Activation of the G Protein-coupled Estrogen Receptor

Activation of the G Protein-coupled Estrogen Receptor Activation of the G protein-coupled estrogen receptor ameliorates salt-induced vascular remodeling Abstract The mRen2.Lewis (mRen2) female rat is an estrogen- and salt-sensitive model of hypertension which may reflect the higher pressure and salt sensitivity associated with menopause. We previously showed in salt-loaded mRen2 female rats that activation of the G protein-coupled estrogen receptor (GPER) does not lower blood pressure but attenuates renal damage. The current study hypothesized that GPER protects against vascular injury in this model. Intact mRen2.Lewis female rats were fed a normal (0.5% Na+) or high salt diet (HS; 4% Na+) for 10 weeks and treated with vehicle or the selective GPER agonist G-1 for the last two weeks of the study. Systolic blood pressure was measured by tail cuff plethysmography, and aortic sections were mounted on a wire myograph or formalin-fixed for histological analysis. Systolic blood pressure increased with HS (137  ± 2 mmHg, n=7 to 224  ± 8, n=9; P0.05). While aortic reactivity to phenylephrine and acetylcholine were not different between groups (P> 0.05), chronic G-1 treatment reduced vasoconstriction to angiotensin II (Pex vivo G-1 vasorelaxation (P Introduction Sodium balance plays an integral role in cardiovascular homeostasis. A high salt diet is considered a major risk for cardiovascular morbidity and mortality independent of other cardiovascular risk factors (Beil et al. Blood Pressure, 1995). Excessive salt intake has been associated with vascular remodeling, including the reorganization of the extracellular matrix and hypertrophy and/or hyperplasia of vascular smooth muscle cells. Although vascular remodeling is considered a protective adaptation to a higher wall stress, it contributes to the development of hypertension by creating a thicker, less compliant wall. Aortic stiffness, which contributes to isolated systolic hypertension in human subjects, is an excellent example of the complications presented by vascular remodeling (Lemarie et al. Journal of Molecular and Cellular Cardiology, 2009). The ability of estrogen to attenuate vascular remodeling in injured arteries may at least partly occur via activation of the classic steroid receptors ERÃŽ ± and ERÃŽ ² in VSMC and endothelial cells (Xing et al. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009). Brouchet et al. showed that estrogen’s protective effects on vascular remodeling were abolished in female ERÃŽ ± knockout mice (Brouchet et al, Circulation, 2001). Moreover, in porcine aortic smooth muscle cells, the downregulation of ERÃŽ ² protein levels by mRNA antisense oligomers abrogated the inhibitory effects of estrogen on mitogen-activated protein kinase (MAPK) phosphorylation, migration, and proliferation (Geraldes et al. Circ Res, 2003; Xing et al. Am J Physiol., 2007). However, the protective effects of estrogen on vascular injury are evident in both ERÃŽ ± and ERÃŽ ² knockout mice, suggesting that another receptor may be necessary (Iafrati et al. Nat Med. 1997; Karas et al. Proc Natl Acad Sci USA. 1999). The novel G protein-coupled estrogen receptor (GPER) is a membrane-bound receptor linked to acute signaling pathways (Revankar et al. Science, 2005; Thomas et al. Endocrinology, 2005). Our previous studies showed that GPER activation lowers blood pressure in ovariectomized mRen2.Lewis rats and attenuates salt-induced renal and cardiac remodeling in intact mRen2.Lewis rats (Lindsey et al Endocrinology, Jessup et al, PLOS one, 2010 and Lindsey et al Hypertension). Therefore, this novel receptor may play an important role in mediating estrogenic effects in the vasculature. In the current study, we hypothesized that chronic GPER activation is protective against aortic remodeling due to salt-sensitive hypertension. To test this hypothesis, we utilized mRen2.Lewis (mRen2) rats, a unique congenic model of hypertension in which HS profoundly elevates blood pressure in females (Chappell et al, Am J Physiol Regul Integr Comp Physiol., 2006). We compared aortic remodeling in high salt-fed rats with or without treatment with the selective GPER agonist G-1. Because estrogen modulates oxidative stress to attenuate vascular remodeling in injured arteries (Hayashi et al, Biochem Biophys Bes Commun, 1995; Xing et al. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009) and GPER reduces oxidative stress in the kidneys of female mRen2 rats (Lindsey et al. Hypertension, 2011), we further determined whether the effects of HS and G-1 were mediated by modulating oxidative stress. To further elucidate the cellular mechanisms responsible for vascular remodeling, we uti lized primary cultured female rat aortic smooth muscle cells to determine the effects of salt on cellular hypertrophy. Methods Animals All procedures were approved by the institutional Animal Care and Use Committee. Hemizygous mRen2.Lewis congenic female rats were obtained from the Wake Forest Hypertension Center breeding colony. Rats had free access to food and water in a temperature-controlled room (22  ± 2 °C) with a 12 hour light to dark cycle. At five weeks of age, the normal salt diet (NS, 0.5% Na) was switched to high salt (HS; 4% Na), as previously described (1, 2). The selective GPER agonist G-1 (400  µg/kg/day; EMD Chemicals, Gibbstown, NJ) or vehicle was administered for two weeks beginning at 13 weeks of age via subcutaneous osmotic minipump (Model 2ML2; Alza Corporation, Palo Alto, CA). Blood pressure was measured via tail cuff plethysmography (Narco Bio-systems, Houston, TX). Animals were randomly assigned to three experimental groups: intact NS (n=7), intact HS+vehicle (veh; n=9), and intact HS+G-1 (n = 9). Vascular Reactivity. After sacrifice, the upper thoracic aorta was submerged in formalin for histology and the lower portion used for vascular reactivity as previously described (Lindsey et al Endocrinology). Aortas were equilibrated with 2 g tension and the responses to 1 uM phenylephrine, 1 uM acetylcholine, 10 nM angiotensin II (Ang II), and 3 uM G-1 were measured. Histology. Formalin-fixed aortas were embedded in paraffin, cut into 5 um sections, and mounted on slides. To evaluate aortic wall thickness, slides were stained with hematoxylin and images analyzed using ImagePro software (XXX company, XXX city,XX state). Aortic medial area was calculated by the subtraction of the area of the inner border of the lumen (inner area) from the area of the outer border of the tunica media (outer area). Collagen staining was performed using picrosirius red and images were taken using a Texas Red fluorescent filter. The medial area was selected and the mean luminosity was recorded for each section. The NovaUltra Orcein Elastin Stain Kit (IHC World, XXX) was used for elastin staining. For analysis of oxidative stress, sections were immunostained with an antibody against 4-hydroxynonenal as previously described (Lindsey et al Hypertension). For analysis of brightfield images, positive staining was identified and the percent of positive pixels in the medial a rea recorded. For all analyses, the average of four cross-sectional measurements was calculated for each animal. Cell Studies. Aortic smooth muscle cells were isolated from adult f emale Lewis rats by explant method. Aortas were excised, cleaned of fat, cut longitudinally, scraped of endothelial cells, laid luminal side down in a cell culture dish containing Medium 199 (Invitrogen, XXX) and 5% fetal bovine serum (Gibco, XXX), and cut into small strips. Cells were subcultured up to four passages. When cells reached 80% confluence, the medium was switched to Medium 199 without phenol red or fetal bovine serum and sodium chloride (Sigma) was added to the increase the concentration to 152 mM, 160 mM, and 182 mM. Add NaCl to make high salt CS medium (152, 160, and 182 mM), Normal medium 142 mM NO, I find 117 mM Add 0.02 g NaCl to 50 ml of normal medium, that makes 152 mM Add 0.045 g NaCl to 50 ml of normal medium, that makes 160 mM Add 0.11 g NaCl to 50 ml of normal medium, that makes 182 mM After 5 days of exposure to high sodium medium, cells were harvested for further experiments. Cells were harvested using trypsin to obtain single cell suspensions. A sample was taken for determination of cell number and diameter using XXX cellometer (XXX company, XXX city, XXX state). Mean cell diameter was determined on 200 randomly chosen cells in each sample. The remaining cells were lysed in XXX with protease inhibitor cocktail (XXX company). Cellular protein content was determined in duplicate using bovine serum albumin as a standard (Bio-Rad Protein Assay Kit). Results As previously reported, a high salt diet (HS) significantly increased systolic blood pressure in intact mRen2 