Teaching as a profession has changed drastically

This is besides a timely issue in southern Florida since one of its school territory ‘s gained national attending late because parents used a societal computing machine web forum to develop the group TINT ( Testing is Not Teaching ) . This grassroots organisation was started by parents who felt that their kids were being overly tested in the public school system. The parents were joined by instructors and pupils and used the societal web to form protests and mass meetings. Two of the groups purposes were to hold the CAO ( Chief Academic Officer ) removed from his place, along with the Superintendent who hired him. The group felt that the CAO was passing out a â€Å" written plan † , particularly in reading, that all instructors were mandated to follow. This plan was designed to increase trial tonss on the FCAT ( Florida Comprehensive Assessment Test ) , given to all pupils in classs 3 through 10. In the terminal both the CAO and Superintendent resigned and TINT is now cl osely watching local and national developments in instruction. In this epoch of high bets proving, territories, schools and instructors depend on the success of their pupils ‘ success on standardised trials. These trials are correlated with national and province criterions and are farther broken down by benchmarks. These benchmarks provide the guidelines for the content instructors cover during the school twelvemonth. Research has shown that effectual instructors participate in the planning and implementing of the course of study but the authorizations from the Federal, province, and local authoritiess take the ownership of learning off and replace it with a course of study that is out of their control. This instance survey will look at the effects of the high-stakes testing motion on single instructors and analyze the functions and duties these instructors believe they have in fixing their pupils for the high-stakes testing. This instance survey was designed to analyze the relationship between the execution of increased high bets proving and teacher efficaciousness and to reply the inquiry do teacher believe they have a function or any duty in determining instructional schemes in fixing their pupils for taking high bets trials? The focal point was on analyzing what educational patterns are working to increase instructor efficaciousness with province mandated standardised testing and looking at schools which have implemented successful plans to help instructors. Three instructors will be interviewed to determine their position in determining instructional schemes within their school that prepare their pupils for the province mandated trials. This qualitative research designed instance survey will interview three instructors in public schools in a territory in South Florida. The interview inquiries will be predetermined and the topics will hold the chance to read these inquiries before being interviewed. There will be four inquiries for each one to reply. These inquiries will be developed by the interviewer and concentrate on the instructor ‘s function sing high bets proving and if it has changed their instruction patterns. They will besides be asked what function they have in their peculiar school in determining instructional schemes for their pupils to win on these trials. The interviewer will both transcribe and tape all the interviews and after the written text is complete it will be given to the instructors for their reappraisal.History of testing:The construct of aptitude testing was introduced during World War II as a method of happening the best and most intelligent soldiers for the United States military, ( Schmidt 2008 ) . In the old ages after the war these trials became incorporated into the American society as a manner to happen persons with superior scholarly capablenesss. The SAT was adapted from Yerkes ‘ trials for the military and was used by colleges and universities as one factor in finding admittances to their installations. By the 1960 ‘s SAT scores began to worsen, raising political and public concerns about the quality of the state ‘s educational system. Before this diminution, many Americans held a positive position of public instruction in the United States. American instruction was thought to both work out society ‘s jobs and besides endeavor to include pupils from diverse backgrounds, ( West & A ; Peterson, 2003, p. 4, as cited in Schmidt, 2008 ) . After publication of the diminution in trial tonss, many Americans became concerned with the province of the American educational system. The standardised testing motion is the consequence of the a series of jurisprudence ‘ passed by the state ‘s Presidents, climaxing in 2001 with the transition of No Child Left Behind ( NCLB ) , by so president George W. Bush. The authorizations of NCLB have proved to be controversial although basic end was â€Å" aˆÂ ¦to create an inducement for pedagogues to guarantee that no one pupil, or group of pupils, is left behind in their reading, linguistic communication, and mathematics abilities † . NCLB had legion demands that provinces and school territories had to follow in order to have federal support. The foundation of the NCLB