Cell-Permeable Stapled Peptides from HIV1 Gene Products

Cell-Permeable Stapled Peptides from HIV1 Gene Products Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products Introduction HIV-1 Integrase (IN), is necessary enzyme for the replication of the virus into the host cells. It catalyzes the integration of viral DNA into the genome of host cells. The mechanisms employed by the enzyme are strand transfer and 3†²-end processing reactions. The enzyme is vital for the virus life cycle and as a result it is a target for anti-HIV-1 drugs. It is reported from previous studies that HIV-1 protein Vpr has inhibitory effect on Integrase activity. The inhibition is a result of protein-protein interactions. Specifically Vpr interacts through its C- terminal domain. Results from previous studies indicate that the active petptide inhibition motif is peptide 1 (Figure 1). Figure 1. Amino acid sequences of peptides 1 and 2, and outline of the study. Regarding the SAR studies, E-K pairs were introduced in i and i + 4 positions to increase the helicity, by forming salt bridges. In the same study to peptide 1 was added an octa-arginine tail, the purpose of which was to improve, cell permeability. The presence of the octa-arginine tail however resulted in increase of cytotoxicity of the peptide. The hypothesis on which the current study was based is that by finding a different way to improve cell permeability without the 8-R tail the cytotoxicity of the peptide would decrease. The idea was to make the peptide more lipophilic, by adding hydrophobic groups on the external of the a-helix, and at the same time improve its helicity. An available method to achieve that is the use of a-helix stabilized peptidomimetics. Specifically, hydrocarbon stapled peptides, in which a hydrocarbon link is formed between successive turns, via a ring closed metathesis (RCM) reaction, were used. By having a hydrocarbon linkage between positions i and i+4 in the a-helix, the helicity is improved because the two positions are covalently bound via the hydrocarbon chain, and simultaneously the lipophilicity and cell permeability of the peptide is increased because of the presence of a hydrophobic hydrocarbon chain on the external part of the a helical structure. In Figure 1 is presented an outline of the study. Design and synthesis of the peptides The lead peptide sequence used was sequence 1 (Fig.1). From previous studies it was known that residues: Phe12, Ile13, Phe15, and Ile17 are vital for IN inhibition activity. Stapling was performed between i and i+4 positions by avoiding substitution of these residues. Protected linear peptides were constructed by Fmoc-solid phase peptide synthesis. The RCM reactions of the protected linear peptides were performed on the resin by treatment with ruthenium-mediated Grubbs second catalyst in 1,2-dichloroethane. All hydrocarbon and all ether stapling was performed, however the first technique resulted in higher yields as it’s presented in Table 1. After RCM, the peptides were deprotected, acetylated, and cleaved from the resin. Purification of the stapled peptides was done by HPLC. However it is not the purpose of this paper to present experimental details. Table 1. Sequences of Designed Stapled Peptides and Their Conversion Yields of RCM Reactions CD Spectroscopy of Linear and Stapled Peptides. CD Spectroscopy was used to analyze the secondary structures of the synthetic stapled peptides, 3S−9S and 11S. Linear peptides, 4L−6L, 8L, 9L, and 11L, were used as control (Figure 3). Negative peaks at 208 and 222 nm, are characteristic for ÃŽ ±-helical structures. All stapled peptides, except 3S, formed ÃŽ ±-helices. The corresponding linear peptides on the other hand including compound 1 showed a broad negative peak around 215 nm, which indicates a ÃŽ ²-sheet structure. It is obvious that stapling of the linear peptides leads to the formation of ÃŽ ±-helices. Figure 3. CD Spectra of stapled peptides (left) and corresponding linear (right). Integrase (IN) Inhibition Assays and MT-4 Luc Assays (anti HIV). The next step was to determine the potency of the synthesized peptides using integrase inhibition assays. IC50 values were determined for stapled and linear compounds regarding both 3-end processing and strand transferring reactions (Figure 4 Left). Anti HIV activity was also screened for all peptides using MT-4 Luc Assays (Figure 4 Right). Figure 4. IC50 Values (Left). MT-4 Luc Assay (Right) All compounds had integrase inhibition activity, however lead compound 2 was way more potent. Regarding the MT-4 Luc assays compound 6S showed similar anti HIV activity as lead compound 2 at concentrations higher than 2.5 um. Compound 8S also showed significant activity at concentrations higher than 5 um. 6S and 2 have almost the same level of anti-HIV activity in cells, however 2 has much higher IN inhibitory activity in vitro than compound 6S. Imaging Experiments Stapled and linear peptides were labeled with fluorescein and imaging experiments were performed to examine their cell permeability. The stapled peptides 6S and 8S demonstrated improved cell permeability compared to the lead compound and the linear peptides. Octaarginine tail functional role investigation. The next step was to study the functional role of the (Arg) 8 tail, besides influencing cell permeability. By using 6S and 6L as lead compounds, a new set of peptides was synthesized (Figure 5). Specifically conjugates of 6S with octaarginine (17) and with the quartet repeat of arginine and glutamic acid (18). For 6L, with the quartet repeat of arginine and glutamic acid (19), and the conjugates of 6S with tetra-arginine (20), penta-arginine (21), hexa-arginine (22), and hepta-arginine (23). IC50 values were determined for the new set of peptides and also MT-4 Luc assays were performed. The presence of the octaarginine tail is necessary for the inhibitory activity however it still makes the peptides cytotoxic. Different lengths in the Arg tail were also examined. Still the octaarginine (17) conjugated peptide is the most potent but compounds 22 and 23 had good potency and lower cytotoxicity than 17, so those compounds were selected as lead compounds for further development. DNA binding experiments were also performed to examine the role of Arg8 tail, and the results indicate that 17 has high DNA binding affinity and that might influence the high inhibition activity of the peptide. Conclusions and Critical Review Stapling caused a significant increase in ÃŽ ±-helicity and cell membrane penetration, and in the expression of potent anti-HIV activity in cells. Stapling and the addition of octa-arginine caused cell membrane penetration. Stapling by itself did not involve cytotoxicity while incorporation of octa-arginine into the structures increased the cytotoxicity of the compounds. Generally it was a well-organized paper. It had good flow of information and background information was provided. The hypotheses were not stated but were easy to understand. The experiments and the data supported the conclusions and the concepts. The figures and the graphs were interpretable and accurate in supporting the conclusions related to them. However there are several interesting points to be addressed. The first point is the configuration of the new double bond formed. It would be interesting to see if the configuration of the double bond would affect the secondary structure and the helicity of the peptides. Another question that need to be addressed is why the stapled peptide 3S did fold into b sheet structure unlike the other stapled peptides which formed a helices. It would be interesting to examine the role of the substituted amino acids of 3S, in the folding of the peptide. Regarding the role of the octaarginine tail, the DNA binding experiments indicate that the octaarginine conjugated peptide has affinity for DNA binding. However it is unclear how exactly the tail affects the potency and the cytotoxicity. Further experiments are necessary to clarify that. I would suggest some NMR experiments to investigate the binding. First 1H-15N HSQC may be performed to the (Arg)8 fused peptide before and after binding with DNA. That would show which residues are involved in binding and would give data to determine the specific interaction. References: Nomura, Wataru, et al. Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products. ACS chemical biology 8.10 (2013): 2235-2244.

