G-protein Cycle and its Regulation by RGS Proteins

G-protein Cycle and its Regulation by RGS Proteins Julia Weigandt G Proteins, also known asguanine nucleotide-binding proteins, are a family of membrane resident â€Å"go-between† proteins that are important molecular switches in the mediation of GPCR signalling1. In their inactive state, G-proteins exist as heterotrimeric complexes composed of ÃŽ ±, ÃŽ ² and ÃŽ ³-subunits. Upon its stimulation, a GPCR will catalyse the GDPà ¯Ã†â€™Ã‚  GTP exchange at GÃŽ ± leading to the dissociation of the trimer complex as a GÃŽ ±-subunit and the GÃŽ ²ÃŽ ³-dimer, both able to interact with a number of effector systems responsible for cellular responses. Upon hydrolysis of GTP to GDP+P by GÃŽ ±, the G-protein mediated signalling is terminated, whereby a group of proteins, the regulators of G-protein signalling (RGS) appear to play substantial role1,2. Every organ system utilises G-protein mediated signal transduction evoking such diverse outcomes as neurotransmission, immunity, cardiovascular function and hormone secretion3. Consequently, GPCRs present a variety of opportunities as therapeutic targets for treating cancer, cardiac dysfunction, central nervous system disorders and pain. In fact, drugs targeting members of this protein superfamily account for 40% of all prescription pharmaceuticals on the market2. GPCRs constitute the largest and most diversefamily of heptahelical transmembrane receptors  that receive a signal (e.g. small peptides, lipid analogues, amino-acid derivatives, and sensory stimuli such as light, taste and odour2)from outside thecelland transmit this signal to the cell interior via interactions with G-proteins leading to activation of downstream effector systems4. In mammals 21 GÃŽ ±-subunits, six GÃŽ ²-subunits and twelve GÃŽ ³-subunits have been described5. Depending on their GÃŽ ± similarity, G-proteins are grouped into four main classes: GÃŽ ±s, GÃŽ ±i/o, GÃŽ ±q/11 and GÃŽ ±12/13 which show selectivity with respect to both, receptors and effectors due to the presence of recognition domains complementary to G-protein binding domains in receptors/effectors6. The main targets for G-proteins include adenylyl cyclase, phospholipase isoforms, Rho A/Rho kinases (a system that controls mainly signalling pathways involved in cell growth/proliferation), and the mitogen a ctivated protein kinase (involved in the control of many cell functions such as cell division), and ion channels7,8. In its inactivated state the complex is freely diffusible in the plane of the cell membrane due to fatty acid chain anchors on each subunit7. Stimulation of GPCRs by agonists leads to conformational changes in the receptor resulting in the acquirement of high affinity to the G(ÃŽ ±ÃŽ ²ÃŽ ³) complex. Due to their subsequent association, a GDP->GTP exchange in the ÃŽ ±-subunit will occur leading to dissociation of the G-protein complex from the receptor in form of a GÃŽ ±(GTP)-subunit and a GÃŽ ²ÃŽ ³-dimer. Prior the activation of the G-protein the GÃŽ ²ÃŽ ³-dimer is bound to a hydrophobic pocket present in GÃŽ ±-GDP. GTP binding to GÃŽ ± removes the hydrophobic pocket and reduces the affinity of GÃŽ ± for GÃŽ ²ÃŽ ³9. Both have a signalling function and can interact with various downstream effector systems 7,9. The duration of G protein-mediated effector activation is dependent on the intrinsic GTPase activity of the GÃŽ ±-subunit. GTP-hydrolysis results in dissociation of GÃŽ ±(GDP) f rom the effector to reunite with GÃŽ ²ÃŽ ³ completing the cycle7. Several studies have shown that the kinetics of G-protein signalling are regulated by RGS proteins that can not only act as GTPase activating proteins (GAPs) on GÃŽ ±-subunits hereby accelerating GTP-hydrolysis, but also as scaffolds to help assemble signalling complexes and providing a critical mechanism of regulation of cellular responses10. Over 30 RGS/RGS-like domain containing proteins have been described and classified into nine distinct subfamilies based on primary sequence homology and presence of additional domains, including the A/RZ (prototype RGSZ), the B/R4 (prototype RGS4), the C/R7 (prototype RGS7), the D/R12 (prototype RGS12), the E/RA (prototype Axin), the F/GEF, G/GRK, H/SNX and I/D-AKAP2 subfamilies3,10,11. They differ widely in their overall size and amino acid identity, and many family members possess a remarkable variety of structural domains and motifs that regulate their actions and/or enable them to interact with other binging partners with diverse cellular roles. RGS proteins have a highly conserved RGS domain of 120 amino acids3,11 which allows for selective binding to the transition state of GÃŽ ±(GTP->GDP+P)8 , accelerating the GTP-hydrolysis up to a 1000-fold5,10 by stabilising this transition. Some studies have shown that RGS proteins can also act as effector antagonists by binding tightly to GÃŽ ±(GTP), hereby blocking effector activation5,11. It has been suggested that simple RGS proteins (those of A/RZ and B/R4) have an almost exclusively negative regulatory function acting as modulators of G-protein signalling as for instance shown by the function of RGS4, an effective GAP protein for GÃŽ ±q family members. In mammalian cells RGS4 doesn’t block the receptor and GÃŽ ±q/11-directed inositol lipid/Ca2+ signalling completely but elicit rhythmic Ca2+ oscillations in mammalian cells10, 11. On the contrary, the larger RGS proteins can link active GÃŽ ±s to other signalling pathways and therefore serve as multifunctional integrators. Integration can occur via activation of kinases, recruitment of cellular scaffolds/associated proteins or by direct receptor interactions11. Two of the R12 family members (RGS12 and RGS14) were shown to coordinate components of the Ras/Raf/mitogen-activated protein kinase signalling pathway8,10. RGS proteins display specificity and selectivity in their interactions not only with G-proteins, but also GCPRs, ion channels and other signalling events3,5 which may be accomplished by firstly, differences in GAP activity towards different types of GÃŽ ±-subunits (e.g. RGS19 was shown to interact strongly with GÃŽ ±i1, GÃŽ ±i3 and GÃŽ ±o, weakly GÃŽ ±i2 but not with GÃŽ ±s and GÃŽ ±q5; secondly, the ability to interact with specific GPCRs or with effectors within the GPCR signalling axis directly, due to presence of characteristic structural domains and motifs (e.g. RGS2 and RGS4 bind selectively the 3rd intracellular loop of M2 and M5 