimer is cloaked by a thick layer of oligosaccharide, even without the mucin-likedomain (Fig. 4). The 19 additional oligosaccharides on the full-length GP (17 on the mucinlikedomain and 2 more on GP1, disordered here) further conceal the sides and top of thechalice. The KZ52 binding site and, presumably, the flexible regions of HR2 and themembrane-proximal external region (MPER) go along exposed and perhaps vulnerable tobinding of antibodies and inhibitors.Lee The development of neutralizing antibodies is limited in natural Ebola virus infection. Manysurvivors have low or unimportant titres1,7, and those antibodies that are elicited preferentiallyrecognize a secreted version of the viral glycoprotein that features an alternate quaternarystructure and lacks the mucin-like domain43. The glycocalyx surrounding EBOV GP likelyforms a harbour 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 tothe viral attachment and fusion subunits, reminiscent of the glycan shields of HIV-1gp12045,46 and Epstein-Barr virus gp35047, perhaps pointing to a common theme for immuneevasion. Alignment of filoviral sequences indicate that regions involved in immune evasionhave a low degree of sequence conservation i.e. GP1 glycan cap (5%) and mucin-like domain(0%), but the N-glycosylation sites in the glycan cap are mostly conserved among all EBOVsubtypes (Supplemental Fig. S6), indicating the functional importance of these posttranslationalmodifications.Sites of receptor binding and cathepsin cleavageAlthough a definitive receptor for EBOV remains to be identified, previous studies32,48,49have 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. Additionalexperimental studies have identified at least 19 GP1 residues, depute into fo ur groups basedon the location in the structure, that are critical for viral entry48-50 (Fig. 5). Many of theseresidues are apolar or aromatic and are involved in maintaining the structural integrity of GP1for receptor binding or fusion. However, six residues (K114, K115, K140, G143, P146 andC147) cluster within a 20 15 surface in the inner bowl of the chalice and may thusrepresent important receptor contact sites. All residues in the putative RBS are highly conservedamong Ebola virus species (Supplemental Fig. S6).Importantly, this putative RBS is recessed beneath the glycan cap and perhaps further maskedby 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 cofactorbinding. It has been demonstrated that endosomal proteolysis of EBOV GP by cathepsin Land/or B charters the mucin-like domain to produce a stable 18 kDa GP1 intermediate whichhas enhance viral bin ding and infectivity22-24. The precise site of cathepsin cleavage isunknown and the role of cathepsins in natural infection is as yet unclear. However, formationof an 18 kDa GP1 fragment implies that cathepsin may cleave near the GP1 13-14 loop(residues 190-213). Indeed, this loop is unresolved in the pre-fusion structure, suggestingenhanced mobility and accessibility to enzymatic cleavage. Cleavage within this loop wouldremove the entire mucin-like domain and glycan cap region (Fig. 5). As a result, 7 to 9strands and their associated loops would become exposed. These regions of GP are in proximityto the previously identified residues critical for viral entry. The fold, location andphysicochemical properties of this site should now provide new leads in the search for theelusive filoviral receptor(s).A summary of the Ebola virus mechanics of infection, including the events of cathepsincleavage and conformational changes to GP2 during fusion, is presented.

Caring for Older People Essay -- Health Care, Diseases, Dementia

Caring for older people highlights many special and difficult issues for nurses and carers, much(prenominal) as separation, illness, loneliness, death and how to provide continued care (Morrissey et al, 1997). This essay discusses the strategies of care delivered for an older person with dementia during my recent clinical placement. Discussions will focus on normal ageing process taking into account the relevant biological, sociological and physiological perspectives and the impact this had on this individuals life experience. Ropers model is utilise as a frame work in which cae is delivered. Other related issues to be considered include the role of informal carers and the impact this had on him. Confidentiality is maintained in conjunction with NMC 2010 code of conduct. Thus a pseudonym (Scot) is adopted where the clients name is mentioned.Scot is a 70 year old man with a long term history of psychosis. Recently he had been diagnosed with dementia. He had been well managed on quia tiapin until he had stopped taking the medication and his psychosis had worsened. And due to his decline in his mental state, he has also been refusing access to his carer (his wife) and was at risk of self neglect.Dementia is a disorder manifested by multiple cognitive defects, such as impaired memory, aphasia, apraxia and a disturbance in occupational or social functioning, Howcroft (2004). Disturbances in executive functioning are also seen in the loss of the readiness to think abstractly, having difficulty performing tasks and the avoidance of situations, which involves processing information. Scot suffers from Alzheimers disease, a type of dementia, which affects the brain cells and brain nerve transmitters, which carry instructions around the brain. The b... ...is terminus and how she can reduce the feelings of anxiety, tension and loss of control that has resulted from the impact of Scots deterioration.By the end of my placement, evaluations showed that although there hav e not been significant changes in Scots mental and physical state, it is also imperative to note that he has been supported and maintained well to carry some of the daily activities of living. Whilst Scots care programme continued to be reviewed, there is also an ongoing support and educational programmes for his wife, which will enable her to effectively care for Scot. Having gained experience working with older people, I have understood that whenever you care for a person especially the older person, one must take a holistic view of the persons physiological and psychological and social circumstance in order to provide effective and continuous care.

