Comparative study two companies in the same area with regard to their Term Paper - 1

Comparative study two companies in the same area with regard to their innovation activity - Term Paper Example Comparative study two companies in the same area with regard to their innovation activity It applies quality techniques that transform an institution to a source of income position as stated in the porters five forces model. Innovation improves a brand through the development of quality products that serve consumer needs effectively. It is achievable through research activities, hiring qualified and creative staff with excellent intellectual capacity and heavy investment. Managers in Samsung and Apple corporations recognize that innovation and creativity are crucial in the current competitive world. It is necessary to use innovation to enhance administration, product development and formulation of credible solutions that address consumer needs (Fernando, Rene & Ileana 27). Innovation also sets the stage for effective administration and formulation of communication systems. It is necessary to explore innovation as a performance measure while focusing on Samsung and Apple because they are big electronic producing corporations. Comparative Study of Companies based on the Inn ovative Background and Product Overview Apple and Samsung are high-ranking organizations with a global network. The corporations produce quality electronic products that match consumer desires and specifications. This is achievable through the innovative processes within their production systems. This has enabled them to produce quality and efficient electronic products, for example, TVs, phones, computers and operating soft wares that match consumer expectations (Horibe 20). The corporations also produce innovative items with modern features, for example, smart phones, IPods, LCD screens and flat screen TVs. Following their inception, Apple and Samsung have refocused their synergies into improving their innovative potentials (Gaynor 2). They conduct research studies on consumer needs and respond to existing items. The organizations are strengthening their production chain through adoption of lean concepts. Additionally, the organization is adopting measures that streamline the valu e chain within the production sequence. This is with the intention of achieving quality at every level of operation. This enables them maximize their potentials and bridge the performance gap that may compromise their ability to realize of objectives (Gaynor 5). Apple Company became operational in 1976. It manufactures and supplies consumer electronic designs that include computer software’s and personal PCs. Subsequently, the company has revolutionized its product portfolio and quality through creative processes that have enhanced performance. It has new products in the market that explains the effectiveness of its innovative practices (Cobbenhagen 49). It has developed viable distribution techniques and improved its quality standards and product specification designs. This has made the company produce new products, for example, Macintosh PCs, computer software’s and iPod phones. These items are portable and efficient enabling users to use them appropriately. Samsung Corporation is a big institution that produces quality electronic. It has strong operating units that distribute items to consumers in real time. The products contribute immensely to the growth of individuals socially and economically (Cardoso, Rene, & Ileana 26). This has seen the corporation record excellent performance over the years Innovation has enabled the companies to meet the operating threshold as

Internet Technology, Marketing, and Security Essay

Internet Technology, Marketing, and Security - Essay Example Social Media includes internet sites which facilitate the communication between individuals with the help of pictures, videos and writings. This essay will focus on the role of Social Media Marketing in the business profit generation. The researcher would consider the contribution of Social Media in marketing activities of Pepsi. In the later stage, the paper would consider several other empirical case studies and enumerate the importance of Social Media Marketing in future. The learnt from the essay would help to understand the importance of internet commercial segments (Bosari, 2012). Growing Popularity of Social Media Marketing CompuServe was the first Social Media networking site, established in United States in the 19th century. With the rise in literacy levels and the progress in technology, the proportion of internet users has increased significantly. Currently, famous social networking sites like, Youtube, are viewed by approximately 4 billion viewers per day. About 1.11 bill ion individuals across the world are regular users of Facebook and the viewership ratings for Twitter are about 500 million (Bosari, 2012). In the contemporary world, such sites are used for both commercial and non-commercial purposes. The corporate business firms often use Social Media for marketing their products to the consumers. In the theory of Customer Behavior Management, Customer Relationship Management plays a pivotal role. There are various reasons for which Social Media Marketing has become so popular in the modern days. There are: Social Media helps the companies to easily reach a wider base of customers across different marketplaces. The marketing activities through Social Media are relatively less costly that the other forms of traditional marketing methods. Online shopping has become a popular shopping destination in the modern world. The growing popularity of the digital marketplaces has forced the companies to set marketing strategies through internet media. Most of the consumers today are preoccupied with their daily activities. The proportion of television or radio viewers is much lesser than the proportion of the internet users. Thus, marketing consumer goods and services in the social networking sites helps the companies to reach out to a wider customer base, within the least possible time. Special Media marketing activities of the companies help to reduce their cost of marketing. The accumulated finances which are saved can be used by the companies for the purpose of growth and development. Social Media marketing is a more comprehensive, flexible and trendy form of marketing as opposed to the traditional methods (Bosari, 2012). Figure 1: Growing Popularity of Social Media Marketing (Source: Acra, 2012) The above bar graph shows that among all the different uses of internet media, Social Media is the most popular of them. Figure 2: Steps of Purchase (Source: Acra, 2012) The above graph shows the marketing stages. Figure 3: Social Fieldwork Cycle (Source: Acra, 2012) The above graph shows that social media marketing gives the maximum importance to ‘consumerism’. Advantages and Disadvantages There are various types of advantages and disadvantages of Social Media marketing. Advantages Social Media marketing activities help to enhance the business-to-customer relationships. It helps to engage the customers in

Physiological Ecology Essay Example for Free

