Low MicroRNA-21 Expression in HPV-Induced Carcinogenesis

Low MicroRNA-21 Expression in HPV-Induced Carcinogenesis Low microRNA-21 expression in the development of a favorable microenvironment for HPV-induced carcinogenesis Introduction Human papillomaviruses (HPVs) are the most common sexually transmitted agents. High risk types of Human Papillomavirus, as HPV16, are the causative agents of virtually all cases of cervical cancer and a significant proportion of other anogenital cancers, as well as some head and neck cancers [1-3]. The K14-HPV16 transgenic mice model is specially used to study the HPV-associated squamous cells cancers. In this model, the expression of early region genes (E2-E8) of HPV-16 is driven by the keratin 14 promoter/enhancer [4]. The K14-HPV16 transgenic mice develop epidermal hyperplastic lesions that progress to dysplastic lesions and ultimately to invasive cancer. The expression of HPV oncogenes E6 and E7 induces epithelial carcinogenesis through well-defined premalignant stages before de novo carcinoma development [5]. The basal cells are mitotically active and thus may develop further mutations in response to a proliferative stimulus, and the expression of K14 has been shown to persist in well-differentiated squamous carcinomas [6]. This model of multistep epithelial neoplasia will facilitate the study of both the epigenetic and the genetic factors that regulate neoplastic progression and coordinate malignant conversion. MicroRNAs (miRNA) are small, noncoding RNAs that regulate gene expression by base pairing with mRNAs, leading to the inhibition of mRNA translation or its degradation. In normal cells, miRNAs control numerous processes including proliferation, differentiation and apoptosis [7]. Furthermore, these molecules are described as key regulators in many diseases including, neurological disorders, cardiovascular diseases, viral infections and cancer. Some miRNAs are lost during tumorigenesis whereas other miRNAs are upregulated. Previous data indicates that miRNAs are important to distinguish subtypes of cancers, where the histological diagnosis is complex and difficult. Furthermore, it also may be a useful tool to diagnose cancers of unknown origin and to study cancer predisposition [8]. MicroRNA-21 (miR-21) has been implicated in various aspects of carcinogenesis. In most solid tumors, miR-21 is overexpressed and thus influences cell proliferation, differentiation and apoptosis [9-11]. However, the interplay between miRNAs, human papillomavirus (HPV) genes and how these interactions contribute to HPV-associated cancers remain elusive and not well understood. The tumor microenvironment associated to miRNAs plays an increasingly appreciated role in cancer (ref whiteside) however, the microenvironment prior to tumorigenesis can influence the carcinogenesis process. In this study we investigated the expression profile of microRNA-21 in K14-HPV16 transgenic mice, using ear and chest skin samples. Thus, we evaluate the importance of the microenvironment associated with the miR-21 expression and predisposition to HPV-induced carcinogenesis. Material and methods Transgenic mice K14-HPV16 mice on a FVB/N background were generously donated by Drs. Jeffrey Arbeit and Douglas Hanahan, from the University of California, through the USA National Cancer Institute Mouse Repository. Generation of K14-HPV mice has been previously reported [12]. After one week quarantine, the animals were kept as breeder pairs in accordance with National (Portaria 1005/92 dated October the 23rd) and European (EU Directive 2010/63/EU) legislation, under controlled conditions of temperature (23 ±2 ºC), light-dark cycle (12h light/12h dark) and relative humidity (50 ±10%), using hardwood bedding. A standard diet (Global Diet 2014, Harlan, Barcelona) and water were provided ad libitum. Health checks were performed daily. Genotyping of HPV-E6 and E2 (referencias genotipagem Hugo?) 15 offspring females from consecutive litters were genotyped at weaning, using tail tip samples. To genotyping were used tail tips of mice of the strain FVB, wild-type or hemizygous. Tissue lysis was performed using MAGNAPure DNA Tissue Lysis Buffer and Proteinase K for 17 h at 65  °C. Nucleic acids were extracted by the High Pure Viral Nucleic Acid Kit following the manufacturers instructions. To test the efficacy of the method of DNA extraction was investigated the presence of mouse-ÃŽ ²-globin gene. The presence of integrated HPV was assessed by amplification of HPV-E6 and HPV-E2 genes by polymerase chain reaction methodology (PCR) in-house. The resulting genotypes were confirmed to the respective phenotypes. After genotype determination, all animals were sacrificed at 22 to 26 weeks-old and completely necropsied. Ear and chest skin samples were collected into TRIzol (Invitrogen) for miRNA analysis and matched samples were collected into 10% neutral buffered formalin for histological processing. For these procedures, 13 skin samples (ear and chest) of 8 hemizygous females (+ / -) were collected. As control were used 14 skin samples of 7 wild-type females (- / -). Histology Skin samples were fixated in 10% neutral buffered formalin for 48 hours, routinely processed and paraffin-embedded. Histological sections (2 µm-thick) were obtained and stained with haematoxylin and eosin (HE) for examination on light microscopy. Samples and their lesions were classified as normal skin, epidermal hyperplasia and epidermal in situ carcinoma by two independent, blind researchers (CL and RGC). miRNA expression analysis To study miRNA-21 expression, the skin samples were macerated with the TRIzol reagent (Invitrogen) for RNA preservation. The extraction of total RNA was performed using aHigh Pure RNA Isolation Kit(Roche Applied Science), according to manufacturer’s instructions. RNA quality was assessed by measuring the absorbance at 260 nm and its purity was evaluated by the ratio of absorbance at 260/280 nm. cDNA synthesis The conversion of miRNA to cDNA was performed using TaqMan ® MicroRNA Reverse Transcription Kit ( PN 4366596 , Applied Biosystems ®, Foster