jurisprudence is that provinces must make AYP ( Annual Yearly Progress ) each twelvemonth. The jurisprudence specified that every province â€Å" aˆÂ ¦must develop, and incorporate into their course of study, a standards-based answerability plan that demonstrates student proficiency degrees in the nucleus capable countries of rea ding, linguistic communication humanistic disciplines, and mathematics † ( Schmidt, 2008 ) . These proficiency degrees are measured by standardised trials given to all pupils one time a twelvemonth and these trials had to be approved by the Department of Education prior to being given ( Abernathy, 2007, p.5 ; Sunderman et. al. , 2005, p. 5 ) . By carry oning one-year testing, territories can closely supervise the advancement, or deficiency thereof, of pupils. No Child Left Behind was the latest reproduction of President Lyndon Johnson ‘s reform of educational reorganisation known as the ESEA ( Elementary and Secondary Education Act of 1965 ) . Both steps stressed the thought that public instruction â€Å" aˆÂ ¦requires a federal presence to guarantee academic advancement and academic equality for all pupils † . Schmidt ( 2008 ) Since the ESEA was passed at that place have been alterations made to its base, with the latest being No Child Left Behind ( NCLB ) The federal authorities has played an of import function in altering public instruction in the United States, the motive for these alterations in public schools were motivated because of concerns for America ‘s worsening trial tonss. The two chief drifts for alteration were worsening trial tonss on the Scholastic Aptitude Test ( SAT ) and the publication of A State At Risk by Terrance Bell. Three of import causes were named in the passing of the ESEA statute law. The first was the worsening public presentation of pupils on the SAT test. The second was studies conducted during this clip that repeatedly placed the United States in the lowest percentile of overall academic accomplishment when compared with foreign educational systems, ( West & A ; Peterson, 2003, pp. 4-5 ; Nichols & A ; Berliner, 2007, p. 4 ) . The 3rd factor was the relentless accomplishment spread that separated minorities and low-income pupils ‘ tonss from kids who came from a more affluent background. ( Nichols & A ; Berliner, 2007 ; p.4. & A ; Kantor, 1991, p. 51 ) . A State at Risk was published 18 old ages after the transition of the ESEA and was written by so Secretary of Education, Terrence Bell â€Å" Nation at Risk: The Imperative for Education Reform in America ( West & A ; Peterson, 2003 p. 5 ; Berry, 1993, p. 215 ) . This study focused on the United States ‘ low academic accomplishment in malice of the federal authorities ‘s focal point on bettering pupil public presentation in public schools when the ESEA was passed. The study stated that, â€Å" aˆÂ ¦the educational foundations of our society are soon being eroded by a lifting tide of averageness that threatens our really future as a State and a people † ( Bell, 1983 ) . Furthermore, the United States achieved a low academic rank when compared to other states and the authors of the study believed that America ‘s educational system was in demand of a drastic reform. The publication radius of a series of reforms that the writers believed would â€Å" aˆÂ ¦reverse the downward spiral of an unequal educational system, ( Schmidt, 2008 ) . The reforms included parental and community engagement at local schools, engaging instructors with advanced grades who were more motivated to learn, and a higher degree of engagement from all degrees of authorities. Although this publication did non excite any alterations on the federal degree, it still remained an of import factor in American public instruction. In 1994, so President Clinton passed a reauthorization of the ESEA called Goals 2000. This federal reform plan was ambitious in nature since it provided pecuniary inducements for public schools that implemented annually proving to demo student advancement towards proficiency, ( West & A ; Peterson, 2003, p.7 ) . This plan provided Title 1 schools with â€Å" aˆÂ ¦federal support â€Å" for developing ‘local reformsaˆÂ ¦the developme nt of standardsaˆÂ ¦enhanced professional development, bettering in engineering, and alterations in administration for answerability † † with the end of increasing pupil public presentation in the aˆÂ ¦ † nucleus capable countries such as, reading and mathematics ( Fuhrman, 1994, p. 84 ) . Goals 2000 laid the basis for NCLB. It was during this clip that the term â€Å" answerability † became of import since it was used as an inducement for provinces to get federal financess. This thought was added to NCLB, but President Busch extended the significance by doing the relationship stronger between the federal, province, and local bureaus. Although the answerability measures set Forth by NCLB have proved to be controversial, its basic end of the Act was â€Å" aˆÂ ¦to create an inducement for pedagogues to guarantee that no one pupil, or group of pupils, is left behind in their reading, linguistic communication, and mathematics abilities † . NCLB had legion demands that provinces and school territories had to follow in order to have federal support. The