Monday, August 12, 2019
Sustainable Solutions Paper, Part II Essay Example | Topics and Well Written Essays - 1250 words
Sustainable Solutions Paper, Part II - Essay Example The first aspect of business that the company needs to develop is its production unit in order to dominate the existing market. The company will need to increase its production by 15% in every consecutive month. Increased production will require the company to increase its influence of coverage of the market. This will require the company to intensify its activities in sales promotion and advertising. Albani expect to increase its markets by 10% at the end of July. In addition, the company expects its products to be available throughout the year including the peak period. Landscape analysis involves a detailed study of a potential opportunity with the aims of establishing its viability (Boar, 2001). Businesses are also interested in analysing the similarity between their business models and actual business situation. Landscape analysis theories relate the risks involved with making a drastic change in a business and the related benefits. Despite the risks, businesses are optimistic that changes within their structure will have beneficial results. The perfume industry is a dynamic industry that is expanding constantly. However, the company is not reciprocating the dynamism of the market. The risk factor resulting from intensive changes within a companyââ¬â¢s operation is the main factor hindering its growth. The conservative nature of the market is the main factor that is discouraging the company from adopting appropriate changes in its structure. The perfume industry will experience constant growth in the next twenty years. However, the growth will not be visible in all sectors of the industry. For instance, the market will not grow proportionately as the production. This is because buyers in the market are not flexible about new products. However, usage of perfume and beauty products is likely to increase considerably due to the increasing market demands and lifestyle changes. Secondly, the target market
Sunday, August 11, 2019
Laeken Declaration Paper Essay Example | Topics and Well Written Essays - 2500 words
Laeken Declaration Paper - Essay Example The crafting of the constitution reinforces the powers and duties of the European Court of Justiceââ¬â¢s embrace of each member stateââ¬â¢s unique constitutional provisions. The first step includes the establishment of the Convention of the Future, a constitutional convention. The Federalist Papers no. 49 (Madison) states ââ¬Å"The people are the only legitimate fountain of power, and it is from them that the constitutional charter, under which several branches of government hold their power, is derivedâ⬠(Eriksen 2004). Lee McGowan mentioned ââ¬Å"The Laekan Declaration on the Future of the European Union was adopted by the European Council at its summit in Laeken, Belgium on 15 December 2001. The Declaration followed a similar Declaration on the Future of the Union adopted a year earlier at the same time as the Treaty of Nice and was significant for the issues it raised for consideration by the Convention on the Future of Europe which was launched in late February 2002 . ... Second, the Laeken Declaration focused on resolving the European Unionââ¬â¢s democratic deficit. The aim of the Laeken Declaration is to establish a European Union political entity grounded on firm democracy, crystal clear transparency and efficiency. Third, the Laeken Declaration centered on simplifying the European Unionââ¬â¢s political environment. The same Declaration emphasized the integration of the treaties into a European Union constitution. Likewise, the Declaration delves on defining the European Unionââ¬â¢s role in enhancing the global environment. Lastly, the Declaration centers on bringing the European Union citizens within one synergy-filled single European Union community1. The Treaty of Lisbon enhanced the concepts of the prior Laeken Declaration. The Laeken Declaration hinted on the importance of constitutional reform policies. The Lisbon treaty included a new reform vehicle that gave a semblance of constitutional intentions, the Convention on the Future of Europe. The word selections were toned to impress a constitutional purpose. Taking into consideration the mandate as well as the character envisioned by the democratic constitutional perspective, the Belgian presidentsââ¬â¢ advocacy for the Treaty of Lisbon was the handiwork of the European Council. European integration can both be an opportunity and a threat. There is no convincing evidence that some of the national governments of the Europe Union will stand to loss if they implement a European Union constitution. To resolve the issue, some European governments have adapted their structures and procedures to keep abreast with the increasing scope of European Union integration. The Treaty of Lisbon, inspired by the Laeken Declaration, states that the national
Saturday, August 10, 2019
Law Term Paper Example | Topics and Well Written Essays - 500 words