CA, USA ), using sequence-specific stem-loop primers from each miRNA (miR-21 and snoRNA-202). The amplification conditions were as follows: 30 min at 15 °C, 52 min at 42 ºC and finally 10 min at 85 °C. miRNA-21 relative quantification We used qPCR technique to measure the relative expression of miR-21 (StepOne Real-time PCR Systems; final volume: 20 uL, with1Ãâ€" TaqMan ® Universal Master Mix II Applied Biosystems, Foster City, California USA; 1x MicroRNA Assay (Applied Biosystems, Foster City, California USA) and 2 uL cDNA. As endogenous control, we used snoRNA-202. Statistical Analysis Data analysis was performed by the computer software IBM ®SPSS  ®Statistics for Windows (Version 20.0). The 2ΔΔCt method, along with Student’s t-test was used in order to evaluate any statistical differences in the normalized expression of the miR-21. To analyze the normalized relative expression (-ΔCt) of the different groups, we considered the results corresponding to 99% representation of the population ( ±2).      Results Genotyping and histological analysis We observed the presence of integrated HPV DNA (E6 and E2 ORF) in 53% of mice. All cases with HPV-E6 expression also presented HPV-E2 expression. All mice with integrated HPV DNA demonstrated, phenotypically, various degrees of persistent epidermal and squamous mucosal hyperplasia, characteristic lesions associated to HPV infection, previously described in Arbeit et al. study [12]. After histologic evaluation we observed that, in all cases with integrated HPV DNA, the ear tissues presented epidermal in situ carcinomas while the chest tissues showed epidermal hyperplasia. In wild-type mice we observed normal histology. MiRNA-21 expression profile in tissue of transgenic versus wild-type mice To investigate a possible direct influence of HPV16 on the miR-21 expression profile, we analyzed the relative expression between the all tissues (ear and chest) of transgenic mice and the tissues of the control group. We did not found statistical difference in expression levels between both groups (p=0,615). When we compare the miRNA-21 expression in ear and chest samples, singly, we also did not found statistical difference in expression levels between transgenic and wild type mice (Fig.2). MiRNA-21 expression profile in normal tissue To study the miR-21 normal expression profile in tissues, we quantified the expression of miR-21 in the ear and chest skin samples of the control group. We observed that the ear tissues have lower expression levels when compared to chest tissue (p = 0.036) (Fig.3 a)). Mir-21 expression profile in tissues of transgenic mice To compare the relation between miR-21 expression and lesion type, we analyzed the histology of ear and chest samples from transgenic mice and we quantified the expression of miR-21 in the same. We detected that lower expression levels of miR-21 are associated with cancerous lesions as in situ carcinomas (ear) compared with hyperplastic lesions (chest) (p=0,043) (Fig.3 b)). Discussion Recent studies have associated miR-21 to the pathogenesis of various diseases, including cancer. (ref) MiR-21 overexpression is observed in the majority of carcinomas and hematological malignancies. However, understanding of the potential role of miRNA-21 in previous microenvironment to the development of HPV-associated lesions remains elusive. In cervical cancer, it is accepted that HPV infection is the most important factor for transition from normal cervical epithelium to cervical pre-neoplastic intraepithelial neoplasia and subsequently to invasive cervical cancer. However, the influence of others factors including the microenvironment are poorly investigated. Microenvironment associated to miR-21 may be key factor to the predisposition of cancer. We studied that the expression of miR-21 in normal tissues could be important in development of HPV-associated tumors. Our results demonstrate that, in transgenic mice, all ear tissues presented epidermal in situ carcinomas and chest tissues showed epidermal hyperplasia. Thus, we hypothesize that these interesting facts could be related to different miR-21 profile expression of both tissues. Our results indicate that there is no statistically significant difference between the miR-21 expression in HPV-positive samples and controls, concluding therefore that the presence of HPV does not directly influence the expression of this microRNA. This result is consistent with the hypothesis that differences in the miR-21 expression existing in the normal tissue microenvironment are an important determinant of the HPV-induced carcinogenesis process. Several studies have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation [13]. Thomas X. Lu et al., identified an IL-12/IFN-g–dependent pathway as the most prominent upregulated pathway in the lungs of OVAchallenged miR-21-/- mice compared with wild-type littermate controls, providing substantial evidence that this is the major pathway dysregulated in the miR-21–deficient mice [14]. As IL-12 is a major cytokine that regulates Th1 versus Th2 decisions primarily by inducing T cells to produce the Th1 cytokine IFN-ÃŽ ³ [15], may be related to inflammation responsible for tumor progression. These facts that relate the miR-21 downregulation with increased inflammation may explain our findings that tissues with lower miR-21 expression are more likely to develop a carcinogenic pathway. Pten has been verified as a miR-21 target in pancreatic cancer, hepatocellular cancer and squamous cell carcinoma [16, 17]. (†¦) References 1.Walboomers, J.M., et al., Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 1999. 189(1): p. 12-9. 2.Watson, M., et al., Using population-based cancer registry data to assess the burden of human papillomavirus-associated cancers in the United States: overview of methods. Cancer, 2008. 113(10 Suppl): p. 2841-54. 3.Major, T., et al., The characteristics of human papillomavirus DNA in head and neck cancers and papillomas. J Clin Pathol, 2005. 58(1): p. 51-5. 4.Coussens, L.M., D. Hanahan, and J.M. Arbeit, Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. Am J Pathol, 1996. 