foundation of the NCLB jurisprudence is that provinces must make AYP ( Annual Yearly Progress ) each twelvemonth. The jurisprudence specified that every province â€Å" aˆÂ ¦must develop, and incorporate into their course of study, a standards-based answerability plan that demonstrates student proficiency degrees in the nucleus capable countries of reading, linguistic communication humanistic disciplines, and mathematics † ( Schmidt, 2008 ) . These proficiency degrees are measured by standardised trials given to all pupils one time a twelvemonth and these trials had to be approved by the Department of Education prior to being given ( Abernathy, 2007, p.5 ; Sunderman et. al. , 2005, p. 5 ) . By carry oning one-year testing, territories can closely supervise the advancement, or deficiency thereof, of pupils. The standards-based instruction reform and answerability motion started in the mid-1980s and raised outlooks of public presentation for U.S. schools ( Buttram & A ; Waters, 1997 ) . The province of Florida took the enterprise to better K-12 instruction and so Governor Jeb Bush instituted the A+ Plan in 1999. This program was created as a standards-based answerability system, concentrating on bettering the public presentation of all pupils, irrespective of their ethnicity, gender, poorness degrees, native linguistic communication or disablement position. The chief premiss of the A+ Plan was that â€Å" every kid can larn and no kid should be left behind † ( Executive Office of the Governor, nd. ) . A brief reappraisal of the literature found a clear division between research workers who found that standardised trials are good vs. those who believe these trials are damaging to education as a whole. Many writers began their Hagiographas by depicting the necessity of standardised testing in today ‘s schools. Bandalos ( 06 ) explained the demand for standardised testing within educational scenes today since these high-stakes trials are the method in which pupil acquisition is assessed and continuously evaluated by instructors, principals, and school territories. Bandalos besides stated that acquisition is the end in all of instruction and the function of appraisal is to assist professionals understand the degree of larning pupils have achieved. Hammeran ( 10 ) besides felt that it was possible to â€Å" learn to the trial † while still covering the of import course of study for a category. This writer studied learning a scientific discipline plan that was aligned to the National Science Education Standards ( NSES ) . She wrote that since the province criterions reflect the national criterions, and standardised trials reflect both the province and national criterions, so concentrating on learning to the trial would guarantee that pupils were having the of import content in scientific discipline category. The significance of the job is clearly discussed The significance of the inquiry of instructor beliefs in their function in determining instructional schemes to fix their pupils for proving is a timely one in the province of Florida. Performance-based appraisal is now compulsory in many schoolrooms but instructors and parents have become concerned about the genuineness of these appraisals and how assessment information can be used as formative feedback to better instruction and acquisition. Although these newer attacks are driven by a motive to do pupil appraisal informations more utile and meaningful than some traditional attacks this alteration was viewed as a positive progress by some research workers while others felt that it was hard to judge the theoretical benefits of these alterations or to get down to consistently research the nature of instructors ‘ schoolroom appraisal patterns. This trouble arises because research workers, protagonists, and specializers in school territories in the state have non arrived at a cons istent definition of what these footings mean or what these patterns look like ( Frey & A ; Schmitt, 2007 ) . Coming to Footings With Classroom Assessment 2007 Bruce B. Frey-University of Kansas, Vicki L. Schmitt-Missouri State University Those who advocate for â€Å" aˆÂ ¦test-based accountabilityaˆÂ ¦ † argue that it increases pupil success by helping instructors to set more accent on the of import content in their capable country, provides wagess for good instruction, and produces informations that is used to do determinations about pupils, instructors, and schools. For such systems to work every bit intended, the policies must advance good direction, and any resulting additions in trial tonss must back up valid illations about increased pupil accomplishment. Research has shown that high-stakes testing does so act upon direction, but these effects are complex and consist both desirable and unwanted alterations in pattern. For illustration, instructors in territories or provinces where high bets are associated with trial consequences tend to concentrate on tried stuff and de-emphasize unseasoned stuff ( see Stecher, 2002 ) . Similarly, research indicates that the additions in tonss on high-stakes trials frequently generalize ill ( or non at all ) to other trials of the same sphere, raising uncertainties about the extent to which these additions