Diabetes Type 1: Stem Cell Research

Stem cell therapy involves the direct transplant of islet cells to potential areas in the pancreas that have the ability to store and facilitate the differentiation of beta cells in the body. Such treatment is currently under progressive study in terms of its effectiveness and the possibility of fortifying the islet transplant’s resistance to autoimmune attacks antibodies. We discuss the actual procedures and different alternatives of stem cell therapy for DMT1 patients. The discussion covers the potential problems being confronted by such treatment, such as stem cell scarcity, autoimmune attacks against the islet transplants, etc.Lastly, discussion also covers the potential alternatives of the treatment, specifically (1) human embryonic stem cells, (2) cultured stem cells and (3) potential xenogeneic resources. In the conclusion, we have found several problems currently being faced by stem cell therapy. These problems include the scarcity of available islet grafts or transpla nts and the autoimmune risks that can dramatically hinder to the success of the therapy. However, various studies are currently being explored in order to obtain potential alternatives, such as xenogeneic stem cell resources, embryonic or progenitor alternatives, etc.Furthermore, we discover different methodologies in stem cell culturing and preparation techniques that confront the immunity problems most especially in post-transplant phase. These include the usage of different immuno-suppressing drugs, such as gastrin, etc. 2. Introduction 1. 1 . Type 1 Diabetes DMT1 is essentially the absence or severe insufficiency of insulin due to the autoimmune (e. g. CD4 interleukin attacks, cellular necrosis, macrophagial reactions, etc. ), environmental or viral destruction of beta cells (e. g. iral infections from mumps, etc. ) or insulin-secreting cells in the pancreas. Although, autoimmune reasons are the most commonly associated etiology that cause DMT1 condition. Apparently, the body an tibodies, specifically interleukins and minor interferons, recognize the antigenicity present on pancreatic islets as foreign substances, which consequently triggers autoimmune responses. The prevalence of DMT1 in United States is approximately 1 in 2500 for the age group of 5 years old, which 1 in 300 for every 20 years of age group.Although the most considerable nature of DMT1 is its autoimmune nature, prevalence of DMT1 in United States and European nations largely depends on two causations: (1) genetics and (2) lifestyle. According to the EURODIAB collaborative study, a registry involving 44 countries in Europe, states an annually increasing rate of DMT1 with approximately 3 to 4%, with a larger increase in some central and eastern European countries . The prevalence of DMT1 among 191 World Health Organization (WHO) member states and for all age groups worldwide is estimated to be 2. % in 2000 and 4. 4% in 2030 . DMT1’s beta cell destruction does not only consider the neg ative effects towards insulin production. Deficiency in insulin can directly lead to moderate to severe hyperglycemia that can further trigger problems, especially in (1) neural systems, (2) peripheral and central vascular regions, (3) cardiac and (4) kidney areas. Vascular complications among DMT1 are associated to different cellular dysfunctions, such as Endothelial Progenitor Cells (EPC) that induce metabolic stress and vascular angiogenicity especially when the cells are decreased.The primary principle that explains the metabolic and cardiovascular dangers of this illness is the increased of tonicity in the blood or also known as fluid hypertonicity. Due to the increased surge of blood glucose levels, fluids, such as blood, lymph, interstitial fluid, etc. , become thicker than its normal viscosity. With this fluid condition, the circulation exerts tremendous vascular and hyperosmolar pressure from major vessels to minor arterioles and veinuoles. Eventually, the prolonged pressur e can lead to various complications, such as eye retinopathy, nephronic damage, nerve ending necrosis, etc.The common treatment being prescribed among DMT1 patients is the continuous administration of insulin injectables in order to fill in the body’s insulin requirements. This is done to temporarily replace or fill in the insulin insufficiency of the body. However, insulin therapy and maintenance are lifetime measures that require continuous commitment, which can greatly interfere in the person’s self-esteem and lifestyle progression. To resolve these potential emotional and psychosocial damages of the temporary insulin therapy, permanent treatments, such as stem cell implants, autoimmune suppressors, etc. are currently being studied with hopes of permanently curing the disease. Stem cell studies have carefully focused in determining the potential strategies in order to induce beta cell differentiation and cellular regeneration, especially among those damaged or destr oyed islet cells. Clearly, with cellular differentiation and regeneration s the goal of stem cell treatment, vast numbers of research discussed in the latter part of the studies have intensively focused their explorations in the disease’s autoimmune nature.Modern studies of beta cells have always been associated to the macrophagial and lymphocytic activities of T-cell mediated antibodies, such as CD4+CD25+, CD+ T-cells, etc. Most studies are determined in configuring the possible strategies of resolving, preventing and/or countering the DMT1’s autoimmune response on both original islets and implant islet grafts. In animal trials, most commonly rodents, autoimmune elements of the disease are somehow resisted when significant dosage of immune-inhibiting drugs (e. g. nfliximab, daclizumab and sirolimus, etc. ) are applied on the islet implants prior to the commencement of stem cell implantation.Several studies (e. g. Gastrin applicationetc. ) have found promising strategi es that can immunize the transplant grafts and possibly the original islets themselves from the autoimmune destruction rendered by the disease; although, modern science has not yet considered the safe applicability and effectiveness among human trials due to the conflicts encountered by the studies, such variations of drug responses or autoimmune actions. On the other hand, the signs and symptoms of DMT1 and DMT2 are both related to the two principal components of diabetes: (1) hyperglycemia and (2) hypoinsulinemia.DMT1 commonly presents its condition with the classic manifestations of polydipsia, polyphagia and polyuria . Physiologically, the three principal signs of DMT1 are extremely integrated and fostered by the body’s sympathetic natural response. For example, due to the hyperglycemic state of the body, the satiety centers of the brain triggers polydipsia in order for the body to increase its fluid intake aiming to dilute the tonicity or increased blood glucose levels. In the process, the body increases the fluid contents in the blood increasing as well the kidney workload in processing urinary output; therefore, producing polyuria.Consequently, fluid loss also causes significant electrolyte losses and glucose malabsorption that trigger body weakness. In order to compensate, the body triggers polyphagia that aims to increase food consumption. The three latter manifestations are considered the cardinal or principal manifestations of DMT1 common to all patients. Weight loss, fatigue, blurred vision, pruritis and muscle wastage are the secondary symptoms that follow with the continuous manifestations of DMT1 cardinal signs .The secondary complications of DMT1 can further aggravate if the physiological hyperglycemia and other associated signs and symptoms are not resolved. Tertiary complications involve severe manifestations that can be fatal in nature, such as diabetic ketoacidosis and possibly diabetic coma. 1. 2. Causes of DMT1 DMT1 has three poten tial origins that are currently under extensive study, namely (1) chronic autoimmune destruction of beta cells, (2) environmental destruction of beta cells that is commonly viral in nature, and (3) genetic abnormality in beta cells and/or insulin receptors .The autoimmune etiology of DMT1, as discussed earlier, involves the activity of interleukin-1 protein cytokine that principally triggers the immunologic response of CD4+ T cells against beta cells. The autoimmune nature has proven the relationship between beta cell destruction and islets’ inflammation due to interleukin invasion; however, studies have not yet determined the principal source of this cytokine production . The issues surrounding the autoimmune proposition in the DMT1 condition is the communicating element/s induced by the disease that activates antibodies’ response against the islet cells.As of the recent studies, no specific communicating agent has been discovered linking both DMT1 condition and its a utoimmune reaction towards islet cells; although, there are numerous evidences that reveal the exact autoimmune attacks against pancreatic islet cells, most significantly on the beta cells. Meanwhile, viral causations have also been associated to the occurrence of DMT1. Common viruses, such as mumps, rubella and coxsackie, have been associated to the destruction of beta cells, which eventually triggers the chronic drop of insulin production .Cytokine-interferon alpha (IFN-alpha) has been associated with the occurrence of DMT1 with hypothetical viral origin. According to clinical reports, IFN-alpha is brought by environmental viruses (enteroviruses) that trigger immune-mediated beta cell destruction. Significantly, therapeutic agents targeting IFN-a may potentially be beneficial in the prevention of type 1 diabetes and autoimmunity . Lastly, genetic abnormalities min beta cell progenitors and cellular differentiations are also becoming part of the controversial cause of DMT1.The idea of genetic causation of DMT1 involves the reduced activity of embryonic progenitors in pancreatic endothelial, which consequently lessens the cellular differentiation of beta cells. With small beta cell count in the body, insulin production becomes insufficient causing cellular tension for insulin production. Prolonged state of hypoinsulinemia or complete absence of insulin in the blood usually results to DMT1 complications. Islet transplantation or stem cell therapy considers the destroyed islet areas that need replacement.According to Rother and Harlan, if patients with greater body mass indices and/or with insulin resistance were also considered for an islet transplant, the 3,000 transplantable islet preparations presently achievable would likely be sufficient to restore euglycemia to fewer than 1,000 patients per year, or less than 0. 1% of patients with T1DM, or approximately 0. 005% of those with either form of diabetes. Despite of the technological advancements of stem cells and islet transplants, most parts of DMT1 condition and autoimmune functionalities are still left undetermined.The scarcity of islet stem cells is not the only problems being faced by islet transplant therapy but also the impending variations of autoimmune activities of the body. Controlled experiments have been conducted on both rodents and primates; however, the results most of the time vary when applied to human samples. Although, such islet therapy have already been applied to human sample and proven to cause independent insulin production; although, medical issues, such as alternative stem cell or islet graft sources, risk of anaphylactic rejections, etc, are still being studies extensively.Therefore, scarcity and further study of the procedure are necessary to further the application of islet stem cell therapy among DMT1 patients. 1. 