Comparing Beowulf and Gilgamesh :: comparison compare contrast essays

A Comparison of Beowulf and Gilgamesh There are many differences and slender comparisons that can be drawn between the epics of Beowulf and Gilgamesh. Both are historical poems which shape their respected culture and both have major social, cultural, and political impacts on the development of western civilization literature and writing. Before any analysis is made, it is vital that some kind of a foundation be established so that a further, in-depth exploration of the complex nature of both narratives can be accomplished. The epic of Gilgamesh is an important Middle Eastern literary work, written in cuneiform on 12 clay tablets about 2000 BC. This heroic poem is named for its hero, Gilgamesh, a tyrannical Babylonian king who ruled the city of Uruk, known in the tidings as Erech (now Warka, Iraq). According to the myth, the gods respond to the prayers of the oppressed citizenry of Uruk and send a wild, brutish man, Enkidu, to challenge Gilgamesh to a wrestling match. When the contest ends with neither as a clear victor, Gilgamesh and Enkidu become close friends. They journey together and share many adventures. Accounts of their heroism and bravery in slaying dangerous beasts spread to many lands. When the devil travelers return to Uruk, Ishtar (guardian deity of the city) proclaims her love for the heroic Gilgamesh. When he rejects her, she sends the Bull of Heaven to destroy the city. Gilgamesh and Enkidu kill the bull, and, as punishment for his participation, the gods doom Enkidu to die. After Enkidus death, Gilgamesh seeks out the pert man Utnapishtim to learn the secret of immortality. The sage recounts to Gilgamesh a story of a great flood (the details of which are so remarkably similar to later biblical visors of the flood that scholars have taken great interest in this story). After much hesitation, Utnapishtim reveals to Gilgamesh that a plant bestowing eternal youth is in the sea. Gilgamesh dives into the pissing and finds the plant but later loses it to a serpent and, disconsolate, returns to Uruk to end his days. This saga was widely studied and translated in ancient times. Biblical writers appear to have modeled their account of the friendship of David and

What it Means to be an Athlete :: Sports Swimming Teamwork Essays

What it Means to be an AthleteA group of high school girls who engage all joined a caboodle team for various reasons. Some are athletes, some want scholarships, some are the right body types, some have never been athletes, some have friends on the team, and some are being made to by their parents. The team is small and no cut and always in need of more rowers. As they row they come together as a team, they all gain in confidence and learn what it is to be an athlete both on and off-key the water. The pro iotaonists are a novice four, that means five girls who have never competed in crew before racing a boat with four rowers and a coxswain (cox for short). The coxswain is normally small, in High School womens rowing they try to get as close to 110 pounds as possible, who yells out commands, steers the boat, and encourages her rowers. She is the alone one facing forward and is generally sitting in the back of the boat. The four rowers in a four face backwards. The stroke is the row er close set(predicate) to the cox and faces her. Behind the stroke are 3 and 2 and bow is in the front or bow. Although the novice four is not the entire team, the boats use in shifts so they codt spend much time with the rest of the team. The five girls are all there for different reasons. The cox, Hannah, is actually the only one who had been multiform in sports before, but she is the smallest, loudest, and most of a leader. Stroke is Amanda, who is tall and has the ideal build for crewing and decided to start in hopes of getting a scholarship when she goes to college. Lauren, the trio seats, is being forced to enter in a sport by her mother and heard that you wouldnt have to run for crew. Diana, two seats, is Amandas best friend, and decided to tag along, and Jessie who thought shed join for kicks is bow. Once they are set into boats, they have their first water practice as a team. Their coach, Molly, grew up having to fight for the right to participate in a sport other th an cheerleading or dance, and feels that the girls have to live up to her legacy. They should be proud and see themselves exclusively as athletes, especially when they don their uniforms.