provide valid grounds of improved pupil public presentation ( Klein, Hamilton, McCaffrey, & A ; Stecher, 2000 ; Koretz & A ; Barron, 1998 ; Koretz, Linn, Dunbar, & A ; Shepard, 1991 ; Linn, 2000 ) . The literature on high bets proving is clear sing the history and development of these trials and how they are being implemented in school territories today. Conversely, the literature is divided into two factions-authors who believe that standardised testing is a good step of pupil acquisition and instruction, and writers who feel that high-stakes proving is a negative influence for instructors and pupils. The function that instructors believe they play in implementing in determining instructional schemes to fix pupils for proving is non a topic that has much coverage in the literature, but the branchings of † learning to the trial † is covered. The research inquiry is designed to understand the function instructors feel they play in determining instructional schemes to guarantee that their pupils achieve success on these compulsory province and authorities needed trials. These are the trials that they themselves are held accountable for the consequences by their schools and territories. If instructors feel they have no function in determining the direction for their ain pupils so for them it will be a affair of â€Å" learning to the trial † . If, on the other manus, they feel in control of direction the term â€Å" teacher efficaciousness † will be applicable to these instructors. Teacher self-efficacy refers to a instructor ‘s belief about his or her competency in holding a positive consequence on pupil larning accomplishment, Ashton, 1984 as cited in Denzilel, 2005. Prior research conducted in the field indicates that teacher self-efficacy is related to a instructor ‘s success in curriculum invention ( Berman & A ; McLaughlin, 1977 ) , beliefs about pupils ‘ capablenesss ( Ashton, 1984 ) and intelligence ( Klein, 1996 ) , quality of pupil relationships ( Ashton & A ; Webb, 1986 ) , assurance in working with parents ( Hoover- Dempsey, Bassler, & A ; Brissie, 1987 ) , clip spent on academic acquisition ( Allinder, 1995 ) , self-efficacy of low-achieving pupils ( Midgley, Feldlaufer, & A ; Eccles, 1989 ) , and the instructor ‘s ability to keep pupils accountable for their acquisition and public presentation ( Ashton & A ; Webb, 1986 ) . In the original Rand surveies, teacher self-efficacy was measured by inquiring two inquiries: ( a ) ‘When it comes right down to it, a instructor truly ca n't make much because most of a pupil ‘s motive and public presentation depends on his or her place environment ‘ , and ( B ) ‘If I try truly difficult, I can acquire through to even the most hard or unmotivated pupils ‘ . The first inquiry was hypothesized to measure instructors ‘ result outlooks, typically labeled learning efficaciousness ( TE ) . In contrast, the 2nd point was hypothesized to reflect personal instruction efficaciousness ( PE ) . From this position, TE relates to a instructor ‘s outcome outlooks and PE is based on the instructor ‘s judgements of his or her personal ability to act upon pupil acquisition. Early Rand research workers grounded teacher self-efficacy in Rotter ‘s ( 1966 ) venue of control concept and placed important accent on outcome outlooks and p ersonal duty when construing efficaciousness tonss. Later, Ashton and Webb aligned the concept with a societal cognitive theoretical position of self-efficacy ( 1977, 1978 ) . In contrast to the venue of control position, the social-cognitive attack emphasizes the dealingss between efficaciousness beliefs and outcome outlooks. Harmonizing to Bandura, result and efficaciousness beliefs are related but can be conceptually and through empirical observation differentiated ( 1986, 1997 ) . For Ashton and Webb, TE and PE represent steps of result outlooks and efficaciousness outlooks, severally. Teacher efficaciousness can be affected by the function they play in fixing pupils for mandated standardised trials. Author Kenneth Vogler ( 2006 ) stated in his article that in the past instructors were merely accountable to their decision makers and local school boards. It was those local boards that developed the course of study every bit good as the criterions for their school system. Now, instructors, every bit good as decision makers, are being held accountable to the populace for the academic public presentation of pupils in their charge. Standardized testing is a world in south Florida and that fact is non altering in the foreseeable hereafter. Students, parents, and instructors have mobilized to alter the importance and weight of these trials, but there is still â€Å" FCAT blackout † where no schools are allowed to take field trips, no personal yearss are given to instructors, and no conferences are held by the territory. After the blackout comes â€Å" FCAT season † where schools are on practical lock-down until all the testing is complete. From personal experience, instructors are ranked by the additions their pupils made, particularly in reading, math, and scientific discipline. When the CAO was in office, each instructor received a â€Å" book † to be completed that twenty-four hours. Sometimes the