3. Therapy for DMT1 Stem cell transplant of islets of langerhans, specifically the ß -cells, is now considered as alternative treatment in tr eating Diabetes Mellitus Type 1 (DMT1); although, not all DMT1 patients are applicable candidates of stem cell therapy. Antigenicity testing and severity of DMT1 manifestations as well as autoimmune response to the treatment are usually evaluated before considering stem cell transplant.Through the process of genetic engineering, the autoimmune response of DMT1 towards the islet cells can now be countered by replacing the cellular necrosis of ß-cells. The study explores the different sections of ß–cells stem cell transplant, particularly on (1) the actual procedure, (2) allogeneic and xenogeneic possibilities, (3) the actual condition of DMT1 and (4) the pathophysiological principles involved in the process of disease progress and stem cell therapy.The case of DMT1 is autoimmune by nature wherein the body acts negatively to the islet cells by recognizing these cells as a form of foreign objects. Theoretically, the body’s macrophages and interleukins are alarmed by the foreign or abnormal structuring of islet antigens, which probably resulted due to the extensive response of the cells thriving within high insulin-needing environment. In response, the body’s immunologic centers trigger macrophagial and anti-body mediators (e. g. GAD65 Ab – Glutamic Acid Decarboxylase Antibodies, Iinsulinoma Antigen 2, etc. attacking and destroying the body’s own pancreatic tissues . During these conditions, islet cells chronically declines in number as macrophagial actions subdue and destroy both progenitor cells in the pancreas and those differentiated islet cells, which include the beta cells. With the destruction of progenitor cells, the rate of cellular differentiations for further beta cells and other islet cell types (e. g. alpha cells, etc. ) decline leaving the body deficient of these endocrine hormones.Furthermore, as the existing and pre-existing beta cells die due to autoimmune damages, the capacity of the islet cells to regener ate also decline, which eventually decreases the number of existing beta cells within the islets. Theoretically, According to Xu, Wang and Hou (2008), as the body’s insulin requirement heightens and prolonged, the remaining beta cells experience physiological stress in insulin production, which, if not prevented, can lead to a negative feedback mechanism wherein insulin production complete shuts off its production.DMT1 patients experience decreased and/or absence of insulin production, and usually peaks between early adolescence (10 to 14 years of age) to middle adulthood (30 and above) . Pancreas manifests lymphocytic infiltration and destruction of islets of langerhans, which consequently causes depletion of insulin production. During the past few decades, studies on islet transplantation through mesenchymal stem cells (MSC) have shown to improve the metabolic conditions of DMT1 patients. However, the performances and study results using MSC remains to be questionable.Trans -differentiation of MSCs into insulin-producing cells (IPCs) is considered the principal concept of the therapy; however, other reports have negated these results claiming that it is too difficult to assume and determine the timing and extent of improvement by only analyzing the effects through trans-differentiation. Cellular differentiation and self renewal can greatly vary depending on various conditions, such as existing drug therapies, immunologic sensitivity, duration of the illness, other existing disorder including complications dealt by DMT1, etc.Similar to other beta-stimulating treatments, MSC is considered growth factor stimulant of the surrounding beta cells, which aids in the mechanism of self duplication rather than cellular proliferation. According to Xu, Wang and Hou (2008), â€Å"MSCs transplantation into diabetic animals may prevent apoptosis of injured pancreatic beta cells and enhance regeneration of endogenous progenitor cells through paracrine actions† ( e. g. angiogenic, cytoprotective, anti-inflammatory, mitogenic and anti-apoptotic effects, etc. ). MSC studies are still on the process of development along with animal trials.MSC therapy alternative is process for treating principally the occurrence of hyperglycemia in DMT1; however, the process remains an assumption and currently being studied. In the study of Ezquer, Ezquer and Parrau (2008), MSC procedure has been detected to also contribute to tissue regeneration (e. g. bones, cartilage, infracted heart, brain and kidney). In the study, a test subject with streptozotocin (STZ)-induced type 1 diabetes (C57BL/6 mice) has shown significant cellular neogenesis on pancreatic and renal function as well structure.Somehow, MSC has triggered a potential role of becoming a promising alternative as pancreatic progenitor cells that possess the capacity to initiate cellular differentiations. After the subject received a 0. 5 x 10(6) MSCs via ex vivo expansion, the sample has shown significa nt reduction in blood glucose levels and euglycemic values after a month. With MSC acting as the islet’s alternative progenitor cells, beta cell differentiation can progress to the development of other beta cells, which if continued can trigger cellular regeneration among produced existing beta cells.According to final conclusions of Ezquer, Ezquer and Parrau (2008), â€Å"MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. † This evidence shows the possibility of using MSC in initiating both cellular differentiation and self-duplication. Altthough, Xu, Wang and Hou (2008) still consider this process as an experimental alternative therapy for DMT1 condition. However, the study sample did not consider the potential effects of human autoimmune responses against these MSC grafts.Autoimmune responses can risk the success of graft transplant considering the increased antigenicity present among these islet transp lants, which is a considerable issue that arises in the results of their study. Meanwhile in the study of Feng, De-quan and Yan-hua (2008), they have focused on MSCs derived from human umbilical cord blood (UCB) in order to facilitate cellular transdifferentiation into beta cell alternatives via in vitro. In the study, UCB samples are obtained, while presenting MSCs are isolated for analysis via flow cytometer.In the process, islet-cellular differentiation has been induced for 15 days with or without extracellular matrix gel. This extracellular matrix gel provides an enriched environment that nourishes cellular requirements aiding in their differentiation and consequent self-duplication. With the help of chemiluminescent immunoassay system (CIS) in detecting glucose activity and insulin response, the studied found out that insulin positive cells (25. 2 ±3. 4%; UCB n=42) within ECM gel have produced functional islet proteins after 9 days of pancreatic differentiation.Considering th e feasible environment setup by ECM, the possibility of creating a zone wherein autoimmune reactions are considered nullified has also become one of the propositions that theoretically explained the results of the study. According to the conclusion of their study, MSC can actually differentiate into islet like cells in vitro and ECM gel. Fortunately, with the advent of modern technology and introduction of somatic stem cell transplant, the depletion of ß–cells can now be replaced with new generating ß–cells through stem cell implantation.In 1990, Scharp et al. has brought reports of success in the process of transplanting islet cells to patients with DMT1 through the process of improved islet isolation techniques (developed by Ricordi, Lacy and Finke et al. 1988) . Isolation techniques aim in discovering alternative progenitor sources of progenitor cells that possess the capacity to differentiate into insulin-producing cells that can serve as essential alternativ e for beta cells.Aside from pancreatic progenitor cells, the study has also discovered potential sources in the kidney, liver, bone marrow and other vital organs of the body. Isolation techniques usually require individualized culturing of islet transplants prior to the actual therapy. With the introduction of ß–cells implantation, different forms of islet transplant (e. g. billiary installation of islet cells, xenogeneic sources of islets, etc. ) have been considered throughout the process of stem cell therapy. On the other hand, certain reaction problems produced during the process (e. . anaphylactic response, incompatible cellular transplant, insulin-sensory impairment, etc. ) have also been observed in throughout the process of therapy. Despite of the potential therapeutic permanence of islet transplant therapy against DMT1 condition, most medical specialists (Kabelitz, Geissler and Soria, 2008; Xu, Wang and Hou, 2008) consider this treatment as last resort therapy for severe cases of DMT1. Stem cell therapy is not yet considered as a general treatment applicable for all sorts of DMT1 conditions.According to Kabelitz, Geissler and Soria (2008), the concepts in the cellular treatment of DMT1 are (1) the replacement of islet cells by islet-like cells derived from embryonic or adult stem cells, and (2) promotion and establishment of immunological tolerance of islet cells towards self-antigens through regulatory T cells and/or tolerance-promoting monocyte-derived cells. Studies have explored possible ways in dealing with the confronting problems of the procedures, such as scarcity, autoimmune sensitivity, etc.In the preceding sections of the discussion, the two concepts are further explained considering the possibility of merging the two procedures in order to attain maximum efficiency in the DMT1 cellular therapy. 3. Modern Techniques in Treatments of DMT1 1. 1 Islet Cell Transplant The principal concept of stem cell therapy is the harvesting of pot ential and/or adult health cells that are transferred to failing or degenerating organs. As for DMT1 conditions, islet transplantation, specifically on ß–cells implantation, is the most impressive treatment that shows promising permanent cure for islets’ autoimmune degradation.According to Hussain and Theise, â€Å"stem-cell therapy here implies the replacement of diseased or lost cells from progeny of pluripotent or multipotent cells. † According to Haller, Viener and Wasserfall et al (2008), UCB-derived MSCs are significant autologous progenitor inducers that can initiate cellular self duplication or regeneration. In their study using 12 autologous UCB infusions, preliminary results show significant slowing of endogenous loss of beta cell degradation among DMT1 children subjects.Aside from the slowing of hyperglycemic actions induced by DMT1, Keymeulen (2008) has proposed the possibility of actually blocking or preventing the autoimmune destruction of beta cells in DMT1 conditions. In the study, Keymeulen (2008) proposes the short-term humanized anti-T-cell antibody treatment that aim to inhibit the t-cell activities and preserve the residual beta-cells for at least 18 months in order to induce cellular regeneration and stabilize metabolic control of the body over the rising glucose levels.By applying Anti-Thymocyte-Globulin, tacrolimus and mycophenolate mofetil to a non-uremic C peptide negative DMT1 patient, marked decrease in autoimmune activities has risen to more than 80%. Another principle of stem cell transplant in islet cell therapy is biologic differentiation wherein a pool of undifferentiated precursors (e. g. Human Islet-derived Precursor Cells or hIPCs, etc. in pancreas appears to be a series of stem cell that further differentiate to islet-endocrine cellular population: (1) Glucagon-producing alpha-cells, (2) insulin-producing beta-cells, (3) somatostatin-producer in Delta cell, (4) pancreatic polypeptide secreting cells . Both of these cellular somas act as the cellular surrogate of ß–cells that shall replace the depleted or damaged cellular source in the pancreas . Cellular differentiation holds the key in inducing growth to the depleted beta cells in the islet of langerhans.According to the study of Abdi, Fiorina and Adra (2008), islet transplantation (ppluripotent stromal cells) provides great potential for diversifying the cellular lineage even with postnatal damaged tissues. The study of of Abdi, Fiorina and Adra (2008) support the idea of cellular renewal and differentiation giving more emphasis on the mesodermal origin. In such case, the study introduces the concept similar to other studies (e. g. immuno suppression of T-cell activity, increasing beta cell antigenitcity resistance, etc. wherein the introduction of MSCs or islet