Etiology of Parkinsons Disease

Etiology of Parkinsons Disease Parkinson’s Disease is the second most common neurodegenerative disease, after Alzheimer’s. Onset typically occurs late in life, affecting approximately 1% of 65 year olds, with the prevalence increasing to 4-5% by age 85 (Dawson Dawson 2003). There are also rare cases of early-onset Parkinson’s, which are usually familial. Research into the gene mutations discovered in such hereditary cases has also contributed to the understanding of the aetiology of the spontaneous, late onset form of the disease. Parkinson’s Disease (PD) is characterized clinically by tremors at rest, bradykinesia (slowness of voluntary movement), muscle rigidity, decrease in postural reflex and facial expression and an altered gait (Kumar et al. 2005). A subset of patients (10-15%) also develop dementia. Symptoms are progressive and result in decreased mobility and eventually severe disability. The symptomatic motor disturbances arise from the progressive loss of dopaminergic neurons in the substantia nigra of the brain. This results in a decrease in the dopaminergic content of the striatum. These areas play an important role in modulating feedback from the thalamus to the motor cortex. AIMS AND OBJECTIVES This report aims to investigate the current knowledge of the aetiology of PD, by examining evidence in the literature. It is crucial to understand the pathological mechanisms underlying the selective destruction of dopaminergic neurons in PD so that effective treatments and prophylaxis can be developed. PROPOSED STRATEGY Researchers have studied the molecular mechanisms of PD pathogenesis using a number of techniques: in vitro tissue cultures of human and animal neurons, post-mortem human brain tissue, mouse models of the disease, genetic studies and more novel techniques such as the use of ‘cybrids’. Evidence from all of these will be amalgamated and conclusions drawn. MOLECULAR PATHOGENESIS OF PD That PD is generally associated with old age must be considered an important clue when trying to elucidate the causal mechanism of PD. The same is also true of the most common neurodegenerative disease, Alzheimer’s Disease (AD). Both are also characterised by an accumulation of protein aggregates resulting in progressive neuronal loss, suggesting a common underlying pathology. Histological brain sections of PD patients shows characteristic, large inclusion bodies in the cytosol of surviving neurons of the substantia nigra, as well as locus ceruleus and surrounding brainstem nuclei, called Lewy bodies (Kumar et al. 2005). These are aggregates of à ¯Ã‚ Ã‚ ¡-synuclein (Spillantini et al. 1997), a protein whose gene (SYN, aka PARK 1) has been linked to familial PD (Athanassiadou et al. 1999), as well as other proteins such as ubiquitin and synphilin-1. It is unclear whether these aggregates contribute to the pathogenesis, are a simple by-product or even part of an attempted protective mechanism, described as the aggresome theory (McNaught et al. 2002). Some evidence has recently been produced by Setsuie and colleagues (2005), using a PD rat model in which proteasome inhibitors caused inclusion formation, which resulted in decreased dopaminergic neuronal death that normally follows 6-hydroxyl dopamine (6-OHDA) administration. Lewy bodies are also found in low numbers in normal aging and AD (Jellinger 2001). However, Lewy bodies are not found in some cases of juvenile onset PD, which suggests that the inclusions are not crucial for neuronal death in the substantia nigra (Fahn Salzer 2004). Animal models of the disease, created using neurotoxins such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or transgenic mice that overexpress human SYN gene (for à ¯Ã‚ Ã‚ ¡-synuclein) mutations, do not faithfully replicate the structure and antigenicity of the Lewy bodies found in PD (Dickson 2001). This highlights the problems associated with designing and producing an accurate animal model of human disease, which can be valuable tools, despite some