149(6): p. 1899-917. 5.Masset, A., et al., Unimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor. Int J Cancer, 2011. 128(2): p. 283-93. 6.Stoler, A., et al., Use of monospecific antisera and cRNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation. J Cell Biol, 1988. 107(2): p. 427-46. 7.Chen, C.Z., MicroRNAs as oncogenes and tumor suppressors. N Engl J Med, 2005. 353(17): p. 1768-71. 8.Paranjape, T., F.J. Slack, and J.B. Weidhaas, MicroRNAs: tools for cancer diagnostics. Gut, 2009. 58(11): p. 1546-54. 9.Chan, J.A., A.M. Krichevsky, and K.S. Kosik, MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res, 2005. 65(14): p. 6029-33. 10.Iyevleva, A.G., et al., High level of miR-21, miR-10b, and miR-31 expression in bilateral vs. unilateral breast carcinomas. Breast Cancer Res Treat, 2012. 131(3): p. 1049-59. 11.Kulda, V., et al., Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet Cytogenet, 2010. 200(2): p. 154-60. 12.Arbeit, J.M., et al., Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice. J Virol, 1994. 68(7): p. 4358-68. 13.Coussens, L.M. and Z. Werb, Inflammation and cancer. Nature, 2002. 420(6917): p. 860-7. 14.Lu, T.X., et al., MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol, 2011. 187(6): p. 3362-73. 15.Gately, M.K., et al., The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol, 1998. 16: p. 495-521. 16.Darido, C., et al., Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. Cancer Cell, 2011. 20(5): p. 635-48. 17.Meng, F., et al., MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology, 2007. 133(2): p. 647-58. Fig. 1 Mice genotyping. The presence of integrated HPV was assessed by amplification of HPV-E2 (b) and HPV-E6 (c) genes by polymerase chain reaction methodology (PCR) in-house. Mouse-ÃŽ ²-globin gene was used as endogenous control (a). Fig. 2 Normalized relative expression of miR-21 in transgenic mice (HPV+) and wild-type mice (HPV-), in ear (a) and chest tissue (b). 1

Privacy and Computer Technology Essay

Privacy is a valuable interest and is now threatened more than ever by technological advances. Privacy is defined as the ability to control the collection, use, and dissemination of personal information (Fast Trac Course ). At one time people could once feel confident that what others may find out about them would be treated in a way that it would probably do any harm. Information technology has been beneficial for privacy. By having access to ATMs and online banking we rarely have to present ourselves to a teller. Online shopping offers similar benefits such as being able to shop without standing in long lines and being able to compare prices and research products before purchasing. However, since so much of what we do daily is done using a computer, it can pose a serious threat to privacy. This information can then be recreated to create detailed personal profiles that could not have transpired in pre-digital days. Furthermore, this information can be distributed far, wide, and immediately without our consent or even knowledge. Judicial remedies are unlikely to produce a satisfying or sensible balance between companies’ economic prerogatives and customers’ privacy interest. New technologies that has either unconsiously adopted or resourcefully applied privacy practices will continue to threaten personal privacy. Business will have to find ways to address this uneasiness. If companies remain complacent, underestimating the degree to which privacy matters to customers, harsh regulation may be waiting in the wings. The best way out is for businesses and customers to negotiate directly over where to draw the lines. (What is Privacy?) There are many databases and Internet records that track or keep record of information about an individual’s financial and credit history, medical record, purchases and telephone calls. Most people do not know what information is stored about them or who has access to it. The ability for others to access and link the databases, with few controls on how they use, share, or exploit the information, makes individual control over information about oneself more difficult than ever before. For example, the caller Id was originally designed to allow you to screen your calls and protect from receiving unwanted calls from harassers, telemarketers, etc†¦ In turn it involved privacy concerns for both the caller and the person called. Over the years, there has been a clash between privacy and advancing technologies, which can make a compelling argument for overriding the privacy intrusions. The challenge of improving security while protecting privacy is called Real Id. The real ID act provides significant challenges. It was signed into law on May 11, 2005 (public law 109-13). After may 11, 2008 â€Å"A federal agency may not accept, for any official purpose, a dirvers license or identification card issued by a state to any persin unless the state is meeting the requirements†. The real ID act defines what information and features must appear on the card, what documentation must be presented before a card can be issued, what verification the state must do before a card can be issued, and security measures to prevent tampering counterfeiting and duplication of the card. The Real Id requires states to confirm the identities and documentation of applicants, Make drivers licence and ID cards extremely difficult to counterfiet, and to assure one driver one record so that you will be able to own only one licence which only go for people that has mutliple addresses . The Real Id Act is really the outgrowth of the 911 commision reccomended that the licence be improved and it should be a national standard. Represenative James Sensenbrenner (R-Wis) who was the cahir of the house judiciary committee said â€Å"American citizens have the right to know who is in their country, that people are who they say they are , and the name on a drivers licence is the holder’s real name, not som alias.