female rats (Figure 1A). Chronic treatment with the selective GPER agonist G-1 for two weeks did not influence blood pressure. G-1 did not influence the aortic response to acetylcholine (Figure 1B) or phenylephrine (Figure 1D). However, G-1 treatment in vivo amplified the vasorelaxant response to ex vivo application of G-1 (Figure 1C) and decreased the vasoconstrictor response to Ang II (Figure 1E). Salt-sensitive hypertension in female mRen2 rats significantly increased aortic thickness, as determined by the media/lumen ratio (Figure 2A-B). This remodeling was associated with a significant decrease in lumen area but no change in the external diameter of the aorta (Figures 2C-D). Chronic G-1 significantly attenuated remodeling, as evidenced by a decreased media/lumen ratio and an increased lumen area, with no change in external diameter. The average measurements for all groups are graphically represented in Figure 2E. In order to determine whether extracellular fibrosis was altered by HS and G-1, aortic sections were analyzed for collagen and elastin content. Figure 3 shows that picrosirius red staining was similar in all groups (Figure 3). Elastin staining was significantly decreased by HS but this effect was not reversed by G-1 (Figure 4). Elastin Breaks Space between elastin fibers Sections were assessed for proliferation using antibodies against proliferating cell nuclear antigen and Ki-67. No evidence of immunostaining was found in the medial sections of aorta for these two nuclear proteins necessary for cellular proliferation (data not shown). However, in comparison to aortas from normal salt-fed rats, HS aortas showed a significant increase in oxidative stress as measured by staining for the lipid peroxidation product 4-HNE (Figure 5). In addition, chronic G-1 treatment significantly attenuated 4-HNE staining. Aortic smooth muscle cells were isolated and cultured in order to determine the Effects of HS and G-1 on cellular hypertrophy. Discussion The present study demonstrated that estrogen receptor GPER activation attenuated salt-induced increase of aortic wall thickness in mRen2 rats. The mechanism for the G-1 effect most likely involves counteracting oxidative stress and reducing vascular smooth muscle cell hypertrophy. This study demonstrating GPER-induced vascular protection nicely complements our previous work showing similar results in the kidney and heart (ADD REF). Interestingly, GPER’s renoprotective effects were also associated with a reduction in oxidative stress. Moreover, the beneficial effects in the heart were similarly independent of alterations in the extracellular matrix but directly associated with a reduction in cardiomyocyte size. Vascular GPER protein is clearly expressed in both endothelial and smooth muscle cells of the aorta (Lindsey et al, Endocrinology, 2009; Ding et al, Am J Physiol Cell Physiol, 2009; Gros et al, Hypertension, 2011). In native vessels, the extracellular matrix (ECM) is composed mostly of collagen, elastin and proteoglycans. These proteins inà ¯Ã‚ ¬Ã¢â‚¬Å¡uence cell functions and play an important role in maintaining vessel structure by providing tensile strength (collagens) and elasticity (elastin) (Lemarie et al. Journal of Molecular and Cellular Cardiology, 2009). One of the earliest steps of vascular remodeling is the reorganization of the ECM. In the current study, we have shown that HS increased collagen levels and suppressed elastin content in the aorta, indicating increased stiffness and less elasticity. Most importantly, the finding that G-1 ameliorates salt-induced collagen increase, without altering salt-induced decreases in elastin content, suggests that GPER activation protects against the remodeling process via suppressing collagen levels, instead of elastin. The amount and composition of collagen depends on a balance between synthesis / deposition and degradation. The exact effects of GPER on collagen protein expression, degradation, or both remain to be investigated. Another important step during vascular remodeling is the hypertrophy and / or hyperplasia of the VSMCs (Lemarie et al. Journal of Molecular and Cellular Cardiology, 2009). To address this possibility, we used primary cultured ASMCs isolated from female mRen2 rats. We found that both cellular protein content and cell size increased in high salt media (160 mM and 182 mM), indicating that high salt induces cellular hypertrophy. The