Monday, August 26, 2019

Charitable Organizations Essay Example | Topics and Well Written Essays - 1750 words

Charitable Organizations - Essay Example They just have to manage funds. Lastly, the intangible benefits are immense when it comes to serving in a charitable organization. As for the disadvantages, employee retention and recruitment is a matter of concern as the salary is low and commitment needed is high. Lastly, when charities are newly established, fund raising is a major issue as people doubt their credibility. Charitable organizations are those companies who are working for the sole purpose of doing something good for the society. The organization has charity-oriented factors as its aims and objectives as opposed to a normal company, whose major aim is to maximize its profits. There can be many types of charitable organizations, namely trusts, foundations and associates which are working as unincorporated (Petit-Zaman, 2006). A company might start off with charitable purposes or might become a charitable organization after some time passes after its establishment. There is a difference between a charitable organization and not-for-profit organizations. Charitable organizations are a subset of not-for-profit organizations. Not-for-profit organizations are those which are incorporated as an organization. They have a separate legal entity. They are neither working for purely charitable purposes nor for profit maximization. ... It is actually the responsibility of the state to fulfill these traditional duties, to work for the welfare of the citizens of the state. But often the state is ignorant of these duties and that is when these charitable organizations step in and do some good work. CHARITIES IN UNITED KINGDOM The United Kingdom has a total number of 200,000 charitable organizations (UK Tax). This is a huge quantity and the graph is rising as the sector of charity is rapidly growing and accelerating. Many of these charities are established as limited liability companies so that the owners, i.e. the trustees, are not liable to pay more than their share of investment in the company and so that this factor results in the establishment of more charitable organizations. Charitable organizations are finding new ways to cater to the humanity. The various charitable organizations are basically registered with three regulatory bodies, namely the Charity Commission, the Office of the Scottish Charity Regulator and the Inland Revenue. These regulatory bodies are essential to supervise and take care of the activities that these charitable organizations are indulging in. these bodies make sure that these charities do not misuse the money that they collect from the general public for charitable purposes . These charities also have to report its activities to the government. This makes the government fully aware of whether these organizations are fulfilling their purposes or not, as their collections are tax free. This reporting aims to see whether any fraud is being done by an organization opened by the name of charity but eating up money for personal purposes. If a fraud is detected, the license of the

Sunday, August 25, 2019

Competition among Hospitals for HMO Business Case Study

Competition among Hospitals for HMO Business - Case Study Example The independent variables are: an index of relative hospital prices for HMO business in each market (price); high tech-capability; teaching status (teaching or non-teaching); ownership status (non-profit, for-profit, or public); and location. To provide answer to the second research question, that is, to account for the effect of the structure of the hospital market on market share, three variables were added: no. of hospitals in the market, no. of HMOs in the market, and the HMO penetration rate. For both price and non-price attributes, the regression test pointed to an effect on market share variables. Hospitals with lower prices had a bigger share of HMO business. The more high-tech a hospital was, the greater the share in the HMO business. Teaching hospitals were more preferred by HMOs than non-teaching ones. On the effect of ownership: on average, nonprofit and public hospitals had less market share than for-profit ones.

Saturday, August 24, 2019

Documenting the Crime Scene Research Paper Example | Topics and Well Written Essays - 2000 words

Documenting the Crime Scene - Research Paper Example The responding offer must assess the scene and treat it as a crime scene through remaining cautious and observing events, potential evidence, persons, and vehicles (Horswell, 2010). According to Orthmann & Hess (2012), the initial responding officer is expected to take not of the physical location, time, address and date of the crime and make observations such as smell and sounds at the scene. Accordingly, the responding officer must take protective and safety measures by remaining attentive while scanning the area for any dangers such as natural gas, gasoline or hazardous chemicals that entail smells and sounds (Pepper, 2010). The next step is provision of medical attention to the victims of the crime without contaminating the scene and minimizing contact with the evidence such as knife tears and bullet holes (Orthmann & Hess, 2012). The officer can take statements from witnesses, the victim and suspects that are at the crime scene and victims or suspects that are sent to health facilities must be accompanied by enforcement officials in order to preserve the evidence (Ogle, 2011). The next step is securing and controlling the scene through limiting the access and movements and separating the suspects and witnesses, removing bystanders, family members and medical personnel in order to prevent scene contamination and destruction of evidence (Dale & Becker, 2007). The responding offers will then put physical barriers to the points of entry and document all people entering the scene.

Friday, August 23, 2019

HSBC Bank Development Case Study Example | Topics and Well Written Essays - 2250 words

HSBC Bank Development - Case Study Example This paper is a review of its strategic planning and resulting growth along with a brief history of the company. The original Hong Kong and Shanghai Banking Corporation was started in 1865 by a visionary Scottish businessman called Thomas Sutherland to facilitate growing trade between China and India and the Europe. The company began rapid expansion in Europe and USA even though the main focus was expansion in Asian countries. The company at that time grew large enough even to fund government projects in many developing countries in Asia. World War II saw many of its operations in Asia being closed down. The bank realised that focusing only on Asia was risky and began a expansion program mainly through acquisitions in Europe, Asia and the formation of a organization in the USA. The prominent acquisitions include the Hand Seng Bank, the Mercantile Bank and the British Bank of the Middle East (all in the Asia-Pacific region), the Marine Midland Bank (USA) and the Midland Bank (UK). "The formation of HSBC Holdings plc in 1991, creating a holding company for the entire Group with its shares quoted in London and Hong Kong, showed that the Group viewed Europe and the London market in particular, as a vital part of its future development." (Group History 1980-1999. 2009). A typical departmental structure is explained here. ... It should be noted that the structure is based on its policies of customer service policies and other strategies. The head of the structure is the CEO followed by nine departments. They are legal and financial control, Operations, Human resources, Commercial Banking, Internal Audit, Marketing, Treasury and Personal Financial Services. There is an administrative department under the financial control department. Under the Operations section, there are seven departments, namely IT, Support services, Property and security, Credit operations, Credit cards, Projects and Cash. The ATM department comes under Cash section. Under Commercial Banking, there are the Trade Services and Credit departments. Under the Personal Financial Services Department there are Customer Service, Teller Area, Consumer Finance and Loan Approving Department (for personal financial services). (Organization Chart. 2008). Group structure of HSBC Holdings Plc: Considering the size of the company, the organisational structure of the bank is extremely complex with seven major division and many other divisions formed under each of the seven ones mentioned above. The seven major divisions are HSBC Latin American Holdings (UK) Ltd, Grupo Financiero HSBC SA de CV, HSBC Investment Holdings Plc, HSBC Finance (Netherlands), HSBC Overseas Holding (UK) Ltd, and HSBC Bank Plc. As the name suggests, HSBC Latin America bases its operations in those countries while Grupo Financiero operates in Mexico. HSBC Investment Holding operates in UK and Taiwan. HSBC Finance headquartered in the Netherlands has operations in several countries (mainly in Asia) like Malaysia, Panama, Middle East, Hong Kong, China, Bermuda and Japan. It has control over the original Hong Kong and Shanghai Banking

The Causes and Effects of air pollution on the people and the Essay

The Causes and Effects of air pollution on the people and the environment - Essay Example In addition, air pollutants are transboundary in nature as they travel freely from the source in which they are produced to other locations and thereby spread the pollutants throughout the region. This nature has resulted in health affects for humans, animals as well as negative environmental impacts on trees, plants and forests which have in turn incurred economic losses through medical expenses and other damages (Air Pollution Effects). Air Pollution – Causes Man-made sources The major causes of air pollution come from human activities while on a minority result from natural causes. The beginning of the industrial revolution has brought with it tremendous growth of industries, population and globalization which have hugely contributed to the growing air pollution across the world. The industrial growth resulted in the establishment of several sectors such as power and biofuel industries, refineries, residential sector and the development of road, rail, and air transport. Eac h of these sectors has liberated pollutants into the air in the form of gases, solid or liquid particles. Among the major gaseous form of pollutants, sulfur-dioxide, which is a colorless gas with a pungent odor, is released during combustion of fossil fuels. The generation of power through electricity and the consequent production of heat produce a cocktail of air pollutants. The combustion of coal, which is a widely used source of energy in the power sector, produces sulfur-dioxide in large amounts in addition to other greenhouse pollutants such as arsenic, lead, and mercury. Other industries which release large amounts of sulfur-dioxide into the atmosphere are the manufacturing and construction industries and those which produce non-ferrous metals. The next major gaseous pollutant released is nitrogen oxides which is present in two major forms: nitric oxide and nitrogen dioxide. These are produced during the combustion of fossil fuels, motor fuel combustion from vehicles, from pow er plants, and deforestation. Carbon monoxide which is a highly toxic colorless, odorless and tasteless gas is also mainly produced during deforestation, combustion of biofuels and vehicular combustion. Ammonia gas, which has a pungent odor and hazardous in nature is produced through agricultural practices such as livestock farming and animal waste. The ozone, which is a colorless, poisonous gas with an irritating odor, is present in the stratosphere and troposphere layer of the atmosphere. While the ozone in the stratosphere layer protects the earth against the harmful ultraviolet rays of the sun, that in the troposphere is a secondary pollutant which is produced as a result of a chemical reaction between other pollutants in the presence of sunlight. Other air pollutants includes solid or liquid airborne particles which are suspended in the atmosphere, volatile organic compounds such as pure hydrocarbons or organic compounds and other persistent pollutants such as pesticides like D DT (Air Pollution Causes). Natural sources The