muscarinic receptors5); thirdly, by formation of an RGS/G-protein complex that prevents the G-protein from binding its receptor or the downstream effectors; and lastly, by co-expression of the RGS-proteins with its target protein(s) in order for selective interactions to take place. An example is illustrated by the expression of the alternative splice d RGS9-1 and RGS9-2 in entirely different tissues, thus having different functions and selectivity for different targets. While RGS9-1 is expressed in the photoreceptor cell layers of the retina and is involved in the phototransduction pathway by regulation of photoreceptors, RGS9-2 is predominantly found in the brain and shows selectivity for the regulation of dopamine D2 and opioid  µ receptor signalling pathways5. RGS proteins play and essential regulatory role in G-protein mediated signal transduction, being able to regulate a great number of GCPR signalling events with great specificity and accuracy. By fully understanding the mechanisms and the significance of their expression, role and targets it can lead science to advances in the development of novel therapeutic drugs against disorders involving G-protein mediated signalling. References Baltoumas, F. A., Theodoropoulou, M. C., Hamodrakas, S.J.; Interactions of the a-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: A critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials. Journal of Structural Biology.2013;(182):209-218 Filmore, D.; Its a GPCR world. Modern Drug Discovery  (American Chemical Society).2004; (November): 24–28 Bansal, G., Druey, K.M., Xie, Z.; R4 RGS proteins: regulation of G-protein signaling and beyond. Pharmacology and Therapeutics. 2007;116(3):473-495 Joost, P., Methner, A.; Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands.Genome Biology. 2002;3(11): research0063.1–0063.16 Xie, G.X., Palmer, P.P.; How regulators of G protein signaling achieve selective regulation. Journal of molecular biology. 2007;366(2):349-365 CABRERA-VERA, T.M., VANHAUWE, J., THOMAS, T.O., MEDKOVA, M., PREININGER, A., MAZZONI, M.R., HAMM, H.; Insights into G Protein Structure, Function, and Regulation.  Endocrine Reviews. 2003;24(6):765-781 Rang, H.P., Dale, M.M., Ritter, J.M., Flower, R.J., Henderson, G.; Rang and Dales Pharmacology. 7th ed. UK. Elsevier Churchill Livingstone ; 2012; 3(32-33) Kimple, A.J., Bosch, D.E., Giguà ¨re, P.M., Siderovski, D.P.; Regulators of G-protein signaling and their GÃŽ ± substrates: promises and challenges in their use as drug discovery targets. Pharmacological Reviews. 2011;63(3):728-749 Oldham, W.M., Hamm, H.; Heterotrimeric G protein activation by G-protein-coupled receptors.NATURE REVIEWS | molecular cell biology. 2008;9:60-71 Keinan, D., Yang, S., Cohen, R.E., Yuan, X., Liu, T., Li, Y.P.; Role of regulator of G protein signaling proteins in bone.Front Biosci (Landmark Ed). 2014;1(19):634-648 Hollinger, S., Hepler, J.R.;. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling.Pharmacological Reviews. 2002;54(3):527-559

A Financial Analysis Of 3m Finance Essay

A Financial Analysis Of 3m Finance Essay Currently, 3M operates in more than 65 countries. The company produces a large variety of products, such as: adhesives, abrasives, laminates, passive fire protection, dental products, electronic materials, electronic circuits and optical films. 3M started operating on the North Shore of Lake Superior in Two Harbors, Minnesota in 1902. Five businessmen (Henry S. Bryan, Hermon W. Cable, John Dwan, William A. McGonagle, Dr. J. Danley Budd) came together to mine a mineral deposit used for manufacturing grinding-wheels. As it turned out, the deposit didnt have much of a value, so they opted to concentrate on sandpaper products. In 1914, 3M launched its first exclusive product: Three-M-ite cloth. Few other innovative products followed: waterproof sandpaper, masking tape, and the very well known Scotch brand tape. In 1929, 3M decided to expand its business internationally and started operating in Europe. The same year, the companys stock was first traded over the counter. In 1946 the company went public on the New York Stock Exchange (ticker symbol MMM). The company is a component of the Dow Jones Industrial Average and of the SP 500.  [1]   1.2 Company Profile 3M Company is an American transnational enterprise based in Maplewood, Minnesota, and represents one of the major players in the conglomerate industry. Below are presented some of the highlights that compose the companys profile: 3M Co.  [2]   3-M Center St Paul, MN  55144-1000 Index Membership: Dow Jones Composite Dow Industrials SP 100 SP 500 SP 1500 Super Comp Sector: Conglomerates Industry: Conglomerates Employees (last reported count): 74,835 1.2.1 Organizational Structure 3Ms general offices and research laboratories are located in St. Paul, Minnesota. Locally, 3M has nine sales offices and operates 74 manufacturing facilities. Outside the United State, 3M has 148 sales offices and 93 manufacturing .3M owns all of its physical properties.  [3]   Key Executive: Bellow, there are presented few of the key people that are currently running this enterprise: Mr. George W. Buckley, Chairman, Chief Executive Officer and President Mr. Patrick D. Campbell, Chief Financial Officer and Senior VP Mr. Inge G. Thulin, Executive VP of International Operations Mr. Brad T. Sauer, Executive VP of Health Care Business Mr. Jean Lobey, Executive VP of Safety Security Protection Services Business.  [4]   2. Major lines of business  [5]   3M serves its customers through six business segments: 1. Consumer and Office (15% of total sales). 3M is providing its customers with a large variety of products such as house cleaning materials and office supplies. Some of the most popular ones are: Post-it ®, Scotch ®, Scotch-Brite ®, Filtreteà ¢Ã¢â‚¬Å¾Ã‚ ¢, O-Cel-Oà ¢Ã¢â‚¬Å¾Ã‚ ¢, Nexcareà ¢Ã¢â‚¬Å¾Ã‚ ¢, and Commandà ¢Ã¢â‚¬Å¾Ã‚ ¢ 2. Display and Graphics (13.5%). As a top technological innovator, 3M provides its customers with products such as: display enhancement films; reflective materials, graphics, and projection systems. 3. Electro and Communications (9.8%). Due to its continuous innovative efforts, 3M managed to provide solutions for customers in many fields: electrical, electronics and communications. They contribute to reliable sources of electrical power, high-performance electronic devices, and reliable, high speeds telecommunications network. 4. Health Care (18.6%). 