† Historically the licence has been a state function so the act tailors the mandate that you must present this identification. The challlenges comes from the act because the real ID act was written by Congress without expressing privacy protections. Some of the privacy challenges are what information should be stored in the machine readanble zone?, who should have access to the information stored in the machine readable zone?, and what information, if any will be centralized in order to facilitate the necessary data exchange among the state?. I feel that there should be some limitations on the information stored in the readable zone and the data systems protect the personal information from unauthorized uses and disclosure. Information about individuals is used by businesses to provide customers with a huge array of targeted goods and personalized services that consumers have come to expect. If it lands in the wrong hands, this same information can result in harm to the very individuals it was meant to serve. The protection of an individual’s personal information has business implications that extend beyond the privacy of any one individual. Private information relative to certain businesses and industries is protected by various laws. For example the Health Insurance Portability and Accountability Act (HIPAA) laws protect private medical information. Many states have enacted their own laws, and the federal government is regulated by the Privacy Act of 1974. Legislatures are increasingly responding to calls for greater protection of private information, and stories of improper disclosures of large volumes of private information receive prominent media attention. At present, there is no broad, general federal law protecting the privacy of customer information; most protections are aimed at particular types of information (such as medical or student records,) or particular types of businesses (such as medical providers, banks, and financial service businesses). Customers and consumers expect their information to be protected and businesses that recognize the need to make privacy part of their business strategy are ahead of the game. Many companies have gone to great lengths to protect information using technological advances. However, the ability of a business to protect private information it collects as part of its business is only as strong as its weakest link â€Å"the human factor† something that technology just can’t overcome. Having knowledge of privacy and security should be aimed at individuals who work with private information to help understand the ways that this information can be disclosed inadvertently. We are now moving into an era where there will always be a digital observer. Unlike footprints left in the sand, our online data trails often stick around long after the tide has gone out and they are growing rapidly. Digital footprints are trails of information left by a person’s interaction in the digital environment (en.wikipedia.org/wiki/Digital_footprint). They existed since day one or even before you were born. Internet users don’t realize that every time they use the internet they leave digital footprints. This includes massive amounts of data in the form of email, documents, images, games, music, apps, movies, login and logouts, visits to a web-page, accessed or created files, chat messages or any other material showing the activities being done on a website. What people don’t understand is when you try to reduce your digital footprint you actually make it larger. When trying to reduce your digital footprints interested parties can still use data they have found for evidence, data mining or profiling purposes. This doesn’t mean that you can’t try to protect yourself but you should take precautions when accessing or posting personal information on websites. People need to be proactive and take control of their digital footprint. Due to increased utilization of social media, we should have a heighted awareness of privacy. Being aware of what personally identifiable information that is included in your online profile is very important. Publicy exposed private information on the web can also be used to steal your idenity and money. With more employers’ using the internet to find out about their current or potential new employees, it is good to know in advance what information is floating around the internet about you. You should only put PII in your profile that you wouldn’t mind the entire world including potential or current employers to view. For example, you can find this out by searching for yourself in Google to see what comes up. Also, be wary of strangers. People can misrepresent themselves and their motives so when posting on any social media website it is good to limit who is allowed to contact you and what you tell strangers with whom you communicate with (U.S. Department of State Priva cy Tips). Privacy is so important not just to my online presence but also to my financial documents. Financial privacy is a another term for a multitude of privacy issues, ranging from financial institutions ensuring that their customers information remain private to those outside the institution as well as individuals ensuring that they are protecting their privacy in the privacy of their homes. These documents can be protected by guarding your social security number, calling carefully, and cleaning your name off call lists. Unless you are paying your income taxes, you shouldn’t place your social security number on checks and don’t keep your number in your wallet. A stolen or lost wallet with your social security number can make it easy for someone to obtain new credit in your name. An 800 number is a convenient cost saver, but not if the company you call isn’t reputable. Your call can be the electronic source for undesirable solicitation lists or cause fraud by giving ou t your credit card number to someone who misuses it. You can ask companies you buy from not to release your name to others. You can also have your name eliminated from mass mailing lists by writing to the Direct Marketing Association. Protecting your financial privacy is something that shouldn’t be taken lightly. The fair credit reporting act guarantees access to your credit report for free. If you at anytime