Thursday, August 22, 2019

From Production Line to Segmentation of Production Essay Example for Free

From Production Line to Segmentation of Production Essay 1. Introduction Competition has changed: Technical Innovations, globalisation of markets, cultural shifts within societies and new and efficient competitors put strain on the organisation of production within a firm. Many markets display a state of saturation that leads to a change in growth: Not quantitative growth is what firms are aiming at, but qualitative growth (Wildemann 1998:1). The improvement of the production is one way to establish qualitative growth its means are twofold (at least): First, it is possible to change the production in order to produce a better output with less cost. Second, it is possible to synchronise production and market as to enable the production to react quickly to changes in the market, i.e. the consumer behaviour. One way to reach both aims is to reorganise the production, i.e. to segment the production: With the establishment of product oriented production units a cheaper production is possible (Maier 1993: 25). Economics owe the focus on the segmentation of production with all its advantages to Wickham Skinner (1969, 1974 and 1986). With his book The Focused Factory he provided the ground for what is nowadays discussed under the headline: segmentation of production. Skinner did not develop a new insight in efficient ways to produce; he transferred to the American and European auditorium what has been practiced in Japan since the beginning of Industrialisation. This paper deals with change; with the change in the way cars are manufactured. A car manufacturers production unit until now divided into different production lines has to be transformed into segmented production. This is a big change; a change, which has to be dealt with in other words, it, is a case for change management. The scope of this paper is therefore not limited to displaying the advantages of a segmented production (which nevertheless will be done in chapter 2), but extends further to the management of the respective change. Chapter 4 is devoted to the change management: How should the new organisation of production be implemented? What problems may occur? What solutions to the problems can be provided? These and more questions will be put and answered in chapter 4. In chapter 3 a brief overview of change management within the (alleged) broader framework of project management will be given. Chapter 5 sums the results obtained in the previous chapters and evaluates the va lue of change management. 2. Efficient production with segmented production units Segmentation of production is according to Wildemann a holistic approach, aiming at a better market- and product orientation of the firm (Wildemann 1998: 31). Therefore, it is necessary to link production units to a specific product. By that, the relation to Skinner is establish, who discovered the focussed factory for the Western Economies: a companys competitive strategy at a given time places particular demands on its manufacturing function, and, conversely () the companys manufacturing posture and operations should be specifically designed to fulfil the task demanded by strategic plans (Skinner 1969: 138-139). A focussed factory means accordingly flexible reactions to market changes and the cost efficient realisation of strategic plans, e.g. the development and introduction of new products. The focused factory is not a big factory. It is rather a small one where the different production units are linked to a specific segment of the market a specific product: A factory that focuses on a narrow product mix for a particular market niche will outperform the conventional plant, which attempts a broader mission (). Its [the factorys with the narrow product mix] equipment, supporting systems, and procedures can concentrate on a limited task for one set of customers. () Such a plant can become a competitive weapon because its entire apparatus is focused to accomplish the particular manufacturing task demanded by the companys overall strategy and marketing objective (Skinner 1974: 114). Given the fact (provided it is a fact) that smaller firms or factories are compared to bigger firms or factories and with respect to costs and production better off, it is not surprising that there is a considerable trend to segmenting the production. Furthermore, transaction costs within a small or segmented firm are smaller compared to the bigger ones. A transaction is the delivery of a property or good via an interface that can be technically divided. One activity ends another starts (Williamson 1990:1). While crossing the interface a sample of costs is produced costs that can be at least in parts avoided: The aim of a segmentation of production is to disentangle production units and capacity. Large units should be divided in small units. Teamwork should be establish small teams giving the individual employee more responsibility. This should result in more autonomy of the individual employee, and boost his or her motivation, thereby increasing the quality of the work done by the employees. In Germany, it was Dietmar Tress who conceptualised for the first time smaller units as an organisational structure. Smaller Units, so his thesis, reduce the time that is needed to produce a product. The lesser time it takes to produce a good or a product, the better the competitiveness of a firm, the better its ability to deliver goods and the smaller the amount of capital needed to produce the respective good or product. While evolving his thesis Tress realised the reasons that stood against an effective production. The reasons mentioned by Tress are: division of labour, old patterns of reasoning and bureaucracy (Feser 1999: 19). Having carved out the problems, Tress submit his solution: He proposes that all necessary functions (for the production) and the aimed link between product and demand should be concentrated in a single hand and that the production flow should be kept within reasonable limits (Tress 1986: 184). According to Tress it is decisive that the production flow is c lear, understandable, and transparent. A single employee should be able to single out his or her contribution to the product (Tress 1986: 185). Segmenting the production further provides capacity utilisation and to reach that goal teamwork is needed: Small groups of employees should work in a self-responsible way within decentralized teams. Furthermore, those teams should take over different tasks. At this point the interrelation between the discussion on segmenting production and the discussion on human resource management becomes obvious. According to Baron and Kreps (1999: 3) Human Resources are the key to organizational success or failure. Human resource management including the concepts of intrinsic and extrinsic motivation may be seen as the countermovement to the alienation of the worker form the product of his work, as observed by Karl Marx in the 19th Century: Workers who contribute more broadly to a final product () are more apt to identify with a product and to reflect pride in its quality (Baron Kreps 1999: 317). Identification with a product raises the working morale, which means that the work satisfaction goes up. Worker or employees, who are content or satisfied with their work, work better. The determinants enabling this comfort are established by segmenting the production. And that is, where the problem starts: How can a segmented production be implemented? How can a factory divided in production lines become a focused factory divided in small working units or teams? The question at hand is a question of change management or project management. In the next part, the project of change will be unfolded. 3. Projects for managing change Change is something that happens all the time and everywhere. But change within a firm or to put it more scientifically change within economics appears to be a frightening prospect. Change cannot be left to itself; it has to be planned, controlled and coordinated. Problems, rising in the pursuit of change, have to be predicted, dangers for the project have to be identified and eliminated. All this is done by change management or within the (alleged) broader scope of project management. To put it differently, change management is the trial to direct change into the right channels. Project management is the trial to direct everything new within a firm into the right channels. It appears that there is not much difference between project and change management, one can almost say, they are different words meaning the same. A project is considered to be something unique, something that will not be repeated (Schelle 1999: 11). Project management means the totality of executive functions, the techniques, and means necessary to carry out a project. Replacing project by change, change management can be addressed as the totality of executive functions, techniques, and means that are necessary to alter something old into something new. At first it is according to most authors of the utmost importance for a change or project management to establish a structure plan, in which the implementation of whatever should be changed, is scheduled according to a time table connected with goals that have to be reached at a certain point in time. The structure plan is according to Schelle (1999: 93) a simple and useful tool. The structure plan is the meta plan. Apart from the structure plan there is the running order listing sub goals and so on. Once a project is initiated the control of the project is of crucial importance. A constant control is necessary to identify deviations from the plan or goal as soon as possible and to steer against unwanted consequences (Nà ¯Ã‚ ¿Ã‚ ½chter 2003: 377). Project control in this sense means to identify problems, to solve the problems, to recalibrate the project after some deviations from the plan occurred and to rescue the goal in spite of serious problems. Problems may emerge from different sources: Externalities may cause problems: Green activists may occupy the land that is designated to host the new factory, due to a seldom species of warbler. The construction of the new building itself may cause problems: A building contractor may file for bankruptcy. A delay in constructing the new factory may lead to an explosion of the costs and so on. Apart form those externalities there are sources that nurture problems within the firm: Employees may fear for privileges, for their job or for loosing power. Resistance to the change may arise from different sources all linked to the fact, that men is unwilling to change what seems to be good and worked well until now. And to convince employees of the benefits that come along with the new way of producing one thing is needed: change management. 4. From production lines to segmented production: An example Company R wants to segment its production. Being a car manufacturer organized in different product lines the company wants to become a focussed factory by establishing two production units each producing a specific type of cars. While segment A is chosen to produce the mini from start to end, segment B should produce the sport car. At the start of the change, company R is organised as follows in part 1 of the company the car body is being build, in part 2 the car body is being varnished and in part 3 the different parts of the car are being assembled. In the future company R shall be structured as follows: in line A the car body of the mini is being build, varnished and furthermore, the mini is being assembled; in line B the car body of the sport car is being build, varnished and assembled; At the moment three interfaces exist within company R: Between the car body builder, the varnish, and the assembler. Between these three parts of the company a steady flow of material has to be ensured. Furthermore, all three parts of the company depend on different suppliers. In the past a bottleneck between car body builder and the varnish has become a rule resulting in a temporarily standstill. So the new structure of the firm should guarantee a full capacity utilisation, by reducing the logistic efforts necessary to provide each of the three parts of the company with its amount of supply to avoid a standstill of machines and employees. Moreover, the link between company R and its markets should become closer. At the moment the company produces a monthly number of cars irrespective of the demand. If the demand goes up, the employees have to work overtime to satisfy the demand. If the demand goes down, the employees do their daily stint and the cars that cannot be sold were stored causing storing-costs. And this is where the project change comes into being. 