Law - Term Paper Example The disastrous effects of these truths could carry forward into our future life which needs to be averted. (150 Words) Outline: Our present energy resources may not last long due to high rate of usage and unbridled consumption, especially by the industrial sectors. Therefore it has become necessary to seek new and alternative means for addressing this issue and providing means of its alleviation and mitigation, if not a long term solution that could effectively deal with this current issue. Developing several ways and means by which the dependence and funds spend on fossil fuels and contemporary energy sources could be reduced and innovative ideas leading to outsourcing of alternative energy sourcing could be developed and gainfully employed. Innovating and development may take time and resources. It is a long drawn process which requires sustained efforts and investments. It is also necessary to develop newer techniques through which existing energy resources could be optimized and effective control measures taken to limit its ineffective and inefficient use, through innovation. Introduction: The subject of seeking alternative and substitute means of generating energy resources needs to be seen in the context of depleting resources, due to mismanagement and slack control mechanism which does not address the core issues. Although much has been said about the need to tackle energy crisis on a war footing and seek renewable and alternative areas like harnessing wind, solar or nuclear energy for the advancement of human society, there are many areas in which improvements could be made for achieving such objectives. In the first place, there is legislation in place that is designed to control the use of energy. This is done by creating hybrid or alternative fuel usage in vehicles. It is planned that by year 2018, nearly 50% of
Friday, August 9, 2019
Research Paper PII Essay Example | Topics and Well Written Essays - 1000 words
Research Paper PII - Essay Example Cyber criminals use numerous technologies in forcing entrance into personal accounts thus obtaining valuable personal information most of which have financial value. It thus becomes prudent for users to understand the technologies effectively thus employing appropriate technology and measures to curb the spread of such costly vises. In order to cushion themselves from such risks, users must ensure to keep their personal information secure in both online and offline platforms. Online platforms refer to the platforms found on the internet. People often store their personal information on the cyber space on such media as emails, social media among other types of online accounts (Fafinski, 2009). Offline platforms on the other hand refer to the use of digital technology in storing data without necessarily connecting to the internet. Such media as smart phones, computers and media players have digital storage spaces. Storing data on such platforms do not require any internet connection but the information stored therein face eminent risk of destruction and unauthorized access features that require effective management in order to prevent. Disclosing personal information online is often the main cause of such loses. This implies that users of such technologies must use the technologies cautiously. Among the scenarios that often require disclosure of such information, include online shopping, online games, online competitions and subscribing to the numerous online services. Using such services therefor3e require extreme caution. In order to prevent the loss of personal information while taking part in such important online activities, users must always investigate the authenticity of both the services and the service providers. Users must take care and engage only the legitimate companies. Engaging legitimate companies and understanding their terms and conditions are important since it becomes possible to investigate cases of loss of personal information.
Thursday, August 8, 2019
OLD DOMINION TRAIL BIKES CASE STUDY Example | Topics and Well Written Essays - 250 words
OLD DOMINION TRAIL BIKES - Case Study Example All these information will propel Tedââ¬â¢s business further to the ladder of success. Tedââ¬â¢s business is involved leasing of bikes, ordering of new bikes from the supplier, keeping sales records and many other business activities. Technology for instance computerization of leasing process so that it can be done only can effectively impact positively on the business. The use of e-commerce in has revolutionized businesses around the world. Tedââ¬â¢s business can integrate an online shopping cat on their website so that customers are able to purchase their products irrespective of their geographical location. This will greatly increase the number of sales. Supply chain management (SCM) will enable Old Dominion Trail Bikes to smoothly carryout the entire operations of its interconnected sections of the business. It will enable Ted as the owner of the business plan, implement and carry out effective monitoring and evaluation of the performance of Old Dominion Trail Bikes. If Old Dominion Trail Bikes uses an effective CRM, it will be able to provide maximum support to their client while collecting relevant information about their tastes and preferences. As a result, the business will experience increase in sales. Before the implementation of Enterprise Resource Planning, Ted will have to look at the resource his business has and the quality control of the plan. As such, Ted will have to plan for his business before taking any