Case Study Russell Hobbs Marketing Essay

Case Study Russell Hobbs Marketing Essay Now a day in this business word everyone wants to be a global company. To expend the business in a new area this module (International marketing strategy) help us to make a clear view how to enter a new market and what criteria have to follow to be successful in international market. By following these organizations can achieve the position within a short possible time. It may be valuable for the organization and also easier for them to understand the facts what they are doing, what they need to do. So they need to develop a strategy what tell them how they can enter in a new market and what the need to change or develop to be successful in foreign market. Because of the competitive business world and economic developments organizations always try to capture the market. And they always look for a new place to do business that increase their business profit. In here I am going to examine the new market environment, market mix strategy and strategy for entering in a new market for Russell Hobbs. This module will help a lot to examine the new market environment, mix strategy and how to enter in a new market. About Russell Hobbs: Russell Hobbs ltd is a UK based private company established in 1952 by Bill Russell and Peter Hobbs. In 1952, they designed the worlds first automatic coffee percolator, the CP1.(  About us  Official Russell Hobbs website) Russell Hobbs has been tantamount with quality, style and innovation for the kitchen and home for over fifty years. The brand led the way by introducing products which offer real consumer reimbursement and technological advancements to make life in the home easier and more enjoyable.   Throughout the decades, in kettles and toasters manufacturing they took the No 1 place, and today they admitted themselves as a leading brand in this area. With this superior track record and legacy, they have since become a leading brand in  irons, food preparation and now floor care. And they extend their business in other markets, such as heating, cookware and bake ware. (http://www.russellhobbs.co.uk/about/#1) Today Russell Hobbs boasts an extraordinary product portfolio and is continuing to develop into new categories. From kettles  and toasters to cooking, cleaning and garment care, each and every product is intended with the consumer in mind to offer the decisive in performance, practicality, ease of use and style.( http://www.russellhobbs.co.uk/about/#1) The name of Russell Hobbs recognised as a leading small kitchen appliance brand in the UK by nine out of ten consumers and has won many awards and product accreditations by leading institutes and organisations. From day one the company was always in profit. It because of the understanding capability of customer needs and demand. And also the new product innovation through introducing new technology their products are always successful in the market. From last 50 years they are the leading kettle maker in Great Britain. And from the foundation of their business they always try to make product which is easy to use and more appealing to their customers. Selection of international market: Selection of foreign market is one of the basic and important factors to launch a product for any company, so the choice of mode of entering in a foreign market is another major issue by which now a days international businesses must tussle. To select an international market company have to understand the business environment of that country it will help them to be successful in foreign market. As per my interest I am going to choose Bangladesh as a foreign market and UK based company Russell Hobbs ltd. is the host country. I am going to choose Kettle one of the best product of Russell Hobbs ltd. So, to do business in Bangladesh its market environment is more feasible. To justify this comment, I am going to use an analytical process that called PESTLE analysis. It will give us a clear idea that the environment of Bangladesh is feasible or not to do business for Russell Hobbs ltd. PESTLE analysis: PESTLE ECONOMICAL SOCIOLOAGICAL TECHNOLOGICAL LEGAL POLITICAL ENVIRONMENTAL A PESTLE analysis is a useful tool for understanding the big picture of the environment in which an organisation is operating. Specifically for understanding risks associated with market (the need for a product or service) growth or decline PESTLE analysis is useful tool, and as such the position, potential and direction for an individual business or organisation.   Political: Bangladesh is a  unitary state  and  governmental democracy. (Constitution of Bangladesh. Parliament.gov.bd. Retrieved 2010-11-28.) In here direct elections took place every five years for the  unicameral  parliament known as  Jatiya Sangsad. Aged 18 or over, can vote to choose a democracies government. The President is the head of state but mainly a ceremonial post elected by the parliament. There are two  major parties  in Bangladesh. They are the  Bangladesh Awami League  and the  Bangladesh Nationalist Party  (BNP). Student politics is particularly strong in Bangladesh, a bequest from the liberation movement period. Almost all parties have exceedingly active student wings, and student leaders have been elected to the Parliament. In the last few years has been consistently good. Bangladesh has most astutely and foresightedly chosen to set up itself as a secular democracy.( BY- Ishtiaq Ahmed, http://www.defence.pk/forums/bangladesh-defence/71487-view-political-economy-bangladesh-ishtiaq-ahmed.html) Economical: Since her independence in 1971, Bangladesh has made significant strides in her economic sector. Although the economy has improved vastly in the 1990s, in the area of foreign trade in South Asian region Bangladesh still suffers a lot. Bangladesh has made some development improving the climate for foreign investors and liberalizing the capital markets; for example, it has negotiated with foreign firms for oil and gas exploration, better countrywide supply of cooking gas, and the construction of natural gas pipelines and power stations. Progress on other economic reforms has been halting because of opposition from the system of government, public sector unions, and other vested interest groups. Bangladesh has seen a remarkable increase in  foreign direct investment. A number of  multinational corporations  and local big business houses such as  Beximco,  Square,  Akij Group,  Ispahani,  Navana Group,  Transcom Group,  Habib Group,  KDS Group,  Dragon Group  and multinationals such as  Unocal Corporation  and  Chevron, have already made a major investment, with the natural gas sector being a main concern. Fiscal Year Total Export Total Import Foreign Remittance Earnings 2007-2008 $14.11b $25.205b $8.9b 2008-2009 $15.56b $22.00b+ $9.68b 2009-2010(Set Target) $17.6b N/A $10.87b Bangladeshs textile industry, which includes knitwear and ready-made garments by the side of with specialized textile products, this area is considered as the nations number one export earner, accounting for 80% of Bangladeshs exports of $15.56 billion in 2009.