limitations. Role of the ubiquitin-proteasome system (UPS) Although the precise role of Lewy bodies in the pathogenesis of PD is still unclear, the accumulation and aggregation of proteins suggests that there is a deficit in the cellular systems that normally remove and degrade abnormal proteins. The ubiquitin-proteasome system (UPS) is one such pathway, and there is growing evidence that implicates this system in PD. In conjunction with the enzymes E1, E2 and E3, ubiquitin is activated and attaches to abnormal proteins to form a polyubiquitin chain. The proteasome recognises this complex and degrades the unwanted protein. The ubiquitin polymer is released from the targeted protein and digested by ubiquitin carboxy-terminal hydroxylases (UCHs), to release ubiquitin monomers back into the system (Alberts et al. 2002). Ubiquitination and recognition of proteins to be degraded are ATP-dependent processes. If the activity of this clearance pathway decreases, misfolded or oxidatively damaged proteins will accumulate rather than being recycled (Sherman Goldberg 2001). Studies of the rarer, familial cases of PD have revealed evidence that this system is involved in PD aetiology, which has aided the understanding of the pathogenesis of sporadic PD. Gene mutations for two proteins that are involved in the UPS are of particular significance. Kitada and colleagues (1998) demonstrated a link between mutations in the parkin gene (aka PARK 2) and familial incidence of autosomal recessive juvenile parkinsonism (AR-JP) in Japanese families. Parkin is an E3 ligase within the UPS, and has been shown to have a neuroprotective role (Petrucelli et al. 2002). Despite this, parkin null-mutant mice exhibited normal behaviour and brain morphology, with no loss of dopaminergic neurons. Dopamine levels were altered, suggesting a possible role in dopamine regulation (Goldberg et al. 2003). Drosophila parkin null-mutants showed a consistent pattern of pathology, with locomotor deficits, sterility and decreased lifespan (Greene et al. 2003). These were attributed to mito chondrial dysfunction, which is also a feature of PD (see below). Research into the potential toxic effects of accumulation of parkin substrates has been inconclusive (Betarbet et al. 2005). Evidence points to parkin involvement in the pathogenesis of PD, but mutations of this protein are not sufficient alone to cause the disease. A missense mutation for the gene encoding the protein UCH-L1 has been detected in autosomal dominant familial cases of PD in Germany (Leroy et al. 1998). In sporadic cases of PD, UCH-L1 is downregulated and oxidized in the cerebral cortex (Choi et al. 2004), the significance of this is unknown. UCH-L1 mutations in mice produce neuromotor signs that are not typical of PD, and are characterised as Gracile Axonal Dystrophy mice (GAD). As for parkin, the evidence confirms some involvement in PD pathogenesis of these elements of the UPS, but points to the need for further research to fully deduce their role. Other genetic mutations have been identified, such as LRRK2 (a kinase;Zimprich et al. 2004) and DJ-1 (aka PARK 7), which is involved in a similar protein degradation pathway (SUMO; Bonifati et al. 2003). It is tempting to attribute the accumulation of à ¯Ã‚ Ã‚ ¡-synuclein to a decrease in activity of the UPS, but evidence that à ¯Ã‚ Ã‚ ¡-synuclein is a substrate of this system is contradictory (Paxinou et al. 2001), with results differing between in vitro cell lines and conditions. Some studies suggest that à ¯Ã‚ Ã‚ ¡-synuclein accumulation may inhibit the UPS, resulting in further protein accumulation (Liu et al. 2005). Role of mitochondrial dysfunction and oxidative stress A significant amount of evidence supports the hypothesis of involvement of the UPS in PD aetiology. In familial cases genetic mutations have been discovered that account for a portion of the susceptibility to, and pathogenesis of PD; but other factors are obviously required for both early onset and sporadic cases to develop. UPS