day-to-day book was 15 pages or longer. All of the control was taken away with respect to instructional schemes and learning to the trial began on the first twenty-four hours of school. The resea rch says that this focussed instruction can be positive or negative. The focal point of this survey is to inquire instructors if they fell they have control fixing their pupils for these high-stakes trials and to analyze what works in their readying and which countries they feel they have no control in direction. The consequences will be good to both the school and territory as we struggle to equilibrate the ends set Forth by the authorities with our pupil ‘s single demands. Teachers ‘ RESPONSES TO HIGH-STAKES TESTING AND THE VALIDITY OF GAINS: A PILOT STUDY. Daniel M. Koretz CRESST/Harvard Graduate School of Education Laura S. Hamilton CRESST/RAND Education Coming to Footings With Classroom Assessment 2007 Bruce B. Frey-University of Kansas, Vicki L. Schmitt-Missouri State University British Journal of Educational Psychology ( 2005 ) , 75, 689-708, 2005 The British Psychological Society www.bpsjournals.co.uk. Confirmatory factor analysis of the Teacher Efficacy Scale for prospective instructors. Gypsy M. Denzine1* , John B. Cooney2 and Rita McKenzie3 1Northern Arizona University, USA 2University of Northern Colorado, USA 3Buena Vista University, USA

Vernacular Approach Passive Design Strategy to Achieve an Optimum Cooling Effect in Belum Rainforest

Common attack inactive design scheme to accomplish an optimal chilling consequence in Belum Rainforest Abstraction The intent of making a survey of common attack inactive design scheme to accomplish an optimal chilling consequence in Belum Rainforest is to understand how the past architecture manners can gives us an indicant of effectual inactive design schemes to better the criterion of life within a place by supplying a construction that is more energy efficient and comfy. In helping the proof of research, literature reappraisals based on the common architecture inactive design were conducted to heighten the procedure. First of wholly, the orientation on the site is really of import to near a good passive design onto the edifice. From the instance survey at Belum Rainforest Resort, the edifices are orientated in a really systematic agreement. Buildings are placed insistent with a consistent distance to let sufficiency air current flows into the edifice. Apart from this, shaded the out-of-door country with planting and supply the shading on the edifice to take down the land temperature. Besides, seting design can work as funnel chilling zephyrs and filtrate the strong air currents. The edifice layout, for illustration the window design, orientation of the gap and shading, roof discharge, raise the edifice in piles, provided the evaporative chilling system and the stuffs used on a edifice is of import because those design schemes would act upon the airing and accomplish optimal chilling consequence inside the edifice. In decision, a standard passive design is one that uses non-energized design characteristics to do the edifice clime responsive. It is of import to observe that the optimal consequence can non normally be achieved by utilizing merely one scheme because the schemes would work best when an integrated attack is used. 1.0 Overview of Belum Rainforest Resort The Belum Rainforest Resort is located in the thick of tropical Eden, Pulau Banding, Perak. Belum Rainforest is one of Malaysia ‘s premier ecotourism vacation finishs. It is a nature lovers getaway finish where can being shut to the nature because it was surrounded by a beautiful lake position and jungle. It accomplishes the environment with arresting positions, escapade, relaxation and repose. Belum Rainforest Resort provide an chance for the nature lovers to see the beauty and enigma of the huge jungle, observe the beauty of the vegetations and zoologies and be intoxicated in the nature beauty scenery that can be found seldom in someplace else. Belum Rainforest Resort make up the rural landscape become more interesting and attractive with the common architecture edifice which is the old wing slang resort ( phase 1 ) , Kampung House and the new flying modernism resort ( phase 2 ) . Common architecture attack inactive design in their ornament, pick of stuffs used and their size and signifier to accomplish an optimal chilling consequence in the edifice. In this paper will analyze about how common attack of inactive design scheme to accomplish an optimal chilling consequence in Belum Rainforest Building.What is the demand for Common architecture to near inactive design?How does the orientation of the edifice influence the airing and chilling consequence inside the edifice.How does the common attack inactive design scheme influence the airing to accomplish optimal chilling consequence in the edifice?How make the stuffs help to accomplish the chilling consequence in the edifice?What is the similarity and differences of inactive design in the old wing resort ( phase 1 ) and new flying resort ( phase 2 ) in Belum Rainforest Resort?2.0 Requirement for Vernacular architecture to near inactive design Natural and inactive methods nearing on a edifice is indispensable