cellular protein content of 152 mM media-treated cells is significantly higher than that of normal media (142 mM)-treated group. However, the cell size has no significant difference. One possible explanation is that the protein started to accumulate inside cells, but cells had not begun to enlarge yet. More importantly, we found G-1 abolished the hypertrophy of cells. The hypertrophy appears to result from an increase in the rate of protein synthesis and / or a decrease in the rate of protein degradation (Berk et al, Hypertension, 1989; Gu et al, Hypertension , 1998). Future studies are required to determine the effects of GPER activation on protein expression, degradation, or both. We further looked into the possibility of salt-induced proliferation in ASMCs. Although it has been shown that GPER induced the activation of MAPK signaling and cellular hyperplasia in VSMCs, other studies have demonstrated that G-1 inhibited serum-stimulated growth in VSMCs lacking ERÃŽ ± and ERÃŽ ² (Haas et al, Circ Res, 2009,; Ding, Am J Physiol Cell Physiol, 2009; Gros et al, Hypertension, 2011). In our study, we did not observe any evidence of Ki67 or PCNA staining in the medial layer of aortas from any group, although significant staining was found in the adventitia. These results are supported by our in vitro studies which show no change in cell number in response to HS. The finding that G-1 attenuates aortic thickening and cellular hypertrophy, without altering blood pressure, suggests that GPER has protective effects in the cardiovascular system that are independent of blood pressure. One possible mechanism is acute increases in oxidative stress. Oxidative stress is linked to damage within the vasculature and may contribute to vascular remodeling (Hayashi et al, Biochem Biophys Bes Commun, 1995; Xing et al. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009). To address this possibility, we first stained 4-HNE, a marker for oxidative stress, in the aorta. We found significantly stronger staining of 4-HNE in HS-fed rats. However, this was attenuated by G-1 treatment, suggesting that GPER activation attenuates salt-induced oxidative stress. To further confirm this finding, we used tempol, an antioxidant, or G1 to treat ASMCs and measured several hypertrophy parameters. Tempol or G-1 treatments abolished the increase of both cellular protein con tent and cell size. Broughton et al demonstrated that G1 reduces NADPH-dependent oxidase activity in isolated carotid and intracranial arteries of normotensive Sprague-Dawley rats (Broughton et al, Am J Physiol Heart Circ Physiol, 2010). Elucidation of the underlying mechanisms of GPR 30 to attenuate reactive oxygen species within aorta awaits future studies. Another possibility is that HS stimulates renin-angiotensin system (RAS) in mRen2 rats. Ang II increased medial thickening of aorta due to VSMC hypertrophy without increase in cell number (Owens et al, Circ Res, 1982 1983). However, GPER activation may reduce expression of the angiotensin II (Ang II) AT1 receptor (AT1R) and angiotensin-converting enzyme (ACE) but increase the expression of ACE2. Alterations in ACE and ACE2 may increase the ratio of Ang-(1-7) to Ang II in tissues (Lindsey et al, Gender Medicine, 2011). Ang-(1-7) inhibited vascular remodeling in rat jugular vein grafts (Wu et al, J Int Med Res, 2011). In the present study, the HS medium (152, 160, 182 mM) was made by simply adding sodium chloride to normal medium (142 mM). This increases both sodium concentration and osmolarity in the medium. It is likely that increased osmolarity plays a significant role in salt-induced hypertrophy. Future studies using mannitol are needed to rule out this possibility. In summary, this study showed a beneficial effect of the GPER agonist G-1 in salt- and pressure-induced vascular remodeling. These protective effects of G-1 may be due to suppression of oxidative stress and associated cellular hypertrophy. What about aldosterone? 1.Chappell MC, Westwood BM, and Yamaleyeva LM. Differential effects of sex steroids in young and aged female mRen2.Lewis rats: a model of estrogen and salt-sensitive hypertension. Gender medicine 5 Suppl A: S65-75, 2008. 2.Lindsey SH, Yamaleyeva LM, Brosnihan KB, Gallagher PE, and Chappell MC. Estrogen receptor GPR30 reduces oxidative stress and proteinuria in the salt-sensitive female mRen2.Lewis rat. Hypertension 58: 665-671, 2011.