3M is considered a global leader in medical and oral care products, drug delivery and health information systems, providing its customers with innovative and trustful products that help care professionals improve the quality of care services. 5. Industrial and Transportation (30.8%) The company supplies a large variety of innovative products such as tapes, abrasives, adhesives, specialty materials and filtration systems to different markets: from automotive to aerospace to renewable energy to electronics. 6. Safety, Security and Protection Services (13.8%). 3Mproducts-personal protective equipment, safety and security products, substantially contribute to the safety, security and productivity of people, facilities and systems around the world. 1.3 Operating Strategies 1.3.1 Mission Statements and Management Objectives: The main mission statement and management objectives, as presented in the companys annual report are: Demonstrate uncompromised honesty and integrity in all activities and relationships. Promote individual initiative , innovation and leadership, Establish and maintain a culture dominated by fairness and trust, where respect and responsibility, are valued and recognized. Create a safe workplace for 3M employees. Satisfy customers with high quality products and services. Provide investors with an attractive return. Respect the social and physical environment worldwide. 1.3.2 Business model and Strategies 3M business model is based on the ability to not only develop unique products, but also to manufacture them efficiently and consistently around the world (3M).   [6]   3M is a diversified technology enterprise with an international presence in different businesses, such as: industrial and transportation, healthcare, display and graphics, consumer and office, safety, security and protection services, and electro and communications. The industrial and transportation business includes products such as food and beverage, personal care, and automobiles. Industrial products include polyester, foil, and tape. Transportation sector provides the market with different types of insulation components and catalytic converters. The health care segment produces supplies and equipment for medical and dental use. The display and office business supplies stationary products, and home-improvement products. Besides the already mentioned business sections, 3M also manages a safety segment and an electro and communications segment. In order to remain a respected leader in its field, 3M employs a series of strategies. The company is continuously trying to increasing market share and the popularity of their brands. Also they make significant efforts to maintain existing customers and attract new ones. This is a very important issue considering the number of substitute products currently available on the market. Besides the already mentioned strategies that 3M employs in order to run a successful business, they also practice a very interesting hedging strategy .Instead of concentrating on a single industry, 3M operations are spread over a large variety of sectors. So, at any point in time, the effect of a slow growth sector is counteracted by the prosperity of another sector. Due to this hedging strategy, the company stock price manages to maintain relative stability.  [7]   Also, they continue to spend significant amount of funds on RD, which is critical for their image as a leading innovator, pay dividends, buy back stock and raise shareholders equity, the chief aim being the ability to offer a good return to all their investors. This is a solid company, with a very high degree of liquidity in an extremely good financial health. Another strategy that makes 3M well known is there acquisition strategies. On an average, the company performs ten to twenty acquisitions every year. This enables 3M to continuously grow, penetrate new markets and explore new technologies. Other strategies that 3M employs refer to continuous innovation, in order to introduce new products to various markets that company operate in, gaining market share in the existing markets and aiming to become more and more important to the end customers. 1.4 SWOT Analysis SWOT is a strategic planning method used to evaluate the strengths, weaknesses, opportunities and threats involved in a business.  [8]   3M SWOT analysis:  [9]   Strengths: The company operates in a large variety of business sectors: industrial and transportation, healthcare, display and graphics, consumer and office, safety, security and protection service, electro and communication. Strong research and development capabilities. (According to 3M 2009 Annual Report, the company spent more than a billion dollars in RD). Multinational presence. The company operates more than 65 countries. Solid financial condition. (A complete Income Statement and Balance Sheet are presented in the annexes). Weaknesses: Low inventory turnover, which impacts inventories and margins. Some key segments are registering inferior performance. Strong and aggressive competitors. Opportunities: Acquisitions in key operating areas. 3M performs an average of 20 acquisitions every year. Continued global expansion. Healthcare spending levels in the US are increasing. Security concerns caused by a weak US economy, combined with some unfortunate events that are threatening the safety of American people, (9/11/2001, N1H1 virus infection) brings new opportunities for 3M security business. Threats: The fluctuation of commodity and energy prices (increasing).In order to mitigate this risk, the company is engaging in a multitude of forward physical contracts and price agreements. Exchange rates fluctuations. The company operates worldwide, so the exchange rates and any fluctuations of it may negatively impact the companys results. Environmental regulations. People are becoming more and more aware of the importance of respecting the environment. Any new rules and regulation may require additional funds to be invested in order to work green. 1.5 Core competencies A core competence represents the companys collective knowledge about how to coordinate diverse production skills and technologies (C.K. Prahalad and Gary Hamel).  [10]   3M runs an extremely diversified business, spread over numerous sectors: industrial, transportation, display and graphics, security etc. In order to manage and keep all this different types of businesses together, the company holds competencies in substrate, coating and adhesives. Besides possessing these competencies, the company also created a multitude of ways to share and apply them. The result of such combination of technology, skills and knowledge, allows 3M to participate on a multitude of businesses and markets. The literature points out that the core competencies of any company should benefit the end customer of the product and should be very difficult to copy by the competitors. 3M is aware that the stronger the customer perception in recognizing the superiority of their products, the less likely the threats of substitutes. The company makes continuous efforts to differentiate its products among the multitude of similarities offered by the competitors and their efforts are successful due to the fact that they are supplying high quality, innovative and reliable products at competitive prices. Moreover, it is a companys core competencies that keeps the businesses together. This aspect is crucial for 3M, as the company operates in multiple business sectors, worldwide. It seems that 3M fully understood this concept and its enormous advantages, because they are investing consistently in their core competencies and ability to innovate, the chief aim being to provide the market and the end customers with innovative products that really stand out. 2. Industry analysis 2.1 Industry Definition, Structure and Major Competitors. The Industrial Conglomerate industry consists of large organizations engaged in multiple business lines within the industrial sector, where at least two business lines comprise a substantial portion of the companys total operation (The New York Times, Oct 1, 2010).  [11]  The industrial conglomerate industry contains the following sectors: Basic Materials, Consumer Cyclical, Consumer Non-Cyclical Energy, Health care, Industrials and Transportation, Technology, Telecommunication, Utilities. Exhibit1. Direct Competitor Comparison  [12]   MMM AVY DD JNJ Industry Market Cap: 63.58B 4.02B 42.30B 174.16B 9.47B Employees: 74,835 31,300 58,000 115,500 28.26K Qtrly Rev Growth (yoy): 17.70% 15.40% 21.80% 0.60% 14.50% Revenue (ttm): 25.39B 6.31B 30.43B 62.59B 10.28B Gross Margin (ttm): 48.78% 28.26% 29.94% 69.98% 33.80% EBITDA (ttm): 7.03B 695.10M 5.42B 19.70B 1.63B Operating Margin (ttm): 23.18% 6.96% 13.08% 26.90% 12.29% Net Income (ttm): 3.94B 250.90M 3.13B 13.53B N/A EPS (ttm): 5.48 2.37 3.43 4.84 1.92 P/E (ttm): 16.28 16.04 13.60 13.06 19.15 PEG (5 yr expected): 1.28 1.44 1.61 2.09 1.28 P/S (ttm): 2.50 0.63 1.38 2.78 1.27 AVY = Avery Dennison Corporation produces pressure-sensitive materials, office products, tickets, tags, labels, and other converted products. DD = EI DuPont de Nemours Co. (DuPont) operates as a science and technology company worldwide. JNJ =Johnson Johnson engages in the research and development, manufacture, and sale of various products in the health care field worldwide. The company operates in three segments: Consumer, Pharmaceutical, and Medical Devices and Diagnostics. Industry = Conglomerates Exhibit2. Comparison between 3M, the Conglomerate Industry and the direct competitors, benchmarked against DOW and SP 500. Source: http://finance.yahoo.com 2.2 Industry profitability and growth. In order to get an idea about the main characteristics of the players in this industry, I have selected few key statistics. The financial indicators listed bellow shows the fact that this are large companies, highly leveraged (most of them), providing the investors with a small to average return. Market Capitalization: 366B Price / Earnings: 13.5 Price / Book: 4.1 Net Profit Margin: 7.5% Price to Free Cash Flow: 27.4 Return on Equity: 12.5% Total Debt / Equity: 242.3 Dividend Yield: 2.4% Exhibit 3. Comparison between the evolution of 3M common stock and the industry. Source: http://finance.yahoo.com 2.3 PEST Analysis of the External Factors affecting the Industry PEST analysis stands for Political, Economic, Social, and Technological analysis and describes a framework of macro-environmental factors used in the environmental scanning component of strategic management.  [13]  Performing such an analysis and applying the findings will give any company a significant competitive advantage. The model identifies four factors that have a major impact on the companys macroeconomic environment:  [14]   Political Economical Social Technological Political Factors: Among the most significant political factors that can affect 3Ms business are: tax policies, employment laws, environmental regulations, trade restrictions and tariffs, and political stability. 3M is making all the necessary investments in order to comply with these laws. In 2009, 3M spent around $15 million for projects regarding the protection of the environment. The mentioned funds have provided among other things, pollution control devices at all its properties. Economical Factors: economic growth, interest rates, exchange rates, inflation rate. Due to large geographical presence, and the fact that 63 percent of its revenue is generated from outside the United States, the companys results may be affected by exchange rates and their fluctuation. In order to mitigate this risk, the company engages in a multitude of forward contracts. Also, the Companys business may be negatively affected by other factors, both internal and external that are beyond its control, such as instability and downturns in financial markets or economies in some countries or regions, in which the Company operates. Social Factors: population growth rate, age distribution, health and safety awareness, career attitude. 3M, through its business policies is aiming to create a safe workplace, to encourage individual initiative and innovation in an atmosphere of flexibility, cooperation and trust, promoting a culture where promise keeping, fairness, respect and personal accountability are valued, encouraged and recognized.  [15]   Technological Factors: RD activities, automation, technology incentives, rate of technological change. Research and development activities constitute an important part of 3Ms business and have been a significant contributor to the companys sales growth. Research, development expenses accounted for $1.2 billion in 2009, $1.4 billion in 2008 and $1.3 billion in 2007.  [16]   2.4 Porters Five Forces Analysis of the Industry Competition Porters five forces is a framework for the industry analysis developed by Michael E. Porter of Harvard Business School in 1979 .The model is based on the idea that competitive advantage came from the ability to earn a return on investment that was better than the average for the industry sector(Thurlby,1998). The model identifies five forces which would impact on an organizations behavior in a competitive market: The rivalry between existing sellers in the market. The threat of new entrants on the market. The threat of substitute products available in the market The bargaining power of the suppliers. The power of the customers in the market. Full comprehensions of each of these five forces and the impact they have on the companys business, provide organizations with the necessary information to enable them to choose the right operating strategy in order to be successful in their market.  [17]   2.4.1. The rivalry between existing sellers in the market The conglomerate industry, although very complex, extending over a multitude of business, seems to be dominated by few key players, and 3M Co is one of them. In order to gain competitive advantage, 3M is aiming to stay ahead of the trend by continuously providing the market with new products and technologies. Given its strong balance sheet, the company is able to react fast to any negative changes in the market (lower the price of its products), in order to maintain existing customers and attract new ones. Moreover, in facing competition the company is offering well differentiated products, well known and trustful brands, the chief aim being extra value added products and services for the end customers. 2.4.2. The Threat of new entrants The threat of new entrants is dictated by the market entry barriers. The entry barriers exist whenever it is difficult or not economically feasible for an outsider to replicate the incumbents position (Porter, 1980b; Sanderson, 1998). Such barriers refer to: Cost of entry: In order to enter this industry and compete against the existing firms, the cost of capital required would be extremely high. 3M is a well known company, with an aggressive mergers and acquisition strategy, holding an impressive market share. Distribution channels: 3M products are sold through numerous distribution channels, including wholesalers, retailers, and dealers in many countries around the world. The company has established a large and very well defined distribution network, developed through long association with skilled marketing and sales representatives. Cost advantages not related to the size of the company, like contacts and expertise play a major role in the companys performance. Government legislations: for example, introduction of new laws might weaken companys competitive position; 3M had to improve their environmental performance via new environmental, health and safety policies in order to comply with new government standard and regulations. Many times this requires additional funds, changes into production processes, products, and that some firms may find it difficult to do so without increasing the prices of their products and services. Differentiation: 3M is a well known brand that already gained customer respect and loyalty and the products that represent this company have a high ratio of value to price. 2.4. 3. The Threat of Substitutes Products available on the market Although the threat of substitutes in this sector is high, due to the fact that there is a large number of a substitute product available in the market, 3M products differentiate themselves through superior quality and innovativeness. The firm invests strongly in RD, in order to insure that they deliver extra -added value products, and the existing customers will not be tempted to choose from the many available substitutes. Other aspects that should be considered when trying to mitigate the risk of losing customers to substitute products refer to: relative price performance of substitute, buyer switching costs, ease of substitution, substandard product, and quality depreciation. 2.4.4. The bargaining power of suppliers In the conglomerate industry, the power of supplier is relatively modest, due to the fact that the companies in this industry are very large corporations. This companies act on an international scale, having access to an increase number of suppliers and the buying is done in bulk, immense quantities. There is still some risk regarding the price fluctuation of commodities, like oil, oil derivatives, energy, due to possible shortage. 3M is trying to mitigate this risk engaging in prices agreements and forward physical contracts. 2.4.5. The bargaining power of buyers. When trying to assess the power of buyers, two aspects need to be considered: size and concentration of the customers correlated with the concentration of the competitors. In the conglomerate industry, the bargaining power of the buyers is relatively high due to the fact that all the players in the market are targeting the same customers via similar products. Also, the end customers are more and more informed, and their expectations are continuously growing. Another aspect that should be considered in this case is that the cost of switching between suppliers is relatively low. A buyer has many options; therefore 3M makes a continuous effort to insure that their products are permanently aligned with customer preferences and needs. 2.5 Summary The nature of competition in an industry is strongly affected by the above mentioned forces. As a rule we can state that, whenever buyers and suppliers have high degrees of power, the result translates into a high competitive industry. The industry of conglomerate is moderate to high competitiveness, due to the fact that new entries are difficult (high capital requirements), but this effect is counteracted by the fact that the players in this sector are extremely large and diversified corporations, with solid resources and very aggressive financial strategies. 