transplant pluripotent cells may induce an immunomodulatory effect, which eventually facilitates cellular regeneration. The study of Seissler and Schott (20 08) also supports the idea of cellular differentiation and self-renewal; however, they have questioned the capacity of supporting the cellular capabilities of stem cells derived from adult pancreas or non-pancreas. During cellular differentiation of endocrine tissue, precursor cells secrete multiple hormones prior to final maturation of differentiated cells that secret single classification of hormone.Most of these hormones are actual growth hormones that enhance cellular differentiations and regeneration. Although these actions are most of the time slow-phased and are very much vulnerable to immunologic attacks, some studies (e. g. Piper, Brickwood and Turnpenny, 2004; Lai, Schneider and Kidszun, 2005) suggest that once islet cells have regained its stable cellular disposition, which can varies depending on the prevailing physiological atmosphere (e. g. decreased immune activity, prolonged hypoinsulinemia, etc. , the cellular proliferation and restorative scheme can pursue more rap idly than its common phasing. In the process of islet transplant, beta cells are produced as part of the general cellular differentiation produced by broad cellular differentiations . According to Rosenburg, Lipsett and Yoon et al (2004), once islet cell quantity have increased to a stable position and the environment requires extensive insulin production, autoimmune response of the body against these cells are seen to decline dramatically.Once islets have differentiated from progenitor populations, the cells migrate towards the surrounding exocrine tissues. With the help of angiogenesis resulted by vascularization of islet’s arteriolar blood flow, specific cells present in the islet progenitors, beta cell progenitor, increase its differentiation phase, which consequently increases the number of beta cells present in the pancreas . As beta cells increase, the body’s glucose-perception also enhances considering the increased quantity of glucose sensing beta cells.The di fferentiated beta cells react against the decreased body insulin levels by producing insulin, which further stimulate beta cell’s massive proliferation in islets of langerhans . Upon stimulation of cellular differentiation under insulin deficient environment, islet transplant may significantly continue with its differentiation and regeneration schemes without the heightened danger of autoimmune attacks. This theoretical physiology can serve as the actual basis for considering the value of restoring stable beta cell count within the body.However, the conflict that needs resolution is the safety of islet grafts upon its initial stage of transplant. Differentiation of beta cells is the primary target of islet stem cell therapy among DMT1 patients. These cells are highly specialized cell type, phylogenetically developed, and regulators of glucose homeostasis in higher forms of organisms. However, some studies suggest (Montanya, 2004; Vinik, Rosenberg and Pittinger, 2004; Hermann, Margreiter and Hengster, 2007) the inverse relationship present between cellular proliferation and differentiation of islet implanted stem cells.The most common problem that arises during post-transplant phase is the decreased differentiation of beta cells, which, in some cases, are not enough to fill in the body’s insulin requirements . However, Dor, Brown and Martinez (2004) assert that Beta cells, during post-stem cell therapy, do not base the production of additional beta cells in the rate of differentiation; rather, beta-cells proliferate through the process of self-duplication .This is considered as an argument in the idea proposed in the latter section wherein it proposes the nullity in achieving cellular stability in both differentiation and regeneration once specific rate of beta cells are reached in the process. Although the proposed theory does not entirely in-distant with the latter, the argument suggests that beta cell proliferation solely derives from the pre-e xisting beta cells obtained via transplant, which further proliferates via the process of cellular regeneration and not entirely differentiation.As for the critique, cellular differentiation is regarded as of little importance due to its low contribution in cellular proliferation. According to Dor, Brown and Martinez (2004), â€Å"Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice†¦ These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment. Xunrong, Hua and Soo (2005) support the argument through their study indicating the process of autoimmune blockage (Transforming Growth Factor-TGF-[beta]1) rather than the concept of cellular differentiation brought by stem-cell therapy . In the study, they have m ention the capacity of growth factors, such as TGF, to provide temporary autoimmune suppression that blocks the hazardous effects of this bodily responses.With increased angiogenesis or vascularization, the newly introduced cells (beta cells) can rapidly and freely proliferate as long as adequate oxygenation from rapid blood supply is present, and autoimmune suppression is being facilitated by the growth factors. According to Xunrong, Hua and Soo (2005), â€Å"Syngeneic islet grafts failed by day 17 in all untreated mice, whereas Ad-hTGF- [beta]1 therapy prolonged survival of islet grafts. Our data demonstrate that systemic TGF-[beta]1 gene therapy blocks islet destructive autoimmunity, facilitates islet regeneration, and cures diabetes in diabetic NOD mice†.TGF-[beta]1 possesses the functions of temporarily blocking the autoimmune response against the transplanted islet graft as well as triggering cellular regeneration channeled through self-duplication. Considering the argu ments propose by the two latter studies, this study still concludes the essential contributions of cellular differentiations brought by pre-existing progenitor cells from stem transplant or original sources; since, these component holds the appropriate physiological distribution of islet cell re-categorization and reproduction. 1. 2 Stem Cell TransplantationContrary to the concept of cellular differentiation and proliferation, post-stem cell transplant on islet cell is said to induce aggressive self-renewal due to the presence of significant growth components (e. g. TGF-[beta] 1, hemo-erythropoetin,etc. ) that enhance pre-existing beta cell proliferation and protect the cells from autoimmune attacks. Through the use of a DNA analog-based lineage-tracing technique , the study has found that precursor cells do not actually contribute to further differentiation of adult beta cells, and not even during acute beta cell regeneration.Rather, beta cells are being produced through self-renew al or duplication wherein a programmed cell division occurs through a refractory period preventing excessive or massive beta cell proliferation. Although, as argued by various studies (Lee, Grossman and Chong, 2008; Gershengorn, Anandwardhan and Wei, 2004), theoretically, differentiation rate usually surges during the initial phase of cellular implantation; however, once the cellular count of these differentiated cells stabilize, self-renewal or cellular regeneration of the existing beta or islet differentiated cells follow.Thus, explaining the inverse relationship between beta-cell proliferation and differentiation. Current studies in both allogeneic and xenogeneic stem cell sources are now being studied with marked emphasis on autoimmunity reversal or even autoimmunity tolerance. According to Lee, Grossman and Chong (2008), â€Å"stem cells from hematopoietic sources, such as bone marrow and fetal cord blood, pancreas, intestine, liver, and spleen, promise either new sources of i slets or may function as stimulators of islet regeneration†.Through stem cell introduction of pancreatic cells, specifically islets of langerhans, the adult human beta cells pre-existing in the stem cell transplant exhibit hormonal expression . Contrary to the concept of cellular proliferation, stem cell transplant essentially increases beta-cell resistance to autoimmune destruction of DMT1, which consequently facilitates the proliferation of beta cell in the islets of langerhans.According to various studies (Linning and Madkuhar, 2004; Strobel, Yuval and Stirman, et al. 006), aggressive beta cell self-duplication is the actual cause of beta cell proliferation whether by implantation of TGF-[beta] 1- induced islet cells or the traditional islet replacement. Implanted islet progenitors, when cultured, expresses 1% of endocrine cell proliferation during the first 48 hours up to 6% after five days . According to Rosenberg, Lipset and Yoon (2004), increasing the mass of beta cells after the event of post-immune destruction induces a 175-amino acid pancreatic acinar cell protein called, Islet Neogenesis-Associated Protein (INGAP) peptide, which acts as a stimulator of beta cell mass stimulator.INGAP peptide, similar to TGF-Beta growth factor, triggers cellular neogenesis enabling the rapid rate of cellular regeneration after significant results from cellular differentiation. The production of INGAP protein is commonly cited during post-phase of islet transplant. However, according to Lai, Irina and Eugen et al. (2008), gene modification present in cell transplantation process is problem considering the extensive cellular processes involved in the adaptation and transplant reception.Although, applications of several viral vectors (e. g. adenovirus-associated vectors, etc. have proven to be successful, but hESC is considered a more potent alternative due to its feasibility for genetic manipulation and self-renewal. During the mass replication of beta cells, the small portion of the cells stops in the process of neogenesis, while other beta cells are reserved for continuous replication at a very slow phase. After this scenario, the counter-attack of autoimmunity is usually expected; hence, treatment regimen that suppresses immunologic reaction on islet grafts are usually being instilled to the transplant sample prior to the therapy.This procedure increases the resistance of the graft cells against the autoimmune reactions triggered by the body. With a disorder such as DMT1, the chances of beta cell recovery become lesser due to the persistent autoimmune destruction of beta cells . The decreased capacity cellular replication in the adult beta cell is very much limited to result in a significant regeneration rate following autoimmune damages . Likewise, chronically increased metabolic requirements, such as increased insulin demand, can cause beta cells’ incapacity to fully cope in the given physiologic environment.This gives the appro priate rationale for implanting islet cells in the area of depleting beta cell in order for the progenitors to differentiate and proliferate mass beta cells in the area. According to the study of Urban, Kiss and Kovacs et al. (2008), hematopoetin centers of the body, such as bone marrow, may harbor cells that can actually influence the self-duplication of beta cells. Such concept is greatly associated to the principle of angiogenesis implying the value of appropriate oxygenation in the area of developing cellular clusters.In the study, sex-mismatched bone marrow cells (BMCs) and syngeneic or allogeneic MSCs are administered to a mice sample with streptozotocin induced DMT1, and consequently led to the rapid tissue regeneration after a single injection of a mixture of 10(6) BMCs per 10(5) MSCs. Other agents that can forcefully differentiate beta cells during post-islet transplant are INGAP (Rosenberg, Lipset and Yoon et al. , 2004; Weir, Toschi and Inanda et al. , 2004), GLP-1 and GL P-1 receptor agonist exendin-4 (Li et al. , 2004), betacellulin and activin A (Brubaker and Drucker, 2004), and the combination of EGF and Gastrin (Rooman and Bouwens, 2004) .These agents can actually force the cellular differentiation providing immediate and ensured processing new beta cells with much more lessened risks of being attacked by immunologic elements. Betacellulin, Activin A and Gastrin are the common immuno-suppressants being applied to most controlled studies on