Global sourcing Essay

1) What is global sourcing? Global sourcing is defined as the process of identifying, developing, and utilizing the source of supply for the enterprise through expanding purchasing activities internationally. It is a part of post reengineering activities which is an useful measure of cutting cost. Global sourcing is a typical example of foreign construction outsourcing firms which process construction by distributing each process of construction work to vendors instead of running on its own. Such construction method not only does reduce costs in terms of managing construction sites such as labor cost and equipment cost including vehicles, but also is being adopted by various companies for value-adding construction management (CM) project. For instance, global sourcing was utilized when building Daewoo Business Center at Warszawa, Poland, on March, 1997. The process of erecting the center was alloted to vendors; construction was executed by VOICE(England), design through RTKL(U.S.), facility management was duty of Dongwoo which is a department of Daewoo Group, hotel management by Hilton hotel(U.S.). 2) Global sourcing factors Global sourcing factors that must be understood and balanced can be segmented into 5 categories. First factor is material cost. The bottom line of execution of global sourcing is reduce cost by minimizing material cost. Another category is transportation cost. Various costs including inventory delivery cost can be dwindled through global sourcing. Moreover, significant amount of transportation expense can be reduced when marketing products at outsourcing regions. Cross-border taxes, tariffs, and duty costs are third factor which form global sourcing. Instead of relying on domestic production but rather outsource each process internationally, costs can be reduce by avoiding trade barriers which include cross-border tax, tariff and duty cost. Next factor is supply and operational performance. With effective resource management and cheap labor cost, supply and operational performance can be efficiently managed which enables global sourcing companies to manufacture high quality-low price merchandises. The last category of global sourcing is supply and operational risks. Cultural and geographical disparities can yield additional costs such as labor cost and transportation cost. If not managed thoroughly, they can militate as huge risks in terms of conducting sourcing. 3) Advantages of global sourcing There are three major merits of performing global sourcing; gumption to changes, reduction of cost, and trade barriers avoidance. To begin with, global sourcing allows a firm to develop capacity to cope with changes in market condition. Importing numerous raw materials and resources economically and steadily can be done through global sourcing. With such abundant resources, a firm can flexibly adopt to environmental alterations when confronting unexpected economic crisis. Secondly, average 20% of cost saving is possible. Components of products or raw materials procured from abroad is advantageous in terms of price. Furthermore, many countries such as American and Europe are sourcing materials to cut cost in terms of distribution industries. As a result, China has become the hub of production base for global sourcing. Even in case of Korea, sourcing products from China are 30%~40% cheaper than Korean domestic goods. In particular, simple functional merchandizes whose design and quality are relatively less considered are largely influenced by global sourcing. Consequently, over 70% of commodities and clothes are imported from China. Last merit of global sourcing is evasion of trade barriers. In case of global sourced goods, the price is lower, leading to economical purchase, by avoiding trade barriers such tariffs and cross-border taxes. On top of that, firms are able to acquire restricted raw materials and resource. Thus, unique and competitive products can be created. 2. Case-Study (Li&Fung) 1) Introduction Li&Fung is a professional trading company which specializes in global sourcing and was founded in 1906. It functioned as a broker between Asian manufacturers and foreign traders and expanded as a trading company later on. Today, Li&Fung acts as a professional sourcing and distribution firm focusing on toys and textile. Becoming an intermediary, it reconstructed the business by forming it as a connection and manager of diverse supply chains. Li&Fung is the representative of ‘smokeless factory’ without owning any equipment and factories regarding production process from raw material to final goods and distribution of final products. 