Wednesday, August 7, 2019
SAM 482 UNIT 8 Essay Example | Topics and Well Written Essays - 500 words
SAM 482 UNIT 8 - Essay Example In the identification phase for risks in crowd management plan, the following factors are considered; crowd behavior and control, noise levels, risks of fire, weather and use of drugs and alcohol that would lead to unruly behavior. The plan also incorporates suppliers and contractors. Risks related to their participation in an event must be identified. These could include incompetence of staff, resignation or absenteeism, theft and loss of assets among others. In the risk management action plan, the risks are identified in order and an action drafted with a timeframe. Responsibilities are allocated to experienced staff and recommendations drafted on how the risk will be monitored. This justifies that an effective crowd management plan must be in harmony with the risk management plan. Incorporate an emergency plan. A written action plan is important for this issue. The staff should be in a position to respond to emergencies promptly. Instructions detailing emergency phone numbers, exit routes, fire extinguisher strategic positions should be accessible to all users of the facility. Any risk and or an accident must be recorded by the event holders. This will assist in planning future events. Transfer of risk is an appropriate strategy for the organization. Before an event, the event organizer should hold Public Liability Insurance with a detailed Risk Management Plan. The plan should incorporate all risks anticipated during the sporting event. Crowd management plan is an integral element of the larger risk management plan for sporting facilities. An effective crowd management plan will mitigate risks to an equal level of the risk management plan. The two plans must be harmonized since their objectives are
Apoptosis - Short Essay Essay Example for Free
Apoptosis Short Essay Essay Kerr, Wyllie, and Currie first used the term apoptosis in a paper in 1972 to describe a morphologically distinct form of cell death, although certain components of the apoptosis concept had been described years previously. Our understanding of the mechanisms involved in the process of apoptosis in mammalian cells transpired from the investigation of programmed cell death that occurs during the development of the nematode Caenorhabditis elegans (Horvitz, 1999). In this organism 1090 somatic cells are generated in the formation of the adult worm, of which 131 of these cells undergo apoptosis or ââ¬Å"programmed cell death. â⬠These 131 cells die at particular points during the development process, which is invariant between worms, demonstrating the accuracy and control in this system. Apoptosis has been recognized and accepted as an important mode of ââ¬Å"programmedâ⬠cell death, which involves the genetically determined elimination of cells. However, there is other forms of programmed cell death have been described and other forms of programmed cell death may yet be discovered Apoptosis occurs normally during development and aging and as a homeostatic mechanism to maintain cell populations in tissues. Apoptosis also occurs as a defense mechanism such as in immune reactions or when disease or noxious agents damage cells. Although there are a wide variety of stimuli and conditions, both physiological and pathological, that can trigger apoptosis, not all cells will necessarily die in response to the same stimulus. Irradiation or drugs used for cancer chemotherapy results in DNA damage in some cells, which can lead to apoptotic death through a p53-dependent pathway. Some hormones, may lead to apoptotic death in some cells although other cells are unaffected or even stimulated. Some cells express Fas or TNF receptors that can lead to apoptosis via ligand binding and protein cross-linking. Other cells have a default death pathway that must be blocked by a survival factor such as a hormone or growth factor. There is also the issue of distinguishing apoptosis from necrosis, two processes that can occur independently, sequentially, as well as simultaneously (Zeiss, 2003). In some cases itââ¬â¢s the type of stimuli and/or the degree of stimuli that determines if cells die by apoptosis or necrosis. At low doses, a variety of injurious stimuli such as heat, radiation,à hypoxia and cytotoxic anticancer drugs can induce apoptosis but these same stimuli can result in necrosis at higher doses. Finally, apoptosis is a coordinated and often energy-dependent process that involves the activation of a group of cysteine proteases called ââ¬Å"caspasesâ⬠and a complex cascade of events that link the initiating stimuli to the final demise of the cell Loss of contro l of apoptosis may result in disease. Excessive apoptosis is implicated in AIDS and Alzheimers disease and insufficient apoptosis may lead to cancer. Morphology of Apoptosis Light and electron microscopy have identified the various morphological changes that occur during apoptosis. During the early process of apoptosis, cell shrinkage and pyknosis are visible by light microscopy. With cell shrinkage, the cells are smaller in size, the cytoplasm is dense and the organelles are more tightly packed. Pyknosis is the result of chromatin condensation. On examination with hematoxylin and eosin stain, apoptosis involves single cells or small clusters of cells. The apoptotic cell appears as a round/oval mass. Plasma membrane blebbing occurs followed by karyorrhexis and separation of cell fragments into apoptotic bodies during a process called ââ¬Å"budding.