islet transplants today due to its availability and decreased result variations; although, some studies still explore the applicability and effectiveness of these agents in the process of triggering cellular differentiation.Meanwhile, Melleoul (2006) suggests that cellular differentiation of beta cell during post-islet transplant is controlled by series of genetic activators and transcription factors . Its absence in mice and humans during embryogenic to postnatal development may actually lead to pancreatic ag enesis. After such condition, cellular differentiation becomes restricted principally to ß cells wherein cellular regulation of genetic expression in ß cell-specific genes occurs.Furthermore, such condition facilitates the mediation of the glucose effect on insulin gene transcription, which shows that any exposure of ß cells to high glucose even with short period of time can actually stimulates insulin gene expression. However, chronic exposure to high glucose levels can actually trigger negative effects, such as alteration in ß-cell functions and gene transcription. PDX-1 transcription breaks down upon exposure to chronic hyperglycemia, while stimulation of beta activity is seen during acute hyperglycemia.Such genetic modifications can actually enhance the survivability of islet transplants within a new host considering the autoimmune function being rendered by continuous DMT1-induced CD4 immunoglobulins. According to Phillips and Tang (2008), using cellular, molecular and gene manipulation strategies, each islet transplant can actually be guarded or attain enhanced resistance even with the hostile environment directing immune rejection, inflammation, hypoxia and apoptosis.Genetic engineering provides cellular modification for constructing gene sequences. Considering the conflict existing in mass beta cell replication and autoimmune destruction, high quantities of beta cell replication during post-islet transplant has been associated to the reduced impact of autoimmune damage. With the help of CTL antagonists in terms of restricting T-cell activity, the regenerative capacity and neogenesis of ß-cells are expected to progress through forced-differentiation therapies.Initial activities between autoaggressive Cytotoxic T-lymphocytes (CTL) and beta cells are terminal event leading to cellular agenesis of ß-cell, which consequently affects both progenitor beta cells and those potential self-replicating beta cells from the pool of potential ß-c ell replenishment . Progression of CTL is unlikely to be stopped; hence, the only appropriate idea of treating the pathogenesis of DMT1 is the replenishment of beta cells that have been damaged throughout the ongoing autoimmune attacks.According to Dor (2006), progenitor cells present in the pancreas, specifically on pancreatic ducts, acini, islets of Langerhans, and other parts of the body (e. g. bone marrow, spleen, etc. ) are even more potent source of beta differentiation . However, these progenitor cells provide variable cellular differentiation rate that can compromise the process of stem cell therapy especially if the non-ideal progenitor cell source are used in the procedure.To compensate, most studies have explored the possibility of using embryonic-obtained stem cells that contain the most feasible progenitor cells aside from the ideal pancreatic progenitors. Although beta cells are differentiated from progenitor cells during embryonic phase of pancreatic development, the progenitors (marked by expression of neurogenin 3 and the paired box protein Pax-4) are seen to disappear upon birth . Such disappearance actually implicates a significant process that are undergoing with beta cells, which actually trigger fundamental change in their mode of maintenance and expansion.The cellular process begins from the embryonic progenitor-cell-based differentiation and further progress to massive self-regeneration. In the study of Nagaoka, Fukuda and Hashizume (2008), betacellulin (BTC) is analyzed as another potential growth factor that can induce progenitor-cell-based differentiation and cellular self-duplication. BTC possesses ErbB receptor tyrosine kinases that induces differentiation and cellular mitosis, especially among acinar-derived AR42J cells, transforming these cells into insulin-producing or beta functioning cells. As supported by Parnaud, Bosco and Berney et al. 2008), BTC-induced purified beta cells within allogeneic islet transplant graft enhanced by ECM have yielded a population of 91. 4 ±2. 8%. Nagaoka, Fukuda and Hashizume (2008) mention that BTC â€Å"independently and preferentially binds to two type I tyrosine kinase receptors, the EGF receptor (ErbB1) and ErbB4†. Significantly, BTC induced graft transplants are seen to contain mutant protein that promotes the rapid differentiation of pancreatic acinar AR42J cells to insulin-producing cells, which is actually the opposite with AR42J cells that contain wild-type BTC protein.Rapid differentiation is not entirely beneficial in nature as this can cause hyperplasia. According to Min Cho, Lim and Yoo et al. (2008), BTC, together with Nicotinamide sustained PDX1 expressions, actually induced cellular differentiation C-peptide proteins; although, insulin mRNA is found to be very low. 4. New Advances in Stem Cell Research The theory between stem cell differentiations versus beta cell progenitor self-duplication still coincide the need to restore pre-existing beta cell p ool from the ongoing damage made by the autoimmune CTL.Stem cell is still an important consideration in replenishing these depleted resources. However, due to the extensive problem on stem cell donors and sources, stem cell therapy is not yet considered part of an ideal DMT1 treatment. According to Korsgren, Lundgren and Felldin (2008), new alternatives for stem cell therapy are currently being explored with aims of determining other contributing components that induce cellular graft survivability and reduction of immunoresponse against DMT1 mediated antibodies.During the process of transplantation, the isolated islets transplant grafts are induced to embolise the liver after its introduction via the hepatic portal vein, which is a procedure that is unique in the area of stem cell implantation. However, such procedure is only an example of low efficacy procedure. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure. As supported by Rother and Harlan (2004), and Hardikar (2004), only 750 patients have already been treated using allogeneic islet transplants since 1974 despite of the billions of DMT1 cases worldwide.Various alternatives have been proposed in order to counter such scarcity, specifically: (1) embryogenic blastocyst and post-natal resources, (2) culturing of stem cells, and (3) stem cell grafting using xenogeneic resource (e. g. umbilical cord, etc). The isolation of human embryonic stem (hES) cells has been introduced as a potential prospect for filling in the scarcity of beta cells, specifically through islet transplantation . Embryonic stem cells are harvested from blastocysts, while adult stem cells are from postnatal organisms.The process involves (1) the culturing and plating of embryoid bodies in insulin-transferrin-selenium-fibronectin medium, (2) supplementation and maintenance using N2, B27, and basic fibroblast growth factor (bFGF), (3) lowering of glucose c oncentration to reduce the physiological pressure on premature beta cell, (4) bFGF is withdrawn to prevent excessive growth stimulation, and (5) nicotinamide addition . Counteracting transcription-polymerase chain reaction found out an enhanced cellular expression of pancreatic genetic chains within the site of cellular differentiated cells.Using the Immunofluorescence and in situ hybridization analysis, the findings have revealed a significantly increased percentile range of insulin-expressing cells within the cellular clusters. According to the study of Xia, Ayala and Thiede et al. (2008), hESCs, with the help of drug-inducing transgene expression (in vitro and in vivo) forms >95% purity level, which significantly implies the high possibility of regulating genetic expression of hESCs. After the islet transplantation, genetic expression of the cells remained stable and regulated with the help of an orally administered drug.Although, according to Chung and Stainer (2008), cellular o rigins that regulate pancreatic B cell induction and genetic expression is not yet fully understood. Differentiation of embryonic stem (ES) cells to islet phenotype, identification and utilization of pancreatic precursor/stem cell from adult sources, and the cultivation of new islets from adult stem cells obtained from various tissue types or directly form other terminally differentiated cell types are the common areas being covered by islet transplant or stem cell research for DMT1 immunogenetics research .In such case, cultured embryogenic or adult somatic islet cells are transferred from its original placement to appropriate locations in the body of a DMT1 patient. Human Embryonic Stem Cell (HESCs) or ES possesses the capacity to continuously differentiate to cells that express both endoderm and pancreatic progenitor function, such as Foxa2, Sox17, Pdx1, and some islet endocrine hormones (e. g. beta cells) . According to Kroon, Martinson and Kadoya et al (2008), cellular therapy for DMT1 requires the renewal of human beta cells and not entirely the replacement of the degraded ones.In order to induce regeneration, pancreatic endoderm must be stimulated through the use cellular mediated glucose-responsive endocrine cells present within hESCs. The hESC-derived insulin-producing islet-like clusters (ILCs) comprises of 2 to 8% of human C-peptide-positive cells, glucagon-positive and somatostatin-positive cells. The study has detected a content of 70 ng of insulin/mug of DNA being produced through these hESC-derived ILCs, which is statistically higher than the innate fetal islets.In addition, cellular differentiation of hESCs induces the formation of Embryoid Bodies (EBs) that stimulate the gene expressions of POU5F1, nestin, FOXA2, ONECUT1, NEUROD1, PAX6, and insulin as long as the glucose environment is within 25mM levels . In the essence, implantation of hESCs in autoimmune-damaged islets can mobilize the islet cell differentiation through genetically expresse d progenitors from the islet transplant medium. Furthermore, continuous genetic expression is expected since the body’s glucose levels also influence the cellular differentiation of beta cells.Stem cells derived from hESCs places markers of development for endoderm, pancreatic and ß-cell development, glucose sensing, and production of mature insulin . Meanwhile, most studies have also centered in protein-based cellular communication involved during cellular differentiation phase after stem cell implants have been introduced. According to Kroon, Martinson and Kadoya (2008), therapeutic tests using a mice sample with 3000 transplanted human islet cells indicate that hESC derived pancreatic endoderm can actually aid in antibody resistance.In the study’s conclusion, they have pointed the definitive evidence proving the capacity of hESCs in generating glucose-responsive and insulin secreting implanted cells. Interestingly, in the study of Yu, Vodyanik and Smuga-Otto et a l (200), hESCs are found to be programmed by specific four genes, OCT4, SOX2, NANOG, and LIN28, which actually determines the pluripotent capacity of the embryonic stem cells and the characteristic of cellular differentiation. Although, the study concludes that the genetic mapping and processes involved within these newly discovered hESC genes are still in the process of intensive studies.Implanted stem cells actually integrate their needed functions for initiating the mechanism of glucose responsive regulation present as pre-proinsulin mRNA and expression of insulin C-peptide in vitro (Clark, Yochem and Axelman, 2007). Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. The results of the study suggest that embryonic germ cell derivatives (e. g. ILCs, etc. ) may eventually function as a potent insulin producing cells .The use of islet-derived or stem cell therapy using embryonic cells remain exp erimental due to the challenges of cellular differentiation. Currently, the problems being faced by the treatment is the availability of stem cells that can possess the appropriate capacity to induce cellular differentiation and regeneration. According to the mentioned studies, simple cellular implantation is not entirely enough due to the greater risks imposed by the body’s physiological reaction against islet grafts.Hence, another issue arises in determining the best anti-immunity function or tolerance enhancer of islet graft transplants; although, latter studies have already discovered potential enhancers that can disregard or at least lessen the impact of cellular degradation brought by DMT1 immunity. Lastly, new advances of genetic modification techniques that shall increase cellular differentiation and renewal rates are already in the process of development. 5. Discussion In the research of Froud, Ricordi and Baidal, islet stem cells are cultured under steroid-free immu nosuppression and are transplanted to 16 DMT1 samples.The cultured islet stem cells have undergone a period of in vitro culture-process with heightened necrosis resistance through TNF- a (Tumor Necrosis Factor) blockade that aim to improve islet engraftment and provide alternative to fresh human islet transportation. The results of the study suggest that the implantation of cultured human islet allografts cause a reproducible insulin independence in all subjects under the series immunosuppressant infusions (a. intial Infliximab infusion, b. daclizumab and c. irolimus maintenance), comparable to that of freshly transplanted islets (Edmonton protocol) .In the absence of supplemental infusions (nfliximab, daclizumab and sirolimus), the results of the study have incurred 11/14 (79%) subjects that produced insulin independence at 1 year, while other 6/14 (43%) samples have gained this capacity after 18 months. Surprisingly, the same test subjects have maintained their insulin independenc e until 33  ± 6 month span. Furthermore, the findings have observed that patients are able to maintain their graft function while under the immunosuppressing infusions.According to the results, 8 out of 14 patients have suffered chronic partial graft losses that are likely immunological in nature considering that 5 of these already received supplemental infusions. Currently, 11 out of 14 subjects are in the receiving immunosuppressing infusions, and 8 (73%) of these are already manifesting insulin independence. The study significantly demonstrates the possibility of withholding the immunologic response upon exposure to certain immunosuppressant (e. g. nfliximab, daclizumab and sirolimus, etc. ).Although, the study has not mentioned the possible side effects and complications that such infusion can provide towards the body as a whole. However, since the stem cells are the only ones infused with these immunosuppressants, the chances of systemic immunosuppression are less likely as l ong as the dosage infused with the stem cells remain appropriate and feasible to the body’s normal function. In another culture study brought by Pinzon, Lakey and Brand (2005), they have used the combination of epidermal growth factor (EFG) and gastrin in order to induce beta cell neogenesis specifically on pancreatic exocrine duct cells .These growth factors also carry the risk of triggering extensive cellular neoplasia over-cellular multiplication; although, studies have already found drug induced techniques that can contain the cellular differentiation and regeneration upon introduction within the body system. In the study, human islet cells are placed under four weeks culture study in a serum-free medium with EGF (0. 3  µg/ml) as the control variable and gastrin content of 1. 0  µg/ml.Beta cells have shown significant increase in cultures with the combined medium of EGF and gastrin (+118%), while +81% for cultures with EGF alone. The EGF-gastrin culture has been obser ved again for the next four weeks, but without the said combination. Impressive results have shown beta cells progressive increase in quantity for the culture previously infused with both EGF and gastrin (+232%). Comparing these results from the latter discussed studies, EGF and gastrin have actually trigger cellular differentiation and self-duplication due to their growth factor properties.In the study of Suarez-Pinzon and Rabinovitch (2008), gastrin growth factor combined with epidermal growth factor (EGF) can actually restore pancreatic islet beta-cell mass and even reverse hyperglycemia even in the absence of immunotherapy in mice samples with artificially induced-DMT1. Reversal of hyperglycemia is most likely due to the increase in insulin production that counters the effects of DMS1. With the appropriate amounts of insulin secretion in the blood, the glucose tonicity will consequently be absorbed by the cells granted that the diabetic anomaly does not consider the insulin rece ptor functionalities within cellular surfaces.In the study, EGF dose of 10 microg/kg and gastrin dose of 30 microg/kg via intraperitoneally have been administered to 10 sample DMT1 mice. In terms of glucose levels, the samples have shown a marked decline from blood glucose of 23 +/- 2 mmol/L to 12 mmol/L within 36 days of individual EGF administration, while 19 days in individual gastrin administration. When combined, the decline in the samples’ glucose levels is already present within 11 days.In addition, the cellular islet counts have increased from 13. 0 +/- 0. x 10(5) cells to 29 +/- 2 x 10(5)cells, and considering the marked decrease of surrounding CD45+ leukocytes have also been observed. Therefore, such combination (EGF plus Gastrin) is confirmed to reduce blood glucose levels, prevent autoimmune activity of DMT1 mediated CD4 cells and increase cellular differentiation. Lastly, aside from hESC’s and cultured islet transplants, another potential source of stem ce lls currently being studied is from animals, known as xenogeneic sources . Pig islets are considered the best option available for xenogeneic transplants.According to Rother and Harlan (2004), such potential alternative are now being studied for different considered potentials, such as: Pig islets have been considered as potential source of islet stem cells aside from human source (a) The fact that humans had been treated with pig insulin for more than 60 years (b) Favorable husbandry — in that the species has large litters with offspring that attain adult size rapidly and with relatively robust islet numbers (c) The fact that pig islets respond to glucose in the same physiological glucose range as human islets (d) Existence of suitable societal-cultural relationship between the speciesDespite of the potential capacity of pig islets in acting as alternative stem cell resource, studies (Hering, Wijkstrom and Graham et al. , 2006; Rood, Buhler and Bottino, 2006) have identified its increased immuno-response towards CTL and autoimmune attacks initiated by DMT1 disease. Autoimmune attacks are the principal conflict considered in the process of islet transplantation wherein even if the graft has been successfully implanted, the risk of failure in the procedure is still considered possible considering the effects of autoimmunity triggered by increased antigenicity in the graft transplant.In one study, acute rejection caused the death of two macaque samples through cellular rejection mediated by CD4+ and CD*+ T cells and macrophages . In order to increase the effectiveness of xenografts after post-transplant phase, different culture infusions have been studied to prolong the life of pig islets xenografts. CD4 antibodies are usually being activated upon detecting significant system foreign antigens, which are usually introduced by bacteria, virus or any material that enters the body systems.In this principle, researchers (Kirchhof, Shibata and Wikkstrom et al. 004) have pointed their assumptions in the possible presence of antigens within xenotransplanted islet grafts. In addition, cellular infusions are considered to be at great risk due to the potential intrusion of incompatible antigens that might induce transplant rejection, and eventually autoimmune degradation of transplanted islet cells in the body. This condition is currently under extensive analysis and consideration since even with successful islet transplant, autoimmune response due to heightened cellular antigenicity can still pose the failure of the stem cell therapy.Due to this genetic dilemma, some studies (Kirchhof, Shibata and Wikkstrom et al. 2004; Komoda, S. Miyagawa and T. Omori et al. , 2004) have focused in determining the potential drug enhancers that can improve transplant antigenicity, especially among xenogeneic sources. First, with the infusion of islets from N-acetylglucosaminyltransferase-III (GnT-III) transgenic pigs, pig islet’s xenoantigenicity have significantly declined prolonging the survival of islets for the next five days of culture study. In another study, pig islets subjected for xenotransplantation are tested with alginate encapsulation.The transplant to tested in a primate, specifically a monkey-Cynomolgus maccacus . Adult pig islets encapsulated in alginate under optimal conditions (n=7) or not (n=5) are transplanted under the kidney capsule of the non-diabetic primate sample. Meanwhile, additional samples have received empty capsules (n=1) and non-encapsulated pig islets (n=2) as controls . The results of the study show the rapid inviability of non-encapsulated and encapsulated islets with no alginate and not in optimal condition.Implanted pig islets under optimum alginate encapsulation showing significant prolonged islet survival for as long as six months. However, despite of the experimental success, the study still regards the conflicts encountered by the processes (e. g. variations of graft antigenicity, etc). 6 . Conclusion DMT1 is a condition manifested by increased and frequent manifestations of hyperglycemia caused by the insufficient production or depleted insulin levels. The most universally recognized cause of beta cell destruction is the autoimmune etiology caused by CD4 interleukins, and other associate antibodies.The aims of the therapy are the induction of cellular differentiation while facilitating as well the renewal of the existing and pre-existing beta cells in the islet graft transplant or in the remaining original islets. However, the principal conflict of the procedure is the interference caused by the autoimmune reaction of the body towards the transplanted islet grafts; although, recent studies have continuously explored different possibilities of suppressing autoimmune responses and forcing cellular activities.Stem cell therapy is a potential prospect for permanently treating the condition of DMT1 considering the main concept involved in its pathogenesis – destru ction of beta cell or insulin producing cells. The processes, physiology and pathological considerations in the stem cell therapy of islet transplant involve the criticality of autoimmune response towards the islet transplant.The controversy of such treatment is the effectiveness of implanting whether the islet cells containing stem cells based on the concept of cellular differentiation or islet cells with pre-existing beta cells based on the concept of cellular self-renewal. Despite of the argument between the two perspectives involve, another main issue arises, specifically the scarcity of stem cell from allogeneic donors. According to the approximated statistics, only 750 cased of DMT1 have successfully obtained the stem cell transplant of islet cells considering the billions of other DMT1 patients existing.In order to resolve such scarcity, various forms of stem cell resources have been proposed and are currently under extensive studies, specifically (1) human embryonic stem cel ls, (2) cultured islet stem cells, and (3) xenogeneic sources specifically the pig islet stem cells. According to most studies, autoimmune damage progress if cell count of beta cells is introduced insufficiently to the recipient body; although, stem cell therapy is nearing towards its potential of being a significant cure as beta cell replacement and insulin producer.