activity has been found to be lowered in sporadic PD patients, with impaired proteasomal activity and reduced expression of subunits in the substantia nigra (McNaught et al. 2003). Whether UPS impairment is a primary cause or secondary to another event is not yet clear. Some researchers believe that the mechanism underlying the dysfunctional UPS may involve mitochondrial dysfunction, which has also been implicated in other neurodegenerative diseases (Hashimoto et al. 2003). During energy production by respiration in the mitochondria, there is a continuous leakage of free radicals, such as reactive oxygen species (ROS), which are also released by inflammatory cells. Antioxidant mechanisms exist to mop these up before they can cause oxidative damage to surrounding molecules, such as proteins, lipids and DNA, but these are not 100% efficient. This results in a gradual increase in damaged cellular components with aging (Vigoroux et al. 2004). Higher levels of oxidization products have been found in brain tissue of patients with neurodegenerative diseases such as PD (Dexter et al. 1994) and suggest an important role for free radicals in its aetiology. Mitochondrial DNA (mtDNA) damage has been hypothesised to accumulate, leading eventually to mitochondrial dysfunction, which further increases free radical leakage. Mitochondrial complex I, in particular, has been implicated. Induced parkinsonism in animal models using the pesticide rotenone has been shown to inhibit mitochondrial complex I (Sherer et al. 2002). Administration of MPTP also induces PD symptoms and inclusion body formation, via the complex I inhibition of its metabolite MPP+ (Ram say et al. 1986). This has been recorded in human subjects following the use of illicitly manufactured narcotics, in which MPTP is produced as a contaminant, but has now been used to reliably induce disease in rodents to further knowledge of the pathogenesis of this disease. As well as providing valuable insights into the mechanisms underlying PD, the ability of chemicals to produce the symptoms and pathology of PD has also raised concerns about the role of environmental factors in the aetiology of the sporadic disease. Some epidemiological studies have linked pesticide exposure to an increased risk of developing PD (Park et al. 2005), as well as suggestions that increased coffee/caffeine consumption and smoking (Wirdefeldt et al. 2005) may have some protective benefits. Exposure to heavy metals, such as manganese has also shown a correlation with PD in some studies, but not all. Heavy metals are known to accelerate free radical formation and hence increase oxidative stress, so it w ould not be unexpected if higher levels were involved in PD aetiology. Results of epidemiological studies that claim to prove these positive and negative correlations with PD are contradictory, and further research is required, which could also take diet into account (particularly ingested antioxidant levels and lifestyle). Mitochondrial dysfunction may cause a decrease in UPS activity, either by reduced ATP production, which is essential for many processes of the pathway, and/or by increasing oxidative stress and damaging vital components of the system (Fahn Salzer 2004). The pivotal role of mitochondria has been elegantly demonstrated by the use of cytoplasmic hybrids. These ‘cybrids’ are formed by taking mtDNA from platelets of patients with PD and inserting it into cultured human neuroblastoma cells that have been depleted of their endogenous mtDNA. These neuronal cells faithfully recapitulate the structure and antigenicity of Lewy bodies (Trimmer et al. 2004), and similar studies have reported other pathogenic features consistent with a role for mitochondria and oxidative stress in PD. It is now widely accepted that oxidative stress is a contributory factor to PD aetiology, with markers of oxidative damage found to be higher than in non-PD controls. Antioxidants have been administered in a number of studies to further explore the impact of free radicals