Physiological Ecology Essay ABSTRACT   Ã‚   Mytilus edulis or the common mussels, very commonly found around the British Isles coast, with large commercial beds in the Wash, Morecambe Bay, Conway bay the estuaries of south- west England, north Wales west Scotland; belongs to the phylum Mollusca e.g. snails, slugs, mussels cockles clams class Pelecypoda e.g. clams, cockles, mussels, oysters scallops. The Mytilus is an extremely widely studies specie, mainly because of its widespread distribution, abundance, ecological commercial importance. It is also used as a bio – indicator. The objective of the study conducted was to find out the effects of respiration, water pumping activity environmental stresses on the mussel’s growth. The environmental stress includes prolonged air exposure, low salinity its action combined with elevated temperature. The main focus was regarding the age growth of the Mytilus. The mussels were challenged to a number of tests to determine their behaviour to record their response to different environments.   The tests prove that Mytilus species that live in an uncontaminated area grow faster than ones that live in polluted areas. This can be deduced effectively by the research conducted along with the experiments. INTRODUCTION   Ã‚   Mytilus are usually present on the rocky shores of open coasts attached to the rock surfaces in crevices, on rocks piers in sheltered harbours estuaries, often occurring as dense masses in cooler waters of the world; usually extending from the Arctic to the Mediterranean in the North east Atlantic. Two important factors that play an important part in the growth life of Mytilus are: TEMPERATURE: it is a vital factor responsible for the growth limitation of mussels. Extreme low temperature causes damage in Mytilus but is minimised due to nucleating agents in the haemo- lymph. The Mytilus is prone to perilous freezing conditions sporadically in even moderate temperatures; large adults can endure lab conditions of -16 degree C. easily for 24 hours are capable of surviving even if the tissue temperature falls below -10 degree C. In Sweden, mussels actively ingested seston at -10 degree C., suggesting that they can utilise spring phytoplankton blooms in boreal waters even at low temperatures. M.edulis can tolerate high temperature desiccation as well, for example the British M.edulis has an upper sustained thermal tolerance limit of about 29 degree C. (Mytilus edulis) SALINITY: in contrast with other biogenic reef species, M.edulis can bear a wide range of salinity. But it is noted that it stops the feeding process when exposed to low salinities. The M. edulis adapts well to low salinities as low as 4-5 %. Exposure to 16% salinity for a month resulted in reduced shell growth as much as 26% to 32%, while in 22% exposure caused a minute drop in growth rate. When exposed to 13% the growth rate recovered from zero to more than 80% in 32% in a month. MATERIALS AND METHODS Materials: Incubation tubes, incubator, cotton, knob, benzoic acid, All samples were divided into four groups. Two groups of prestine A and prestine B were compared with polluted A and polluted B. Pristine A Pristine B Polluted A Polluted B Curves were drawn to compare Pristine A with Polluted A and Pristine B with Polluted B. With change of temperature change in mass was observed. Mytilus were cultured in flat trays measuring 20-40 cm. Two trays had pristine while remaining two were for polluted growth. Affect of temperature change was observed in all the four trays with consequently change in mass. Mytilus was put over the trays to be cultured. Tests conducted in five different labs are being analyzed to prove that the Mytilus favor a pristine environment as compared to a polluted one. LAB #1    This particular lab deals with the energy content in a food substrate or in animal tissue which is considered as the most important component for growth of any organism. The method used to determine the energy content of biological materials is the micro- bomb calorimetry method; by using susceptible microelectrodes to assess the heat produced by igniting a pellet of dry tissue within a stainless steel bomb. The calibration is obtained through a chemical having fixed energy content; the temperature change can be transformed into energy content for the tissue. In order to deal with a small sample, a micro- bomb calorimeter is used, filled with oxygen a small wire, that works like a light bulb filament is used to ignite the tissue    Using the oxygen supplied by potassium dichromate; a strong oxidizing reagent, contained with concentrated sulfuric acid, the tissue is burnt chemically. The orange Cr is reduced to green Cr, while burning; this change can be quantified using a spectrophotometer. LAB #5:    By determining the effects of geometric constraints biological processes, the allometric isometric relationships of organism are studied. The lab deals with the examination of gill area, shell volume foot weight scale with the size of mussels; observing how the size of the mussel effects the different biological processes. The allometric scaling is explained by equations of the form Y= Ax B; the A as a constant, B an exponent, X is mass Y is a biological process. Allometric relationships are represented as curves on linear axes, but when plotted on log/log axes they become straight. The scaling exponent of the function is determined by the slope of the line. LAB #6:    This lab’s research aims to calculate the following at ambient temperature using a meticulous mode: The respiration rate of one mussel from polluted area The respiration rate of one mussel from a pristine area control respiration    The materials employed in this test are a fiber optic oxygen electrode indicating vestiges on the quenching of light emissions from a Ruthenium compound due to oxygen presence, so as to calculate the flux of oxygen in due course.   To measure the respiration rates, the mussels will be enclosed in individual restrained Respirometers, filled with seawater connected to an oxygen electrode located with a slow flow of water from a peristaltic pump, in a separate chamber. Set up the oxygen system to record data every minute for an hour. Place a cleaned mussel, attach the lid submerge the chamber. Place the electrode in the holder attach hoses to pump chamber, so that the water is flowing past them, turning on the pump to slow. The data logging will go on for an hour start a mark for a downward slop in the recorded readings. Measure the volume of chambers the water level in hoses length of the mussel to estimate the tissue weight Mussel volume to ascertain the exact volume of water in the chamber.   LAB # 7:   Ã‚   The labs main concern was to calculate the protein content in mussel tissues, by using the Lowry chemical assay, which comprises of combining a dye reagent with soluble protein to produce coloration that is directly proportional to the amount of protein present. Protein is often used in physiological ecology as it plays a functional structural role by normalizing the data, through its direct association with functional components within the cells. Often in this experiment, the Bradford assay has been used since it is an alternate method for protein determination. Dilute copper tartar- ate solution is added to the protein that forms a complex. To develop the coloration, the Folin reagent is added to the protein – copper complex, within 15 minutes it results in a blue color. This has a peak absorbance at 750nm can be quantified at this wavelength using a spectrophotometer. A calibration must be done with a known construction of known concentration of protein a calibrated line constructed.   Ã‚   The reagents in the assay when reacted with a series of known protein solution (0.2- 1.5 mg/ml) dissolved in a sodium oxide buffer to remove buffer effects in the calibration. Prepare a series of clean 2ml snap cap tubes. The likely concentration series will be made by diluting the stock Bovine Serum Albumin from concentrations stock: –x x/10 x/2 x/4 3x/4   Ã‚  Ã‚  Ã‚  Ã‚   Into the 1.7 ml soap cal tubes, transfer 25ul of the standards then add 125ul of reagent A. swirl warily. In each tube add 1.0 ml of reagent B vortex carefully. Leave for 15 minutes then measure the absorbance against 750nm distilled water. Plot the protein content along the X axis the absorption along the Y axis to obtain the calibration line. The calculation of the calibrated line can be done to estimate the protein content X from an unknown absorption Y; in the form Y= A – BX LAB # 9:   Ã‚  Ã‚   This lab research is to study the functional attributes of living enzymes, employing a quantitative approach to their measurement. By using a simple spectrophotometric assay to quantify the enzyme citrate synthase in two populations of Mytilus, any possible consequences of this variation will be identified by its functional value. The enzyme Citrate Synthase limits the rate mediating the transfer of pyruvate into the TCA cycle as citric acid. The process determines: Quantification of CS activity Quantification of the protein content to allow the CS content to be normalized. The extraction of the living tissue in a way that the enzymes remain operative is the base, on which the reaction is dependant on. The DTNB is reduced by the CoASH which is a stiochiometric by product of the reaction. The DTNB changes color, as is reduced with a peak absorbance of 412um. The procedure relies on the extraction of the CS in a cold buffer. A small portion is diluted with an Acetyl-CoA solution, the reaction begins when the Oxalo- acetate solution is added, as a result the color changes which can be monitored in a spectrophotometer. RESULTS      Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Results clearly show that mytilus grow more in pristine as compared to polluted areas. There are several factors that affect mytilus growth in polluted areas. Graph polluted A (obtained from polluted A readings) Lab 6 The threshold salinity levels were recorded for the individual age groups consisting of a variation of behavioural response to salinity fluctuations. Low levels of water salinity below the critical values caused the isolating responses like closing the mantle cavity, withdrawal of siphons closing the shell valves in Mytilus. Another factor noticed was that the age did not influence the sensitivity of mussels to low salinity elevated temperature. However the older mussels exhibited a slightly lower critical salinity value after going through the fluctuations.   Ã‚   The scope for mussel growth except under treatments of no algae high silt; remained positive when carbon assimilation true, the rates of respiration excretion were balanced against energy intake. In estuarine systems, where the seston quality quantity is variable, makes the mussels living there evolve a feeding strategy involving minimal metabolic cost, at the same time maximizes energy assimilation while acquiring food from the environment. DISCUSSION AND CONCLUSIONS      Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   A number of factors can hinder growth of mytilus in polluted areas. In polluted areas the change in mass of mytilus was much greater with slight variations of temperature. However, contrary to this the change in mass was negligible in pristine area. Several factors can hinder growth of mytilus on polluted surface. Pollutant in water and air can hinder their growth. Pollutants also destroy the food stuff and nutrients, hence, the mytilus species may find difficulty in getting well nourishment. Environmental variations have also deep affect on their growth. The blue mussels can subsist in air for 10 14 days at a varying temperature from 10 -20 degree C. even longer at lower temperatures. Like many other intertidal mollusc, M. edulis uses a complex behavioural physiological bio chemical mechanism to tolerate prolonged periods of air exposure extreme salinity changes or other un- favourable environmental conditions. Mussels that are smaller medium in size are not as predisposed to air exposure unlike large mussels, mainly because of higher absolute values of metabolic rate in the large mussels. In our experimental research, the size did not play a role in survival in air. The factors change from specie to specie, for example in some species of mussels the resistance increases the developmental age of the animal, and once it reaches the maximum level it may be possible that the process reverses.   Ã‚   When blue mussels M. edulis were exposed to high concentrations of copper Antarctic scallop Adamussium colbecki to high concentrations of cadmium, the age factor did not influence the survival; however the capacity to convalesce deteriorates with age.   Ã‚  The physiological traits of food ingestion rate, carbon assimilation efficiency, and respiration excretion rates are integrated by the energy accessible for growth, by supplying a prompt quantitative estimation of the energy status of the mussels. Conducting researched on this fact can provide insight into the growth process the influence of physiological activities. The Geukensia demissa or commonly known as the ribbed mussels can exert a profound influence on ecological processes of salt marshes on the Atlantic coast of North America. These mussel species are quite vulnerable to predators in the sub tidal area, since they have relatively thin shells; however they are very much physiologically adapted to the extreme environment where they are exposed to 70% air of the tidal cycle, this exposure draws the mussels against some severe stress since they are unable to perform feeding, defecation other essential physiological functions due to limitation of time. The mussels favour a pristine environment over REFERENCES â€Å"Mytilus edulis† Environmental Requirements: (n.d.) UK marine special areas of conservation [Accessed 4 December 2007] http://www.ukmarinesac.org.uk/communities/biogenic-reefs/br3_4.htm Tyler-Walters, H., 2007. Mytilus edulis. Common mussel. Marine Life Information Network: Biology and Sensitivity Key Information Sub-program [14 September 2007] Plymouth: Marine Biological Association of the United Kingdom. [Accessed 4 December 2007] http://www.marlin.ac.uk/species/Mytilusedulis.htm Sukhotin, A.A. Lajus, D.L. Lesin P.A. (28 October 2002) Influence of age and size on pumping activity and stress resistance in the marine bivalve Mytilus edulis L: Journal of Experimental Marine Biology and Ecology [Accessed 4 December 2007] 284: 129– 144 http//:www.elsevier.com/locate/jembe Huang, S. C. Newell, R.I.E. (5 February 2002) Seasonal variations in the rates of aquatic and aerial respiration and ammonium excretion of the ribbed mussel, Geukensia demissa (Dillwyn) Journal of Experimental Marine Biology and Ecology [Accessed 4 December 2007]270: 241– 255 http//:www.elsevier.com/locate/jembe Eder1, E. B. Lewis, M. N. (28 April 2005) Proximate composition and energetic value of demersal and pelagic prey species from the SW Atlantic Ocean: MARINE ECOLOGY PROGRESS SERIES [Accessed 4 December 2007]Vol. 291: 43–52, Arifin, Zainal. Leah I. Bendell-Young (27 March 2001) Cost of selective feeding by the blue mussel / Mytilus trossulus as measured by respiration and ammonia excretion rates: Journal of Experimental Marine Biology and Ecology [Accessed 4 December 2007] 260 259–269 http//:www.elsevier.nlrlocaterjembe

Diagnosis of Systemic Lupus Erythematosus (SLE)

Diagnosis of Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a multi-systemic autoimmune disease that was first described in 1941, by Klemperer and colleagues (Gonzalez-Buitrago and Gonzalez, 2006). It is a disease that can attack almost any organ or system in the body, where imbalances in self tolerance create an abnormal immune response to self proteins resulting in autoimmunity (Male et al, 2006). SLE is a disease that has a strong correlation to defects in apoptosis; however no specific cause of the disease is known (Arbuckle et al, 2003). The prevalence of the disease is worldwide; however it commonly affects people of African descent, particularly in Europe and Northern America (Kumar et al, 2009). Environmental triggers are known to contribute to the disease manifestation; although genetic links have also shown association with all HLA classes (I, II, III) on chromosome 6. Other transcription factors such as IRF5, STAT and proteins such as PTPN22 have also been seen to contribute to the manifestation (Mal e et al, 2006). SLE is particularly common between the ages of 15-50, where patients present with positive antinuclear antibodies (ANA). ANA are a group of heterogenous antibodies that are capable of binding to components of the nucleus, resulting in damage of DNA. The initial screening method for patients with AIDs such as SLE is via the ANA test. 80-90% of patients with SLE present with a positive ANA (Bonilla et al, 2007), however other AID such as Sjà ¶grens syndrome, Rheumatoid arthritis, Autoimmune hepatitis, Scleroderma and Polymyositis Dermatomyositis, also see positive results. Antigen specific assays such as extractable nuclear antigen (ENA) and double stranded DNA (dsDNA) must then be performed to confirm a diagnosis, as approximately 70% of patients with SLE have antibodies to dsDNA (Rahman Isenberg, 2008). Positive results can be seen within the aging population as the immune system begins to deteriorate. Nilsson et al, (2006) supports this and found that positive ANA results were fo und particularly in elderly patients over 85 years. 