(Sandeep Mahajan, Bangladesh: Strategy for Sustained Growth, Poverty Reduction and Economic Management Network, World Bank (July 26, 2007). Web.worldbank.org. Retrieved 2010-07-03)  Bangladesh considered as 3rd in world textile exports behind Turkey, another low volume exporter, and China which exported $120.1 billion worth of textiles in 2009. The industry employs almost 3.5 million workers in this country. Till date current exports have doubled since 2004. The economy of Bangladesh is constituted by that of a developing country. ( Population Division dourboyz.com. 2010. Retrieved, 03-12-03-2010.) Its per in 2008 was est. US$1,500 (adjusted by purchasing power parity). Bangladesh ranked as the 48th largest economy in the world in 2009, (According to the International Monetary Fund) with a gross domestic product of US$256 billion. Over the past few years the economy has grown at the rate of 6.7% p.a. Sociological: Bangladesh is the most densely populated no island nation in the world. With approximately 125 million inhabitants living in an area of 55,813 square miles, there are about 2,240 persons per square mile. The majority of the population (98 percent) is Bengali, with 2 percent belonging to tribal or other non-Bengali groups. Approximately 83 percent of the population is Muslim, 16 percent is Hindu, and 1 percent is Buddhist, Christian, or other. Annual population growth rate is at about 2 percent. (http://www.everyculture.com/A-Bo/Bangladesh.html) Bangladesh has a number of excellent universities in its largest urban areas that offer both undergraduate through post-graduate degrees. The most prominent universities, most of which are state supported, include: Dhaka University, Rajshahi University, Chittagong University, Jahngirnagar University, Bangladesh University of Engineering and Technology, and Bangladesh Agricultural University. Now days in Bangladesh there are a number of good private universities that provides world class education as well. Technology: The need for faster technological development is gradually more felt in Bangladesh. Development plans of Bangladesh have emphasized science and technological research to develop technologies through espousal of imported technology as well as development of aboriginal technologies. As the country is heavily dependent on imported technologies, proper planning is required for its effective transfer through acquisition, absorption and adoption.   Government has been formulated and adopted new science and technology policy. It has laid down the directions for S and T activities and research, institutional and manpower development, dissemination and documentation facilities.   Legal: LEGAL SYSTEM III.C.1. Common Law System The legal system of Bangladesh is based on a common law system. On the other hand, unlike other common law jurisdictions, Bangladeshs Supreme Court has the power to not only construe laws made by the Parliament but to also declare them null and void and enforce fundamental rights of the citizens. Although founded on the English common law system, the laws of Bangladesh take a statutory form which are enacted by the legislature and interpreted by the higher courts. The govt. regulations or the legal condition of Bangladesh is also not a big obstacle at starting new business or to launch new product. But in terms of introducing new consumer product, a company must obtain the approval of BSTI (Bangladesh Standard Testing Institute). So to launch a product the company must obtain BSTI approval. FOREIGN INVESTMENT INCENTIVES IV.A. General Incentives for Foreign Investment The government has been keen in promoting foreign investment and continues in its efforts to attract such investment as a means of alleviating the economy. In addition, the government has liberalised the industrial and investment policies in recent years by reducing interfering control over private investment. Investment Incentives: Tax Exemptions: Generally 5 to 7 years. However, for power generation exemption is allowed for 15 years. Duty: No import duty for export oriented industry. For other industry it is at 5% ad valorem. Tax Law: Double taxation can be avoided in case of foreign investors on the basis of bilateral agreements. Exemption of income tax up to 3 years for the expatriate employees in industries specified in the relevant schedule of Income Tax ordinance. Remittance: Facilities for full repatriation of invested capital, profit and dividend. Exit: An investor can wind up an investment either through a decision of the AGM or EGM. Once a foreign investor completes the formalities to exit the country, he or she can repatriate the sales proceeds after securing proper authorization from the central bank. Ownership: Foreign investors can set up ventures which are either wholly owned or in collaboration with a local partner. (www.lexmundi.com/images/lexmundi/PDF/guide_bangla.pdf) Environment: Environment of Bangladesh is more feasible. Though, Bangladesh is a central point of reference for the inequality of climate change. Its per capita energy utilization is the equal of about 1 litre of oil per week, causative a small fraction of 1% of global greenhouse gas emissions, yet the country is listed in various risk assessments as  one of the most susceptible in the world to the effects of climate change. Rising sea levels intimidate inundation and salty interference in the southern coastal area, the risk accentuated by prediction of larger cyclone intensity. In a climate pincer movement from the north, melting Himalayan glaciers may disrupt the flows of the three great rivers, first with excess flooding and ultimately with diminished volume. Unreliable monsoon patterns and longer periods of deficiency in the north complete the roll call of climate predictions for Bangladesh. (http://uk.oneworld.net/guides/bangladesh/climate-change?gclid=CIaE58-6xqYCFQ8f4QodOTBuIA) Marketing Mix Marketing Mix  is the set of marketing tools that the firm uses to follow its marketing objectives. Marketing mix has a classification for these marketing tools. These marketing are classified and called as the Four Ps: Product Price Place Promotion The most fundamental marketing tool is product which includes product