4.1. Planning the change There are a lot of variables that administer a certain influence on the project deciding whether it is going to be a success or a failure. According to Eckrich (2003) two of those variables can be dubbed as structural and cultural conditions imposed by the environment within the firm or company. Structural conditions relate to the hierarchy within the company, while cultural conditions describe the way the employees within a company treat each other. Eckrich distinguishes cultural conditions into behaviour, attitudes and values, a distinction that reminds at concepts indigenous to social psychology. While social psychologists quarrel with each other on the relation between attitudes and behaviour (some of them even asking if there is any relation between both, cf. Six 1975, Bierhoff 1993: 280-288), Eckrich holds the opinion, that the behaviour of people is influenced if not determined by their attitudes, and by knowing the attitudes one can deduce the behaviour. Consequently, he recommends a questionnaire at the beginning of the change management project to discover the attitudes of the employees concerning the change of their working environment. Company R is a rather small company, employing 803 employees. It is best described as a company with flat hierarchies, stratified in management, departmental managers and masters. While the aim of this paper is to show the problems associated with the project change (or at least those that may be associated with the project change), I assume that the employees of company R take a critical stance to the change of the production, some of them even form a sort of resistance. Especially among the masters resistance is widespread. They fear they might loose responsibilities and some of them think they might even loose their job. The core of this paper is therefore concerned with what is called by Uebel and Helmke (2003: 415) escalations caused by individuals (personenbedingte Eskalationen). Escalations caused by individuals have to be distinguished from quantitative escalations and from qualitative escalations at least according to Uebel and Helmke (2003: 416). Of particular interest for this paper are escalations caused by individuals. (One might wonder if there are escalations which can be though of as being not caused by humans.) 4.2. Controlling the change Control is a matter of plan. To evaluate the progress of the project, the project manager has to look at the structure plan. He has to compare whether what has been reached is identical with what should have been reached. According to Nà ¯Ã‚ ¿Ã‚ ½chter (2003: 395) this is crucial, since it is the only possibility to identify deviation from the plan. To serve the purpose of early warning system the structure plan must be enriched with data, with the amount of time worked on a particular (interim) goal of the plan, with the state of the art and so forth. With respect to company R these rather general advices come to life: Important for the success of the segmentation in the company is an additional qualification of the employees. Furthermore, their work after the segmentation will be varied, i.e. they will have more different tasks to fulfil. This is in accordance with the results of the human resource management saying that employees that are not tied up in their daily routines, but kept busy with a bunch of different tasks show a higher degree of motivation and in the end do a better job than employees tied up in their daily routine. Independently from the results of the human resource management the change in company R is more than some can bear. For some employees the additional qualifications they are expected to achieve are a heavy burden and for the masters it becomes clear that the new structure of the company can only be reached by taking away the responsibilities from the masters. And in the end, Angst (fear) arises, and An gst (fear) is the widespread cause for resistance. 4.3. The problems of change Angst (fear) has been identified as the main reason of those showing resistance to the project of change. Following Uebel and Helmke (2003: 424), Angst (fear) can be subdivided into fear for power and fear for subject. While those with fear for power oppose the project due to their expectation that they will loose power, which means in the first place influence within the company, those with fear for subject oppose the project due to their expectation that they will loose responsibilities. The distinction is not a sharp, but rather arbitrary one. It is not obvious that the loss of responsibilities is not accompanied by a loss of power. However, those with fear for subject are anxious that they might loose reputation, end up with a smaller budget and so on. It has to be mentioned that Angst is a rather peculiar word for what is meant by Uebel and Helmke. They describe the common place that change has its pros and its cons. While change brings some advantages, some advantages of the old times will be lost. In other words, change may become a trade-off or worse, change might mean redundancy. Therefore, it is obvious from the very beginning that change management has to deal with problems. Problems are not something that arises as a matter of bad circumstances. Problems are the natural companion of change. In company R there are problems. The change of the production modus has been scheduled for spring and that was a mistake. In spring the demand for sport cars is high and a high demand and a different work environment is too much. The employees faced with frequent delays and the necessity to work overtime is dissatisfied. Resistance rises to protest. It starts with unofficial meetings held be employees and ends up in strike. The production stands still and so does the project. Change, it seems, has stopped. Uebel and Helmke write a lot about Angst (fear) and the different shapes it may use, and the risks Angst holds for the success of the project. But, as is the fact in company R, what can one do, if the problems are that massive that the project can be doomed to failure? Uebel and Helmke provide no answer. Instead they pronounce the value of plans for the crisis. One has to formulate worst-case scenarios within those plans (Uebel Helmke 2003: 428). Worst-case scenarios may be back or forward oriented. Backward orientation means that the problems can be solved and the goal of the project can be reached. Forward orientation means the contrary. The project is a failure and the plan has to include the plan X the withdrawal with as less causalities as possible. This provides no solution for company R. Is the change from line production to segmented production a failure? Is there a possibility to carry on? Hansel and Lomnitz (2003: 131-134) mention that there are no possibilities to reduce resistance with respect to specific goals of projects: An employee who will lose his job will not act in favour of the proposed change. To expect that, is out-of-touch. Furthermore, there are employees for whom it is dubious whether they will win or loose in the course of the project. So: resistance is natural and the only way to deal with resistance is communication and information. Transparency is the golden rule. The employees should know what change would bring, why change is necessary (Hansel Lomnitz 2003: 134-135). Maybe information can lead to a good end for company R. Rumours are the cause for concern in company R. Rumours about the real aim of the project being a job killer. Other rumours concern plans to reduce salary suspecting the hidden intention behind the plan to segment production is to cut down salaries. Those rumours may be dealt with in an agency theoretical framework: The relationship of agency is one of the oldest and commonest codified modes of social interaction. We will say that an agency relationship has arisen between two (or more) parties when one, designated as the agent, acts for the other, designated the principal, in a particular domain of decision problems (Ross 1973: 134). Starting from here it has to be considered that both sides face some information shortcuts, with the employees having no distinct knowledge of the goals pursuit by the management and the management having no accurate assessment of the behaviour of the employees during the course of the project and thereafter: In the course of the action some problems may arise due to the fact that information is not fully spread. The problems are labelled within the Agency theory as averse selection, meaning that one cannot be sure, if what the principal or the agent claims to provide is in fact what he can provide, moral hazard, which means that an agent or an principal can defect after the contract is established and hidden intention, speaking for itself (Krapp 2000). This excursion trip into the fields of agency theory results in the knowledge that Hansel and Lomnitz are right: The solutions to the problems the agency theory analysis is usually a form of information included in a contract. (Leaving the monitoring of the agent by the principal and the bonding of both to given promises aside.) So information, i.e. the spread of information may be a possible escape from the deadlock for the project change of company R. First, as a signal of confidence the project manager has been dismissed. He has proven to be unable to manage conflict. Under his rule rumour mill flourished and the actual state of the (project) art is much behind the expected state. The new project managers first act was to hold a meeting with all employees and to tell every single employee what he has to expect. In the end he succeeds in cranking the project. 4.4. The change or the end of the project In the course of the project experiences and knowledge should be collected for further or future change management, so as to learn from the errors made. The end of the project is marked by stocktaking. What has been reached is confronted with what should have been reached. Company R is nowadays a car manufacturer with a segmented production and therefore able to adapt its production in short time to the demand of the market. The segmented production started some weeks later than it has been scheduled, which is owed to the problems reported above. But the policy adapted by the new project manager has proven to function. He has succeeded in creating a common spirit and calming down the moods. The fact that work will be much more varied after the change has increased the motivation of most employees, the success of the project has become the intrinsic motivation for those employees: According to this survey, a large percentage of employees seem motivated at work by something other than the compensation received. () 72% responded that theyd continue to work even if they were already financially comfortable for the rest of their lives. Half the survey respondents agreed with an item stating that what I do at work is more important to me than the money I earn' (Baron Kreps 1999: 101). There is a specific quality inherent to work, a quality that is different from the motive to make a living. Intrinsic motivation stands for the fact that some or many or most of the workers want to do a work that is interesting, sophisticated, and provides a certain amount of reputation. Some of the employees of company R realised that a segmented production goes along with new job opportunities, with more responsibilities, with a flexible work scheme and so forth. Those employees made the change to their own project, a project they wanted to support and did support. 