and therapeutic/prophylactic options. Transgenic mice that overexpress the endogenous antioxidant Cu,Zn-superoxide dismutase did not show any symptoms or DA neuron loss following exposure to paraquat (herbicide)-maneb (fungicide), compared to non-transgenic controls (Thiruchelvam et al. 2005). Studies involving exogenous antioxidants have produced inconclusive results, and more research is required in this area. The specificity of dopaminergic neuronal loss, mainly in the substantia nigra pars compacta, in PD is replicated in chemically induced animal models of disease. The reason for this consistent and specific pattern of neuropathology may be due to the oxidation properties of DA, with highly reactive DA-quinones being generated. These are able to form complexes with à ¯Ã‚ Ã‚ ¡-synuclein and may inhibit mitochondrial complex I (Asanuma et al. 2003). This has important implications for the commonly used L-DOPA therapy, which may also contribute to neurodegeneration. Some researchers also believe that inflammation may play a role in PD, as microglial cells proliferate in affected brain regions (McGeer McGeer 2004). CONCLUSION The aetiology of Parkinson’s Disease is multifactorial, with a combination of genetic, environmental and possibly immunological factors, many of which are still unknown or poorly understood. There is growing evidence from a variety of research techniques that oxidative stress, mitochondrial dysfunction and deficits in protein degradation pathways, such as the UPS are interlinked. The aetiological factors initiate a process that culminates in the accumulation and aggregation of proteins, mainly à ¯Ã‚ Ã‚ ¡-synuclein, in dopaminergic neurons of the nigrostriatal system, which leads to cell-death. Further research is required to fully elucidate the precise molecular mechanisms that underlie the neuropathology of PD, so that effective treatments or prophylactic advice can be established. REFERENCES Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, Molecular Biology of the Cell. 4th Ed. New York: Garland Publishing. pp.359-363. Asanuma, M., Miyazaki, I. Ogawa, N. 2003 Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinsons disease. Neurotox Res 5, 165-76. Athanassiadou, A., Voutsinas, G., Psiouri, L., Leroy, E., Polymeropoulos, M. H., Ilias, A., Maniatis, G. M. Papapetropoulos, T. 1999 Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding alpha-synuclein. Am J Hum Genet 65, 555-8. Betarbet, R., Sherer, T. B. Greenamyre, J. T. 2005 Ubiquitin-proteasome system and Parkinsons diseases. Exp Neurol 191 Suppl 1, S17-27. Choi, J., Levey, A. I., Weintraub, S. T., Rees, H. D., Gearing, M., Chin, L. S. Li, L. 2004 Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinsons and Alzheimers diseases. J Biol Chem 279, 13256-64. Dawson, T. M. Dawson, V. L. 2003 Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J Clin Invest 111, 145-51. Dexter, D. T., Holley, A. E., Flitter, W. D., Slater, T. F., Wells, F. R., Daniel, S. E., Lees, A. J., Jenner, P. Marsden, C. 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W. 2003 Altered proteasomal function in sporadic Parkinsons disease. Exp Neurol 179, 38-46. McNaught, K. S., Shashidharan, P., Perl, D. P., Jenner, P. Olanow, C. W. 2002 Aggresome-related biogenesis of Lewy bodies. Eur J Neurosci 16, 2136-48. Park, J., Yoo, C. I., Sim, C. S., Kim, H. K., Kim, J. W., Jeon, B. S., Kim, K. R., Bang, O. Y., Lee, W. Y., Yi, Y., Jung, K. Y., Chung, S. E. Kim, Y. 2005 Occupations and Parkinsons disease: a multi-center case-control study in South Korea. Neurotoxicology 26, 99-105. Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. Q., Lee, V. M. Ischiropoulos, H. 2001 Induction of alpha-synuclein aggregation by intracellular nitrative insult. J Neurosci 21, 8053-61. Petrucelli, L., OFarrell, C., Lockhart, P. J., Baptista, M., Kehoe, K., Vink, L., Choi, P., Wolozin, B., Farrer, M., Hardy, J. Cookson, M. R. 2002 Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36, 1007-19. Ramsay, R. R., Dadgar, J., Trevor, A. Singer, T. P. 1986 Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP. Life Sci 39, 581-8. Setsuie, R., Kabuta, T. Wada, K. 2005 Does proteosome inhibition decrease or accelerate toxin-induced dopaminergic neurodegeneration? J Pharmacol Sci 97, 457-60. Sherer, T. B., Betarbet, R., Stout, A. K., Lund, S., Baptista, M., Panov, A. V., Cookson, M. R. Greenamyre, J. T. 2002 An in vitro model of Parkinsons disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22, 7006-15. Sherman, M. Y. Goldberg, A. L. 2001 Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29, 15-32. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R. Goedert, M. 1997 Alpha-synuclein in Lewy bodies. Nature 388, 839-40. Thiruchelvam, M., Prokopenko, O., Cory-Slechta, D. A., Richfield, E. K., Buckley, B. Mirochnitchenko, O. 2005 Overexpression of superoxide dismutase or glutathione peroxidase protects against the paraquat+maneb-induced Parkinsons disease phenotype. J Biol Chem. Trimmer, P. A., Keeney, P. M., Borland, M. K., Simon, F. A., Almeida, J., Swerdlow, R. H., Parks, J. P., Parker, W. D., Jr. Bennett, J. P., Jr. 2004 Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimers disease worsen with passage in culture. Neurobiol Dis 15, 29-39. Vigouroux, S., Briand, M. Briand, Y. 2004 Linkage between the proteasome pathway and neurodegenerative diseases and aging. Mol Neurobiol 30, 201-21. Wirdefeldt, K., Gatz, M., Pawitan, Y. Pedersen, N. L. 2005 Risk and protective factors for Parkinsons disease: a study in Swedish twins. Ann Neurol 57, 27-33. 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New Beginnings in Whos Afraid of Virginia Woolf :: Whos Afraid Virginia Woolf

New Beginnings in Who's Afraid of Virginia Woolf  Ã‚   Edward Albee's Who's Afraid of Virginia Woolf is a disturbing and powerful work. Ironically, it is disturbing and powerful for many of the same reasons. As the audience watches George and Martha tear savagely at each other with the knives of hurled words, sharpened on pain and aimed to draw blood, the way in which these two relentlessly go at each other is awful to see, yet strangely familiar. Like wounded animals, they strike out at those closest to them, and reminds one of scenes witnessed as a child between screaming parents from a cracked door when one is supposed to be in bed. In this age of psychoanalytic jargon, George and Martha are the quintessentially dysfunctional couple. Yet, with all their problems, Albee reveals that there is a positive core of feeling that unites these two troubled people and that helps them look beyond their self-created hell. The truth of their relationship is exposed layer by layer as the play progresses, like the peeling of an onion, and though the pattern of this truth appears vague at first, with each cycle of revelation, the pattern becomes more distinct, and the picture is fully revealed in the final, cathartic scene. One of the most consistent themes of the play is the question of George and Martha's "child," and all that this child, and children in general, symbolizes for them. The "child" seems not only a desire for fecundity within their relationship, but also a projection through which they express many of their personal desires, needs, and problems, and, in this context, the child's subsequent "death" signifies a mi lestone in their understanding of their marriage and of themselves. By the end of play, after much suffering and flagellation, George and Martha appear ready to deal with their lives in a new way. George and Martha have a history. They are also emotionally trapped by this history, especially that of their respective childhoods. As a consequence, both are plagued by low self-image and self-doubt. The audience learns of this history slowly, in bits and pieces. Martha tells Nick and Honey in Act 1 how she lost her mother early and grew up very close to her father. She was married briefly, but her father had the marriage annulled. She returned to live with her father after college, and met and fell in love with George.