to do an indoor environment comfy with keeping a low temperature scope in a edifice. An optimal design house is non merely designed base on their residents for assorted practical demands but yet for a comfy indoor environment. In common architecture, it simplest signifier of turn toing human demands is successfully achieve a sustainable edifice with those natural and inactive methods and yet it besides encompassing the regionalism and cultural edifice traditions, supplying the construction more energy efficient. In traditional manner, a common architecture edifice was been built with the natural resources around the site and have to do certain that those stuffs application would giving a good responsive to the clime to do the indoor environment comfy. Besides that, orientation of the edifice is considerable to do the edifice takes the advantages of climatic characteristics such as Sun and chilling zephyrs. Orientation of the edifice is the basic application for a sustainable and inactive design decides the edifice layouts, window design, shadowing and etc. 3.0 Building Orientation influence the airing and chilling consequence inside the edifice Orientation of the edifice, on of the basic inactive design strategic should be see on the site because it is really of import to cut downing the energy ingestion and supplying the edifice environment comfortable. A good orientation of a edifice can assist to cut down the edifice heat addition and provided a good airing and chilling consequence onto the edifice. Because of the Sun rises on the E and sets in the West, all the edifices in Belum Rainforest Resort was orientated their long facade to the North and South way and short facade to the E and west way with a really systematic agreement for illustration every individual of the Kampung House and the stage 2 resort are confronting their entryway and life room on the North way and holding an enclosed facade on the West to forestall the edifice upper limit exposure to the sunshine. There will be a long roof shadowing on the E and west facade of the edifice while the North and the south facade will be decorated with short crucifix sh adowing. Most of the gap would be placed on the North and south way due to the inactive design strategic to forestall the edifice most of the clip was been exposed to the sunshine and besides it can assist to cut down the heat addition of the edifice. In others manner, the edifices are placed insistent with a consistent distance to let sufficiency air current flows into the edifice. To accomplish high natural airing inside the edifice, opening should confront on the strong air current way. For illustration, more gap was been placed on the North East way due to most of the clip at that place have strong natural air currents blows towards. Due to the topography of Belum Rainforest Resort which is an island surrounded by the rain forest, the environing mountain was reclaimed as the higher topography comparison to the lower topography which is the location of Belum Rainforest Resort. Thus, the higher topography helps to barricade the Sun irradiate to the lower topography when the sundown. In regardless of the site contrast, the mountain was acted as a shading to profit the Belum Rainforest. 4.0 Common attack inactive design scheme influence the airing to accomplish optimal chilling consequence in the edifice. Based on this subject, the method of common attack inactive design scheme influence the airing to accomplish optimal chilling consequence in the edifice of Belum Rainforest Resort would be discussed. There are some of the common design scheme could be applied on the edifice to chilling down the edifice such as the evaporative chilling system, gable roof discharge, roof stack airing, huge gap, constructing rise in piles and the overhang for the shading. 4,1 Evaporative chilling system To accomplish a comfy environment, evaporative chilling system is one of the ways to do the environing environment ice chest with the evaporated H2O vapour in the environing air. For illustration, in Belum Rainforest Resort, we can establish there is pool and swimming pool been decorated in the courtyard outside the resort. As the H2O evaporated, about 2500 J of heat energy is consumed. It wet the environing edifice and the H2O pull out the heat from its environing country to do the environing ice chest. Evaporative chilling system is suited to continue outside the edifice alternatively of inside the edifice particularly is our state which is a really hot and humid to avoid the elevating of inside edifice humidness. 4.2 Stack Ventilation and Roof Ventilator Stack airing usually will be go oning in the common architecture house with the map of ventilate the inside and trapped the hot air underneath the roof and so cut down the heat addition inside the edifice. The air motion usually is from the high denseness country of air to a less denseness of air. The ventilator roof articulations or the Malay funnels shaped roof at each gable terminal allowed the hot air rises with perkiness inside the edifice and is infiltrated out therefore the temperature inside the edifice could be lower down and accomplish a chilling consequence inside the edifice. On the other manus, roof blowhole besides could be found in the common architecture house. Due to the Phase 1 Resort in Belum Rainforest Resort is design base on the common architecture manner, the rectangular gable roof blowhole hole was been founded near to the extremum of the roof. The inactive gable roof blowhole map effectual as the natural air can flux in and out to the edifice. 