3. Economic Outlook 3.1 Global Outlook There is no doubt that we are on the path of economical recovery, but the speed of things moving in the right direction is slow, considering the severity of the financial crisis. In advanced economies, such as U.S., small improvements in labor markets, housing markets, and corporate bonds market generated some positive developments in the overall economy. In the emerging and developing economies, (such as China, India, and Brazil) the recovery process seems to be much faster. Even among the advanced economies, the recovery process happens at different speeds, depending of the way that the local government has chosen to deal with the crisis. If we compare The United States with Europe or Japan, we see that the American economy is doing much better than the other two. This phenomenon may have something to do with some of the following: fiscal stimulus was larger in US, the nonfinancial corporate sector is less reliant on bank credit, bond markets have improved which stimulated investments, and many financial and nonfinancial organizations went radical restructuration and improved productivity. In Japan, due to the appreciation of the yen, the countrys exports f eel dramatically, which ultimately impacts the recovery process. Similar situation can be observed in Europe. Some of the economies of this region suffered a major contraction, not only because of the financial crisis, but the real estate too. Overall the economical and financial conditions present themselves as fragile and difficult. There are some signs of recovery, especially in the emerging economies, and is expected that this will help along the recovery process of the advanced economies.  [18]   3.2 Regional outlook Asia is leading the global recovery and the regions contribution to global growth will continue to exceed that of other regions in the next two years, (Source: The International Monetary Fund). China registered 8.4 percent growth last year, and the projections for the next year are similar (9%growth in GDP for 2010). In the region, the GDP has increased 6.8 percent in 2009. The recovery process has been driven by exports combined with low internal demand and ultimately low household consumption. The inflow of capital in the region has increased, stimulating investments and speeding up the recovery process. According to IMF, for the next period of time, Asias main policy challenge will remain to achieve a rebalancing of growth from external to domestic sources. On global level, there is a political and economical issue regarding the Chinese government decision not to appreciate their local currency, and the way this decision is affecting the world trade. Europe, especially the emerging nations, was strongly hit by the financial crisis. In this region the GDP decreased by approximately 4.6 percent in 2009. The projections for 2010 GDP show an increase of 2.3 and 2.2 percent in 2011. The growth rates in most economies in the region will remain slow, due to major contraction in exports and weak capital inflow. Besides the already mentioned factors, other variables such as : high unemployment, real estate crisis, bank restructuring operations, tight credit policies, and high interest rates will also restrain the recovery process. Other regions, such as Latin America and the Caribbean seem to be dealing with the crisis a little bit better than other countries .The last year GDP registered a 2.6 percent drop, and the prognosis for 2010 and 2011 are quite optimistic showing a growth of 3.1 percent and 3.6 percent, respectively. The recovery process is still relatively slow, due to weaker investment and not enough tourism, both important sources of external finances. The lack of tourism may be explained by high unemployment in United States and other high-income countries. The Middle East and North Africa region experienced, an overall GDP growth slowing to 2.9 percent in 2009. The forecasts for 2010 show an increase in GDP of 3.7 percent in 2010 and 4.4 percent by 2011. These projections regarding the recovery process are based on few assumptions such as: the global demand for oil will increase, and oil prices will stabilize. The financial and economical crisis and their effects were not felt as deep in the region of South Asia. In this area, the GDP registered 5.7 percent growth in 2009. This represented a slowing of growth comparing to the boom period, mainly due to a significant decrease in investments, correlated with low domestic demand. The projections for 2010 and 2011 look optimistic: 6.9 and 7.4 percent respectively. 3.4 Local outlook According to the U.S. Bureau of Economic Analysis (BEA), the US economy is still growing, but at a slower pace than the first quarter of 2010(2.4% versus 3.7% in the first quarter of 2010). Some of the reasons that will restrain the recovery process are the following: The financial institution will need to recover from losses due to loan defaults. In order to boost the recovery process, the government offered numerous stimulus packages. The housing market registered slight improvements, but failed to meet the expectation. The main disruption in the housing sector was caused by a dramatic drop in house prices, and hou

Violence In Sports :: essays research papers

Violence in Sports To: Mrs. Woods From: Jean-Philippe Do you think there's a connection between sports and violence? If you do, do you think it should be banned? I too think that it's connected but, unlike most people, don't think it should be banned. I have many reasons to believe so and I will state them in my essay. First I will point out that not all sports include violence. Not many actually express violence, the only ones that do contain violence are team sports. I'm not saying that I dislike team sports, au contraire I love team sports, they help build team spirits. All I'm saying is that sports like football contain lots of violence, unlike individual sports like ping pong or kayaking. Some sports are now becoming so violent that it's almost impossible to remove the violence without removing the sport itself. Lots of people protest because some sports are too violent and they're trying to take the violence away by banning them. What they don't realize is that there are billions of fans that are obsessed by those sports and by taking a sport away from them, could ruin their lives. Trying to stop the violence is almost like trying to declare world peace. There will always be someone who either picks a fight or builds an underground organization. Football, hockey, soccer, and all those other violent sports will be practiced until the end of the world. Another reason why I don't want these sports to be cut is because when you practice a sport like football it helps you release all that frustration and energy you have inside. By releasing all that pressure it helps you relax for a period of time. Getting rid of popular sports like hockey or football could put a lot more kids on the streets because they would have nowhere else to go or nothing else to do. Some people tell others to keep their kids out of team sports to avoid getting involved in a gang. What those people don't realize is that those kids that never played a team sport