design, quality, features, branding, and packaging. An essential marketing tool is price which determines the amount of money that customers pay for the product. It also includes discounts, allowances, credit terms and payment period. Place is another important marketing mix tool. And it includes a range of activities that the company undertakes to make the product easy to get to and available to the customer. Some factors that choose the place are transport facilities, channels of distribution, coverage area, etc. Promotion is the last marketing mix tool which includes all the activities that the company undertakes to converse and promote their product to target market. Promotion includes sales promotion, advertising, sales force, public relations, direct marketing, etc. (http://www.scribd.com/doc/8719148/Pepsi-Marketing-Mix) Product In marketing, a product is everything that can be presented to a market that might assure a want or need of customers. There is of two types of product, Tangible (physical) and Intangible (non-physical). Since services have been at the front position of all modern marketing strategies, some intangibility has become important part of marketing offers. All products offered in a market can be placed between Tangible (Pure Product) and Intangible (Pure Service) range. Russell Hobbs product: Russell Hobbs introduces a lot of quality products to their customer. And because of the quality and new technology uses on their product these are most successful being the time those introduced. It is a multinational company and it is not limited to one product. Through the years they have invented and introduced many products than their main Kettle product. They are offering a range of household products like Kettles, Toasters, Irons, Coffee maker, Food preparation, Cooking Baking, Floor care, Cookware etc. Price In economics and business, the price is the assigned numerical pecuniary value of a good, service or asset. To develop a marketing plan price is one of the essential variables in the marketing mix model. Pricing is a big part of the marketing mix. Choosing the right price and the right pricing strategy is decisive to the marketing process. The price of the product is not always fixed. On the other hand the price of the product depends on lots of other factors. Some times the price of the product has got nothing to do with the real product itself. The price may proceed as a way to catch the attention of target customers. Russell Hobbs price: It was a company that ruling the markets before others entered. Previously the price of its product was cost based. It was decided on the cost which was exhausted on making the product plus the profit and other expenses. But after the appearance of other companies it started with a pricing strategy based on the basis of competition. Nowadays additional expenses are spent on advertising products of the company relatively than on manufacturing. Place Place is a term that has a diversity of meanings in a lexicon sense, but which is principally used in a geographic sense as a noun to denote location, though in a sense of a location identified with that which is located there. In marketing, place refers to one of the 4 Ps, defined as the marketplace. It can mean a geographic location, an industry, a group of people (a segment) to whom a company wants to sell its products or services, like a young professional women (for selling cosmetics) or middle-aged family men (for selling family cars). Promotion Promotion is one of the four aspects of marketing. Promotion comprises has four subcategories: Advertising Personal selling Sales promotion Publicity and public relations The arrangement of these four variables creates a promotional mix or promotional plan. A promotional mix specifies how much awareness to pay to each of the four subcategories, and how much money to budget for each. A promotional plan can have a large range of objectives, including- sales increases, new product reception, creation of brand equity, positioning, competitive retaliations, or creation of a corporate image. Foreign market entry strategy for Russell Hobbs: To enter any foreign market there are some strategy that should be follow to be successful. After doing the market analysing by using pestle analysis and doing marketing mix strategy I have come to know the market and what will need to capture a new market. Now I am trying to evaluate a market entry strategy for Russell Hobbs to enter Bangladesh Market. My approach to develop a market-entry strategy follows a proven and structured process, based on extensive industry experience and in-depth understanding of all aspects that feed into a commercial launch. To enter a new market they have to analysis the market first. And also have some approach like: Decrease the financial ambiguity that derives from lack of comprehensive market analysis and a structured strategic plan Make a possible business plan collaboration and financial planning Preliminary business case assumptions need to be revisited to superior communication with market conditions and chosen market position Create launch competence by delivering a structure for consequent planning of strategic launch activities, coordinating and prioritising tasks for launch team Make a contingency plan for risk management and market perception control Launch organisations face immense pressures on market entry, created by internal and external prospect. Some of these pressures can be relies by developing a clear and planned market-entry strategy and efficient functional plans. Market entry strategy Vision and Mission Objective Overall strategy Positioning Brand Target segment Strategic decisions Pricing Brand and communication Sales and distribution Products and services Customer service Launch phasing Tactical launch plan Contingency plan Products services Pricing Brand and communication Sales distribution channels Customer service Internal and external factors Conclusion: So from the above finding I am came on conclusion that for making entry in any international market we should follow the rules and enter in a market with perfect strategy, and my focused on launching my product, and I am focused on market mixed strategy and from the depth of the research which I do for my launching of the product so I find that Bangladesh is the best place for launching my product, because it is the place which fulfil all the requirements which I am looking for, This involved, marketing plan marketing strategy and a sound marketing mix decision. Having completed this, the report then concluded of what best entry strategy Russell Hobbs can undertake to successfully launch business in Bangladesh.