4.3 Opening Huge fenestration is really indispensable for a edifice. It plays an of import function for wind circulation from outside to inside of the edifice. To accomplish a good passive design edifice, the orientation of the gap is really of import. Huge fenestration should be layout on the North and south facade of the edifice to forestall most of the interior surface country of the edifice been exposed to the sunshine. In Belum Rainforest, most of the North and south edifice facade are designed with operable huge fenestration such as the gap of eating house in Phase 1 resort and the Kampung house. Those operable gap helps to cut down the energy ingestion in the edifice and brings the natural airing into the edifice. There is besides some sort of inoperable fenestration from the Phase 1 Resort at Belum Rainforest Resort. The inoperable bamboo fenestration design act as a shading on the edifice facade and in the same clip it is besides an gap with could let the airing flow into the edifice. 4.4 Stilt Building Piles edifice are the edifice which is raised up by stacking over the dirt to the edifice land floor. It is one of the feature of common architecture manner. Chiefly, piles house is used to forestall house been flooded by H2O and forestall the wild animate being such as rat or bite to mount up to the edifice. In add-on, pile edifice besides present good itself in inactive chilling design with the method of air current flows under the edifice land floor. The good airing system enable the hot been exchange with the cold air and therefore it maintain the edifice land floor ice chest all of the clip. By the same item, because the dirt under the edifice all of the clip was been shaded and less exposed to sunlight, it keep the land floor with low temperature and do the edifice environment lupus erythematosus with heat addition. The saloon & A ; kitchen which connected with the Phase 1 Resort and the Kampung House in Belum Rainforest Resort was been designed with pile. Those edifice are full fill the demand of common architecture inactive design manner non merely with the application of aesthetic traditional design but besides with their inactive design strategic for illustration lower down the temperature of the land floor edifice to accomplish an optimal chilling consequence into the edifice. 4.5 Overhang Roof Overhang roof is the most simple and most obvious engineerings for salvaging energy to maintaining the edifice environing cool in the summer. Overhang Roof is portion of roof that extends beyond the walls. It functions as a roof shadowing to protect the facade of the edifice been maximal expose to the solar radiation. Larger overhang roof will be occurred in the E and west edifice facade while the North and south facade decorated with smaller overhang due to the place of the Sun rise and Sun set. 4.6 Shadowing by tree and Vegetation Planting a batch of trees on our environing country is the most good because seting can do our environment beauty and nicer, provided shadowing to our environment which can cut down the sum of sunlight perforating into our edifice, better the environing air quality which can assist to filtrate the harmful air and supply O to do our environing fresh. In Belum Rainforest, trees was been planted in the surrounding of the edifice. The plantation make the environing looks really aesthetic and full of poetic feeling when walking through under the trees. Most significantly, those plantation plays an of import function to protect the edifice been extremely exposed to the sunshine. It acts as a shading of the edifice to take down the temperature of the edifice and the land temperature and besides can be used to filtrate the chilling zephyr and strong air currents.Sustainable stuffs helps to accomplish the chilling consequence in the edificeChoice of environmental friendly building stuffs is o ne of the indispensable design schemes in order to construct a sustainable edifice, add-on to accomplish a standard chilling consequence in a edifice. Green edifice stuffs have lightened the footmark of any building undertaking as they have lower energy ingestion comparison to others non-sustainable stuffs. Green edifice stuffs include bamboo, wood, stones or rocks and sand which can be found of course on Earth, and besides the usage of recycled stuffs, for case, bottles, bricks, steel and the similar. These green and harmless edifice stuffs are non-toxic, reclaimable, and able to renew and hold a extremely lasting. Bamboos, wood, which are both the bing stuffs on the Belum Rainforest Resort are been used as a wall, shadowing or barrier. The ground why bamboo and wood been chosen to utilize for the edifice stuff because the energy embedded in their transit can be minimize and extracted and manufactured locally the edifice stuffs to the edifice site. In Belum