5. About change and its management The aim of this paper is twofold: on the one hand the subject is change management. But change management is a general concept, which one can describe in general terms as did Uebel and Helmke (2003). The problem is, that general terms despite sounding good have nothing to say about the management of change. Therefore, an example have been chosen to elucidate what change management really is. Change of a car manufacturers production from production lines to a segmented production, has been chosen as an example. The segmentation of the production is expected to be a project of change management that can often be found in reality. This is due to the advantages a segmented production provides its users with: a more flexible reaction to the demands of the market and a less costly production. Having established the example used to exemplify the change management it was necessary to describe what is known as project management. Thereby, it could be shown that the topics of project management and change management are not different as they both deal with new things that should replace old things. So it has been decided to treat them as equal. Then company R has been introduced. Company R is a medium sized company with flat hierarchies and massive problems occurring during the course of the change from production line to segmented production. The problems or escalations as some dub them are related to individuals, individuals or employees who resist for different reasons the proposed change. To deal with resistance and to provide the ground for the new organisation of the production is the task of change management. And, it appeared, that the best way to manage change is by adapting an open communication policy. This is what Hansel and Lomnitz propose and what has been derived from a brief look at the agency theory: Both sides trying to establish a deal have an information deficit on their side. Both do not know, if their counterpart is opportunistic in the sense of Williamson (1990), i.e., that he is trying to cheat. This is what the rumour mills in company R produced: the segmented production is a fake used by the management to cut down salaries, sack employees and rationalize the company. In the end, the project manager had been sacked and the segmented production had been established. The key to the solution was information and intrinsic motivation. Information had been provided by the new project manager, telling the employees that no one will be sacked and that salaries go if anywhere than up. Furthermore, the hint that a new organisation of the production provides new opportunities for qualification and new responsibilities raised the intrinsic motivation of many employees. They made the change to their project and supported it. And at the end of the paper a rule for change management can be derived: For a successful management of change it is necessary to involve the employees and to improve intrinsic motivation. 6. Literature Baron, James N. Kreps, David M., 1999: Strategic Human Resources. Frameworks for General Managers. New York a.o.: John Wiley. Beer, M., Eisenstat, R.A. and Spector, B., 1990: The Critical Path to Corporate Renewal. Boston, Massachusetts: Harvard Business School Press Bierhoff, Hans-Werner, 1993: Sozialpsychologie ein Lehrbuch. Stuttgart: Kohlhammer. Burghardt, Manfred, 2002: Projektmanagement. Leitfaden fà ¯Ã‚ ¿Ã‚ ½r die Planung und Steuerung von Entwicklungsprojekten. Erlangen: Publicis Corporate Publishing. Feser, Bjà ¯Ã‚ ¿Ã‚ ½rn, 1999: Fertigungssegmentierung. Strategiekonforme Organisationsgestaltung in Produktion und Logistik. Wiesbaden: Deutscher Università ¯Ã‚ ¿Ã‚ ½ts-Verlag. Hansel, Jà ¯Ã‚ ¿Ã‚ ½rgen Lomnitz, Gero, 2003: Projektleiter-Praxis. Optimale Kommunikation und Kooperation in der Projektarbeit. Heidelberg, Berlin, New York: Springer. Krapp, Michael, 2000: Kooperation und Konkurrenz in Prinzipal-Agent-Beziehungen. Wiesbaden: Deutscher Università ¯Ã‚ ¿Ã‚ ½ts-Verlag. Lewin, K., 1947: Frontiers in Group Dynamics: Concept, Method and Reality in Social Science; Social Equilibria and Social Change. Human Realtions, 1 (1); 5-41 Maier, Denis, 1993: Einfà ¯Ã‚ ¿Ã‚ ½hrungsstrategien fà ¯Ã‚ ¿Ã‚ ½r Fertigungssegmentierung. Eine empirische Untersuchung. Università ¯Ã‚ ¿Ã‚ ½t Mà ¯Ã‚ ¿Ã‚ ½nchen: Dissertation. Marshak, R.J., 1993. Lewin Meets Confucius: A Re-View of the OD Model of Change. Journal of Applied Behavioral Science, 29 (4): 393-415 Mintzberg, H., 1978: Patterns in Strategy Formation. Management Science, 24 (9): 934-948 Nà ¯Ã‚ ¿Ã‚ ½chter, Norbert P., 2003: Projektkontrolle. S. 375-392 in: Bernecker, Michael Eckrich, Klaus (Hrsg.): Handbuch Projektmanagement. Mà ¯Ã‚ ¿Ã‚ ½nchen, Wien: R. Oldenbourg. Nà ¯Ã‚ ¿Ã‚ ½chter, Norbert P., 2003: Projektsteuerung. S. 393-411 in: Bernecker, Michael Eckrich, Klaus (Hrsg.): Handbuch Projektmanagement. Mà ¯Ã‚ ¿Ã‚ ½nchen, Wien: R. Oldenbourg. Rinza, Peter, 1998: Projektmanagement. Planung, à ¯Ã‚ ¿Ã‚ ½berwachung und Steuerung von technischen und nichttechnischen Vorhaben. Heidelberg, Berlin, New York: Springer. Ross, Stephen A., 1973: The Economic Theory of Agency: The Principals Problem. American Economic Review 63 (2): 134-139. Schelle, Heinz, 1999: Projekte zum Erfolg fà ¯Ã‚ ¿Ã‚ ½hren. Projektmanagement systematisch und kompakt. Mà ¯Ã‚ ¿Ã‚ ½nchen: dtv. Skinner, Wickham, 1986: The Productivity Paradox. Harvard Business Review 64, 55-59. Skinner, Wickham, 1974: The Focused Factory. Harvard Business Review 52, 113-121. Skinner, Wickham, 1969: Manufacturing Missing Link in Corporate Strategy. Harvard Business Review 47, 136-145. Six, Bernhard, 1975: Die Relation von Einstellung und Verhalten. Zeitschrift fà ¯Ã‚ ¿Ã‚ ½r Sozialpsychologie 6, 270-296. Tress, Dietmar W., 1986: Kleine Einheiten in der Produktion: Wer wachsen will, muss kleiner werden. Fà ¯Ã‚ ¿Ã‚ ½hrung und Organisation 55, 181-186. Uebel, Matthias F. Helmke, Stefan, 2003: Eskalationsmanagement in Projekten. S. 413-429 in: Bernecker, Michael Eckrich, Klaus (Hrsg.): Handbuch Projektmanagement. Mà ¯Ã‚ ¿Ã‚ ½nchen, Wien: R. Oldenbourg. Wildemann, Horst, 1998: Die modulare Fabrik. Kundennahe Produktion durch Fertigungssegmentierung. Mà ¯Ã‚ ¿Ã‚ ½nchen: TCW-Transfer-Centrum GmbH. Appendix 1 Theoretical Framework Phase Models of Organizational Change Any change process can be thought of as going through distinct phases or stages. The purpose of this section is to provide theoretical background information of phase models of change. Linear Models Linear models see the change process as linear, progressing from a present state, through a transition state to a future state. The implicit assumption is that the future state is more desirable than the present state. Lewin provided one of the early fundamental linear models of the change process. He observed that any living system is always in a state of change, but will tend toward a quasistationary equilibrium. (Lewin 1947: 15-16). The level of behaviour of the system at any moment is the result of two sets of forces: those striving to maintain the status quo and those pushing for change. When both sets of forces are equal, current levels of behaviour are maintained. In order to change the equilibrium, one can either increase those forces pushing for change or decrease those forces maintaining the current state. Lewin viewed the change process as consisting of three phases or stages (Lewin 1947: 34-35): 1. Unfreezing. This step involves the forces maintaining the systems behaviour at the current level. Unfreezing is accomplished by introducing information that shows discrepancies between behaviours desired by group members and those behaviours they currently exhibit. 2. Moving. This step shifts the system to a higher level of group performance. It involves developing new behaviours and attitudes through changes in structures and processes. 3. (Re-)Freezing. This step stabilizes the system at a new state of quasi-stationary equilibrium. It is accomplished through the use of supporting mechanisms that reinforce the new state, such as systems, structures and policies. The new equilibrium can thus be made relatively secure against change (Lewin 1947: 35). Circular Models While the linear models follow the European science, East Asian and Confucian traditions offer a very different theory of change. The model of change underlying Confucian philosophies was summarized by Marshak (1993). As shown in Figure 1, there is continual cyclical movement among the five elements that make up the universe. Movement is a natural process and occurs in a specific sequence. When it is out of balance or out of order, unfortunate consequences result. Thus in this model everything and everyone is interconnected and part of continuous cycles of change. Figure 1: Five agents cyclical change according to East Asian philosophy (source: Marshak 1993:399) Appendix 2 Theoretical Framework Overview of the Three Forces for Change In the literature of organizational change, there is a widespread disagreement whether change should be implemented top-down or bottom-up. Top-Down Direction Setting Top-down change is seen to have the advantage of a clear direction towards an end state, to provide the integrated perspective that only top management can provide and to promise rapid change. However, top-down change can often lead to resistance and lack of commitment from middle managers and employees who might feel that top management does not really understand the problem. With regard to the RM Division, it becomes clear that management follows a top-down approach. RM`s general managers take major decisions on new technology an workers are not included in the decision-making process. The result is a lack of commitment and machine operators use any means they could to beat the system. Bottom-Up Performance Improvement The other line of argument favours a bottom-up approach to change, as this seems to address many of the shortcomings of top-down change by actively involving employees in the change process. But also a pure bottom-up approach has its problems. It often lacks direction and a link to corporate strategy, it can lead to costly duplication of effort, it often leads to little transfer of learnings and it can be slow to get results (Beer et al. 1990: 68). The RM Division did not follow a bottom-up approach for implementing the change. It is worth mentioning at this point that the RM management missed, as a result of not actively involving the employees into the change process, to address the disadvantages of a top-down approach. In addition, the above-mentioned advantages of a bottom-up approach were not realized during the change process. Horizontal Process Redesign Recognizing the limits of the pure top-down or bottom-up approaches to change, some authors have therefore argued that the solution is to combine the two approaches (Beer et al.1990). A combination of the two approaches holds the promise of obtaining their respective benefits while minimizing their disadvantages. However, it is argued, that fundamental change requires not only top-down direction and bottom-up performance improvement, but also a third force for change: horizontal process redesign. Horizontal process redesign views organizations as made up of key processes that produce a result for the customer. It attempts to bring the benefits of process thinking to the whole organization and emphasizes the importance of redesigning a small number of core business processes that cross the traditional functional boundaries. Likewise, it can occur at three levels: across organizations, across functions and within functions (see Figure 2). Horizontal process redesign sees reengineering as a key activity at all levels of the organization. However, in order to avoid sub-optimisations, one should start at the top management by mapping out the high-level processes first. In this way, once the subprocesses are considered, their role within the higher level processes are clear. This was not being realized at the RM Division: Instead of defining and explaining the new processes to the workforce, only immediately prior to the introduction of the new technology management had explained to the workforce the basic principles behind automation, disregarding the need for understanding the new processes. Particularly a proper introduction of the new core processes across functions was neglected. These mainly included the fact that previously, operators were involved in setting and adjusting machinery and now were simply operating their machines. At the same time, the process control department was to take greater responsibilities, and to be expanded. Would management have explained the new processes properly, operators would have been clearer about their role in regard to the process control department. Instead they found themselves in a favourable position, performing wider functions than management expected of them. In addition, they could use non-optimum methods to achieve the best possible piecework rates for subsequent production and only reluctantly gave up any rights to use the controls. This all can be seen as a result of a missing explanation of the redesigned core processes to the workforce. The second major problem was that of re-establishing piecework rates on the new machinery, because operators were enjoying average earnings and resisted this move. At this point it would have been helpful to establish a detailed timeframe in which the phases of the change process are listed, in connection with the procedure of handling the piecework rates during and after each phase. The basic agreement, which was being made, did not serve this purpose.