Paths Of Life :: essays research papers

The only way to know for sure if a path is right for you is to take and follow the path all the way to the end. Unfortunately life can only allow so many misdirection plays and crossing of paths. There are many paths to choose from and every decision everyday of one’s life can lead further down a path or force you to back up. Many people believe in one path and stick with it while others try to follow every path they get a hint of. Only one person can make this decision of a single or multiple path life and that person is you. There are many paths, but in specific four distinct groups. Every event in life can be placed on one of these four paths.   Ã‚  Ã‚  Ã‚  Ã‚  The first major path in life is most closely related to the American Dream. This path takes one through a normal life. As the old American dream clichà © goes one grows up in a family with two stable parents and one other sibling. They go through their school years doing every activity from the second grade play to the senior prom. They eventually go through a four-year college and end up marrying a woman who has had a similar existence. Both work for a job they particularly like and wind up having two children, one boy, one girl and living in suburban America. They have a three-bedroom house, two cares and a wonderful bunch of neighbors. Their children will eventually follow in the same path. This path is the middle of the road path and either has a step up or a step down.   Ã‚  Ã‚  Ã‚  Ã‚  A step down from the American dream path would be the underachiever path. This starts with a person growing up in a somewhat dysfunctional family and winds up hating their early life. This path leads to a bad school experience and a state of anti-social behavior where the person misses every activity from the second grade play to the senior prom. This person will decide not to struggle through college and joins the work force out of high school. This person has no real life and completely hates their job. This person suffers though life in many different areas, which include socially, financially, and emotionally. They will wind up not having a family and will finish their life alone and sad. Thankfully there is always a step up from that crappy old American dream clichà ©.

Censorship - A Clash of Wills and Morals Essay -- Argumentative Persua

Censorship - A Clash of Wills and Morals A list of the greatest literature of the English language could be compiled almost solely by using a chart of the works most often censored by schools and libraries. Some people believe that the books most frequently banned consist only of trashy paperbacks and frivolous â€Å"beach-reading.† However, usually in censorship cases, there is a clash of wills and morals between the teacher or librarian who finds a work worthy of students’ and community members’ time and the parent or citizen who sees little literary value in the work of choice. Seldom is the teacher or librarian alone in thinking a work justified for reflection. More often than not, the controversial work has made it into several canons of great literature and onto several great books lists. The conclusion that may logically be drawn is that something about these controversial books is special enough to cause commotion on both ends of the critical spectrum. It may even be suggested that a book is censored for the very same reasons it is canonized. The great works of the literary canon are each striking texts that encapsulate a new voice, idea, point of view, or controversial subject matter; each of these works contains a new and exciting concept. If there were nothing striking about these works, they would never have been canonized. However, with these new ideas and points of view comes suspicion and fear. If one critic lauds a novel for giving a new perspective on a controversial issue, there is no doubt that there will also be a citizen looking to maintain the status quo and suppress these new ideas. It is quite clear that the controversial works of great lit... ....bb.com/bbbanned.cfm. Burress, Lee. Battle of the Books. Metuchen, NJ: The Scarecrow Press, Inc., 1989. Garry, Patrick. An American Paradox: Censorship in a Nation of Free Speech. Westport, CT: Praeger Publishers, 1993. Heins, Marjorie. Sex, Sin, and Blasphemy. New York: The Nex Press, 1998. Karolides, Nicholas J., Margaret Bald, and Dawn B. Sova. 100 Banned Books. New York: Checkmark Books, 1999. Kranich, Nancy. â€Å"Develop Yourself: Expose Your Mind to a Banned Book.† American Library Association, 2000. Online. www.ala.org. Levine, Michael G. Writing Through Repression: Literature, Censorship, Psychoanalysis. Baltimore: Johns Hopkins University Press, 1994. Noble, William. Bookbanning in America. Middlebury, VT: Paul S. Eriksson, 1990. Woods, L. B. A Decade of Censorship in America. Metuchen, NJ: The Scarecrow Press, 1979.