90% of patients with SLE are women, suggesting a hormonal link (Rahman et al, 2008). Hormonal imbalances are seen in women with SLE, thus it becomes difficult to maintain immune tolerance. Increased oestrogen levels result in increased antibody production and Th2 response, whilst decreased levels of androgens depress the response resulting in an abnormal immune response (Danchenko et al, 2006). 1.2 The clinical significance of ANA testing The diagnosis of SLE is dependent on a variety of factors including clinical details, family history, age, race, sex, medication and infection (Stinton Fritzler, 2007). The classical symptom for SLE is a butterfly-shaped rash which is commonly seen on the face (Figure 1.1). In 1982 the American College of Rheumatology (ACR) described a set criterion (Table 1) (updated in 1997), for the diagnosis of SLE aiding clinicians to correctly diagnose patients. Four points of the criteria must be met, for a definite diagnosis of SLE. The criterion for SLE includes symptoms, immunological and haematological tests. Points 10 and 11 are of particular importance, as they are confirmatory of SLE. A study by Arbuckle et al, (2003) examined the onset of SLE in 130 patients and found that 115 patients had positive indirect immunofluorescence (IIF) ANA, before diagnosis. 1. Malar Rash A butterfly rash usually seen on the face 2. Discoid rash red, scaly patches on skin that cause scarring 3. Photosensitivity Skin rash as a result of unusual reaction to sunlight 4. Oral ulcers Oral or nasopharyngeal ulceration 5. Nonerosive Arthritis tenderness or swelling of joints 6. Pleuritis or Pericarditis Pleuritis inflammation of the pleura, the lining of the pleural cavity surrounding the lungs Pericarditis small amount of fluid builds up between the two layers of the pericardium. 7. Renal Disorder Persistent proteinuria Cellular castsmay be red cell, hemoglobin, granular, tubular, or mixed 8. Neurologic Disorder Seizures 9. Hematologic Disorder Hemolytic anemiawith reticulocytosis Leukopenia Lyphopenia Thrombocytopenia 10. Immunologic Disorder Anti-DNA: antibody to native DNA in abnormal titer Anti-Sm: presence of antibody to Sm nuclear antigen Positive finding of antiphospholipid antibodies on: 11. Positive Antinuclear Antibody An abnormal antinuclear antibody by immunofluorescence Once a positive ANA test has been performed there is no reason to repeat the test, however if clinicians have a strong suspicion of an evolving connective tissue disease (CTD) negative ANAs should be re-requested (Blerk et al, 2008). Other immunological tests such as complement components (C3 and C4), C-reactive protein, anti-phospholipid antibodies and anti-histone can also be tested to investigate SLE; however these may not always aid all patients (Egner, 2000). 1.3 History of ANA testing and how the diagnosis of SLE evolved The ANA test has been around for over 40 years and is the most widely performed autoantibody test, worldwide. The test is commonly performed within Immunology laboratories and has evolved very little over the years. ANAs originated from lupus erythrocytosms, also known as the LE cell phenomenon. LE cells were discovered in 1948 by Hargrave, who saw that patients with SLE have polymorphonuclear leukocytes, which had phagocytosed nuclei, within the bone marrow (Hepburn, 2001). Following the discovery, Lee et al, (1957) showed that the LE cells were formed by gamma proteins in leukocytes which were thought to be antibody. Fluorescent labels were also introduced in 1957, to show homogenous patterns on human tissue (Hughes et al, 2008). By 1961 rat sections substrates were introduced, enabling patterns such as homogenous, speckled and nucleolar to be seen in patients with rheumatic diseases. The use of rat substrates brought about a new discovery, which saw that washing cells in saline, c aused alterations to cells within slides, thus altering patterns seen, thus the precursor of the ENA screen was introduced. By the 1970-80s Human epithelioma type 2 cells: CCL-23 (HEp-2) substrates were widespread and National quality assurance schemes began to establish. 1.4 Techniques implemented in laboratories for ANA detection There are many techniques available for the testing of ANAs; these can be seen in the UK National External Quality Assessment Service (UKNEQAS) report found in Appendix 1. 1.4.1 Indirect immunoflourescent (IIF)-ANA Indirect immunoflourescent (IIF) is a general screening technique performed to identify patients with autoantibodies. It enables scientist to link autoantibody patterns present within a patient sera, to help diagnose and monitor their progress during treatment. ANA testing using IIF was developed by George Friou in 1957, where initially substrates such as chicken erythrocytes were used (Kumar et al, 2009). ANA substrates were traditionally prepared in-house using rodent tissue where thin layers of tissue were sliced using a cryostat. However as demand for the screening of autoantibodies increased (Figure 1.2), preparing slides was no longer feasible, as it was time consuming and laboratories could no longer manage rodent houses as they required expert attention. Commercial companies then began to produce ready to use tissues substrates, offering a greater sensitivity. However as many commercial substrates are now available, variability between kits, manufactures, substrate, conjugate and the degree of cellularity (good monolayer of cells and a number of mitotic spindles), make it difficult to standardise methods of detection and reporting. In order to produce accurate results, substrates must be present in the correct phase of the cell cycle (Figure 1.3). Identification of IIF-ANA patterns is dependant on the true state of chromosome. Most autoantibodies are directed against antigens expressed during interphase. Interphase is divided into 3 stages: G1, S and G2, where cytoplasmic organelles and fibres structure are most visible and the nucleoli appear well differentiated. A mix of mitotic and non mitotic forms of cells are needed in the metaphase stage as it is influential in interpreting IIF-ANA patterns, especially centromeres and homogenous patterns (Sacks et al, 2009). The HEp-2 substrate is commonly used in ANA detection and was introduced commercially in 1975 (Kavanaugh et al, 2000). HEp-2 provided a greater sensitivity for the testing of SLE as they were composed of human laryngeal squamous cell carcinoma, allowing the recognition of over 30 nuclear and cytoplasmic antigens (Gonzalez-Buitrego Gonzalez, 2006). HEp-2 substrate contains various organelles (Figure 1.4) allowing uniform distribution of cells, showing large nucleolus, meaning no interference of the intercellular matrix is seen (Gonzalez et al, 2002). The introduction of the HEp-2 substrate was a big step forward in identifying patients with the ribonucleoprotein complex (anti-Ro). The anti-Ro antigen is particularly significant in patients with SLE as it offers a poor prognosis. However this antigen is seen to overlap between different autoimmune diseases such as Sjà ¶grens syndrome, thus the detection of the antigen must be precise. The Ro (SS-A) antibody is seen to target protein antigens associated with small RNA molecules known as hY-RNAs11, 12 and are of unknown function (Cozzani et al, 2008). HEp-2 cells were seen to destroy the Ro antigens during fixation, so commercial companies began to devise ways around this. To overcome this problem, HEp-2 cells were genetically modified to produce extra Ro antigen and this substrate was known as HEp-2000. HEp-2000 substrate is uniquely produced by ImmunoConcepts (Sacramento CA, USA). The slides have 10-25% mitotic human epithelia and offer a greater sensitivity (Table 2) in the diag