â⬠Apoptotic bodies consist of cytoplasm with tightly packed organelles with or without a nuclear fragment. The organelle integrity is maintained and all of this is enclosed within an intact plasma membrane. These bodies are subsequently phagocytosed by macrophages, or neoplastic cells and degraded within phagolysosomes. Macrophages that engulf and digest apoptotic cells are called ââ¬Å"tingible body macrophagesâ⬠and are found within the germinal centers of lymphoid follicles or within the thymic cortex. There is no inflammatory reaction with the process of apoptosis nor with the removal of apoptotic cells because: (1) apoptotic cells do not release their cellular constituents into the surrounding interstitial tissue; (2) they are quickly phagocytosed by surrounding cells thus likely preventing secondary necrosis; and, (3) the engulfing cells do not produce anti-inflammatory cytokines. Distinguishing Apoptosis from Necrosis The alternative to apoptotic cell death is necrosis, which is considered to be a toxic process where the cell is a passive victim and follows an energy independent mode of death. Oncosis is used to describe a process that leads to necrosis with karyolysis and cell swelling whereas apoptosis leads to cell death with cell shrinkage, pyknosis, and karyorrhexis. Although the mechanisms and morphologies of apoptosis and necrosis differ, there is overlap between these two processes. Necrosis and apoptosis represent morphologic expressions of a shared biochemical network described as the ââ¬Å"apoptosis-necrosis continuumâ⬠.For example, two factors that will convert an ongoing apoptotic process into a necrotic process include a decrease in the availability of caspases and intracellular ATP Whether a cell dies by necrosis or apoptosis depends in part on the nature of the cell death signal, the tissue type, the developmental stage of the tissue and the physiologic milieu (Zeiss, 2003). It is not always easy to distinguish apoptosis from necrosis, they can occur simultaneously depending on factors such as the intensity and duration of there stimulus, the extent of ATP depletion and the availability of caspases (Zeiss, 2003). Necrosis is an uncontrolled and passive process that usually affects large fields of cells whereas apoptosis is controlled and energy-dependent and can affect individual or clusters of cells. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma that result unregulated digestion of cell components Some of the major morphological changes that occur with necrosis include cell swelling; formation of cytoplasmic vacuoles; distended endoplasmic reticulum; formation of cytoplasmic blebs; condensed, swollen or ruptured mitochondria; disaggregation and detachment of ribosomes; disrupted organelle membranes; swollen and ruptured lysosomes; and eventually disruption of the cell membrane. This loss of cell membrane results in the release of the cytoplasmic contents into the surrounding tissue, sending chemotatic signals with eventual recruitment of inflammatory cells. Because apoptotic cells do not release their cellular constituents into theà surrounding tissue and are quickly phagocytosed by macrophages or normal cells, there is essentially no inflammatory reaction. It is also important to note that pyknosis and karyorrhexis are not exclusive to apoptosis (Kurosaka et al., 2003). Mechanisms of Apoptosis The mechanisms of apoptosis are highly complex involving an energy dependent cascade of molecular events. Research indicates that there are two main apoptotic pathways: the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway. However, there is now evidence that the two pathways are linked and that molecules in one pathway can influence the other. There is an additional pathway that involves T-cell mediated cytotoxicity and perforin-granzyme dependent killing of the cell. The perforin/granzyme pathway can induce apoptosis via either granzyme B or granzyme A. The extrinsic, intrinsic, and granzyme B pathways converge on the same execution pathway. This pathway is initiated by the cleavage of caspase-3 and results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, crosslinking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. Caspases have proteolytic activity and are able to cleave proteins at aspartic acid residues, although different caspases have different specificities involving recognition of neighboring amino acids. Once caspases are initially activated, there seems to be an irreversible commitment towards cell death. To date, ten major caspases have been identified and broadly categorized into initiators (caspase-2,-8,-9,-10), effectors or executioners (caspase-3,-6,-7) and inflammatory caspases (caspase-1,-4,-5). Caspase-11, which is reported to regulate apoptosis and cytokine maturation during septic shock, caspase-14, which is highly expressed in embryonic tissues but not in adult tissues . Extensive protein cross-linking is another characteristic of apoptotic cells