feel your credit has been compromised you should visit the Federal Trade Commission’s website. (How to Deal with a Security Breach) In summary, There are many threats to privacy but there are ways you can prevent compromise by criminals and by privacy invading infestations. There are many things you can do to increase to increase your privacy especially online. Protecting your privacy online requires keeping your computer safe from many types of online dangers. Some of the ways to prevent online dangers are making sure the sites you vist is safe beofre sharing personal information. This incluses your real name, email address, credit card number, etc†¦.The next way is to make sure your online account is properly configured for ideal privacy protection. This includes making sure to use a password that are hard to break. The next way is to protect wireless connection from dangers or intrusions. When connecting to the internet via a wireless connection make sure that you re suing a protected password. The next way is to remove yourself from search databases. This can be done by sending a email through a reputable website such as private eye, 123people.com, or intelius.com. Another way is by increasing the privacy of your browser. This a very important part of protecting your online privacy but it also secures your computer against malware and other threats. Lastly, use a temporary credit card number that is linked to your financial account but is only valid for single or limited transactions. Bibliography (Wikipedia, pg 1) en.wikipedia.org/wiki/Digital_footprint Fast Trac Course How to Deal with a Security Breach The Three Basic Forms of Business Ownership What is Privacy?

HND in Business Accounting& Management Essay

Operations Management explores the way organizations produce and distribute goods and services. Everything you wear, eat, sit on, use or read comes to you courtesy of the operations managers who organized its production and distribution. Goods such as automobiles, airplanes, computers and houses, must be produced, as do the services provided by hospitals, ski resorts, trucks, and airlines. It’s the job of an operations manager to make sure these activities occur when and how they are planned. This explanation reflects the essential nature of operations management: it is the central activity in organizing things. Operations Management is the systematic development and control of the processes that transform inputs into goods and services. The operations function comprises a significant percentage of the employees and physical assets in most organizations. Operations Managers are concerned with each step in providing a product or service. They determine what should go into an operating system, such as equipment, labour, facilities, materials, energy, and information, to produce the output. Operations Managers are also responsible for critical activities such as materials management, capacity planning, purchasing, scheduling and quality. The importance of Operations Management has increased dramatically in recent years. Significant competition, shorter product and service life cycles, better educated and quality-conscious consumers, and the capabilities of new technology have placed pressures on the operations function to improve productivity while providing a broader array of high-quality products and services. Such like IEKA An organization that gets the binomial concept â€Å"operations and business management† right is more likely to experience short-term success and run efficient activities. The business might, for example, prevent errors in its record-keeping processes and rein in waste in money-eating mechanisms — a perennial source of concern for top management. Given the importance of operational management, company principals may work with department heads and business-unit chiefs to draw up strategic blueprints and ask them to remain discreet about the company’s operational tactics. The goal is not to convene a periodic top-level meeting and plot strategy in a warlike room, but to set sound procedures to make sure the architects of the company’s blueprint keep mum about its objectives, resources and action plans. TASK2 Ikea because according to the specific market environment for the correct operation strategy, that was a huge commercial success.Ikea’s household concept in the beginning of its creating had clear definition, that is: to provide a wide variety, beautiful and practical, ordinary people can afford the household articles for use.However, with the development of The Times, and constantly changing consumer demand, ikea’s household concept also constantly enrich and perfect.Then, on the basis of the original, ikea household concept began with environmental factors.In particular, household concept of ikea is mainly in household concept of the masses.In most cases, expensive home furnishings is well-designed for a few people can afford to buy.From the early stages of creation, ikea will chose a different path, ikea decided to stand with most people.This means that ikea should meet the household needs of most people in the world, which meet with many different need, grade, dreams, and financial resources, at the same time hope to improve household needs and create a better life.In ikea, everywhere can see pasted on the wall of the ikea business motto: â€Å"ikea will provide a wide range of design at a low price beautiful, fully functional household products, ensure that most people have the ability to buy.