2) Business area / Present condition Li&Fung won the rewards in ‘Fabulous 50†² selectied by Forbes Asia, ’50 for 2012’ from Morgan Stanley, and ‘The most influential companies 25’ from Business week. The sales of Li&Fung in 2007 was 92.4 billion in Hong Kong dollars, approximately 36% increase in sales compared to that of 2006. Net income reached 30 billion dollars(2007) and Li&Fung Co. Ltd. succeed in gaining 19.8% increase in sales (110.7 billion Hongkong dollars)than that of previous year. After 1998, foreign companies such as The Limited, Gymboree, American Eagle, Warner Brothers, Abercrombie & Fitch, Bed, Bath& Beyond, Tesco, Avon Products, Levi-Strauss, Reebok have become major customers of Li&Fung, and Royal Ahold, Guess Jeans, Bebe also joined as major customers of Li&Fung in 2000. As a result, Li&Fung currently has 68 offices in the 38 countries, and shareholders numbers 17,900. In addition, it consists of 107,000 employees engaged in the business associated with Li&Fung, especially 40,000 related businesses only in the United States. Thus, it can be said that Li&Fung has entered plateau stage as a company settling new form of SCM rather than just being a simple trading firm. 3) Platform / Operation System Li&Fung is one of the enterprises which effectively employ platform strategy. In terms of strategy, Li&Fung adequately balances SRM and CRM strategy to manage producers and customers. Li&Fung distributes textile component orders to vendors as soon as receiving orders from textile industries. It makes most of 15,000 subcontractors which are located around the globe. When producing a jacket, for example, Li&Fung procures materials from diverse vendors; outshell is from Korea, Zipper from Japan, lining is done from Thailand, and trademarks and thread from Hongkong. Fabric is dyed in Southern Asia, China sews, and finally quality inspection and packaging are done in Hongkong. Then, headquarter in Hongkong generally manages cash flow and value-added process. 4) Success Factors Success factors of Li&Fung can be categorized into three elements. The first factor is IT evolution. Through IT development, product lead time dwindled through forming network among producers and customers, and even efficiently manage vendors. Another facet is SRM and CRM, especially have strength on SRM. Li&Fung analyze customer’s needs and scrutinize supply chain to meet the desires. Since firms tend to focus on maximizing their capability instead of in accordance with needs, Li&Fung can otherwise strive to fortify supply chain or value chain for customers. In other words, the key role of Li&Fung is to direct manufacturers of supply chain to the intended direction. For that specific purpose, it establishes education to producers on scattered network management rather than having strict control system for managing vendors, and emphasizes on trust and active empowerment. Lastly, Li&Fung follows 30/70 rule, which is to set a standard(from 30% to 70% of total production) on production quota to Li&Fung. This enables Li&Fung to have loose liaison among subcontractors. Minimum 30% of total production allows Li&Fung to possess minimum supply from each subcontractors and prevention vendors from being subordinates can be done by setting maximum 70%. The core objective of this principle is to assure vendors of gaining huge profit from being a member of the network and on the other hand guaranteeing flexibility of business and availability of a room for growth. Other vendors also benefit from the principle by being expose to opportunities to work with others, which help them to learn and come up with innovative ideas. Such principle demonstrates value of Li&Fung on making supply chain more dynamic and lively. Thus, change in partners frequently happens in supply chain of Li&Fung. In conclusion, Li&Fung shows contradictory management of pursuing stable and long-term partnership whereas also demanding loose network instead to forming strict organization. 3. Problem & Solution 1) Wage stagnation / Pricing pressure The first problem of Li&Fung is wage stagnation of China. China accounts for 60% of total global sourcing of Li&Fung, which means that shift in China impact Li&Fung heavily. After the economic liberalization of China, China has been able to attract world companies as the most suitable production base due to cheap and abundant labor. As a consequence of substantial growth, China’s wage has been increasing 16% annually. As labor cost takes up the largest portion of garment industry’s costs, Li & Fung’s first half of 2011 net income dwindled 18%. Therefore, there is high necessity for finding a new production base(a new partners) and gain price competitiveness through such measure. Second problem is overseas buyers’ desire to lower supply pricing due to high uncertainty from global recession. As shown in the ‘average import price of textile in the U.S.’ graph on the right, the average import price has been continually decreasing, from $3.18 in 20 06 to $3 in 2009. Heavy pressure on supply pricing is having negative impact on net income of Li&Fung. 2) China & U.S Trade conflict Third adversity is potential trade disputes between the United States and China. This trade conflict, which is referred to as protectionism, is noteworthy of a notice as 69% of total production of Li&Fung is sold to the United States. The United States has criticized China on the currency exchange rate manipulation, along with accusation of exchange dumping. In addition, Section 421 is an article which can be executed in a situation where increased import of Chinese products acts as a severe damage to American domestic industries. Accordingly, it is inevitable to exclude potential trade conflict between two countries on account of high possibility of implementing additional countervailing duty by executing section 421. 