nosis of SLE. They have aided in reducing the number of ANA negative SLE patients; however detection of Ro is dependent on the stability of actin, as it can denature easily. Although HEp-2000 substrates were seen to be more beneficial in detection of Ro antigen, they limit the identification of the different epitopes of the Ro antigen. At present HEp-2000 substrate can only identify the 60kDA Ro antigen; but since the 52kDA Ro antigen also exists, patients with this epitope are missed. A study by Cozzani and colleagues (2008) looked at 5,949 people over a 5 year period. All participants were photosensitive and 2,315 of these had connective tissue disease (CTD) such as SLE. The study found that the anti-Ro was easy to identify on HEp-2000 slides with a sensitivity of 81% according to the Altman test, of accuracy. However a study by Bossuyt and Luyckx (2005) compared IIF to EIA and saw that patients with anti-Ro antibodies were missed using HEp-2000 slides, as the undetected patients contained the Ro 52 antibody; although they reported a sensitivity of 82.9%. One patient in this study was negative for IIF-ANA, but was shown to have a positive Ro antigen by EIA. A study by Dahle et al, (2004), looked at HEp-2 and compared three ANA methods; Enzyme immunoassay (EIA), double radial immunodiffusion (DRID) and IIF. 3,079 patients were examined and overlapping results between IIF and DRID were seen and 60% of IIF-ANA gave a positive homogenous pattern. However results for EIA showed that positive IIF results appeared negative by EIA. In 2006 the LGI performed a study looking at 18,320 samples, requesting ANA tests by IIF. The study found that 1 in 5 patients, identified as negative or weak positive by IIF, showed positive for anti-Ro via EIA. This proved that Hep2000 cells cant detect the different epitope of Ro, thus concludes that antigen-specific testing is required following the ANA test. This agrees with Morozzi et al, (2000), who suggest that a combination of 2 or more methods are required for the detection of the anti-Ro antibody in patients. This study looked at 64 people with connective tissue disorders and tested them by IIF, EIA and DRID. Results showed that 54 people were positive by at least one method and the specificity of each technique was good, whilst sensitivity varied. Sensitivity for IIF-ANA via HEp-2000 was 89%, EIA (Ro60) was 89%, EIA (Ro52) was 67% and DRID presented with a sensitivity of 76%. Although the NEQAS report shows that DRID is no longer used within laboratories, results from thi s study suggest that EIA has the ability to detect the different epitopes, preventing misreading of the anti-Ro antigen. Thus to ensure that all SLE patients are identified antigen-specific tests such as extractable nuclear antigen (ENA) should be used to detect the various epitopes (Cozzani et al, 2008). Conjugates play a significant role in the determination of IIF and EIA results. Fluorescein-conjugated antibodies produced from goat, sheep or rabbit are commonly used. These are usually bought from commercial companies, which produce pre-diluted conjugate, raised against mouse or human, which aims to achieve optimal sensitivity and reactivity. Immunoglobulin fraction can be also be used; however fluorescein conjugates such as fluorescein isothiocyanate (FITC) are preferred as they produce less background staining. A fluorescein/protein (FP) molar ratio is employed, with in-house diluted conjugates. The ratio varies between kits, however a 1:3 dilution with phosphate buffered saline (PBS) is usually used (Egner, 2000). At LGI the conjugate used for detection of ANAs is IgG, as it allows accurate diagnosis and monitoring of diseases such as SLE. IgM-ANA can also be employed, although this indicates milder or non-specific diseases, whilst IgA-ANA gives little information so arent used. Due to the use of fluorescence conjugate, slides fade overtime, thus it is particularly important to determine results as soon as possible as photographs are not taken. As IIF varies daily due to slides and condition of the microscope, it would be appropriate to carry out daily checkerboards to see which working dilution is best for the conjugate, improving consistency; however this is no longer feasible in high-throughput laboratories. When reporting ANA three factors require evaluation: the pattern observed; substrate used and the titre of the positive test. Experienced scientist can interpret ANA slides and distinguish titre levels; however this takes years of experience. The screening dilution is important in patients presenting with positive results, as it helps determine an individuals severity of disease and can prove beneficial to clinicians. Serial dilutions at 1:10, 1:20, 1:40, 1:80, 1:160 and 1:320 can be performed, where the titre value is the one at which positive sample becomes negative. 5% of a healthy population can present with a positive low ANA titre, with no disease activity and are commonly women aged over 60 (Shmerling, 2003). Peterson et al, (2009) found that beside patients with SLE patients, other diseases also present with positive ANA titres. 1:20 healthy people presented with a positive ANA and the number of positives increased to 1:3, with a dilution of 1:40. To reduce the number of fals e positives, titres are commonly performed at 1:80. At LGI titres were performed on all positive samples and pregnant women, regardless of whether they are positive or negative. Pregnant women are closely monitored as a precaution as IgG antibodies cross the placenta, thus anti-Ro/La antigen is capable of causing fetal heart block (Rahman Isenberg, 2008). Patients who presented with symptoms for SLE were also titrated; however lots of weak positive results were seen as a dilution of 1:40 was employed. As workload increased titrations became laborious and impractical, thus performing titres routinely was abolished and titres are now only performed upon request. Cut-offs exist, however these are modified around the local population, to give a better sensitivity (Stinton Fritzler, 2007). Shmerling, (2003) has suggested that ANA titres can correlate with disease activity, but as positive samples undergo antigen specific testing via EIA, titres should be abolished, unless there are specifically requested by the clinicians to monitor changes to disease. Wieser et al, (2001) found that there was a lack of correlation between the clinical features of patients and laboratory results obtained. The study looked at 3 cases with varying antibody titres and established algorithms seen in Figure 1.5. Similarly Hanley et al, (2009) suggested algorithms help in diagnostics (Appendix 2). As a small number of cases were analyses, it appears that there is not sufficient evidence to develop an algorithm; however both the studies have been adapted in Europe as they were seen to prevent patients with detectable antibodies being missed and to avoid the unnecessary testing and time of laboratory staff. Slide processors are available to prepare IIF slides. They first appeared in the late 1990s and include platforms such as ASP1200 and AFT from Binding Site (Figure 1.6). These slide processors ensure that all samples are prepared quickly, reliably and accurately, avoiding cross reactivity in sample preparation. Slide processors perform IIF via indirect antibody reactions as seen in Figure 1.7. Patient serum is incubated with a substrate, followed by washing to remove any unbound protein. A second antibody, FITC is added and this reacts with immunoglobulins which have combined with the substrate. Another washing stage is performed and slides are ready to be mounted and interpreted manually, however this causes subjectiveness. IIF-ANA result interpretation is dependent on the operators setup of the microscope, type and number of hours the bulb (mercury) has been used, type of objective lens, filters and most importantly magnification. At the LGI the Leica DMRB mercury microscope is employed and allows cells to magnify at X200, X400 and X500. Positive results fluoresce an apple-green colour (Table 3), whilst negative samples have