†General household the management idea of success is based on partnership between ikea and customers.On the one hand, ikea ikea do the right thing to do.First of all, ikea designers and manufacturers to cooperate, in order to find out the use of the existing production process manufacturing furniture clever way.Then, ikea’s purchasing companies around the world with the most appropriate suppliers of raw materials.Finally, ikea in global bulk purchase, ensure that ikea can get the lowest price.On the other hand, the customer do what they should do, namely through the ikea catalogue, visit the ikea store, choose furniture and customize the warehouse take delivery.Since most goods using tablet packaging, customers can easily to carry it home and assembled.In this way, customers can save a lot of cost.As a result, building with ikea low price, together create a better everyday life.Visible, ikea shows popular household concept for most people service business ideas.In high-end household take the high-quality goods in the 1950 s, ikea this breakthrough will surely shows its forward-looking strategies. Ikea is not just a product, it has its own retail system.Ikea’s retail chain system adopted the operating strategy, in the global retail business through a wholly-owned crown stores and franchisees two modes of operation (blue and red group).As of August 31, 2003, 186 ikea stores in 43 countries and regions, including Europe, Asia, North America and Oceania region, ikea also continues to increase.There are 165 as a wholly owned stores, distribution in 29 countries and regions.In addition, in Australia, the united Arab emirates, Greece, Saudi Arabia, Kuwait, Israel, Malaysia, Singapore, Iceland and Hong Kong, China, Taiwan and other 14 countries and regions, there are 21 franchise, except for the ikea group a franchisor to own and run.Ikea’s chain operation has been a huge success, and thus a high international reputation for ikea.In 2004, ikea’s operating income of 12.8 billion euros, net profit more than 1.1 billion euros, employs 84000 workers, as the world’s biggest household goods retailer.Low price strategy is refers to through continuous compression cost, thus reduce prices, to win the market strategy.Ikea has been that only provide beautifully designed, practical series of products is not enough, also should make most people can afford to buy, in order to for most people rather than a few people to create a better life.After all, money is not much can meet the needs of the household consumer satisfaction.Therefore, ikea emphasizes the low-price strategy in the management strategy.Low price strategy ikea is the core of the operating strategy, ikea has unusual significance.Both household concept, cost control and other aspects of management measures, in the final analysis is to ikea’s low price strategy.The success of ikea’s low price strategy mainly from the following several aspects: adhere to the principle of small profit, principle of small profit in business is braving the down the sharp weapon, but also an important guarantee of ikea’s low price strategy to success.After 60 years of development, ikea has always unswervingly implement the principl e.Low-cost system, guarantee the normal way of thinking of most enterprises, first in terms of product design and pricing, however, ikea has a tradition, price the product first and then followed by the specific design, finally find suppliers according to the established design.So it will be in the system design ensures the ikea, low prices.Ikea’s pricing method is also unique, often use price matrix method for new product pricing.Ikea has three price – high, medium and low grade, four basic style, modern, country and young Swedish – northern Europe.In order to identify market opportunities, which is responsible for the product will take in charge of the committee’s instructions, the existing product prices to fill him in grid, and then look for space.First start from the little space of committee instructions, for example, have been found in the high price of ikea products for a large number of independent kitchen island, but he has lost those suitable f or apartment or office cheap kitchen supplies.Then, head of products through the investigation to determine the cost of the new product competition, the goal is to lower than competitors’ prices by 30% ~ 50%, in this way, the price of ikea point occurs.This is the product manager for the low price of products of ikea kitchen utensils and appliances.The pricing model is kill two birds with one stone, it reflected the ikea has always been the production of standard and sales of the original and cheap, and also contains all to determine the content of the device in the conceptual design . TASK3 Operational management deals with the nitty-gritty basics of how a company operates, such as keeping track of spending costs and cash flow as well as maintaining a supply line. Some of the best managers have been those who have found ways to make the basic operations of a company more efficient. Operational management requires knowledge of a constantly changing variety of data and variables, and skillful and flexible planning is required. Strategic management does not merely have to do with setting broad and lofty goals, but works to establish a plan over the long term that will work toward those goals. This involves taking into account such factors as competition and consumer demand. The most successful business visionaries have been able to establish very realistic pictures of the market and operate within the constrictions that they were given by the market. Strategic management takes a great deal of common sense. Despite the clear distinctions we are making it is also important t o understand that operational and strategic planning are interrelated and complementary decision processes, which must link to each other, inform and support one another for effective management of strategies. Operational planning is the day-by-day, week-by-week, and month-by-month planning for a myriad of local and functional activities; strategic planning sets the overall direction of your organisation as a whole, its destiny if you will. The decisions that constitute the strategic plan include what the enterprise is not currently doing, but should be doing. The choices of what to do imply other things that the organization deliberately chooses not do. The strategic plan embodies very big decisions with major consequences for the overall performance. Strategic and tactical planning are different in kind. The two forms of planning must be linked, and integrated, and must not be confused. About IKEA: IKEA is a privately-owned company founded in Sweden