Evaluation of Strategic Marketing Models in Fashion Industry Essay

Introduction Fashion essentially involves change, defined as a succession of short term trends or fad and the very nature of fashion, where change is intrinsic, gives different emphasis to marketing activities (Eeasey, 1994). Furthermore, process research, according to Pettigrew (1992), in strategic management is paradigmatically diverse and empirically complex. Therefore, analysis of process model of strategy specific attention should be paid in fashion industry. Since it is significant without any doubt for a fashion company to choose the proper model to complement marketing strategy, evaluation of strategy process model could be essential. This essay attempts to evaluate Johnson & Scholes’ traditional model and Hill & Jones’ model in fashion industry by analysing and comparing these two models via a few cases of fashion companies. By virtue of making a case study of a listed company, Metersbonwe Group, analyzing its strategy it could have an evaluation of Johnson & Scholesâ€℠¢ traditional model while the â€Å"Bravo† of Burberry would illustrate advantages of Hill & Jones’ model despite of certain limitations. Evaluation of Strategic Marketing Models in Fashion Industry Overview of Models ââ€" Exploring Corporate Strategy model (Johnson and Scholes, 1999) The exhibit above indicates the three main processes in a linear sequence: understanding the strategic position; strategic choice; turning strategy into action (Johnson and Scholes, 1999). Johnson and Scholes (1999) pointed that each process is supposed to be regarded as closely associated, and none has priority over another process realistically for these three processes are interrelated and interconnected  in circles. In Exploring Corporate Strategy model, according to the Johnson and Scholes (1999), strategic position means that strategic analysis and understanding of the impact on strategy of the external environment, an organisation’s capability (resources and  competences) and the expectations and influence of stakeholders, which lays the foundation of the future strategies. In the strategy creation and choice part, there are several strategic options available for manager making a reasonable decision to choose congruent methods. Next, the strategy implementation involves the ensuring that chosen strategies are actually put into action. ââ€" Strategic Planning Process model (Hill and Jones, 2004) Evaluation of Strategic Marketing Models in Fashion Industry The figure shows that there are five major processes of the Hill and Jones’ model: selecting the corporate mission and goals; analyzing the organization’s external competitive environment to identify opportunities and threats; analyzing the organization’s internal operating environment to identify the organization’s strengths and weaknesses; Selecting strategies that build on the organization’s strengths and correct its weaknesses in order to take advantage of external opportunities and counter external threats, which should be consistent with the mission and major goals of the organization; implementing the strategies (Hill and Jones, 2004). Analysis of Comparison and Evaluation From the description of the processes of two models, it could be found that there is a difference in process between Johnson and Scholes’ model and Hill and Jones’ model. In this part, evaluation would be concluded by case analysis. In Johnson and Scholes’ model, they prefer to analyses the impact on strategy of the external environment, external elements (resources and competences) and the expectations and influence of stakeholders before  choosing a congruent strategy between several options. Take Metersbonwe Group as an example, the company, which was created by President and Founder, Zhou Chenjian in Wenzhou, Zhejiang, in 1995, is a listed company specialized in casual wear apparel designing, manufacturing and retailing,  playing its role as a leading casualwear apparel company (Shiwei and Hengjing, 2011). It had achieved great success in past several years. To extend their business, Metersbonwe had a new strategy to imitate the fashion model, which was i nitiated by Zara. In the market process, the company made an analysis of it internal and external environment. However, they had an imprecise market prediction of fashion trend, which made the company’s sales not as expected thus increasing company’s inventory in the dynamic market. According to China Scope Financial (2011), as of September 30, 2011, Metersbonwe’s inventory value was CNY 2.98 billion, 83% of its net asset and although Metersbonwe’s cash flow in the third quarter of 2011 became positive for the first time since the third quarter of 2010, the growth of its income and profit has slowed down. One of the main characters of Zara’s fast fashion model is that in the rapid supply chain maintaining low inventories of this model is the basis for profit (Maolijief, 2012). On contrary, the Metersbonwe had committed a fatal error in their process of strategy choice, declining inventory rate and slowing operation time many times. In fashion industry, high inventory each retention day means devaluation (Maolijief, 2012). In addition, on account of the management of the Metersbonwe, the positioning issues were all important for Metersbonwe when it is confronted with the high inventory crisis and decline of their brand image. The external environment offered the threat and ever-growing competition from other brand such as Semir. Its strong Apparel brand and existing consumer group were key advantages for  defending its position. In the dynamic market, especially in the fashion market, which is undergoing a myriad of changes in the twinkling of an eye,  if the company made an inappropriate strategic option and could not change to cope with the unpredictable situation in their process of strategy, they would turn from a success into a failure while proces s of strategy planning is essential. In contrast, in Hill and Jones’ model, analysis of organization’s external competitive environment and the organization’s internal operating environment are followed by a clear mission. The UK fashion brand Burberry will suffice to illustrate this point. Burberry started a new strategy after appointing Rosie Marie Bravo in 1997 as chief executive, which has made Burberry from boom. In the new strategy, Rosie Marie Bravo (CEO) set a mission to reposition the Burberry’s brand by selecting the corporate mission and goals, which could be regarded as the first step of Hill and Jones’ model. Burberry’s goals were to rebuilt Burberry brand image, to keep the traditional consumer base as well as attract a new, more fashion forward client base by regaining control over distribution and taking back the power over design and product development. In the process of analyzing the company’s external competitive environment, Burberry made a decision of opening a flagship store on New Bond Street in London, competing with stores such as Gucci, Versace, Prada and Chanel by placing itself on the level of these luxury fashion brands. Besides, Burberry’s fashion shows in Milan, as other luxury fashion brands usually do, was a congruent approach to draw the fashion media’s attention and to enjoy media  coverage, thus empower itself highly competitive