Color symbolism in the great gatsby

Nick Caraway, the narrator, Is one of the few characters who does not exhale the major laws that the other characters do. He Is able to see what Is wrong In society, at the same time as what Is positive about people, and his viewpoints are what characterize those In the novel. Nick moves to West Egg In the summer of '22 and begins his life as a bond man after the Great War. It Is who he meets In that summer that the novel Is about, using rich colors to describe his surroundings and having long pollens of people.Colors within the novel help to characterize the people around Nick, describing the nature and characteristics of people by associating them with certain colors. BLUE Nick tends to have a positive opinion of Jay Gatsby, often putting him on somewhat of a pedestal in comparison to many others he met in the summer. Gatsby is a war hero that Nick knew in the war and who later is his neighbor on West Egg. Gatsby is often associated with the color blue, blue only coming up a few ti mes when not associated with Gatsby, the only other reference to blue is of T. J. Eagleburger eyes.Blue is used to characterize people as watchers, or omnipresent people. After Wilson, a mechanic and husband, loses his wife Myrtle in a car accident, Wilson looks out the window at â€Å"the eyes of Doctor T. J. Cocklebur, which had Just emerged, pale and enormous, from the dissolving night. ‘God sees everything†(107). Wilson describes the eyes of Cocklebur as the eyes of God, seeing through the deception his wife had played on him for so long. The Cocklebur eyes are a billboard in the Valley of Ashes, they have been there for a long time and oversee everything, much like a man on a pedestal or God would be able to do.Cocklebur is viewed as God with his blue eyes seeing everything. Nick notices the eyes â€Å"brood over the solemn dumping ground†(15). People often blame events on God or claim his nonexistence because they do not erectly see an outside help when the y have problems. People claim that God only sees what happens on Earth and does not actually help his creations, leaving them to fend for themselves and having them make their own decisions. No one directly helps In the situations that are within the book; no outside hand helps with the problems nor guides any character to righteousness.Cocklebur sees but does not do. He Is a God. Gatsby Is much Like Cocklebur In the fact that he watches without action. Gatsby went to war and left behind Daisy, his love, only to find her married when he got home. Gatsby then saved up and bought a home across the bay from Daisy and watched from afar, watching over her but never contacting her. Nick goes out to his lawn the in the night after having reconnected with his cousin Daisy and, Nicks old heavens†(14). He notices Gatsby on and that â€Å"he stretched out his arms toward the dark water in a curious way'(1 5).Gatsby is reaching for, what we later learn, is the light at the end of Daisy's dock. While he wants to partake in Daisy's life, like many believe God wishes to do in our lives, he restrains himself. He instead watches for Daisy and takes clippings about her life from the newspaper. Nick says that they are choosing their part of the local heaven, and God presides and watches from heaven. Gatsby watches and overlooks Daisy's life like God would humanity. Gatsby is characterized as a God character because of his inaction; this puts him on a pedestal, elevating the view of him.God is not hated, he is loved, and Gatsby is well loved by Nick. Gatsby would be free from Nicks criticism due to his love for him. Gatsby has parties in his â€Å"blue gardens†(25† that chauffeurs dressed in â€Å"robin's-egg blue†(27) invite people to. Parties are where Gatsby looks to find Daisy, hoping that she will one ay stumble into one and he will be reunited with her. Gatsby is always present at these parties but no one can ever remember seeing him or talking to him when asked. Furthering the idea of omnipresent, Gatsby has control over the chauffeurs and they follow as he says.He is watchful through them but doesn't need to be seen. WHITE Gatsby is often associated with blue, but he is also connected to white. Many characters are seen in white at some point in the novel and it is used to describe the appearance of innocence or false purity. Daisy and Jordan are both introduced in a Larry of white: â€Å"The windows were ajar and gleaming white against the fresh grass outside that seemed to grow a little way into the house. A breeze blew through the room, blew curtains in at one end and out the other like pale flags twisting them up toward the frosted wedding-cake of the ceiling†¦ Woo young women were buoyed up as though up upon an anchored balloon. They were both in white, and their dresses were rippling and fluttering as if they had Just been blown in after a short flight around the house† Jordan and Daisy are given almost an d ethereal appearance in the scene, like little angels or cherubs. They wear white like young innocent brides at a wedding, innocent and pure. Their appearance of innocence is dusted in white, from the curtains, to the ceiling, to the dresses on their bodies. They are almost described as birds, flying around the house in the wind and finding themselves tied to the ground again.Not only birds, but birds captured in a room or cage, making you feel sorry for them and wanting to set them free into the wind. They seem dainty and young, the innocence of babes surrounding them and protecting their view of the world. In reality though, Jordan and Daisy are both corrupt. Everyone likes to say that white in The Great Gatsby means innocence, probably because (1) that's easy to say and (2) everyone else is saying it. Buddhist is hardly the picture of girlish innocence. At the end of the novel, she's described as selfish, careless, and destructive.Jordan cheats on her golf matches, moving the ba ll closer to the hole, and Daisy has affairs and is unfaithful in mind and body. Neither is as innocent as they would like you to believe. Their innocence is false and used to protect the image of femininity the characterized Jordan, and especially Daisy. Gatsby is also described in white, showing his desire to be liked and seem innocent and pure. Gatsby is gone from Daisy for 5 long years, in which she had related to Daisy, there became opportunity for Gatsby to reconnect with his old love.Nick invites both Gatsby and Daisy over for tea one afternoon and Gatsby wears â€Å"a white flannel suit, silver shirt, and a gold-colored tie†(55). Gatsby has not seen Daisy in over 5 years and wants to make a good impression on her, to make her see him as good and honest, better than the man she was currently married to. He may have known her when they were young but the time had past and he wanted to remind her of the times before all that had happened and when they were innocent and e re, before they were tainted by the lives they currently lead.He wanted to remind Daisy of the time they spent together in Louisville in her â€Å"white roadster†(49). Gatsby uses white to seem innocent in the moment and to show his pure intentions towards Daisy. While the use of white by characters in their dressing might be unintentional, they subconsciously want to send a message to another party within the novel. There is an underlying nervousness with Gatsby involving his meeting of new people or the reconnection of him and Daisy. The focus on color and the appearance of purity indicates the desire to have a specific image about them.Nick also dresses up in white flannels to make a good first impression. Upon being invited to on of Gatsby great, grand, glorious parties Nick â€Å"dress[sees] up in white flannels† and crosses the short distance between his house and Gatsby (27). Nick had never met Gatsby before and even told Jordan at dinner, the same one where he reconnected with Daisy and Tom, that he had never met his neighbor but knew that he was Gatsby. Nick is nervous, to the point of becoming drunk one of two times in his life, and wants to make sure that Gatsby likes him.Nick searches out his host, trying to be a good guest and thank him for the invitation, further indication that Nick wants to be seen in a favorable light. Nick is searching out, not only Gatsby, but Gatsby approval of who he is. He is like a small school boy trying to please the teacher by bringing them a glistening apple on the first day of school. Nick is brining himself, dressed up in his nice, white duds, to please the metaphorical teacher of Gatsby. While Nick seems least corrupt and has the fewest flaws of all of the characters within the novel, he wants the others to know Just how good of a character he has.While Nick is not flawed like the others within the novel, he is still human, and there is a falsity of the persona he puts on to show people. Nick does no t want to be seen as the rest of the crowd. He does not share their flaws but he is not above them all. The distinction of the way he acts is accentuated by the color white, furthering his appearance of innocence in the events of the summer. GOLD White is pure like the shell and outside of an egg. The problem is that the white part never indicates if the inside will be rotten or not. While â€Å"white is unblemished morality' and false purity, gold is corruption, greed, and money (Huber 2011).Nick and the others in the novel live on either East or West Egg. The eggs are similar in shape but different in personality and culture. On the outside though, everyone on either egg tries to hide who they are and their corruption with their white clothing, homes, and decorations. Many of the characters have corruption associated with them, even if the measure of how bad it is differs. Gatsby and his golden feasts with â€Å"pigs and turkeys bewitched to a dark gold†, show his money an d corruption (26). While Gatsby is characterized with beautiful language and pleasant interaction with and that is where his money came from.All of his purchases were paid for with money gained through illegal means. While the nature of Gatsby and his intentions are pure, like his white flannel suit, his money is not. Gatsby also wears a â€Å"gold tie† upon meeting Daisy again at the tea that Nick planned(55). Gatsby wants to prove that he is good by wearing his white flannel suit but he unconsciously also announces his wealth to Daisy. Daisy has always been attracted to wealth and opulence, and Gatsby achieved his status in an effort to win Daisy over again with the money she always desired him to have. The gold tie represents Gatsby money, but not only that.It is also the corruption required to gain the money so quickly and continuously throughout the years. His corruption goes beyond Just the fact that he gained money through ways that were immoral and against the law. He also pursued a married woman, having an affair with her. Gatsby, had he been able to let go of the past, would have been able to accept that Daisy was married and that he could no longer pursue her or have her in any way, even physically. Before they commit any sins of adultery, Nick and Daisy go to Gatsby house after tea. In Gatsby garden there is the â€Å"pale gold odor of kiss-me-at-the-gate†(60).No regrettable actions have occurred yet but the sentiments that will soon occur are alluded to by the flowers color-scent and its presence in Gatsby yard. Gatsby will eventually send his servants away to protect his secret affair with Daisy, but the affair never is open to the public like that of Myrtle and Tom's. Gatsby and Daisy have to â€Å"kiss at the gate† before they rush home. The scent of the flowers and its association of gold coincide with the nature of the relationship that Daisy and Gatsby carry out. An affair is never indicating positively of ones character . Gatsby and Daisy both have flaws that lead hem to the affair.Daisy did not marry out of love, but out of greed and desire to be wealthy. It is that same sort of desire that led her back to Gatsby. While she was now a married woman, she continued to fulfill her fantasy and pursue the love she had with Gatsby. Gatsby is corrupt because he knowingly took a married woman, pursued her, and then proceeded to have an intimate relationship with her. He did it because he thought it would benefit both him and Daisy later, that they would be happy. Gatsby corruption is a unique kind, not directly for his own benefit but for someone he thinks will benefit his life in the end.Gatsby has Daisy and Nick has Jordan. From the beginning of when they met, Daisy desired to match Nick and Jordan up together â€Å"Ill sort of- oh- fling you together†(13). Nick never stated that he wanted Jordan, one of Daisy's flaws is assuming she knows what others want, and they usually will consent because sh e has a way about her that is hard to ignore, but they never usually tell her that they want it in the first place. Nick never stated that he desired Jordan; he was interested and confused by her aloof nature but never stated a desire for her. Nick is an upstanding individual with no real flaws of nature or morality.Jordan, despite Nick's initial knowledge, is actually a liar and corrupt in her own nature. At one of Gatsby parties earlier in the summer, Nick found Jordan and went around with her â€Å"slender golden arm resting in† his (28). Jordan plays golf, a rich mans sport, and was accused of cheating by moving her ball closer to the hole than it actually fell. Jordan denied the accusations, claiming that she played a fair game and was not a liar. Later the retracted their statements, presumably under the influence of a large stack of bills pushed their way. Jordan buys her innocence with money and corrupt action to cover ere other corrupt actions.While the white of an e gg seems pure and delicious, the rotten inside will eventually be seen. Jordan can cover herself with white dresses in a white ceiling room with white curtains around, but she cannot alter her true and corrupt nature. GREEN A major idea of the novel is corruption of society, additionally the American dream is expressed as a want from all of the characters. They all want to live they perfect life, have families, and to be able to have no worries of money. The desire and hope is seen through the emotions and sentiment connected to the color green.Daisy has green light at the end of her dock and Gatsby reached for it â€Å"trembling†(1 5). Daisy is Gatsby everything, his dream, his hope, his future. Gatsby went off to war believing that he would come home to find Daisy waiting for him, that they would have a happy future. He had the hope to believe that he would be able to leave for war and come back to everything being as it was, as if stopped in time. Gatsby is described by Ni ck in the beginning of the novel â€Å"it was an extraordinary gift for hope, a romantic readiness such as I have never found in any other person and which it is not likely I shall ever find again†(2).Gatsby was a romantic person with the ability to wait for long periods of time purely on the hope that the future would come and be what he wished. Gatsby realizes Just what the green light means to him when he is reunited with Daisy and she is on his lap: â€Å"If it wasn't for the mist we could see your home across the bay said Gatsby You always have a green light that burns all night at the end of your dock. ‘ Daisy put her harm through his abruptly but he seemed absorbed in what he had Just said. Possibly it had occurred to him that the colossal significance of that light had now vanished forever.Compared to the great distance that had separated him from Daisy it had seemed very hear to her, almost touching her. It had seemed as close as a star to the moon. Now it was again a green light on a dock. His count of enchanted objects had diminished by one†(61-62). Gatsby had desired Daisy for so long that he had not realized that he substituted the green light at the end of Daisy's dock for the real and actual Daisy. Gatsby had had that light as a hope and beacon for all that he did. It was a hope for the future, for the coming day, for what he would do next.The green light directed and guided him in the night and day, eloping him chose in difficult situations and lending him guidance on his life choices. Gatsby life goes downhill from the moment he reconnects with Daisy and loses hope and his sense of direction for the future. He knows he wants to be with Daisy but he has already done everything he had planned for the past 5 years. He is at a loss and doesn't know what to do next. He loses hope and starts destroying the life he built. He fires servants, stops the parties, and loses the spark that made him so likable in the beginning of the nov el. It [green] represented the hope of a better life ND the birth of the American Dream because in this new found land you could have anything you wanted if you worked hard enough†¦ Green also represents corruption and the failing or death of the American Dream† (â€Å"Color Symbolism in the Great Gatsby'). The green light is not the only green associated with Gatsby, of the few instances the color is mentioned, Gatsby or something Gatsby owns is usually hope and loss of hope he has when he is younger, Just before becoming Jay Gatsby. When Dan Cody meets him, â€Å"It was James Gate who had been loafing along the beach in a torn green Jersey' (98).Gatsby came from a penniless family and did not have very much to have hope in, given his circumstances. He was without means to make anything of himself and there was not much hope in the lower income classes of the time for gaining anything higher than their current position. The â€Å"torn green Jersey' represents the hope lessness of Gatsby prior to his meeting of Dan Cody. Once he had met him, Gatsby had a goal, he Joined the army, met Daisy, and became very wealthy. After he had met Cody he no longer wore the green Jersey, he had other, nicer clothes and he no longer felt the hopelessness associated with the lower income groups of society.His transition away from this hopelessness shows character growth and gives background to Gatsby story. CONCLUSION The Great Gatsby, a novel by F. Scott Fitzgerald, highlights characteristics in characters using the colors blue, yellow, white and green. Blue is the omnipresence of both Gatsby and T. J. Cocklebur, the characters that keep vigil over the long island sound and the people in it. They are those who represent God's presences and judgment of the actions of those throughout the novel. Yellow is corruption and money.Gatsby wears gold and has golden items, thing he bought with dirty money room a false business. Cordon's golden arm helps her cheat in golf, a nd Daisy is obsessed with Gatsby money and has no negative thoughts of the affair she carries on with Gatsby. White is the false innocence of the characters and the protecting of femininity for Jordan and Daisy. They are characterized with white but are not as pure as they seem and the association is always in accordance with their femininity: their dresses or physical appearance. Green is the ever present hope and desire for Daisy and the past she and Gatsby shared.