Fitness Training :: essays research papers fc

Most fitness and training facilities now have stability balls, foam rolls, balance boards and other â€Å"fun† toys as part of their conditioning equipment. These are part of a new trend in the strength and conditioning field called â€Å"functional training†. Definition Functional training is the action of training â€Å"function†, a general term that meaning â€Å"role or duty†. Functional training is the science of training the body to meet the specific demands of life and sports. It is based on 1) the principle of specificity and 2) muscle function. The principle of specificity also known as SAID (Specific Adaptations to Imposed Demands) means that the body responds and adapts specifically to the type and amount of physical demands under which it is placed. In other words, you only improve what you’ve specifically trained. Since muscle form dictates the role and function of each muscle, muscle needs to be trained the way it is designed to funct ion. Origin Functional training is nothing new and comes primarily from the rehabilitation field. For many decades, therapists have been experimenting with ways of helping their patients regain function. Their goal is to retrain muscles to work properly using special exercises. In their quest to help their patients to become more functional, they have a developed functional training approach. Traditional vs. Functional Traditional strength training usually consists of trying to develop strength and build muscle through isolating specific muscle groups. This type of training could be called dysfunctional training and only develop segmental strength. Traditional strength training is adequate for building muscle but it does not train the body to meet the specific demands of life and sports. It does not reproduce real life conditions and only serves to create non-functional strength. Peter Twist, Vancouver Canucks Strength and Conditioning Coach, explains: â€Å"Typical strength traini ng attempts to develop the body through a piecemeal approach, isolating specific muscle groups. Worse yet, this is often done with the body unloaded, sitting stationary on a machine while moving one isolated body part through a controlled range of motion, usually in a strict linear, straight ahead motion†. Traditional strength training train isolated muscle function while functional training train the body to work as a unit. The central nervous system is programmed to make the body function as a unit, not to work in terms of isolated muscle function. Functional training is â€Å"functional† since it trains the body the way it has been designed to function.

Relationships Essay -- essays research papers

Whether it occurs in the home, at work, or many other places, human beings maintain relationships everywhere they go. People have different types of relationships. A person keeps a relationship with their mother, pastor, friend, and boss, but those relationships are all different. There are many different elements to analyze when discussing a relationship. Many factors are involved, such as amount of time spent, amount of intimacy, types of activities participated in, and dependability of the relationship.The first type of relationship a person typically has, are ones that are formed within a religious setting, such as a church, temple, or synagogue. The amount of time spent within this relationship varies depending on how much type an individual devotes to his or her religion. However, the amount of intimacy is usually very high, as one divulges most, if not all, of their personal problems and issues. The relationships formed within the religious setting is usually dependable in that one can rely of the people within the religious circle for advice and counsel, through the bond of a common faith. One participates in limited activities within this relationship, ones that are exclusive to activities that are in the religious setting, such as church bake sales and Sunday mass.Secondly, another type of a common relationship are formed within a club setting such as athletics and parties. The people one encounters in these types of settings may be very close to them, but only within the boundaries of a club. For example, two people on a football team may shed blood, sweat, and tears for each other, but not necessarily be the best of friends after the season. In sports, the time spent with each other is usually a lot, a couple of hours every day at the very least. The amount of intimacy shared within athletics is not always abundant. The information shared between usually shared between teammates stays within the boundaries of the particular sport in which they are participating. Likewise, dependability is not required for purposes other than those related to athletics. For example, a football player can depend on his teammates to block for him in the game, but not to pay off his mortgage. Activities shared with teammates are most often limited to athletic practices, games, and gatherings related to the particular sport.In comparison to athletics, party fri... ...huge factor. Nobody knows and cares for a person better than their family. Likewise, when someone is trouble or needs some advice, the family is usually the most dependable people to go to. One's family will help them get through mostly everything. From monetary problems to marital problems, one's family will always be there for a shoulder to lean on. Activities shared within a family are just about anything that is family-related, like a nightly dinner or family reunions.Throughout one's life, many types of relationships are developed, each with their own guidelines and elements. It is impossible for a person to go through life withouthaving at least one type of relationship. Even hermits like the Unabomber had relationships here and there. He had teachers, family, friends, and co-workers, just like the rest of the population. Whether it occurs at someone's workplace, church, school, or in their home, people maintain relationships wherever they go. Just as there are many factors involved, such as amount of time spent, intimacy, types of activities, and dependability of the relationship, all different types of relationships are a necessity for one to live a normal, healthy life.