The Past, Present and Future of the Hubble Space Telescope :: Exploratory Essays Research Papers

Throughout the ages, humans have been looking for a way to see into the past. In the year 1990, astronomers from NASA made this possible. Sending the Hubble Space Telescope into orbit with the space shuttle Discovery, NASA would make historical discoveries beyond their wildest dreams. Earlier this year they discovered a galaxy approximately 13 billion light years from Earth. Viewing the object at 750 million years after the big bang, scientists have looked into a time shortly after the "Dark Ages," a time before the first galaxies and quasars were formed. This incredible discovery was made with the aid of a cluster of galaxies known as Abell 2218. Being as massive as it is, Abell 2218 bends and amplifies any light that passes through it, working as a natural telescope ("Hubble"). The Hubble Space Telescope has become a great and valuable astronomic tool that NASA says is too costly and dangerous to keep running, a decision that may be premature. Originally planned to launch in 1986, the Hubble Space Telescope has seen its share of problems. Starting with the explosion of the Challenger space shuttle, the Hubble's birth into space was delayed four years (Raven). On April 24, 1990, NASA put the telescope into orbit, only to discover that its primary mirror had a systematic aberration. To fix the problem, a mission in December 1993 set out on the space shuttle Endeavor. The astronauts of the Endeavor replaced the High Speed Photometer with the Corrective Optics Space Telescope Axial Replacement (COSTAR). This device was designed to correct the aberration of the primary mirror. Even before the Endeavor mission, the space telescope produced many interesting images and was much more accurate than any Earth telescope. With the lack of atmosphere, the HST can look at objects at an angular distance of only 0.05 arcs second apart. The traditional ground-based telescopes can only resolve images about 0.5 arcs second apart, even under perfect sky conditions. With the new improvements, the HST could perform at the level for which it was designed. It could more accurately calculate the rate at which a galaxy is "receding from the Milky Way as a function of their distance" (qtd. in "Hubble"). For those confused by that statement: the HST would take a picture of a galaxy at one point and three seconds later (or any other given amount of time) take another pictur e of the galaxy and measure how much farther away it is.

The Success of Wemmick in Great Expectations Essay examples -- Great E

The Success of Wemmick in Great Expectations  Ã‚  Ã‚  Ã‚      Wemmick provides a complicated, yet interesting separation of his home life and work life. His home and work lives are as different in physical appearances as they are in personality differences. Many of his home habits allow him to express his care and decency, which contrasts with his mechanical work which lacks good value. Wemmick dedicates himself to separating the two so that he may keep his virtues intact while he works in the filth of Newgate. Wemmick is alone in his success of separation when compared to others such as Jaggers and Pip. Such dedication to keeping good values alive gives Wemmick so much integrity that he immediately becomes a favorite character.   The castle in Walworth has a drawbridge, a cannon, and a fountain. We see the effects of these defenses first when he raises the drawbridge "it was very pleasant to see the pride with which he hoisted it up and made it fast; smiling as he did so, with a relish and not merely mechanically"(229). He "relishes" or gains pleasure in the working of the drawbridge; as opposed to his mechanical office mode, he really smiles. With this first insight into Wemmick's other side, a simple integrity is revealed. The cannon, named Stinger, is mounted upon "a separate fortress, constructed of lattice-work. It was protected from the weather by an ingenious little tarpaulin contrivance in the nature of an umbrella"(229). The latticework and umbrella cover express Wemmick's imagination in planning the castle. Another of Wemmick's contraptions is his fountain. A mill and a cork run it. The water splashes out enough that it lands on any viewer of the fountain, which the Aged greatly enjoys. He lists his skills and says "and ... ...s the victor in the battle of lifestyles, because his is definitely much more agreeable. In regards to Pip, he cannot separate his home life from his expectations. He is uncaring towards his family and doesn't associate with them. He lives only in expectations as Jaggers does work. Only Wemmick succeeds in separating the two. Those of us who are suffering from a work-centered life should look to Wemmick for inspiration. We can learn from him how to allow ourselves to be able to enjoy life at home, without sacrificing out integrity at the workplace. Wemmick attains a freedom to live life to the fullest and he does it with incredible integrity. He is alone in his success, all the other characters have failed miserably, and have been left unfulfilled. Works Cited: Dickens, Charles. Great Expectations. Ed. Janice Carlisle.Boston: Bedford/St. Martin's, 1996.