How UML and Agile Development fit together Essay

How UML and Agile Development fit together - Essay Example 2. How can software affect both product development and product management? In the current competitive environment, development of products that win the appeal of the customer is very important for success in the market. On the other hand, the success of any product is dependent upon the skills and competencies of the product manager; the latter is responsible for development of products. The product development and management process includes processes such as product requirement definition, release definition, and product life cycles. However, product development and management is complex and includes numerous stakeholders, responsibilities and processes. This means that contemporary product managers have to be heavily assisted by technology, including appropriate software (Gorchels 23). There is need for the right kind and combination of software to be applied for the desired product to be achieved. 3. List and explain the common tasks performed during software architecture. Some of the common tasks performed during software architecture include; Proposal development: A software architect develops proposals for new software based on new product needs or customer requirements. Design: This involves the design and creation of new software on the basis of proposals made. Software realization: This involves supervision of the whole process of software development from design through creation up to the point that the software is ready to be launched. Software validation: A software architect plays the role of validating software for a company especially when such software has been outsourced or is new. This involves ascertaining the effectiveness of the software and ensuring it is fit for purpose. Report writing: The software architect is charged with producing periodic reports during the course of software development. 4. What are the common inputs, constraints, and outputs found during architectural problem solving? Software design inputs are very helpful towar ds formalization of architecture requirements and constraints. Some of the common inputs in software design include use cases, usage scenarios, functional requirements, non-functional requirements, and technological requirements (Clements et al. 72). Some common constraints in software design include poor technology, fast changing scenarios and unanticipated functional or non-functional requirements. 5. Why is it important for software architects to be familiar with the discipline of requirement engineering? Requirements engineering is mainly concerned with the identification and communication of the purpose of a software-intensive system, and contents in which it will be used. Basically it acts as the bridge between the need of software users, customers, and other groups affected by a software system, and opportunities and capabilities provided by software (Malan and Bredemeyer 1). It is important for software architects to be familiar with requirements engineering because it provi des them with the opportunity to understand how to bridge the gap between what users need and system design to meet those needs. 6. What are the four main activities performed during requirement engineering? Explain. The following activities are performed during requirement engineering: Requirements discovery: Involves Requirements analysis: this involves

Discussion Questions Assignment Example | Topics and Well Written Essays - 500 words - 14

Discussion Questions - Assignment Example It is also applicable to companies that have bulky and variable production consignment, inability to meet changing demand patterns and possess excessive inventories due to the need for outsized safety stocks. The strategy has many advantages in the advertising sector especially in reducing expenditure. Conversely, a pull promotional approach creates awareness for a specific service or product, which is fashioned with an objective audience in mind (Schultz, 2002). This audience then demands the merchandise from channel partners. In this system, the consumer requests for the product and pulls it through the release channel. The strategy is based on consumed or actual demand unlike the push tactic that is based on forecast demand. The pull tactic can be applied in a situation where production and distribution are demand driven. A company may also apply it to that bit of the supply chain where order uncertainty is high. Elsewhere, it is applied in instances where a company is experiencing a decrease in lead-time, has no inventory, or is responding to specific demands. It greatly influences sales promotions and discounts, word of mouth appointments, mass media promotion and advertising. Pull promotional strategy is what our company utilizes mostly as we advertise, build on customer relationship management, and carry out sales promotions and offer discounts (Schultz, 2002). Just one strategy has proven not to give much of good returns in the businesses, which are in line with my career. In the course of work, I have had to balance both push and pull strategies. The result has been a powerful marketing mix that strongly entices customers to buy the wares I have had to sell for the company. From observation and experience in customer interactions throughout my career, it has come out that consumers react differently to marketing strategies used on the same product. This has necessitated the

A critical comparison of texts Term Paper Example | Topics and Well Written Essays - 1500 words

A critical comparison of texts - Term Paper Example Most of the Chuan qi stories involved some aspect of the supernatural, and often involved humans interacting with supernatural creatures and spirits. The Chuan qi genre is only one of the five forms of fictional Chinese literature, and has four thematic story groups within it, those being historical stories, supernatural stories, stories of knighthood and errantry, and love stories. The love stories of the genre deal with the acts of keeping faith and breaking faith. A creature of another realm could attain human form and gain its liberty by keeping faith with a human; likewise, a human who broke faith with a spirit entity could take on bestial habits and become beasts themselves. The idea behind the two was that one could not happen without the other; there was an even exchange that took place, and as long each participant offered something essential, no retribution took place. But, if one party broke the equation or the exchange, the situation became serious. The moral being that a balance was always to be maintained.1 (Pg.518). T’ang writers brought about the Chuan qi style at a time when the neoclassical movement in prose created a steady foundation for story narration. T’ang subject matter and literary material was taken from the rich, invigorating, cultural livelihood of the big city. Writers of the Chuan qi stories were mostly well-educated men who gathered in the capital city trying to make a name for themselves through either fame or through political advancement. While the Chuan qi genre of story telling often employs elements of the supernatural, the writers tried to tell interesting stories that were straight forward, and devoid of flowery poetic language. Supernatural events occur alongside human interaction, instead of replacing it, and city workers and dwellers are depicted in their everyday lives. Chuan qi stories can be described as tales of the marvelous, and are usually written in the classical