in international fashion market. The next process after selecting the mission was analyzing the internal situation such as their narrow scope of customers and lacking of controlling design and product distribution, then Burberry made a strategy to establish six new brand levels under his direction and incorporated several alternative fashion directions previously ignored thus leading Burberry to attract majority of the potential consumers. With these new brands extending their range varying from traditional menswear to womenswear, children’s apparel, and accessories, Burberry could cope with their weaknesses of narrow scope of customers to achieve their mission. In  addition, Burberry made a plan to renegotiate with these foreign companies that the licenses previously endorsed. In this way, Burberry enabled itself to overcome company’s internal design and distribution disadvantages. In the fourth steps, Burberry took a new strategy in three aspects, according to the company’s mission and analysis of both internal and external situation to turnaround Burberry: plenty of approaches to marketing and rebranding; controlling product design and manufacture; changing distribution policy. After the implementation of the new strategy, Burberry achieved considerable improvement in its financial performance, showing a profit increase of 630 per cent between the years of 2000 and 2003 and constructing itself as a fashion luxury brand. The Burberry case demonstrates the characters and significance of every process in Hill and Jones’ model. Although, Hill and Jones’ model has its limitations as well as merits, just as Katja Kanngiesser (2004) pointed out that traditional strategy process paid much attention on analysis, reason and period of stability and presume that based on their analysis they could make reliable future prediction. Hill and Jones (2004) admitted that valuable strategies often emerge from deep within the organization without previous planning. Furthermore, other researchers hold the opinion that the real world is unpredictable and they doubt the role that lower-level managers could play in the management process (Gavetti, Levinthal, and Rivkin) Conclusion This essay presents two generalizable model of firm strategy in the fashion market and illustrates model with two cases. From the analysis of two kinds of strategy process model in company cases, it could be concluded that Hill and Jones’ model has an advantage over Johnson and Scholes’ model by virtue of analysing of Metersbonwe and Burberry while Johnson and Scholes’ model and Hill and Jones’ model have many similarities in the process of strategy model. Both Johnson and Scholes’ model and Hill and Jones’ model have its limitations as well as merits. Bibliography Andrew, M. Pettigrew. (1992), The Character and Significance of Strategy Process Research. Strategic Management Journal, Vol. 13, Special Issue: Fundamental Themes in Strategy Process Research (Winter, 1992), pp.5-16 Christopher M. Moore, Birtwistle G. (2004), The Burberry business model: creating an international luxury fashion brand, International Journal of Retail & Distribution Management, Vol. 32 Issue: 8 pp. 412 – 422 Emerald Group Publishing Limited. (2005),†Bravo† for Burberry: From bust to boom – creating a luxury fashion brand, Strategic Direction, Vol. 21 Issue: 1 pp. 22 – 24 Eeasey, M. (2009) Fashion Marketing, Oxford: Wiley Blackwell G. Gavetti, D. Levinthal, and J. W. Rivkin. (2005), Strategy Making in Novel and Complex Worlds: The Power of Analogy, Strategic Management Journal, Vol. 26: pp.691–712. Hill, C. & Jones, G. (2004) Strategic Management Theory, New York: Houghton Mifflin. Johnson G. & Scholes K. (1999) Exploring Corporate Strategy, Hemel Hempstead: Prentice Hall. Kanngiesser, K (2006) The Strategy Process in Dynamic Markets. Diploma Thesis, European Business School Evaluation of Strategic Marketing Models in Fashion Industry Shiwei X, Hengjing L. (2011), Constructing core competencies of virtual enterprise with information technology a case study of Metersbonwe Fashion & Accessories Co., Ltd. Business Management and Electronic Information (BMEI), 2011 International Conference on 13-15 May 2011, Vol. 1: pp.456–459. China Scope Financial, (2011). Metersbonwe Faces High Inventory Pressure. [online] Available at: http://www.chinascopefinancial.com/news/post/1736.html [Accessed 27 December 2011]. Maolijief, (2012). Metersbonwe brand clothing high inventory problem analysis. [online] Available at: http://mens-clothes-online.tm96.net/20120724/metersbonwe-brand-clothin g-high-inventory-problem-analysis-2.html [Accessed 24 July 2011].

Dysfunctional Families Essay

The term â€Å"Dysfunctional Family† to me means (very basically) a family that is impaired in its functioning, but still operates as a family, with the inherent love underneath all the neuroses and abnormalities. Dysfunctional families seem to have become the norm I believe. Part of the reason for this seems to be that many adult children are educators or counselors (adult children is the term for adults who are still functioning based on some of their childhood traumatic events). These adult children have evolved at a very high level intellectually but emotionally still carry unhealed wounds from their own childhood traumas. We should understand that dysfunctional families occur for many reasons. A family can become dysfunctional if any compulsive behavior is present, mental illness, rigid rules, religiosity and any situation where the outer circumstances seek control rather than facilitate the emergence of a strong inner sense of self, personal power, and life skill development. Emotional and verbal abuse are extremely destructive to one’s sense of self. The wounds for both are difficult to â€Å"make real.† Emotional abuse is less recognized, less understood, and more difficult to overcome. Dysfunctional families are universal. Addiction treatment professionals suggest 80-95 percent of families are dysfunctional to some degree. If the norm is dysfunctional, then what attributes describe a functional family? A functional family provides children with a safe and nurturing environment, supports learning during the different developmental stages, affirms the child’s worth and nurtures a sense of self confidence and autonomy. Those of us who grew up in a dysfunctional family or who were neglected or abused in different ways are disenfranchised in our grief. Our losses in childhood have not been honored; they have been disregarded. As children from dysfunctional families, we have disowned our true self; we did so to survive. I think that some children may even have a defunct family (one that was completely non-existing and dead). I wonder if â€Å"defunctional family† is a term ever used†¦if not, it should be. Rules of the dysfunctional family: While all families have rules, dysfunctional families have rigid rules which are often unspoken and unhealthy. These often include: Don’t talk (about what is really going on). Don’t trust anyone (but yourself). Don’t feel or have needs (because there is no one available to validate or respond to you). Deny there is a problem. Roles of a dysfunctional family: Family roles create special strengths in children from dysfunctional families but also â€Å"hide the scars† these children develop. These roles