Analyzing Diversity in the Workplace

This paper is about designing a model to analyze the dimensions of diversity and implement a training program to implement the results. It is important to break the personality down into three dimensions. Doing this will increase productivity of a company because the employees will work easily together and have less tension. Happy employees increase productivity. The cultural make up of an organization can make or break an organization if it is not understood by its managers and leaders. It is extremely important for a supervisor to analyze the diversity of its organizational members and see how the cultural differences effects the organization. It is important for the leaders of an organization to design a model to analyze the diversity of their the organization so they can develop a cultural diversity training program. In order to understand diversity in culture, you first must break down the culture and person you are trying to understand. We would need to design a model that would break down the dimensions of diversity. It is important to understand the personality of the person. The personality can be broken down into three layers of dimensions; Internal Dimensions, External Dimensions, and Organization Dimensions (knicki) It is important to understand each dimension because if you understand the personality of a person, you will begin to understand how they combine to make a culture. Internal dimensions consist of six different categories which are age, gender, sexual orientation, physical ability, ethnicity, and race. (Knicki) These are things that we cannot control. External dimensions include geographic location, income, personal habits, marital status, parental status, personal status, recreational habits, religions, educational background, work experience and appearance. These, for the most part, are things that we can control. (knicki) Organizational dimensions include functional/classification, work content/field, management status, division department/unit/group, seniority, work location, and union affiliation. These are also mostly our control. (knicki) The above dimensions of personality need to be researched for each employee of an organization. This can come in the form of a survey or questionnaire to each employee. This can also come in the form of a one on one interview asking questions to the employee. The information learned from each the dimensions for each person need to be banked in a data base where the results can be compiled and looked at. (Irwin) After finding out just who is in the organization and finding out their cultural background, the leaders would be able to design a training program for the employees. The program would teach employees about one anothers cultures, and show them how to appreciate each others differences. They would also need sensitivity training. (Loden) Once the organization has undergone a training program dealing with cultural diversity, productivity will increase. When an employee is happy at their job, they tend to work harder and increase their productivity at work. Increasing productivity at the workplace will increase sales which will increase profits. (Jogulu) In conclusion, it is very important to design a model to break down the cultural barriers between employees in a organization. If there are no barriers between people, communication will increase and people will be happier. This will make an organization run more smoothly and there won't be many problems.

Numbermatching.com business strategy

Advertising is an impersonal selling and confabulation method which makes use of various types of media to puree the purport public in suddenly time. Advertising aims at gaining exposure, creating aw arness, changing attitudes of butt customers in favor of sponsors product and operate and also at effecting sales and upward(a) corporate image.Media Selection for No. 1 match Media planning includes decisions relating to which media should be employ and when and how often should advertisements be placed in the selected media. The basic purpose of media planning is to optimise the communication reach to the relevant auditory sense within the available budget. Effective and cost-effective adverting rests on decisions based on collect data from appropriate internal and foreign sources.a) Press (including all types of newspapers and magazines) wider circulation, circumscribed life, full for mass communication and varan mental object.b) purport Mail Restricted circulation, flexible usage, confidential in nature, high impact.c) Outdoor (including hoardings, posters, nor-east signs) local circulation, durable, reminder media.d) Radio bulky reach, cuts through illiteracy barriers, quick reminder messages doable.e) Television Combines both Audio and Visual, limited reach, high grad of visual senseers involvement, competent for product demonstration.f) Miscellaneous (such as order of battle/fairs) Local reach, good product demonstration, impactful solvent. advancement It is through Budget, theme, media, timing. If major resources are to be committed, plan for measurement of promotional military strength should be include feedback from the market place, merchandise research. Like products and prices, customization of advertising and promotion are very much possible in cyber marketing. Besides customization, the customer is contacted when he is well-favoured full attention to the website. In fact, when a customer views any site he has d nonpareil so after discuss and conscious effort and choice. This increases his commitment to the message that he is viewing on the internet.It generates a hierarchy