by Ingvar Kamprad. He first started to sell pens, wallets, picture frames, table runners, jewellery and nylon stockings and decided to add furniture in 1947. IKEA has now around 260 stores, much of which are located in Europe, the United States, Australia and Asia. Nowadays IKEA is known for selling modern and utilitarian furniture at low prices their vision is â€Å"To create a better everyday life for the many people†. IKEA motto is â€Å"Affordable Solutions for Better Living†. Their operations management are strongly focused on achieving this goal; they use their resources effectively to gain profit by developing a more economic way for the production of their wide range of service. This has involved them in working closely with their suppliers in order to control aspects of their business from the production line. Unlike most furniture stores, IKEA sells goods which need to be assembled by the consumer; this has enabled them to use space more efficiently in their warehouse. The company has developed methods to satisfy customers with their Unique Selling Point (show room, children’ area) and a wise use of technology (stock control, internet). TASK4 TASK5 The three-es that is economy, efficiency and effectiveness. MANAGEMENT EFFICIENCY Efficiency can be measured in terms of the inputs required to generate the outputs. It is about the way in which work is completed. It is part of a manager’s job to help improve efficiency. For example, if the same work can be completed using less inputs or resources then efficiency has improved. Measuring efficiency means that the process followed to complete the work must be defined and then each part of the process studied to see what resources are required. This becomes the starting point or benchmark for measurement. Future work is then measured against the benchmark to see if it has taken more or less resource. Process changes are also measured to see if they are more or less efficient. It is also useful to measure one team’s efficiency against another and then adopt the most efficient methods as best practice– always assuming that effectiveness is maintained. MANAGEMENT EFFECTIVENESS Effectiveness can be explained in terms of what is achieved. It is about whether targets are met or not. Performing effectively means that the right work is being completed. Managers are responsible for making sure that this happens. If a team is working really hard but not delivering what is needed, then they are not effective. Effectiveness is measured by setting out clear objectives before work starts and then evaluating whether the objectives have been met or not. MANAGEMENT ECONOMY Economy is the third element of the three Es model, covering the financial aspects of work being done. It could be argued that economy or finance is just one of the factors to consider when improving efficiency, but because finance is so important in today’s organisations, economy has become the third element. Economy is measured by looking at the cost of the resources consumed and the value of the output delivered. TASK6 The maximization of quality and productivity in each and every individual industry is the foundation of every economy aspiring to prosperity.Improve the companies income by making the production more acceptable to the customers: by providing longlife, greater usefulness, maintainablity,etc.Giving employees control includes giving them the power to make job-related decisions, the flexibility to organize their work in the way they find optimal, and the authority to find make improvements on how their job is done. Making this work requires providing employees with the training, coaching, and information they need to make intelligent decisions. Make Sure Supervisors Know How to Bring Out the Best in People – Supervisors play a huge role in employee morale, performance, and stress level. Supervisors who know how to provide guidance, support, and encouragement minimize employee stress. Supervisors with poor management skills or with personal problems, not only can’t help empl oyees deal with stressful times, they themselves are a tremendous source of stress. The time and financial resources you invest in selecting and training managers will pay huge dividends in reducing employee stress, increasing productivity, and minimizing turnover.

Epic of Beowulf Essay - 1531 Words

Beowulf Word has traveled across the seas to Geatland of a great disturbance in Heorot. A threatening creature has befallen on Hrothgar, King of the Danes, and his people. In no time, a Geat by the name of Beowulf arrives at Heorot. However, why would one man, an unpopular man at that, not known of possessing any strength or talent, travel a great distance to offer his services to the Danes? Textual evidence provides that Beowulf, although he proves himself brave and strong, expresses his ego through boasting of his epic deeds, illuminating on his strength and wit. In addition to feeding his ego, it can be proved that Beowulf is out to make a legend of himself since he comes from a broken lineage, and in the time of the Danes and†¦show more content†¦A young character by the name of Unferth challenges Beowulf and his boasts. It begins with Unferth, at the feet of the King, in response to a challenge, â€Å"Are you the Beowulf who took on Breca in a swimming match on the open sea, risking the water just to prove that you could win?† (p.43, lines 504-508). This statement not only challenges Beowulf, but also goes on to suggest that Beowulf is indeed a boaster (â€Å"risking the water just to prove that you could win?