and is achieved through the expression and activation of tissue transglutaminase. Another feature is the expression of cell surface markers that result in the early phagocytic recognition of apoptotic cells by adjacent cells, permittingà quick phagocytosis with minimal compromise to the surrounding tissue. This is achieved by the movement of the normal inward-facing phosphatidylserine of the cellââ¬â¢s lipid bilayer to expression on the outer layers of the plasma membrane. Externalization of phosphatidylserine is a well-known recognition ligand for phagocytes on the surface of the apoptotic cell. PATHWAYS Extrinsic Pathwayââ¬âThe extrinsic signaling pathways that initiate apoptosis involve transmembrane receptor-mediated interactions. These involve death receptors that are members of the tumor necrosis factor (TNF) receptor gene superfamily. Members of the TNF receptor family share similar cyteine-rich extracellular domains and have a cytoplasmic domain of about 80 amino acids called the ââ¬Å"death domainâ⬠. This death domain plays a critical role in transmitting the death signal from the cell surface to the intracellular signaling pathways.The sequence of events that define the extrinsic phase of apoptosis are best characterized with the FasL/FasR and TNF-à ±/TNFR1 models. In these models, there is clustering of receptors and binding with the homologous trimeric ligand. Upon ligand binding, cytoplasmic adapter proteins are recruited which exhibit corresponding death domains that bind with the receptors. The binding of Fas ligand to Fas receptor results in the binding of the adapter protein FADD and the binding of TNF ligand to TNF receptor results in the binding of the adapter protein TRADD with recruitment of FADD and RIP. FADD then associates with procaspase-8 via dimerization of the death effector domain. At this point, a death-inducing signaling complex (DISC) is formed, resulting in the auto-catalytic activation of procaspase-8 . Once caspase-8 is activated, the execution phase of apoptosis is triggered. Death receptor mediated apoptosis can be inhibited by a protein called c-FLIP which will bind to FADD and caspase-8, rendering them ineffective. Another point of potential apoptosis regulation involves a protein called Toso, which shows to block Fas-induced apoptosis in T cells via inhibition of caspase-8 processing . Intrinsic Pathwayââ¬âThe intrinsic signaling pathways that initiate apoptosis involve a diverse array of non-receptor-mediated stimuli that produceà intracellular signals that act directly on targets within the cell and are mitochondrial-initiated events. The stimuli that initiate the intrinsic pathway produce intracellular signals that may act in either a positive or negative fashion. Negative signals involve the absence of certain growth factors, hormones and cytokines that can lead to failure of suppression of death programs, thereby triggering apoptosis. In other words, there is the withdrawal of factors, loss of apoptotic suppression, and subsequent activation of apoptosis. Other stimuli that act in a positive fashion include, but are not limited to, radiation, toxins, hypoxia, hyperthermia, viral infections, and free radicals. All of these stimuli cause changes in the inner mitochondrial membrane that results in an opening of the mitochondrial permeability transition pore, loss of the mitochondrial transmembrane potential and release of two main groups of normally sequestered pro-apoptotic proteins from the intermembrane space into the cytosol. The first group consists of cytochrome c, Smac/DIABLO, and the serine protease HtrA2/Omi. These proteins activate the caspase dependent mitochondrial pathway. Cytochrome c binds and activates Apaf-1 as well as procaspase-9, forming an ââ¬Å"apoptosomeâ⬠The clustering of procaspase-9 leads to caspase-9 activation. Smac/DIABLO and HtrA2/Omi are reported to promote apoptosis by inhibiting IAP activity. Additional mitochondrial proteins interact with and suppress the action of IAP The second group of pro-apoptotic proteins, AIF, endonuclease G and CAD, are released from the mitochondria during apoptosis, but this is a late event that occurs after the cell has committed to die. AIF translocate to the nucleus and causes DNA fragmentation and condensation of peripheral nuclear chromatin. This early form of nuclear condensation is referred to as ââ¬Å"stage Iâ⬠condensation. Endonuclease G also translocates to the nucleus where it cleaves nuclear chromatin to produce oligonucleosomal DNA fragments. AIF and endonuclease G both function in a caspase-independent manner. CAD is released from the mitochondria and translocates to the nucleus where, after cleavage by caspase-3, it leads to oligonucleosomal DNA fragmentation and a more pronounced and advanced chromatin condensation. This later and moreà pronounced chromatin condensation is referred to as ââ¬Å"stage IIâ⬠condensation The control and regulation of these apoptotic mitochondrial events occurs through members of the Bcl-2 family of proteins .The tumor suppressor protein p53 has a critical role in regulation of the Bcl-2 family of proteins.The Bcl-2 family of proteins governs mitochondrial membrane permeability and can be either pro-apoptotic or antiapoptotic. 