Wednesday, August 21, 2019

Anti-aging Mechanism Using Bacteriphages | Experiment

Anti-aging Mechanism Using Bacteriphages | Experiment We all have been familiar with many infectious diseases since many centuries ago. Some bacteria have killed millions of our lives, some viruses have great potential to consume many people health and wealth and both are still hugely haunting our humankind. We did discover Penicillin, scientists have developed many antibiotic and antiviral drugs to kill and combat against these bacteria and viruses. This is the war that will have no end. I have been thinking and studying about these microorganisms since my undergraduate degree emphasizing about the diseases and their basic features. In this study, I wanted to explore many facts about the bacteria and viruses for advantages of our medical sciences and I found out that there had been many researches and discoveries about using the bacteria and viruses for our goodness and amazingly there will be more and many potential for our future medical sciences. The most interesting thing I have studied is the prokaryotic viruses called Bacteriophage and they really have the very strong potential to be used as a weapon against many infectious diseases including multi drugs resistant bacteria infection and against cancer such as very deadly brain cancers and even the possible cure of many types of cancer by selectively targeting only the cancer cells without affecting the normal ones and I also have studied about the telomerase enzymes that have the potential against human cellular ageing. OBJECTIVES OF MY INDEPENDENCE STUDY As we are living on the world interacting with the ecosystems containing different sorts of unicellular and multi cellular organisms, most of our evolutions and pros and cons are tightly associated with these organisms and the first objective of my study is to know or link the beneficial effects we may obtain from our organisms by understanding them and also understanding ourselves scientifically. To know and if possible, to propose or to make the steps to develop very effective possible future anti cancer treatment using bacteriophage. To propose the possible anti-aging mechanism using bacteriphages. To develop drug which can be effectively used for the many multi drug resistant bacteria infections such as multidrug resistant Tuberculosis using bacteriophages and to identify the possible methods for the drug development and their respective infectious diseases with the delightful and precious help from my supervisor SCOPE After studying and emphasizing upon the general main advantages that we get from the bacteria and virus for our medical sciences, I want to focus my study upon the Bacteriophage viruses which can possibly be used as a vector for gene therapy and gene regulation for my desire against aging of human being and in another word against our inevitable part of our human life called death. Another scope is to use the phage as very specific cancer cell killing agent for many tumors containing specific surface markers or receptors such as brain cancers. I want to study by reading books and journals and also with my innovative thinking step by step, from general to details and to solve all the questions as much as I can and then to propose the very new techniques using molecular levels and receptors levels. Schedule If we want to know something, we must first understand it basically and so, my very first important thing to do is to know about the general important and some very detail characteristics of the bacteria and viruses. Without the general knowledge of them, it is not possible to find out more about them. Many reference books and internet links and help me with this part and to know the many beneficial effects of them for Medical Sciences. After this, my important plan is to study deeply inside the bacteriophage viruses and their current and future usage for Medicine and then accessing the knowledge with my innovative thinking and advices of my supervisor I hope that I will be able to learn, study and find many things about for Medical Sciences. 2. Bacteria 2.1: Introduction to bacteria All prokaryotic organisms are classified as bacteria and they are divided into eubacteria which includes all the bacteria of medical importance and archae-bacteria which is a collection of evolutionarily distinct organisms. TYPICAL BACTERIA: Most of them have shapes such as rod like, sphere or corkscrew. Their cells are smaller than the eukaryotic cells and all of them except the Mycoplasma have the rigid cell wall surrounding the cell membrane. Apart from the shapes, the cell wall defines whether the bacteria are Gram Negative or Gram Positive. Bacteria cells reproduce by binary fission. Atypical Bacteria are the distinct bacteria groups lacking of significant characteristics structural components or metabolic capabilities. They includes Chlamydia, Rickettsia and Mycoplasma etc. 2.2 ADVANTAGES OF BACTERIA FOR OUR BODY AND MEDICAL SCIENCE Although bacteria can cause many diseases and health problems to human being, they also have many beneficial effects for our human body and medical sciences. NORMAL FLORA: Many different micro-organisms mostly bacteria are continuously inhabiting the human body without giving any harm. Human body is usually sterile when a healthy new born enters the world. But, after birth, the body acquires normal flora from the environment and food. The very important fact is that the species of that flora can not be rigidly defined because they differ from one individual from another as a result of physiological differences, diet, age and geographic habitat. NORMAL FLORA AGAINST THE INVADING HARMFUL INFECTIONS The bacteria need receptors and nutrients for their metabolism. The invading infections will face with the competence of normal flora for these essential receptors and nutrients. Some bacteria of the bowel can even produce the antimicrobial substances so that the invading organisms can be killed. But, the substances producing bacteria themselves are immune to their own substances. These effects can reduce the possibility of the infectious diseases and act amazingly as a defense mechanism against the infections. GERM FREE ANIMALS: The significant of the normal floral are now well explored by studying the germ free animals which have no normal flora as conventional animals. They are produced by special cesarean sections and then they are maintained in special isolators. Experiments showed that in the germ-free animals, the alimentary lamina propria is underdeveloped, the motility of the GI tract is reduced and the intestinal epithelial renewal rate is just half of the normal conventional animals. In studies with antibiotic treated animals also suggest that the normal flora can protect our bodies from the pathogens. The researchers first treated the animals with Streptomycin to reduce the normal flora and then made them infected with the Streptomycin resistant Salmonella bacteria. In normal condition, about 10000000 Salmonella were needed to cause the establish infection but in Streptomycin pre treated ones, only 10 organisms were needed to cause infection. NORMAL FLORA FOR OUR IMMUNE SYSTEMS Bacteria colonization of a new born infant is the very powerful stimulus for the development of immune system. The studies showed that the antibodies concentration after infections is significantly reduced in germ-free animals indicating the defect in acquired immune system. Bacteria are also the important providers of important nutrients such as Vitamin K and they also help with digestion and absorption of nutrients. REFERENCES LIPPINCOTTs ILLUSTRATED REVIEWS of MICROBIOLOGY 2007 EDITION INTRODUCTION TO BACTERIA , page 1 -6 Normal Flora Page , 7 10 KAPLAN USMLE TEXT BOOK (MICROBIOLOGY)2009 EDITION HARRISONS PRINCIPLES OF INTERNAL MEDICINE 2006 3. VIRUSES 3.1 INTRODUCTION TO VIRUSES A virus is an infectious agent containing genome which is either RNA or DNA and a protein capsid designed to protect the genome. Many viruses have additional structure like envelope which is protein containing lipid bi-layer. The sort of nucleic acid in the virus is the most fundamental and important of properties of virus. The nucleic acid may be single stranded (ss RNA ss DNA) or double stranded (ds DNA or ds RNA). The Single stranded RNA genome are subdivided into the positive (+) polarity which is, of messenger RNA sense that can be used as template for protein synthesis. Negative (-) polarity or antisense which is complementary to the mRNA sense and so they can not be used as temperate for protein synthesis directly. 3.2 THE REPLICATION CYCLES OF VIRUSES The cycle begins with the attachment of the virus to the host cell called adsorption phase, 1. ADSORPTION: The initial attachment of a virus to the host cell is with the interaction between specific molecular structure on the surface of the virus and receptor molecules in the host membrane that can recognize the structure. The receptor molecules on the host cell membrane are specific for the family of the viruses and they are the molecular structures that usually carry out normal cell functions. The receptors for the viruses are present only on specific cells or are unique for one animal species. So, the absence or presence of the host cell receptors is so important determination for the susceptibility or resistance of a species to a given virus. If we can genetically manipulate the specific receptor affinity for the viruses, we will be able to attack or kill or change the desired targeted cells. Fig: HIV virus adhering to the cell, attachment is accomplished by the SU fragment of the env gene product on the surface of the HIV which binds to the CD4 molecule. So, the HIV viruses can only infect the helper T cells, monocytes and dendritic cells which contain the CD4 protein in their cell membrane. 