Project Proposal Essay Example | Topics and Well Written Essays - 1000 words - 1

Project Proposal - Essay Example To help strengthen the players in the banking sector in Nigeria and to ensure longevity and shareholders’ returns in the long run, the consolidation of banks was enforced by the Central Bank of Nigeria. The banks would either have to raise their capital base to N25 billion or face liquidation and quit the industry (Upaka, Akpata & Olasope, 2005). The purpose of the reforms was to reduce poverty and generate employment while leading to wealth creation. This was expected to lead to GDP growth over a period of time. Many of the small banks were plagued with low capital base and weak corporate governance. Consolidation of the banking system was to ensure a diversified, strong and reliable banking sector, ensure safety of depositor’s money, play active developmental roles in the country’s economy and make Nigerian banks competent and competitive players in the global financial system (Poyi, 2006). This would lead to diversification and emergence of specialized banks. The lending rates of the banks were very high and lending was concentrated in the short term due to lack of long term savings. The impact of the consolidation of the banks was felt in different sectors but there is not much literature available on the after-effects. The aim of this research is: Theory suggests that consolidation of banks could potentially increase the bank size which could in turn increase the bank returns through revenue and cost efficiency gains (Ajayi, 2005). It could also reduce industry risks through elimination of weak banks. This helps to eliminate the weak banks. The top ten banks account for nearly and account for more than 50% of the total assets. The small banking sector suffers from concentration of risks. They can provide fewer services and the costs for providing such services are high. Because of lack of effective competition, they are unable to exploit economies of scale. Consolidation became essential because there was over

Impact Of Minimalism Art Movement Has On Art Community During 1960s Research Paper

Impact Of Minimalism Art Movement Has On Art Community During 1960s -1970s - Research Paper Example There cannot be any design without a designer; the individuals who trail blazed in this field or whose works, in the strict sense of the word, can be termed as minimalistic art are people like Donald Judd, Carl Andre, Robert Morris, Sol Lewitt and Dan Flavin (Marzona p7). What then is minimalism? Strickland, 2000, 7 defines minimalism as a movement, primarily in post war America towards an art-visual, musical, literary or otherwise- that makes its statements with limited if not the fewest possible resources. Though as Marzona argues, the term minimalism is confined to the visual arts with a major focus on painting. The movement did make a profound a impression on art that was to be seen years later. In artistic sense, it implies using limited materials to create a desired effect, which is, pure and simple. This is created by eliminating the non-essentials features, firms or concepts. In general, minimalism art movement does include synopsis, key ideas, artworks, artist about resource s. This study therefore focuses on how the minimalists, even though they did not want to be labeled as such, impacted on art and the art community with their minimalistic art activities. The minimalism movement did start in the 1960s, as earlier stated, in the United States and the process influenced the modern art as exemplified in such works as painting, sculpture and installation. During the time of its inception, minimal artists desired to have their respective artworks to be enjoyed without disruptions of the conventional aesthetic field. They focused on descriptions like color, and geometric structures and shapes. It is worth noting that the work of the minimalists did transform not only the way art was being viewed but it also elevated the social status of the discipline in the society. A look at each of the minimalists’ works confirms and sheds more light into the elements and purpose of the minimalism art movement. Donald Clarence Judd is one among the leading artist s who contributed immensely to this field. Scheldahi et al p 212 confirms that Judd is the renowned figure behind minimalism, even though he renounced the label and preferred to be known as the ‘maker of objects’ The man credited for having revolutionized art during his time especially in the 1960s and left an impression which was to stay long after he had gone. A Masters Degree graduate in Art History from the University of Columbia, Judde’s work of art has been described as one which is unique and as Scheldahi et al puts it, his work is unfailing elegance even lapidary in a grandiose sort of a way. The major contributions of Jude, notes Arts Foundation, were in the forms of ‘stacks’, ‘boxes’ and ‘progressions’. One such work is untitled, which Arts Connected 2012 confirms became Jude’s trademark. It was simple and austere. Through this, he challenges the viewer to consider the concepts of boredom, monotony and repet ition. He used an artistic style that moved away from illusionism but focused on constructions in which materiality is a key central part to the owners work. Thus Jude’s work of art would be described as one which was created using real materials in real space (Arts Connected 2012). His works bring closer home the understanding of the relationship between art and space. Marzoma notes, as does other writers in this field, the transition of Jude from being a painter to a sculptor. Concrete, plywood, galvanized steel and aluminum are some of the key ingredients in Jude’s recipe in articulating an effective minimalist sculptor. The Green Gallery exhibitions of Jude’s pieces of art work in 1963 appear to have catapulted him to the limelight of the international scene as a renowned minimalist. 12th of February 1994

Business Information Systems etc Research Paper

Business Information Systems etc - Research Paper Example Similarly, on the hardware and software side, firms are increasingly using cloud computing as the valid alternative to process information. The concept of software as a service is not new and increasingly, firms are using these services to take advantage of large data volumes as well as better efficiency and management of the information technology resources. Cloud computing has also allowed the firms to reduce their IT costs by hosting or using third party systems to achieve the same level of productivity and efficiency. The expansion of global e-commerce markets has been assured due to rapid changes in the telecommunication and internet infrastructure. The high speed wireless internet access through mobile phone devices has allowed firms to directly access their customers on their cell phones and deliver personalized advertisement messages to their customers. This paper will therefore attempt to research and analyse the emerging trends in the business information systems and inform ation technology. Information System Trends One of the key trends which have emerged during last few years is the use of peer to peer structure for the management and distribution of information. This new design is based upon the self organization principles and rather than depending upon the central points locations, allow systems to coordinate with each other freely and become more scalable as well as robust. Peer to peer infrastructure is also considered as an innovation in the hardware component of the information systems with better and more robust infrastructure to share and disseminate information at least cost.1 It is also important to note that organizations are increasingly relying on virtualization as one of the key information technology tools which can help them to reduce cost as well as present their message to their targeted audience. It is also important to note that virtualization has also necessitated changes in the software as well as hardware requirements too und er which organizations are shifting towards more handheld devices to use. Virtualization of business systems is also considered as a part of the autonomic computing in which computer systems will regulate and manage themselves on their own based on the computing activity. This trend therefore may be one of the key trends suggesting a gradual shift towards the use of information technology in a relatively new manner. It is also important to note that virtualization takes place both in software as well as in hardware. Hardware virtualization can be done by replicating the whole system through a virtual machine with its own operating system. It is also important to note that businesses can go for complete as well as partial virtualization. Cloud Computing Probably one of the most important emerging trends in the business information systems and information technology in general is the rise of the cloud computing. Cloud computing is used as a service instead of a product and as such req uires an extensive coordination between the service providers and the firms. (Finnie, 2011) Under the cloud computing shared resources, software as well other utilities are provided over a network. Cloud computing is increasingly become more common because it can significantly reduce the overall costs for the firms as well as offer them enough capability to utilize state of the art technology

The Treatment of Heroes in Ancient Poetry and Modern Film Essay

The Treatment of Heroes in Ancient Poetry and Modern Film - Essay Example However, these solutions often leave a wake of destruction behind them. At the base of each man's soul is a deep-seated sense of respect for the tenets of honor and courage. One of these men is Odysseus, king of Ithaca. Agamemnon and Menelaus drag him away from his peaceful home, where he leaves his wife and infant son for a war that will take ten years, and a journey home that will take twice that, stories chronicled in Homer's Iliad and Odyssey. The other is Detective Martin Riggs of the Los Angeles Police Department. The Lethal Weapon movie series shows how he tries to find and maintain a sense of personal peace while being pulled into chaos by criminal after criminal. Both of these men fit the description of the hero that has transcended time to become an idea that audiences all over the world have enjoyed since performance art began. The most dominant force in the hero is "competitiveness".1 The ancient Greeks loved athletic competitions, and it is no surprise that Homer's twin epics feature them: Odysseus must watch the games at Phaeacia before he is allowed to journey home, and Odysseus sets up a deadly contest in his own castle in Ithaca, ostensibly to give away Penelope to one of the suitors, but actually to trap all the suitors in his home. These are not just set-pieces used for plot purposes, however; the suitors in Odysseus' home while away the years by having contests of strength and agility virtually every day. In the example of Martin Riggs, the competition is somewhat different. While there are no athletic events in his story, he and his partner, Det. Murtaugh, go back and forth about the relative effects of aging on both of them, and they badger each other in a semi-humorous fashion about which one of them has better aim with a gun, can run faster to catch a criminal, and so on. Each of the movies in the series finds it climax in a hand-to-hand combat scene, using the competitiveness to build suspense within the audience. This idea of competition also appears in the 1959 classic Ben-Hur, where Judah and Messala engage in a friendly spear-tossing contest, aiming at a point where two wooden beams meet in the ceiling.2 Honor, and its attendant condition, fame, are also important to heroes across time. In Greek culture, the winner of a competition would receive "public acknowledgment of his superioritymarked by material tributes and gifts."3 This could take the form of gifts of land, sitting in honored seats, being given the best cuts of meat at feasts, among other honors. The central conflict between Achilles and Agamemnon at the beginning of Iliad is related to the king's prerogative to select the booty from a particular battle. At first, Agamemnon does not want to give back the Chryseis, the priest's daughter that he brought back from their previous war. Once Apollo's command becomes clear, however, Agamemnon gives her back, but only after taking Achilles' new prize, Briseis, from his tent. Achilles' anger over this lack of respect keeps him from fighting with the rest of the Greeks against Troy until Patroklos dons Achilles' armor and is slain in battle, and so the importance of honor and respe ct to the