of impacts like creation of awareness, interest, swear and military action on the consumer. Internet has been make to be amenable to finer set for most of these impacts. As a result, it is possible to better transport the customer from one level of impact to the next high one and do so much quickly. The combination of this factor with the feature of individuality makes the output very powerful.Direct sellingAll corporate marketing activities boast to be necessarily carried out in such a way that they tether to generation of surplus funds. Market air division helps in optimising the marketing mix for a segment.The output of a segmentation synopsis is a profile of customer target group focusing on expatiate that result best help to spring up product, promotional, pricing and distribution strategies.The set of benefi ts sought-after(a) to build the configuration of benefits sought and wherefore select benefits in our offering that will constitute a critical proceeds to act as the buying inducement. section of a market is not an dictatorial process, but neither is there a unique set of segments to be discovered. The two approaches, top down and bottom up (logical division and offering) which are used for breach up.Public Relationsmeasuring the degree of success of a public dealings campaign or improving the response of personnel in numbermatch.comMeasuring surgical process against standardsMeasurement of performance against standards should ideally be a forward-looking or on proactive basis with a view to detecting deviations in advance of their occurrences, and should be avoided by appropriate corrective action in advance. The project gutter can often predict presumptive perceive much ahead of schedule, it should be uncovered as early as possible.ReferencesPhilip Kotler (2002), 11th ed ., Marketing Management, PHI-New Delhi

Mia Hamm Research paper Essay

At the beginning of the taradiddle Alice starts off being pressured into marring a man she doesnt even love. Her sister tells her to go get matrimonial and give out merely happily ever later onwards wish her but her husband is cheating on her. I calculate Alices call was when she kept spotting the sporty rabbit in the bushes and began to issue forth him in the spirit of getting purposed to. Also subsequently she fell polish the hole the rabbit was severe to explain to her who she is and how shes supposed to be the acquaintance for wonderland. peg 2 Refusal of Call Alice starts to refuse when she begins notification them that she is not the right Alice their looking for for.I didnt think she would still be refusing even after they showed her the scroll of what happened. I kind of thought she was just saying no because she was afraid of what was ahead of her if she took on the challenge of becoming the champion. Through bug out the beginning and middle of the movie sh e Lyric Perry 9/22/13 World Literature was trying to convince everyone that this was her dream and every social occasion would be ok when she woke up. spirit level 4 go through the first sceptre I thought during the altogether story I think she crossed more than one threshold.The first one was when she fell muckle the hole and entered wonderland because the trees by the two holes were both malformed and looked very similar. Her coming out of the hole to Wonderland to me was like the hybridizing in a new secret land. Another threshold was when she made it up in her mind that she was the hero and started believing in wonderland and the impossible. Stage 5 Belly of the Whale The belly of the whale is when a character is fully enclosed in the new world or adventure. I think she entered the belly of the whale when she began to accept the fact that it wasnt a dream and wonderland is a authorized place. I think that Lyric Perry9/22/13 World Literature the only way she was sledd ing to get out and go back to the real world was to complete her quest and slay the jabberwocky. Stage 6 Road of Trials Alice had lots of trials during her journey such(prenominal) as when the dog/polar bear thing started to chase her and turn up her arm. At the tea party when the red queens knight, soldiers, and bloodhound came looking for Alice I mat it was a trial because if they were to hurt caught her she wouldnt have been able to complete her goal. The passageway of trials is a very important stage because I think they help the character get fixate for what they are or so to embark on.Stage 11 The Ultimate Boon The ultimate boon to me was when she cut the head off of the jabberwocky. This was really important because the undivided fate of wonderland was in her hands. I think the white queen was dep demiseing on her the most because she really treasured the crown and for the red queen to stop anguish Wonderland. Stage 15 Crossing the Return Threshold At the end of th e story I power saw two returning thresholds the first one when she climbed out of the hole and when she started standing up to everyone at the party back home. When she was climbing out of the hole she was crossing back over to the real world and her convention life.She started telling everyone the truth and saying what she really felt even things that sounded impossible. Stage 17 Freedom to get laid I thought this happened for Alice at the very end of the movie because thats when she really decided to live her own life and do what she wanted. Such as she told the man she wasnt red ink to marry him she was going to find someone she loves. Alice starts talking to the man about his business and how he should move it china. Her falling down the hole to me was on purpose to get her to really follow her own bliss not everyone elses.