3) Expanding partners in Southern Asia In preparation for deterioration of China’s production environment and falling competitiveness of China as a sourcing region, Southern Asia is evaluated as the most practical alternative for strategic sourcing of Li&Fung. In terms of percentage change in world textile industry sourcing, diminution of China is noticeable, as –7%, whereas Vietnam and Bangladesh show growth, respectively displaying 1% and 20% of sourcing uprising rate. To demonstrate suitability of sourcing to Banladesh, environment of Bangladesh such as social infrastructure and facilities, and educational level should be thoroughly examined. Nevertheless, wage of Bangladesh is much cheaper than that of China, Bangladesh being one third that of China, in terms of only considering unit labor cost. Furthermore, Bangladesh is likely to be significantly equipped with garment-industry infrastructure judging from the large number of textile industries sourcing to Bangladesh. Therefore, it is no hasty conclusion that Bangladesh is the most appropriate region for new production base of Li&Fung. 4) Quality management system Controlling over 15,000 vendors is demanding and the possible drawback is failure of consistency in quality. Since quality is prerequisite these days, stricter vendor’s quality management system should be made. One of the tools that Li&Fung can utilize and apply stricter is ‘Vendor compliance index’. There are six indexes Li&Fung should keep attention to; efficient operation, productivity, process innovation, ensuring the quality, purchase the appropriate law material, and good working condition of labor. By balancing and fulfilling following vendor compliance indexes, Li&Fung will be able to afford products to customer with coherent quality. 4. Conclusion The concept having used by Li&Fung is highly familiar to us as global sourcing is also deployed by domestic companies such as Samsung and LG. Global sourcing can be divided into two factors; risk element and opportunity element. These two elements are in trade-off relation which means that change in one element accompanies the other, while endeavoring to maximize opportunity element. Thus, taking advantage of opportunity and risk element in a timely manner is the premise for successful global sourcing and in-depth analysis on local region and strategy should be followed when implementing global sourcing.

Eyewitness Auschwitz

During the attempted extermination of the entire Jewish population, many Jewish prisoners were ordered to assist in the killing of their own people. Sonderkommandos were a major part of this eradication. A sonderkommando aided in the disposal of the corpses that were victims to the gas chambers. Through the vivid testimony by Filip Muller, â€Å"Eyewitness Auschwitz† allows the reader to fully understand the difficulties and graphic situations that occurred daily at Auschwitz. Filip Muller was born on January 3, 1922 in Sered, Czechoslovakia.In 1942 at the age of 20, he was deported to the death camp. He was one of the few Sonderkommandos to have survived Auschwitz. The memoir greatly details the resilience of the human spirit, the choices individuals were faced with and decided to act upon and, the treatment of those who had succumbed. The personal choices that some made were extremely unmoral. â€Å"†Every day we saw thousands and thousands of innocent people disappea r up the chimney. With our own eyes, we could truly fathom what it means to be a human being.There they came, men, women, children, all innocent. They suddenly vanished, and the world said nothing .. † An example of an unmoral prisoner was the Kapo Mietek, who was trusted to discipline the working prisoners. According to Muller, it was not necessary for Mietek to treat his fellow prisoners as human beings but rather beat them mercilessly to gain appreciation from the Nazi leaders. Another theme that Muller presents in his testimony is dehumanization of the camp’s victims.Approximately seventy percent of the prisoners that arrived at Auschwitz were immediately gassed. Their hair was shaven and their bodies were exploited in order to find valuables for the Nazi’s economic gain. A memoir is by definition â€Å"a  record  of  events  written  by  a  person  having  intimate knowledge  of  them  and  based  on  personal  observationâ⠂¬ . While Filip Muller’s testimony could be extremely accurate, it could also be extremely flawed. As a prisoner at a death camp-watching people die daily, it can weigh heavily on one’s conscious.This in turn can alter one’s memory and/or create an entire new memory that never happened. The validity of Muller’s memoir could all be a figment of his imagination due to the emotional and physical stress and agony of being a prisoner although I highly doubt that the validity is compromised. â€Å"Eyewitness Auschwitz† is a key document of the Holocaust. It is published with an association of the United States Holocaust Memorial Museum, which is highly renown. â€Å"Eyewitness Auschwitz† is a personal testimony of the hell that resided within the death camps.Filip Muller does an excellent job of describing the daily activities of a Sonderkommando, which few lived to tell about. At times it is extremely difficult to read due to the graphic nature of the text. Muller discusses themes that the entire camp system was set on such as dehumanization and the immorality of the soldiers as well as fellow prisoners. Filip Muller wrote a very powerful book that reaches deep within the reader and wrenches on their emotions.