25 genes have been identified in the Bcl-2 family. Some of the anti-apoptotic proteins include Bcl-2, Bcl-x, Bcl-XL, Bcl-XS and some of the pro-apoptotic proteins include Bcl-10, Bax, Bad, Bim, and Blk. These proteins can determine if the cell commits to apoptosis or aborts the process. It is thought that the main mechanism of action of the Bcl-2 family of proteins is the regulation of cytochrome c release from the mitochondria. Mitochondrial damage in the Fas pathway of apoptosis is mediated by the caspase-8 cleavage of Bid. This is one example of the ââ¬Å"cross-talkâ⬠between the death-receptor (extrinsic) pathway and the mitochondrial (intrinsic) pathway. Serine phosphorylation of Bad is associated with 14-3-3, a member of a family of multifunctional phosphoserine binding molecules. When Bad is phosphorylated, it is trapped by 14-3-3 and sequestered in the cytosol but once Bad is unphosphorylated, it will translocate to the mitochondria to release cytochrome C. Bad can also heterodimerize with Bcl-Xl or Bcl-2, neutralizing their protective effect and promoting cell death When not sequestered by Bad, both Bcl-2 and BclXl inhibit the release of cytochrome C from the mitochondria. Reports indicate that Bcl-2 and Bcl-XL inhibit apoptotic death primarily by controlling the activation of caspase proteases. An additional protein designated ââ¬Å"Avenâ⬠appears to bind both Bcl-Xl and Apaf-1, thereby preventing activation of procaspase-9. Puma and Noxa are two members of the Bcl2 family that are also involved in pro-apoptosis. Puma plays an important role in p53-mediated apoptosis. It was shown that, in vitro, overexpression of Puma is accompanied by increased BAX expression, BAX conformational change, translocation to theà mitochondria, cytochrome c release and reduction in the mitochondrial membrane potential. Noxa is also a mediator of p53-induced apoptosis. Studies show that this protein can localize to the mitochondria and interact with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. Caspase-3 is the most important of the executioner caspases and is activated by any of the initiator caspases (caspase-8, caspase-9, or caspase-10). Caspase-3 specifically activates the endonuclease CAD. In proliferating cells CAD is complexed with its inhibitor, ICAD. In apoptotic cells, activated caspase-3 cleaves ICAD to release CAD. CAD then degrades chromosomal DNA within the nuclei and causes chromatin condensation. Caspase-3 also induces cytoskeletal reorganization and disintegration of the cell into apoptotic bodies. Gelsolin, an actin binding protein, has been identified as one of the key substrates of activated caspase-3. Caspase-3 will cleave gelsolin and the cleaved fragments of gelsolin, in turn, cleave actin filaments in a calcium independent manner. This results in disruption of the cytoskeleton, intracellular transport, cell division, and signal transduction. Phagocytic uptake of apoptotic cells is the last component of apoptosis. Phospholipid asymmetry and externalization of phosphatidylserine on the surface of apoptotic cells and their fragments is the hallmark of this phase. The mechanism of phosphatidylserine translocation to the outer leaflet of the cell during apoptosis has been associated with loss of aminophospholipid translocase activity and nonspecific flip-flop of phospholipids of various classes. Research indicates that Fas, caspase-8, and caspase-3 are involved in the regulation of phosphatidylserine externalization on oxidatively stressed erythrocytes however caspase-independent phosphatidylserine exposure occurs during apoptosis of primary T lymphocytes. The appearance of phosphotidylserine on the outer leaflet of apoptotic cells then facilitates noninflammatory phagocytic recognition, allowing for their early uptake and disposal.This process of early and efficient uptake with noà release of cellular constituents, results in no inflammatory response. (Fadok et al., 2001). The process for apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. Excessive apoptosis results in diseases such as Alzheimers disease, Parkinsons disease. Cancer is an example where the normal mechanisms of cell cycle regulation are dysfunctional, with either an over proliferation of cells and/or decreased removal of cells. Tumor cells can acquire resistance to apoptosis by the expression of anti-apoptotic proteins such as Bcl-2 or by the down-regulation or mutation of pro-apoptotic proteins such as Bax. The expression of both Bcl-2 and Bax is regulated by the p53 tumor suppressor gene Alterations of various cell signaling pathways can result in dysregulation of apoptosis and lead to cancer. The p53 tumor suppressor gene is a transcription factor that regulates the cell cycle and is the most widely mutated gene in human tumorigenesis. The critical role of p53 is evident by the fact that it is mutated in over 50% of all human cancers. p53 can activate DNA repair proteins when DNA has sustained damage, can hold the cell cycle at the G1/S regulation point on DNA damage recognition, and can initiate apoptosis if the DNA damage proves to be irreparable. Tumorigenesis can occur if this system goes awry. If the p53 gene is damaged, then tumor suppression is severely reduced. The p53 gene can be damaged by radiation, various chemicals, and viruses.
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