†). Beowulf goes on to confirm his boastfulness: â€Å"†¦when the going was heavy in those high waves, I was the strongest swimmer of all,† (p.43, lines 533-534). To top it all off, Beowulf insults Unferth and makes him out to be a coward, which helps Beowulf portray his strength and skills even further, which is to his advantage and thus satisfying his goal more. Now I cannot recall any fight you entered, Unferth, that bears comparison. I don’t boast when I say that neither you nor Breca were ever much celebrated for swordsmanship or for facing danger on the field of battle. You killed your own kith and kin, so for all your cleverness and quick tongue, you will suffer damnation in the depths of hell. The fact is, Unferth, if you were truly as keen or courageous as you claim to be Grendel would never have got away with such unchecked atrocity, attacks on your king, havoc in Heorot and horrors everywhere†¦But he will find me different. I will show him how Geats shape to kill, (p. 44-45,Show MoreRelatedBeowulf : The Epic Of Beowulf1027 Words   |  5 Pages To begin, Beowulf the poem has a unknown author, Beowulf is an epic poem. In Beowulf he is challenged by the murderous monster Grendel, Grendel is eating and slaughtering Hrothgar the King of the Danes men and people, the king needs Beowulf s help in defeating Grendel, Beowul f ends up killing the monster and is now tormented by the monster s mother that is much larger, she is no match for Beowulf and he kills her as well, lastly it is Beowulf’s last battle after he has been king of Geatland forRead MoreThe Epic Of Beowulf By Beowulf2577 Words   |  11 Pagesoriginal aspects of these different religions. Due to the construction of this Beowulf, students and professors are able to study and get a true understanding of a pagans’ demeanor and how life evolves through their eyes. Throughout the epic poem Beowulf, paganism is exemplified as this epic hero falls victim to fate while embarking on his journey through life fighting monsters and chasing after his fame. To begin with, Beowulf was composed in Old English by an anonymous writer between the sixth and seventhRead MoreThe Epic of Beowulf733 Words   |  3 PagesBeowulf is the oldest anglo-saxon poem written in English. The poem describes the heroic deeds of Beowulf in his fight against monsters. Even if the events narrated in the poem take place in Denmark, the poem was transmitted by oral language between the anglo-saxon even 200 years after its creation. Anglo-saxons did not consider themselves british, but vikings, and their heroes were always from Scandinavia. The author of Beowulf is anonymous. The original poem was written on sheep tanned leatherRead MoreBeowulf as Epic823 Words   |  4 PagesWhat makes an epic? Is Beowulf an epic? ï‚ · ï‚ · ï‚ · What is an epic poem, and how does it differ from other kinds of poetry or storytelling? How have epic poems traditionally been transmitted from generation to generation? How do tellers remember these long and complicated stories? According to Robert Harris’s Glossary of Literary Terms, he defines an epic as the following: Epic. An extended narrative poem recounting actions, travels, adventures, and heroic episodes and written in a high style (withRead More Epic of Beowulf Essay - Beowulf as Epic Hero844 Words   |  4 PagesBeowulf as Epic Hero Epic heroes usually exemplify the character traits most admired in their societies, and Beowulf is no exception.   Beowulf is set in the Anglo-Saxon society, a time when war was rampant among the many peoples trying to take over the different kingdoms of England.   In this dangerous, violent time people lived in constant peril and jeopardy.   These conditions only allowed people of great bravery to survive and men of outstanding courage were admired the populous.   TheseRead MoreThe Epic Of Beowulf As An Epic Hero1519 Words   |  7 Pageswhisked away following a journey, you have most likely read an epic. An epic by definition is â€Å"a long poem, typically one derived from ancient oral tradition, narrating the deeds and adventures of heroic or legendary figures or the history of a nation†. Every epic has a main character that undergoes the same archetypal journey as all other heroes, an epic hero. There are specific qualities one must have to be considered an epic hero. Each epic hero possesses superhuman strength, displays a strong senseRead MoreComparing Beowulf And The Epic Of Beowulf937 Words   |  4 Pagesthe Roman Empire. In the story Beowulf, his actions portray him, indeed be an epic hero. Both Christianity and Paganism are both portrayed throughout the epic Beowulf. Beowulf frequently speaks of God throughout the story, while there are also many Pagan elements that are evident throughout the story as well. In addition, It s hard to ignore the Christian and Pagan elements in Beowulf. These types of elements are what define the heroic warrior in the epic Beowulf(Vengeance the Pagan and ChristianRead MoreThe Epic Of Beowulf As An Epic Hero711 Words   |  3 Pagesthan the writer. These â€Å"epic heros† are protagonists that fulfill their potential of greatness through using their bravery, strength and humility for good. The near ancient tale of Beowulf is a classic example of an epic story that contains an epic hero. In this tale Hrothgar, the king of the Danes, has been terrorized by a beast known as Grendel. This beast has been murdering the king’s people and no one has come close to stopping this killer. A Geat warrior named Beowulf hears of the King’s predicamentRead MoreThe Epic : An Analysis Of The Epic Of Beowulf701 Words   |  3 PagesBeowulf is one of the longest surviving Anglo-Saxon poem. The epic takes place in the sixth century in what is now Denmark and Sweden. The poem opens with Hrothgar, whose successful rule is signified by a glorious mead-hall called Heorot. For 12 years, a massive man-like ogre named Grendel, a descendant of Cain, has raided Heorot and killed the kings warriors. Beowulf, a young warrior from Geatland (Sweden), comes to Hrothgar’s aid, bringing 14 of his best men with him. At a feast before the endRead MoreBeowulf : An Epic Hero930 Words   |  4 Pages The story of Beowulf shows its reader many characteristics of why this Anglo-Saxon poem is an epic. First of all, Beowulf is a warrior of epic renown by the time he formally introduces himself in the poem. Next, Beowulf is the warrior that many strive to be in life. In addition, Beowulf finds himself tackling many quests that involve dangerous beasts, or as he might call them, demons. The next quality shown by Beowulf is his bravery and honor. The reader is able to easily identify this characteristic