Tuesdays With Morrie Film Analysis - 949 Words

The film Tuesdays with Morrie ( TWM) has shaped my understanding of the consequences of change through the main themes of change in perspective, change in relationship power dynamics, Mitch’s increased commitment and the ripple effect that change causes. The representation of mitchs perspective throughout Tuesdays with Morrie, has shifted my understanding of the consequences of change through the importance of various relationships Mitch has developed and the importance of an alternative perspective to initiate self-improvement. The film Tuesdays with Morrie speculates the change of the protagonist Mitch Albom, and the process of how that change was achieved. The genesis of the film shows Mitch to have a very overloaded lifestyle, this†¦show more content†¦In the film Tuesdays with Morrie, the representation of the shifting emotional dependency that is portrayed between Mitch and Morrie has caused me to perceive the ways in which a relationship can change positively for both parties. When the relationship between Mitch and Morrie was first revealed to the audience it was clear that Mitch was emotionally dependent on Morrie and deeply valued the wisdom that he was being taught. This is shown in the scene where Mitch buys a ta pe recorder to record the lessons that Morrie is teaching him, Mitch states â€Å"well if youre going to keep giving me this meaning of life stuff I want to remember it† in this scene there are many close up shots and slow panning between Mitch and Morrie.This reveals to the audience that Mitch is dependent on these teachings to help him in his current life situations. The relationship in the beginning of the movie slowly changes from the teacher-student relationship as the film progresses into a more genuine friendship. This is becoming more evident as Morries health continues to deteriorate. The film techniques that are used to portray this are darker lighting and the use of high angle shots with the intention to make Morrie look small and fragile. The change in the dependency between Mitch and Morrie has revealed to me how the change inShow MoreRelatedTuesdays With Morrie Film Analysis1757 Words   |  8 Pages This paper will examine the following; the description of Loss, Grief / Bereavement faced by the main character from the film, an indebt analysis of defined concepts/examples, theories and models connected with the main character, as illustrated in the film, the summary/developmental issues of loss, grief/bereavement, the distinction of common, normal and anticipatory grief, different stages/models of grief, cultural response to grief, the application of relevant theoreticalRead MoreOprah Winfrey – the Story of an Entrepreneur4292 Words   |  18 Pagesvalue, Oprah’s shows (and her various ventures) helped change lives for the better. THE OPRAH/HARPO EMPIRE During the 1990s, Oprah expanded her business into many areas besides the television. She entered various fields such as publishing, music, film, heath and fitness and education. In 1994, Oprah’s initiatives for the protection of children against abuse were rewarded when the then US President, Bill Clinton signed the ‘Oprah Bill,’ a new law designed to protect children against abuse. InRead MoreAmazon Your Industry: Extracting Value from the Value Chain4647 Words   |  19 Pagesmodel. For example, consider the 30-plus percent return rate for adult hardcover books through traditional channels, versus the 3 percent return rate through Amazon.com. Although many have examined Amazon.com - the icon of the Digital Age - our analysis goes beyond Amazon.com to identify a number of Internet axioms worth consideration by dot-com startups and traditional retailers alike: * Inefficient supply networks are at risk from new players. * First-movers gain advantage from scale.