2 PENETRATION: The two mechanisms the virons enter the cells crossing the cell membrane are the receptor-mediated endocytosis: the viron binds the cell surface receptor and the cell membrane invaginates enclosing the virion in and endocytotic vesicle (endosome). The virion then enters the cytoplasm by various mechanisms depending upon the viruses. It is facilitated by one or more viral molecules in general. C:Documents and SettingsuDesktopendoem.jpg f Membrane Fusion: Some enveloped viruses enter the cell by fusion with their envelopes with the membranes of host cells. Glycoproteins of the envelope can promote this and viral membrane then still remains associated with the plasma membrane of the cell and just the nucleocapsid is released into the cells. HIV viruses enter the cells by this fashion. 3 UNCOATING: This is the stepwise process of disassembly of the viron that enables the expression of the viral genes that carry out viral replications. Most of the steps occur inside the cells and depend on cellular enzymes and in rare occasions, newly synthesized viral proteins are needed to complete the process. The loss of one or more structural components of the viron will lead into the loss of ability to infect another cells reflecting as the eclipse period of the growth curve. 4 REPLICATION: DNA virus replication: There is a wide macromolecular event variation between families of viruses for the replication processes depending primarily upon the viral genome sizes. The smaller the viral genome, the more the virus must depend on the host cell to replicate. Also the mechanisms of replications for ss DNA viruses and ds DNA viruses are different. RNA virus replications Type 1: RNA viruses with a single stranded genome of (+) polarity that replicates with complementary (-) strand intermediate. In this, the infecting parental RNA serves as both mRNA and later as a template for synthesis of the complementary (-) strand. Type 2: Viruses with ssRNA genome of (-) polarity which replicate with a complementary (+) strand intermediate. (-) polarity genomes have two functions, one is to provide information for protein synthesis and the second is to serve as template for replication. But they can not accomplish without prior construction of complementary (+) strand intermediate. Type 3: Viruses with ds RNA genome: dsRNA genome is segmented, with each segment coding for one polypeptide. But, the eukaryotic cells do not have the enzyme to transcribe dsRNA. So, mRNA transcripts are produced by virus-coded, RNA dependent RNA polymerase (transcriptase) located in the sub viral core particle. This particle contains dsRNA genome and associated viral protein, including the transcriptase. In replications, the (+) RNA transcripts are not only used for translation, but also as templates for complementary (-) strand synthesis, resulting in the formation of dsRNA progeny. Type 4: Viruses with a genome of ssRNA of (+) polarity that is replicated with with a DNA intermediate: the conversion of a (+) strand RNA to a double-stranded DNA is accomplished by an RNA-dependent DNA polymerase, commonly known as reverse transcriptase, which is contained in the virion. The resulting dsDNA becomes integrated into the cell genome by a viral integrases action. Viral mRNA abd progeny (+) strand RNA genomes are transcribed srom this integrated DNA by the host cell RNA polymerase. 4 ASSEMBLY AND RELEASE OF PROGENY VIRUSES: The assembly of the nucleocapsids generally occurs in the cytoplasm for most RNA viruses and in the nucleus for most DNA viruses where the viral nucleic acid replications take place. REFERENCES LIPPINCOTTs ILLUSTRATED REVIEWS of MICROBIOLOGY 2007 EDITION , Unit-Viruses , 233-243 KAPLAN USMLE TEXT BOOK (MICROBIOLOGY) 2009 EDITION HARRISONS PRINCIPLES OF INTERNAL MEDICINE 2006 EITION BACTERIOPHAGE Introduction to Bacteriphages Bacteriophages are the viruses that replicate inside the bacterial cells. It contains nucleic acid encapsulated by the protective protein coat. The nucleic acid may be DNA or RNA depending on the phage and may be single stranded and some are double stranded ranging from the length of 3000 bases to 200,000 bases. The replication starts with the attachment of the virus to the receptors of the cell surface of bacteria. Then the phage injects the nucleic acid into the cell leaving all or most of the protein outside the cell. This is the obvious difference between the virus that infects the vertebrates and the virus that infect the bacteria. In former case, the virus is entirely taken up by the cell and its nucleic acid is released inside the cell. (1) The phage nucleic acid takes over the biosynthetic machinery of the cell to replicate its won genetic materials and to synthesize phage specific proteins. When new phage proteins and new phage DNAs have accumulated, they self-assembly into mature phage particles, the phage specific enzyme ( lysozyme ) that dissolves the bacterial cell wall and the phage is released from the bacteria. A single phage can produce millions of progeny at the expense of bacteria cells in culture. (1) (2) 4.2 Virulent phage Phage are classified as virulent or temperate depending on the nature of their relationship to the host bacterium. Infection of a bacterium by the virulent phage results in the lysis of the bacterium and death releasing newly replicated phage particles. One phage can produce hundreds of progeny within twenty minutes under optimal condition. The interesting thing about that virulent phage is that the phage that attack one bacterial species do not attack other species. (1)(2) That is a huge advantage to use phage as an antibiotic because the phage against E coli bacteria will only kill that species and will not affect the others including the normal floral of our human body. So, they will be the most specific antibacterial agent. (1) (2) 4.3 Temperate Phage The temperate phages are different from the virulent one in that they have two possible fates after infecting the bacterium. Some cause the lysis and death of the bacterium just like the virulent phages do but they do have another alternative outcome. After entering the cell, the phage DNA integrates with the chromosome of the host cell. During this state (prophage) the gene expression of the phage is continuously by a protein (repressor) encoded by the phage genome and therefore no new phage particles are produced, the host cell survives and the phage DNA replicate as part of the host cell. (1)(2) 4.4 LYSOGENIC BACTERIA The bacteria which carry the prophage are called lysogenic bacteria and this phenomenon is called LYSOGENY. The association of the phage and the bacteria is very stable unless the host DNA damage or the exposure to the ultraviolet light occurs. When the DNA damage occurs, the repression of phage gene is lifted and the lysis occurs and the host cells die. (1) (2) 4.5 MOLECULAR DETAIL OF LYSOGENY In Lysogenic mechanism, the genes for the lytic process will have to be turned off and this process is caused by the phage coded repressor gene. This may be proteins or sometimes anti sense RNA. The repressor genes can turn off almost all the transcriptional initiation and so most of the gene transcriptions including the essential ones for the lytic mechanism are inhibited. But the repressor gene acts only onto the few promoter genes and the gene for lysis mechanisms in late part of the processes are only indirectly inhibited by the lack of early gene transcriptions tuned off by the repressor proteins or anti sense RNAs. The early gene products are needed to activate the subsequent gene expressions and their absence make the whole lysis process inhibited. The repressors also promote their own transcriptions to ensure their functions. The lysogenic state is very stable and only one in 100000 cell divisions may undergoes lysis by spontaneous activation. There are also many ways to stop the lysogenic state in experimental such as heating in which the repressor proteins become denature, treating with the UV ultraviolet light in which the specific system called SOS system of the bacteria is activated. The SOS system is the global regulatory system which responds to DNA damage. The breakdown products such as oligonucleotides activate the Rec A proteins co-protease activity and this protein in turn inactivate the main protease protein called LexA and then repressors and the lysogeny state is ended. (1) (2) There is also a type of protein called anti-repressor protein and they inhibit the repressorss activities and this anti-repressor synthesis is turned off in the lysogenic cells by the maintenance protein called Mnt protein. CII gene: In order to achieve the stable lysogenic state, both the establishment of the repression of the lytic gene and the integration into the chromosome of the cell are needed. CII is a transcriptional activator which is coordinated with the lysogeny. Within the CII gene, the gene called CI gene which transcription needs the CII-dependent promoter establish the repression of the lytic genes. This promoter is activated only for a short period during lysogenization and after the repression has been established, the CII gene is repressed itself. The CI gene is then transcribed only from the pM gene which is the maintenance