little fluorescence. Two independent observers interpret the slides to prevent reading errors and any conflicting results are followed by an anti-ENA and anti-DNA screen. Automated commercial slide readers are now available to allow interpretation of ANAs. Images are automatically scanned and stored within computer systems, where positive and negative ANA results are determined by the amount of flourenscene emitted. The operator can then scan through positive ANAs, identifying their patterns. This aims to improve the subjectiveness seen between scientists and aims to improve accuracy; however these are not robust so not widely used. The advantage of IIF-ANA is that it is easy, inexpensive, available from a wide range of commercial companies, sensitive, reliable and has reduced cross reactivity and background fluorescence. The disadvantages of IIF-ANA are that it is laborious and requires a high degree of technical expertise. Within most Immunology laboratories the ANA test is not linked to the pathology computer systems, so tests cannot be picked up via an interface. This can be problematic as wrong samples can be analysed and reported. The use of barcode readers can overcome this problem. Homogenous Homogenous Pattern is the most common pattern seen in 60% of Systemic Lupus Erythematosus (SLE) patients. However it can be seen in drug induced lupus, Rheumatoid Arthritis. Positive patients are then further evaluated against: Anti-dsDNA, Anti-Smith Speckled Speckled Pattern can exist as coarse expressing is Sm, U1-RNP antigen or fine expressing Ro or La. Sm positive is seen in 4-40% of SLE patients, whilst RNP is seen in high titres in patients with Mixed Connective Tissue Disease (MCTD). Patients with Scleroderma and Sjogrens Syndrome also present with positive results. Centromere Centromere pattern is seen in 57-82% of patients with CREST syndrome and Raynauds. The suspected antigen is CENP A, CENP B, CENP C. Nucleolar Nucleolar Pattern seen in patients with Scleroderma. There are multiple nuclear antigens, such as fibrilliarin. Positive patients are then further tested against Scl-70 (Anti-Topoisomerase I). Table 3: Shows the various ANA patterns seen by IIF on the HEp-2000 substrate (Produced by Nisha Lad, 2010) As different laboratories use different substrates and conjugates, IIF-ANA lacks standardisation worldwide (Bonilla, 2009). A study by Blerk et al, (2008) showed that if laboratories employed the same cells, substrate and conjugate they were able to report the same staining patterns. Over 157 laboratories across Belgium participated and each looked at 9 different samples. Looking at the results it is clear that after considering the variable factors, participants that employed the same HEp-2 slide substrates (Medica, USA) and method of detection were able to produce consistant results, suggesting standardization can be achieved. Although IIF-ANA is subjective, replacement with EIA or bead technology is suggested to increase sensitivity. Bonilla et al (2007) performed a study in the USA suggesting that IIF had a sensitivity of 90.6%, whilst bead technology had a sensitivity of 41.9% and the specificity of IIF was lower at 76%; however for bead technology was 87%. Having tested 385 patients a conclusion was made saying IIF was a better technique for diagnosis of patients with SLE. Olaussen and Rekvig (1999) also produced similar results, where two commercial IIF assays and two commercial ELISA kits consisting of a range of antigens, significant in the diagnosis of SLE were used. The study showed correlation between IIF and ELISA, where sensitivity for IIF was 88%, whilst that for ELISA was 86%. Specificity however varied with 67% for IIF and 60% for ELISA. Another study by Gonzalez et al, (2002), analysed 709 samples comparing IIF and EIA for the diagnosis of ANA. Results showed good reproducibility in both as says, but found that the antibodies which produced a homogenous and speckled IIF patterns were best detected via EIA. On the other hand a study by Nifli et al, (2006) compared routine technology in a selection of Clinical Immunology laboratories and analyzed 11088 samples, using IIF and ELISA at the University Hospital of Heraklion in Greece. Results showed a highly significant correlation for ANA performed by ELISA; however it suggested that as IIF had a low sensitivity of 58%, this could be replaced by multiplex technology, allowing multiple antigen measurement. Looking at these studies closely it appears that although there were similarities between technologies, different kits and manufacturers were used, producing variable results. 1.4.2 Antigen-specific assays for the detection of ANA Many different patterns can be seen by IIF-ANA, however to determine autoantibody specificity further antigen-specific assays are needed. Antibodies against Sm, native dsDNA and chromatin are used in the diagnosis of patients with SLE (Hanley et al, 2009). Currently ANAs are categorised into two main groups; ANA to DNA and histones (dsDNA) and ANA to extractable nuclear antigens (ENA). Enzyme-linked immunosorbent assay (ELISA), also known as an enzyme immunoassay (EIA) are now available for antigen specific testing, providing a new horizon for SLE testing, as they are able to identify individual antigens. ELISA/EIA is the most commonly performed technique, implemented in laboratories today. In the past, ELISA plates were assembled in-house, however as a successful assay requires careful assembly of the different layers, this soon became difficult to achieve, thus commercial ELISA kits were developed in the 1980s to overcome assay failure and to overcome the subjectiveness of IIF-ANA. The ELISA assay can be performed either manually or via automated technologies. 96 well plates coated with the same antigens are commonly used, however Phadia produce an EIA platform, whereby pens containing singles wells with individual antigens can be used, allowing multiple antigen recognition and analysis. Both ELISA/EIA operate via immunometric methods of detection for anti-ENAs and anti-DNAs. The principle (Figure 1.8) of this technique is via microplates which are coated with purified antigens of interest. Patient serum is incubated in the wells and unbound antibody is then washed away, followed by the addition of a conjugate such as alkaline phosphotase (AP) or horseradish peroxidase (HRP). Another wash stage is performed and colorimetric results develop, which are proportional to the initial concentration of antibody in the patients sample. Results are dependant on kit standards, which produce a calibration curve and then the optical density of the wells is taken to give a q uantitative result (Branda et al, 2009). ELISA are a versatile assay, where the amplification of the signal, increases the overall sensitivity of the assay, as it uses an antibody which are specific to the type of antigen/protein being measured. Studies suggest that ELISA is a sensitive assay, however lacks specificity so false positives results are detected (Castro and Gourley, 2009). The advantage of ELISA is that it can be performed both manually and via automation. Analysers can also be linked to the pathology computer systems, preventing transcription errors in result interpretation. However disadvantages for ELISA are that purified antigens need to be prepared via HPLC, meaning assays are not cost effective and can be time-consuming. As microtitre plates are now purchased with one antigen, there is a limited dynamic range of detection; however EIA pens now overcome this problem. To produce successful assays, instrumental conditions need to be carefully considered. Washing errors, contamination of substrate or inadequa te incubation times may produce little signal amplification resulting in false negative results (Castro and Gourley, 2010). 