lead to patterns of behavior which can be problematic and difficult to let go in adulthood. These roles include: The responsible child or caretaker – attempts to maintain peace by assuming responsibility for the needs of their siblings and their parents. The family hero – is helpful within the family and successful outside of the family. The enabler – enables the alcoholic to continue drinking by covering up her or his deterioration. The scapegoat – diverts attention from the real family problems by acting out  and engaging in self-destructive behavior. They often act out the tension in the family. The clown – reduces the family’s tension with humor. The lost child – the child who copes by making as few waves as possible, their goal is to draw as little attention as possible. Growing up in a dysfunctional family can have a significant impact on adult functioning. Adults struggle with the following issues: Difficulty knowing what is â€Å"normal†, in part due to the absence of adequate adult role models. A tendency to be extremely self-critical as a result of having internalized frequent parental criticisms. In response to living with unpredictability, a strong need for control. Difficulty with intimate relationships due in part to inconsistent parental affection. Problems recognizing and expressing feelings. May confuse feelings or allow only certain feelings (sadness but not anger; anger, but not sadness). Difficulty expressing needs because they have lost touch with their own needs or are fearful of â€Å"burdening† others. An exaggerated sense of responsibility. Counter-productive perfectionism. A tendency to engage in â€Å"all or nothing† thinking and feeling. Having become accustomed in childhood to crises, feeling anxious when life seems like it is going okay. A tendency to be hyper-vigilant (keep their eye on everything, always worried). Fear of anger (their own and others). In response to parental abandonment or neglect, they develop the belief that they are not good enough, significant or lovable, and in the absence of a â€Å"good enough† sense of self are prone to feelings of shame and inadequacy. Difficulty being spontaneous and having fun. Those who did grow up in a dysfunctional family can also develop some unique strengths. These include: Increased ability to be empathic – to understand and care about others Heightened sensitivity & awareness. Tendency to take less for granted. Maturity, competence and the ability to solve problems and take charge. Greater commitment to having a healthy family and raising children with caring and compassion. Is my family dysfunctional? My family may not be dysfunctional, but I think the lifestyle and personality of my immediate family are responsible in many ways for my shyness. To put it simply, my parents are very quiet people. They don’t have, and never have had, a wide circle of friends, and they virtually never go out (apart from  the obvious, like shopping, eating, going to church and that). Because they were my role models during the early part of my life, I think I probably had trouble mixing with the other kids, (simply because I never saw them mix with other people) and this has kind of stuck with me throughout life. Not that I would say this sort of stuff to their face, because they are my folks and I love them dearly. I can only say that I’m glad I had the opportunity to move away from home, as I think it’s improved my life beyond all recognition.

Compare war poems Essay

Many terrible things happened in World War 1 or the Great War. For me one of the main points were the injustice of it all, how the officer class treated the young ordinary soldiers, mostly from the working class, I have chosen two poems by Siegfried Sassoon which pick up on these themes â€Å"Base Details† and â€Å"Does It Matter? † In both these poems, Sassoon uses sarcasm to magnify his feelings of both anger and frustration, and this makes both poems particularly poignant. In â€Å"Base Details†, Sassoon portrays the role of an army commander back at headquarters (â€Å"the Base†), well away from the front line. As soon as you read â€Å"Base Details you can tell how much Sassoon hates these base areas, in which the generals lay behind. The sarcasm he uses is so utterly obvious of his hatred and he shows this by using a simple rhyming scheme as if a ? Even in the title, Sassoon begins his sarcasm by punning on the word â€Å"Base† i. e. describing both the place, but also the â€Å"base† behaviour in his view of the people there. Sassoon shows his disgust for such people by portraying men who took themselves so seriously, in their bright red uniforms: â€Å"If I were fierce†¦ I’d live with scarlet Majors†¦ â€Å", but are in reality pathetic, puffing figures: â€Å"†¦ bald, and short of breath† What Sassoon particularly hated was how these pompous people sent miserable young men to die at the Front: â€Å"†¦ speed glum heroes up the line to death† Whilst they were safely tucked away at Base, eating and drinking the best of food and wine: â€Å"Guzzling and gulping in the best hotel† It was so irritating hearing the patronising words of sympathy: â€Å"†¦ poor young chap, I used to know his father well† And of course when the war was over, these officers could return safely and uninjured to England, unlike countless millions of ordinary soldiers and other officers: â€Å"And when the war is done and youth stone dead, I’d toddle safely home and die – in bed. † Every line drips with sarcasm which powerfully brings out the unfairness of how the war was conducted. This brings me to my second point, and what happened when the many injured soldiers returned to Britain, which is what is â€Å"Does it Matter? † is about. In this poem, Sassoon deals with soldiers with physical and mental injuries of all sorts. â€Å"†¦ losing your legs† â€Å"†¦ losing your sight† â€Å"†¦ those dreams from the pit† Having returned, people at home tried to be nice and understanding, but really had no appreciation of how these words would be felt as patronising and how it is to feel you are being pitied in this way. Sassoon again uses a form of sarcasm here, although less bitter than in â€Å"Base Details†. In each of the three stanzas of this poem, Sassoon asks with irony: â€Å"Does it matter? † that the soldier had such and such an injury when it clearly matters whether you have lost you legs, or sight or are going out of your mind with awful nightmares. In each case he paints a picture of how hurtful and frustrating it was for these soldiers to hear people at home almost dismiss their injuries, when they can then happily go about their own lives in a way that the soldiers cannot: â€Å"†¦ when the others come in after hunting (with legs! )† It really was so patronising, even if unintentional, to say: â€Å"There is such splendid work for the blind† Or â€Å"And people won’t say that you’re mad; For they’ll know that you fought for your country And no one will worry a bit. † It is really like saying â€Å"there, there† to a child. War is always an awful thing, and causes much misery for all concerned. In the above poems about the Great War, Sassoon focused on two aspects, the awful unfairness of how ordinary soldiers were sent to their death by useless and vain superiors, and the anguish of those who returned injured caused by the patronising pity of those at home.