promoter gene. The another protein called Integrase which is essential in integrating of the phage nucleic acid with the chromosome is also transcribed from the CII dependent promoter called PI. The pAQ which is also the CII dependent promoter makes an antisense transcript that opposes the Q gene expression. Q genes products stimulate the late gene expression and late gene products which could kill and lyse the cell and they are not made by the CII expressing cells and so the CII gene is so essential for the lysogenic state and only these cells expressing CII gene effectively become lysogenic cells. (1) (2) REFERENCES LIPPINCOTTs ILLUSTRATED REVIEWS of MICROBIOLOGY 2007 EDITION Bacteriophage in chapter 7 Bacteria genetic , gene transfer , Page 60-61 RICHARD CALENDAR THE OXFORD TEXT BOOK OF THE BACTERIOPHAGE 2nd EDITION 2006 part II, Life of Phages, Page 66-104 BACTERIOPHAGE AS AN ANTIBIOTIC 5.1 WHAT PROPERTIES NEEDED AS AN ANTIBIOTIC? The antibiotic must be effective in the treatment of infection because of their selective toxicity. That means the drug should kill or effect against the invading desired organism without harming the cells of the host. In most of the cases, this toxicity is just relative rather than absolute, requiring that the concentration of the drug be carefully controlled to attack the microorganism while still being tolerated by the host. (1) 5.2 WHY PHAGES AS ANTIBIOTIC? As the PHAGE viruses can infect and kill the bacteria, they can be used as a drug targets against the Bacteria. Phage Therapy: Phage therapy is the use of lytic phages to kill specific bacteria as an alternative to antibiotic. The lytic mechanism of the Bacteriophages ensures the effective antibiotic mechanism of the Phages. The other useful thing is that the specific type of Bacteriophage attacks only the corresponding bacteria and so the other normal bacteria will not be affected by the specific Phage Therapy targeted to the aimed bacteria. So, the Phages have more specificity than all antibiotics in attacking the bacteria. 5.3 Host Vs Phages The phages are immunogenic and could initiate the immune responses. This effect may limit the uses of Phages because the Bacteriophages may be destroyed by our immune system even before attacking the desired target bacteria and also the strong immune responses may trigger the allergic reactions and also the human immune system produces antibodies against the Phages. Despite these matters, the good news is that their clinical uses reveal only very few side effects or allergic reaction. The best way to avoid the sensitization is to use the Phages only when it is necessary as in the case of multidrug resistant infection and using the Intra Venous IV Administration method. 5.4 BACTERIOPHAGE AGAINST TB Tuberculosis, one of the oldest diseases known to affect humans, is caused by bacteria belonging to the Mycobacterium tuberculosis complex. The disease usually affects the lungs, although in up to one-third of cases other organs are involved. If properly treated, tuberculosis caused by drug-susceptible strains is curable in virtually all cases. If untreated, the disease may be fatal within 5 years in more than half of cases. Transmission usually takes place through the airborne spread of droplet nuclei produces by patients with infectious pulmonary tuberculosis. MULTIDRUG RESISTANT TUBERCULOSIS: This condition arises when the Bacteria undergo point mutation in their genome which occurs at low but predictable rates. There are two types of drug resistant Primary drug resistant: This occurs when the strain infects the one who has never been treated before and Acquired drug resistant: In which, the resistant develops during treatment with inappropriate regimen. Apart from the resistant, some of the patients are not appropriate to give the usual dose of conventional treatment due to their co existing diseases like renal failure, hepatitis or liver failure. (1)(6) MYCOBACTERIOPHAGE Mycobacteriophages are the bacteriophages that infect against mycobacteria, the bacteria causing Tuberculosis and many other diseases like Leprosy. Mycobacteriophages were first discovered by the in 1946.They are the double stranded DNA viruses with non contractile tail belonging to the Siphoviridae family of the Bacteriophage. They also infect the pathogenic bacilli of the Mycobacterium Tuberculosis complex and now more than 250 mycobacteriophages have been indentified. They are either lytic or temperate. Some mycobacteriophages like DS6A can exclusively infect the Mycobacterium tuberculosis alone. Phages like 13, D 29, TM4, Bxz2 and Chel 2 infect both Mycobacterium tuberculosis and other Mycobacterium bacteria. Their morphological variation is limited but their genomes show extra ordinary genetic variability. The implications of phages in mycobacterial diseases may be greater than previously realized. (1) (2) (3)(7) 5.6 PHAGE THERAPY We can use lytic phages to kill specifically pathogenic bacteria as an alternative to antibiotics treatment especially for the multidrug resistant Tuberculosis. Lack of knowledge of bacteriophage biology and the quality monitoring during the preparation of therapeutic stocks had made the therapy difficult though the first known therapeutic use was in 1919.The M. Tuberculosis infections are hard to treat because the bacteria are naturally resistant to many antibiotic. The bacilli may remain in the latent or dormant state avoiding the action of drugs that require replication of the bacteria. So, the treatment of Tuberculosis requires multiple drugs for extended periods of time to effectively cure and avoid the drug resistant. The minimal duration for the treatment is four months with four drugs and then two months with two drugs. The most important thing is the emergence of multi drugs resistant strains and that makes the Phage Therapy more interested. (1) (2) (3) Dr Margaret Chan, the director-general of the World Health Organization said,The situation is already alarming, and poised to grow much worse very quickly. She and Bill Gates also stated that they only had little help from the modern drugs for the disease that is affecting 9 millions people each year killing nearly 2 millions of them. The conventional drugs are useless against some strains of tuberculosis and they addressed the situation OUT OF CONTROL and A POTENTIALLY EXPLOSIVE (5) TIM JOHNSON, Mc Clatchy Newspapers Animal study: One of the Mycobacteriophage, DS6A, showed reduction in the observed in the lesions in spleen, lungs and livers of guinea pigs infected with (Challenged with) Mycobacterium tuberculosis and the study showed that the anti bacterial effect of the phages is at least as good as Isoniazid monotherapy. The results are promising in the treatment of tuberculosis using phages. 5.7 MYCOBACTERIM INSIDE THE MACROPHAGES: Mycobacterium can reside in the macrophage cells of our immune system. They can even persist inside the phagolysosome where many bacteria and pathogens are killed. It was uncertain whether the mycobacteriophages can survive and replicate inside the hostile intra-cellular environment with reduced PH. (8)(9) 5.8 MYCOBACTERIUM SMEGMATIS, THE VEHICLE INTO THE MACROPHAGES: The above problem can be solved by using the vector bacterium Mycobacterium smegmatis. The technology was introduced in 2002. In this technology, the non-virulent bacteria Mycobacterium smegmatis act like a carrier into the macrophages. Macrophages infected with the Mycobacterium Tuberculosis or Mycobacterium avium were treated with the additional Mycobacterium smegmatis infected with Mycobacteriophage TM4. After they are ingested and destructed by the macrophages, the TM4 phages were released within the macrophages infecting and destroying the pathogenic bacteria even within the macrophages. The experiments showed the significant reduction of both the Mycobacterium tuberculosis and Mycobacterium avium. (9) 5.9 D29bacteriophages: This D29 are capable of entering the Macrophages without the need of any carrier and they can infect the mycobacterium and kill them effectively. So, the mechanisms of action of mycobacteriophages are completely different from the conventional drugs and will be so important in the multi-drug resistant cases. The Phage therapy also dose not need repeat dosing because the viruses do increase within the target bacteria and new virions are released on lysis. The endotoxin may be released into the body after the bacteria has been lysed and this could trigger the immune reactions but till now the clinical use of bacteriophages revealed only very few cases of side effects or allergic reaction indicating that our human body can really tolerate them. The other advantage is that they are cheaper and easier to produce than antibiotics. (10) REFERENCES LIPPINCOTTs ILLUSTRATED REVIEWS of MICROBIOLOGY 2007 EDITION HORACE T. ADAMS CONTEMPORARY TRENDS IN BACTERIOPHAGE RESEARCH 2009 EDITION RICHARD CALENDAR THE OXFORD TEXT BOOK OF THE BACTERIOPHAGE 2nd EDITION 2006 http://www.microphage.com/technology/phageBiology.cfm WHO, world health organization, Global Tuberculosis control Geneva Harrison text book of Practice of Medicine , USA 6th edition Fuller, KJ and Hatfull GF 1997 Mycobacteriophage L5 infection of Mycobacterium bovis BCG implications for phage genetic in the slow-growing mycobacteria Mol Microbiaol 26 755-766 Kaufmann SH 2002 Protection against Tuberculosis cytokines T cells and macrophages Ann Rheum Dis 61 Sulll 2 ii54-58 BroxmeyerL Sonsowaka DMiltner 2002 killing of Mycobacterium by a mycobacteriophage delivered by non virulent mycobacterium , model for phage therapy of intracellular bacterial pathogen, J infect Dis 1155-1160 Trollip A Albert H and Maskell 2001 Bacteriophage based technology for the rapid diagnosis and drug susceptibility testing of tuberculosis Am Clin Lab 20: 39-42 Phage as cancer curing agent 6.1 PHAGE DISPLAY is a process by which a peptide or a protein is expressed as an exterior fusion to a surface protein of a phage particle. The peptide or protein sequence can be deduced from its encoding DNA sequence that resides in the phage particle or in a transductant. Amplification of the DNA of interest can take place by phage/transductant propagation or by polymerase chain reaction PCR. By producing large amount of phage particles, each expressing a unique peptide or protein peptide and protein libraries can be obtained. The peptides or proteins interacting with defined molecular targets (most often proteins) can be isolated from such libraries by enrichments through repeated cycles of panning. So, the phage display can be regarded as a search engine of protein-target interaction. (1) Phages are bacterial viruses that have no native affinity to mammalian cells. But we can amazingly genetically reengineered to display peptides fusions to coat proteins that can recognize and bind to our mammalian cells. Oligonucleotide sequences encoding for foreign peptides are cloned into phage coat protein genes resulting in combinatorial libraries of billions of different phage clones displaying encoded peptides on their surfaces. This phage display libraries can be easily screened against various biological targets including the intact mammalian cells to give binding molecules with desired target-specific characteristics. Even the cell-specific peptides indentified through phage display can be used as delivery moieties for construction of gene therapy vectors, liposomes, or targeted drugs to diseased cells in many sorts of disorder including the cancer. (2)(3) 6.2 PHAGES AGAINST BRAIN TUMORS Malignant brain tumors are very difficult to treat because they are heterogenous, migrate far into adjacent essential brain normal tissues, are resistant to chemotherapy and radiotherapy and also protected by the blood brain barrier. (1) (4) The phage display might be so much effective against this fatal condition by following means. Phages can optimize the targeted delivery platforms to malignant brain cells using the cell specific peptides. The emerging of phage probes for profiling of brain tumors in individual patients and then making the personalized treatment based on the profiles of these tumors. To identify Death Penalty in Britain: Past and Present Death Penalty in Britain: Past and Present This paper analyses the past and future of the death penalty in Britain, examining the rationale for abolition in 1965 together with the potential and merits of re-introduction in the future. The death penalty was abolished in 1965 in Britain following a 1953 Royal Commission[1] and pressure by abolitionist groups. While the 1953 Report went outside its remit, to examine the effectiveness of hanging, it addressed the issues of deterrence and retribution; often heralded as the twin foundations of the death penalty and consequently used as the main arguments for the failure of the punishment. Bailey summarises deterrence theory by stating that â€Å"criminal sanctions must be severe enough to outweigh the pleasures†[2]. A fundamental concern is that deterrence can be broken down into various components. The apex of deterrence is a swift, public, just, and painful execution. A death penalty that combined all of these features could be said to have the maximum likelihood of deterring potential criminals. It is generally believed that the majority of death penalty mechanisms in existence lack at least three if not all four of these qualities. Whether the death penalty in fact deters is the subject of numerous studies; when read objectively they give no definite answer. Retribution is in many respects the antithesis of deterrence. Deterrence focuses on logic; retribution deals with the emotional reaction of society, with the oft quoted foundation being â€Å"an eye for an eye†[3]. In many respects this is concurrently the most and least powerful argument for the death penalty. It is difficult to argue, in particular in the most heinous cases, that society and specifically the victim’s relatives should not have the satisfaction of retribution. Concurrently it is an argument based on emotion; an element that justice strains to minimise. The fundamental difficulty was discussed by the US Supreme Court in Roper v Simmons[4] where Justice Kennedy made it clear that retribution can be justified only in certain cases; not in the case at hand. It is this fragmenting of the death penalty, with exceptions and splintered rationales developing, that has led to gradual reduction in the use of the death penalty. While a number of Royal Commission Reports and campaigns debated the issues mentioned above and below, it is likely that one particular argument dealt a hammer blow to the death penalty; the concept that innocent people may be executed. This realisation was a contributing factor to Justice Blackmun’s famous dissenting statement â€Å"I feel morally and intellectually obligated simply to concede that the death penalty experiment has failed†[5]. Year after year, new, modern evidence uncovers miscarriages of justice that lead to innocent men and women being released. In 1991 the ‘Birmingham Six’ were released following police errors and new evidence. Had they been convicted 30 years earlier, there would have been nothing more practical to do than grant posthumous pardons. Hood argued[6] that one of the main reasons for America still using the death penalty was that it was a populist measure. If this is so then there must be strong support for this argument of potential injustice, above the more specific, clinical reasoning, that persuades individual citizens of the dangers and risks that are inherent in the â€Å"machinery of death†. The modern addition to these time honoured theories is the popular focus on rehabilitation over punishment. The Criminal Justice System clarifies this by placing rehabilitation on an equal plane with punishment[7]. The rationale for this is uncomplicated and is based on the importance of working with the individual in order to help them contribute to society as a whole. The death penalty fairly obviously has no place within this new philosophy. The theoretical objections discussed above are merely the tip of an iceberg capable of sinking at least an ocean liner. Were there to be an inclination to re-introduce the death penalty, and in 1994 a bilateral coalition of 403 MPs favoured abolition, the European Convention on Human Rights would still have to be faced. Through the Human Rights Act, the United Kingdom is a signatory to the Act and is prohibited from imposing â€Å"degrading punishment†[8]. The issue has arisen predominantly with regard to cases of extradition to death penalty countries, and the courts have made it clear that even to extradite to such countries would constitute prohibited punishment. Further, to contemplate such a policy reversal would risk international condemnation. Amnesty have been vocal in condemning America and would turn their and others focus to Britain in an instant. While awareness of the factors above has been instrumental in 122 countries abandoning the death penalty either in its entirety or in practice[9], the evolution has also been the result of constant pressure from Human Rights groups including Amnesty International. Unlike America, Britain has traditionally been more dependent on the friendship of sister nations; a friendship that could conceivably shift dramatically. In short, the practical objections to a re-introduction of the death penalty would require a change in British foreign and domestic policy; the effects of which would be felt for decades. CONCLUSION This paper has addressed the death penalty in succinct terms; the question asks if it is the only way to â€Å"dramatically reduce crime†[10]. The analysis on deterrence and retribution show that far from this lofty status, there is no guarantee that it will reduce any crime. BIBLIOGRAPHY Bailey WC ‘Murder, Capital Punishment and Deterrence: A Review of the Literature’ (part of ‘The Death Penalty in America, Current Controversies’ Edited by Bedau H,  Published by Oxford University Press Hood R ‘Capital Punishment’ (1998) (part of ‘The Handbook of Crime and Punishment’ Edited by Tonry M,  Published by Oxford University Press Hood R ‘The Death Penalty: A World-wide Perspective’ 2nd Edition Turow S ‘Ultimate Punishment’,  Published by Picador GB Royal Commission on Capital Punishment: Report of the Royal Commission on Capital Punishment (1953) http://www.cjsonline.gov.uk/the_cjs/how_it_works/punishments_and_rehab/index.html http://web.amnesty.org/pages/deathpenalty-countries-eng European Convention on Human Rights Callins v Collins (1994)510 US 1141 Roper v Simmons (2004) 543 US 551 1 Footnotes [1] GB Royal Commission on Capital Punishment: Report of the Royal Commission on Capital Punishment (1953) [2] Bailey WC ‘Murder, Capital Punishment and Deterrence: A Review of the Literature’ [3] Exodus 21:23-25 [4] (2004) 543 US 551 [5] Callins v Collins (1994) 510 US 1141 [6] Hood R ‘Capital Punishment’ (1998) [7] http://www.cjsonline.gov.uk/the_cjs/how_it_works/punishments_and_rehab/index.html [8] Article 3 [9] http://web.amnesty.org/pages/deathpenalty-countries-eng [10] see question