1.4.2.1 Anti-dsDNA Anti-dsDNA were first described in 1957, by Ceppelini and colleagues. Anti-dsDNA are found in patients with SLE and are mainly found in the form of nucleosomes. Nucleosomes are fragments of chromatin that cells release during apoptosis. dsDNA antibodies bind to the nucleosome to form complexes which settle in the glomeruli, resulting in glomerulonephritis and increasing the risk of lupus nephritis flare, thus detection is crucial as it helps to determine the therapy required for treatment. à ¯Ã‚ Ã‚ ¡-actinin (100kDA) is a microfilament skeletal muscle protein, which aids in maintaining the function of podocytes in the kidney. This protein is not specific for SLE, although it can act as a marker for renal involvement (Raheman et al, 2008). The dsDNA assay can be performed via (Figure 1.9); IIF with Crithidia luciliae substrate (CLIF), Farr assay also known as radioimmunoassay (RIA), however the most commonly used technique is EIA/ELISA as described in 1.4.2. The Farr assay is regarded as the gold standard technique for the detection of dsDNA (Launey et al, 2010). It uses cultured cells labelled with thymidine and idocythidine, which act as radioactive DNA. In the assay bound and free DNA is separated by precipitating immuglobulins and ammonium sulphate. Although this method is good, it misses low avidity anti-DNA antibodies due to a nitrocellular filter, which allows the passage of free DNA and however double stranded DNA (dsDNA) cannot be filtered. Thus the radioactivity is said to be proportional to serum anti-DNA (Isenberg Smeenk, 2002). The Farr assay can detect high affinity antibodies, with relatively high specificity; however it requires precision in pipetting as there must be sufficient labelled DNA to bind to samples in order to reach an endpoint. Although the use of radiolabels within the Farr assay provides highly reproducible results, it becomes very costly, dangerous and difficult to dispose of the radioactive isotopes. Other limitations with this assay are that it only detects IgG and cannot determine any other immunoglobulin isotopes (IgA/IgM), thus patients presenting with dsDNA antibodies to IgA/IgM can be missed (Egner 2000). UK NEQAS shows that the Farr assay is still being used (Figure 1.9), as it is a more accurate confirmatory test that can be used in the diagnosis of SLE. The accuracy of the Farr assay can be seen in many studies. A study by Launey and colleagues (2010) compared the Farr radioimmunoassay to three commercial enzyme immuoassays and CLIF staining. The study looked at 99 patients with SLE and found that the Farr assay was the best assay, offering greater sensitivity and specificity of 95%, than the three other ELIA and CLIF assays. Derksen et al, (2002) also showed similar results. He compared the Fa rr assay with the Varelisa EIA assay and found that the Farr assay was superior to the EIA assay as it presented with a specificity of 95% and a sensitivity of 72%, whilst in EIA specificity corresponded to sensitivities at 44%. Many laboratories also perform follow-up DNA tests by EIA, using CLIF to determine the avidity of anti-dsDNA antibodies. However CLIF can also be used alongside IIF to measure anti-DNA (IIF-DNA) and this does not requiring any specialist equipment, other than a fluorescence microscope. The CLIF assay allows detection of high affinity antibodies through titrations, however this requires precise pipetting. CLIF detects antibodies to kinetoplast of organisms, which consists of circular dsDNA and allows both IgG-anti-dsDNA and IgM-anti-dsDNA to be tested (Gonzalez-Buiterego Gonzalez, 2006). The test is highly reproducible and is particularly suitable for a limited number of samples. Although the assay offers the highest specificity for ANA testing, it has a relatively low diagnostic sensitivity for SLE. Due to the degree of accuracy of the Farr assay, it is undoubtedly the best assay for the detection of dsDNA and so has been approved by the World Health Organisation (WHO) and operates under the WHO80-IRP standard. However due to the risk of handling radioactive substance and the cost of the assay; this is not routinely used within Immunology. 1.4.2.2 Anti-ENA Positive IIF-ANA are typically followed up by extractable nuclear antigens (ENA). ENAs were discovered in 1966 by Smith and colleagues, offering a greater specificity, to allow a more accurate disease diagnosis, in correlation to the initial IIF-ANA screen. Originally ENAs referred to proteins found in a saline extract of cell nuclei, however since then the components have been identified and these consist of cytoplasmic molecules. A whole spectrum of approximately 100 antigens can be screened; however most have no clinical significance. In order to cover the majority of inflammatory autoimmune diseases 6 clinically significant antigens (Table 4); Ro, La, Sm, RNP, Scl-70 and Jo1 are used within most laboratories across the UK. It can be seen that SLE is associated with many of the antigens in the screen. Although ENAs are commonly performed via EIA (Figure 1.10), other methods such as qualitative gel precipitation assays, passive haemagglutination, immunoblotting, counter current immunoelectrophoresis (CIE) and antigen microarray can also be used (Kumar et al, 2009). Sceening of ENAs is expensive in comparison to IIF-ANA as it allows specific antigen detection, offering a greater sensitivity as approximately 90% of positive IIF-ANA produce negative results via EIA (Dahle et al, 2004). Gel precipitation assays such as double immunodiffusion (DID) and counter current immunoelectrophoresis (CIE) are still being used within laboratories; however these were discovered over 5 decades ago. CIE uses an electric current to accelerate the migration of antibody

Essay --

Taylor and AJ, both now twenty years old, have known each other since they were in first grade. They spent the majority of their time during high school in a relationship with each other. In December of 2013, a year and a half out of high school, they were planning to get married until a surprise deployment was sending AJ to Afghanistan. Because time no longer allowed for a December wedding, they chose to take their vows just days before he was sent overseas. The couple made this life-long decision together, so upon AJ’s return from deployment, he would be able to arrive at an apartment that Taylor has already made a home for them. Taylor has gotten a fair amount of negative feedback about her marrying a military man at a young age from individuals who know her directly or indirectly. When asked how she feels about those comments and how, if at all, they affect her, she tells me that they have no effect on her at all. She explains that she understands that she is at a differen t level of her life than many people at her age and she just hopes that those people who are aiming negativity toward her get to one day experience the happiness that she has received from her relationship and marriage. Taylor is nothing but over joyed and happy with how her life has developed into one that she is able to share with her best friend until death do they part. Despite some of the negative comments that Taylor has experienced, the amount of support she receives from her family and other military wives and girlfriends is tremendous. She reveals to me that her mother has raised her alone and that she has been one of the most supportive people in this experience. The decisions she has made along the way to marry AJ was not revealed to have any negat... ... of our foreign affairs. It has been shown that families of service men or women begin to suffer more than in the past (Lamanna & Riedmann, 2012, p. 58). The fact that Taylor does not foresee any damages caused with her husband’s military career results in concern for her and her family’s future. The interview performed with Taylor has allowed another to see the success that young marriages and military relationships can have. Although not all relationships work out this way, it is very refreshing to see the happiness that has been brought to Taylor and AJ’s life. It was expressed that it is very difficult for Taylor to be away from AJ, but it’s all worth it because of love. One may believe that love is not always enough, but for this couple it is. They deserve all the support in the world for being so willing to be together at such a difficult time for our society.