Reporting Abuses Essay

Every child must be protected from harm because it can cause many negative effects like trauma, physical and psychological disorders and any other illness that may effect their growth. So, the government makes a law that helps the child from being abused. This law can be found on Penal Code Section 11164 – 1174.4.3 (California Child Abuse and Neglect Law, 2007). This law aims to protect children and to give the rights of every child. This law also states that failure to report any abuses will consider a crime. In this way, everyone will be aware that they have the responsibility to protect every child, even if you don’t know them (California Child Abuse and Neglect Law, 2007). There are several cases of child abuse in our society but with the help of other people, it has been stopped like the story of Jenny (not her real name). She is a 4 year-old girl that lives with her father. Her mother was in the other country to work. Jenny was abused by his father and the poor little kid can’t do anything. One concerned neighbor report this incident. She reports all the maltreatment Jenny’s father do. Jenny’s father was caught and the child was claimed by the social welfare society until her mother arrives. Now, Jenny is living with her mother and her father was still in jail. This incident is an example of child protection. Jenny’s neighbor, even though she never knew her, helps Jenny and gives her the right to enjoy childhood. Based on Ethical Standards of Human Service Professionals, we must protect them from any harm. We must guide, educate, and provide them what they need for them to grow physically, psychologically and socially normal (Ethical Standards of Human Service Professionals, 1996). Reporting child abuses doesn’t mean that you won’t get any protection. The law also states that any reporters will get the protection needed to protect them. In this way, the concerned people won’t be afraid of reporting anyone who commits this crime. Their identity will remain confidential and they will have immunity for civil and criminal liability. The government also ensures that every report is true because if it is false, the reporter will suffer the consequences (The Code of Ethics and Good Practice for Children’s Sport in

Office Depot

â€Å"Office Depot† The First Office Depot opened in 1986 in Lauderdale Lakes, Florida. The Office Depot is a global supplier of office products and services and has experienced a dramatic growth process over the past twenty-five years. In 1990 the Office Depot Companies bought â€Å"The Office Club Inc. †, and immediately became the largest office retailer in North America. Having built its business within the United States and having secured a firm business foundation, Office Depot expanded internationally in 1992. In 1996, Office Depot took its’ catalog and delivery service(s) online.Office Depot opened about 125 stores between the years 2000-2004. With the economic downturn of 2007, new strategies had to be put in place, and by 2009, 125 stores in international markets were closed. Office Depot exited the Japanese market entirely. Today, Office Depot provides office supplies and services through 1,678 retail stores worldwide, a dedicated sales force, top-rate d catalogs, and global e-commerce operations. Office Depot has annual sales of $11. 5 billion, employs roughly 39,000 employees, and serves customers in 61 countries.Their distribution channels include stores, direct mail, contract delivery, the internet, and B2B e-commerce. Viking Office Products, their wholly owned subsidiary, currently operates one of the industry’s leading direct mail marketers of office products worldwide. The competitive strategy that the Office Depot will approach is a â€Å" best-cost provider strategy† to become #1 in the office supply business. For online purchases, customers will be offered free shipping on any purchase over $25. 00. A promotional discount will be applied for 20% off, on the next purchase for every $100. 00 spent by the customer.There will be a rewards program for customers and businesses that continue to shop with Office Depot. Based on the number of office supply items purchased, the next item will be free and additional d iscounts will be applied to future purchases. After the retail store(s), prices will be lowered on items bought primarily by back-to-school customers and also year-round casual shoppers items. The retail stores will monitor active inventory for excess quantities and slow moving items and record adjustments as necessary to lower the price(s) if the anticipated realizable amount is below cost.Also, estimate and determine what items to stock and at what level, and what items to discontinue and how to value them prior to sale. The large-format retail stores will be reduced to half of the current square-footage, and staff will focus only on supplying consistently purchased merchandise. Items that tend to sit dormant at retail will be provided online only. If a retail store cannot maintain projected sales quotas, the store will be closed in that market area. New government contracts will be provided at 20% discount based on the number of office supplies purchased.Office Depot will retain business with local, state, and federal governments’ and non-profit organizations contracts by offering a lower cost than other competitors. Office Depots long term strategic direction is to be consumer focused in terms of product assortment, store layouts, new service offerings, and compelling pricing that sends a positive value message to its’ customers. This falls in line with the â€Å"best cost provider strategy† giving customers more value for the money while satisfying buyers’ expectations on key quality/features/performance/service attributes beating their price expectations.One of the main ways that Office Depot has responded was with its’ Magellan innovation, a three-year program which significantly enhanced IT capabilities. The new system will provide such benefits as improved forecasting, better support for planning, and improved profitability. This can be achieved through better utilization of store space, better pricing and data integ rity, better stocking, and reduced inventory with the end results benefiting the customer.In 2011 Office Depot announced that it is boosting their capital expenditure budget for 2012 to approximately $160 million, with a heavy emphasis on e-commerce and other IT investments. The retailers’ digital investments will be particularly important given its plans to shrink both the average size of its brick-and-mortar stores and its product assortments. Office Depots’ e-commerce sales have become an integral part of the company. Office Depot is the number (2) U. S. e-commerce retailer, second only to Amazon. com Inc.Office Depots’ aggressive Internet strategy has also generated twice the e-commerce sales of its’ rival Staples Inc. Office Depot SWOT Analysis Strengths: * Strong private label product line increases sales nationally and internationally. * Large, diverse customer base (individuals, small business, and large businesses) both nationally and overseas. * Company transitioning to smaller store format will increase presence in high growth markets. * As a direct result of negative economy, company has shuttered underperforming stores. * Cash liquid business with total assets of over four- billion dollars U.S. Weaknesses: * Little opportunity for real growth in U. S. market due to over-saturation. * Increases in competition in U. S. products market, combined with a reliance on low profit- margin electronics. * Due to the downturn of the economy coupled with continued nationally high unemployment rates†¦ sales, profits, and some business markets have diminished. * Accusations of overcharging Government Contract customers have been made public. Opportunities: * Money spent on office equipment and related items increasing among small and medium businesses. Increased ability to enter into more densely populated areas, while also reducing costs. * Increased opportunities of acquisitions due to strong cash reserves. * Increasing line of private label products geared towards â€Å"green† technology. Threats: * The global financial downturn. * High unemployment, coupled with an increase in office vacancies, compounded by low consumer confidence results in decreased spending. * Low cost/low quality imported equipment and products can lead to quality related issues. * Low switching costs increases competition and can lead to â€Å"price wars†.