The Life and Writings of Edgar Allan Poe Essay -- Authors

Edgar Allan Poe is a famous poet from the 1800. He was born in Boston, Massachusetts on January 19, 1809. His parents were David and Elizabeth Poe. David was born in Baltimore on July 18, 1784. Elizabeth Arnold came to the U.S. from England in 1796 and married David Poe after her first husband died in 1805. They had three children, Henry, Edgar, and Rosalie. Elizabeth Poe died in 1811, when Edgar was two years old. Giordeno also mentioned, â€Å"She had separated from her husband and had taken her three kids with her. Henry went to live with his grandparents while Edgar was adopted by Mr. and Mrs. John Allan and Rosalie was taken in by another family. John Allan was a successful merchant, so Edgar grew up in good surroundings and went to good schools† (Giordeno). Before Poe became a writer he was enrolled in the army at eight teen years old, but he did not stay long her was soon dismissed. Poe was very poor while he was living and did not become famous until after his death in 1849. He is most famous for writing border line horror stories and poems. Some of his most famous poems are The Tell-Tale Heart, The Raven, The Fall of the House of Usher, and The Pit and the Pendulum. In The Raven Poe discusses many different literary terms. The three that stand out the most is symbolism, tragedy, and beauty. In The Raven Poe uses symbolism. One way he demonstrates symbolism is the bust of Pallas. Poe explains about the bust of Pallas when he says, â€Å"Perched upon a bust of Pallas just above my chamber door -Perched, and sat, and nothing more† (Poe l41-l42). Courson thinks that the bust of Pallas symbolizes intellect, â€Å"Then Remorse enters, and fixes itself firmly on his mind, ‘the bust of Pallas,’ the emblem of intellect.† (Courson) However, Za... ...emy of American Poets, 2012. Web. 12 Jan 2012. Smith, Dave. "Edgar Allan Poe and the Nightmare Ode." Southern Humanities Review 29.1 (Winter 1995): 4-10. Rpt. in Nineteenth-Century Literature Criticism. Ed. Lynn M. Zott. Vol. 117. Detroit: Gale, 2003. Literature Resources from Gale. Web. 12 Jan. 2012. Wardrop, Daneen. "Quoting the Signifier 'Nevermore': Fort! Da!, Pallas, and Desire in Language." ESQ: A Journal of the American Renaissance 44.4 (1998): 274-299. Rpt. in Poetry Criticism. Ed. Timothy J. Sisler. Vol. 54. Detroit: Gale, 2004. Literature Resources from Gale. Web. 12 Jan. 2012. Zayed, Georges. "The Symbolism of the Poems." The Genius of Edgar Allan Poe. Cambridge, Mass.: Schenkman Publishing, 1985. 127-136. Rpt. in Nineteenth-Century Literature Criticism. Ed. Lynn M. Zott. Vol. 117. Detroit: Gale, 2003. Literature Resources from Gale. Web. 12 Jan. 2012.

Deutsche Brewery Question and Answer

1. What accounts for Deutsche Brauerei’s (DB) rapid growth in recent years? What strategic choices were made? The Ukraine account grow rapidly in the recent years. The strategic is just expanding, more focus on the sale/volume, not on how to turn the order to money. It can be understood that the local distributors need some policy support from DB, because they just start, still at the beginning of capitalization period. The current credit policy is applicable for the starting phase, but long term it needs to be adapted (e. g annual bounce on the pay on time accounts).Meanwhile because of fast expansion, more investments on the Assets in Ukraine is needed. The financial plan includes a 7 million euro investment in new plant and equipment for the Ukrainian operations in 2001, followed by a 6. 8 million euro investment in 2002 for a new Ukranian warehouse and distribution center. Which is reasonable, but need more detail plan/business case before make the decision. I would say, h alf of the amount should be financed by Ukraine team itself, if they are able to turn the account receivable to cash. 2.What is the credit policy for DB for distributors in the Ukraine? Why is it different from other sales? Is it appropriate (examine the business models in both instances). The credit policy for Ukranian distributors from 2 percent 10, net 40 to 2 percent 10, net 80 (clients could take a 2% discount if payment was made within 10 days of the invoice, otherwise payment was due in full within 80 days). The credit policy for Ukranian distributors differed because Ukrainian entrepreneurs, who are ambitious to grow but without support from the bank as in Germany.The credit policy for the Ukranian distributors is applicable, which can support the distributor to expand, buy new equipment, and required more time than usual to pay. Also is a good investment for DB to build up the relationship with the distributor and meanwhile invest for the futurn. But on the other hand, long payment turn cost bad cash flow. In Ex1, the account receivable increase a lot, which 3. Why does this profitable firm need increasing amounts of debt? If the company wants to expand, they need cash.It seems that DB is profitable, but because of the big account receivable, which cause actually cash tie-up. In order to still keep expanding, DB have to increasing amount of debt for investing. 4. Something about dividends: The quarterly dividend proposed is 698,000 euro, an amount equal to 25% of the projected 2001 dividends (2,793 k). However, this dividend increase is based on projected earnings, and several factors affect whether those earnings. Better to reserve a part of money till end of the year. . What should Greta do with respect to: the proposed raise for Pinchuk, the quarterly dividend and the financial plan for 2001? Regarding the credit policy for Ukranian distributors, Oleg argues that this process is profitable for the company. Actually, Ex1 in the base case shows accou nts receivables in the Ukraine increased 30% from 1999 to 2000, and is projected to increase for the next 2 years (50% then 30% based on the previous year). Having a large amount of money tied up in receivables is risky.My idea will be short the payment to 40 days, pay in 10 days will have even bigger discount 3-4%, meanwhile, if the account can pay all the bill on time (40 days), can get annul bounce (tbd). For the investment, I will be more careful, Although the data should the growth of sale and assent is not hand in hand. But because of the high debt/equity ratio, I will be more careful on the investment, avoid to have too high debt. We can try to work together with one or two local disctributors (e. g. Kiev, Odessa) to have JV project.About the dividends, I will maybe go for 60% of earning, which mean 15% of the projected annual dividends for the quarterly pay. Just in case, if the actual data is not as good as predicted data, we still have enough cash to run the business. 6. S ome observation of Ex4. Profitability: low return Leverage: high risk (high debt) Asset utilization: receiveables growth rate high longer payment. Difference between sale growth and asset growth. Sale Growth is much higher than assent growth, need to consider investment. Liquidity: short term financial commitment. Quick ratio is too high.