Rainforest Resort, bamboo is been used as a wall, barrier and shading. The agreement of the bamboo as a barrier or shadowing giving a high efficiency allowed the outside airing swimmingly flow into the edifice and by the same clip the sunshine can somewhat perforating into the edifice. for illustration, in the old wing resort, every individual window from the resort is been shaded with row of bamboo. It brings the advantages to the edifice which the energy ingestion on the edifice could be reduced. In add-on, bamboo is one of the edifice stuffs which is low heat absorbent. To do the edifice more sustainable and experiencing comfy with a low temperature, all the ceiling of the edifice are been decorated with bamboo. The ornament of bamboo as a edifice stuffs is sustainable, high efficiency and besides really aesthetics. Furthermore, wood besides act as one of the sustainable edifice stuffs on the site. Using wood as edifice stuffs can easy cut down the heat addition inside the edifice because of the thinnest of light colour of the stuffs. For case, the Kampung House in Belum Rainforest Resort have a really high thermic efficiency because the edifice was built with wood wall, wood flooring and roof. Therefore, this sustainable stuffs make a really high chilling consequence in the edifice. What is the similarity and differences of inactive design in the old wing resort ( phase 1 ) and new flying resort ( phase 2 ) in Belum Rainforest Resort? The old wing resort which is phase 1 in Belum Rainforest Resort is design base on common architecture manner while the new wing resort which is Phase 2 is more modernism architecture manner. In comparative both resort which is phase 1 and phase 2, the inactive design strategic of stage 1 edifice would be more efficiency so the stage 2 edifice. First of wholly, the differences of both stage is the edifice stuffs. The envelope edifice in stage 1 most of all is built with wood and bamboo while the envelope edifice in stage 2 is all built with concrete and rage Earth. Old flying resort do good execute in inactive design comparison to the new wing resort base on the differences of their edifice gap. In the old edifice, there is more opening. There are row of bamboo act as a window shading in every individual resort room. The ornament make the facade looks aesthetic and besides lower down the energy ingestion of the edifice because of the window shadowing which can let a good airing flow i nto the edifice and somewhat incursion of sunshine into the edifice. For the new wing, there is less outside airing can be flow inside the edifice because of the enclosed concrete wall and less fenestration. Other than that, the temperature of old wing edifice would be more ice chest than the new wing edifice. The ground is the old wing edifice was surrounded with a batch of flora plantation comparison to the new wing resort which is missing of flora on the surrounding. As a decision, Belum Rainforest Resort has to the full adopted common attack as a inactive design scheme to accomplish ideal chilling effects for the comfort of the residents in the edifice. Natural chilling attack gives advantages to human and besides our environing environment. Orientation of edifice, flora as shadowing device, uses of natural edifice stuffs, more gaps confronting north and south way, elevate the edifice, circulation of air flow and the blending of edifice with topography were taken into considerations when the designer is planing and building the Belum Rainforest Resort. The installing of these inactive chilling devices in Belum Rainforest Resort are non merely helps to continue the site to the minimal detrimental degree, it besides helps to better our environing air quality as deforestation is non needed, trees absorbs C dioxide and release O to assist to clean the air. These inactive chilling methods besides helps to salvage more energy as they have replaced those mechanical chilling devices which consume big sum of energy. Therefore, lesser emanation of nursery gasses. Greenhouse effects can be prevented as no harmful gasses are being released, earth surface temperature can be maintained, and human wellness will be improved. Last but non least, inactive chilling attacks are required for every designers when planning, planing and building a edifice in order to make a cleaner and uncontaminated ambiance for our hereafter.

To answer question Assignment Example | Topics and Well Written Essays - 1250 words

To answer question - Assignment Example This is because his body is not used to the climate in Ivory Coast which is a West African tropical country. The Wald Test and the Blood Culture Test carried out on him came out negative. The liver function was elevated and the white blood count was higher than the normal haemoglobin level. Moreover, he had reduced platelet count. The C-reactive protein level was elevated, an indication that the body was infected with a microorganism. The body was trying to fight with the infection, thus having a higher count of the white blood cells. As per the case study, the most likely diagnosis is that he was infected with typhoid. This is from the symptoms that were being exhibited and the results from the Wald Test and the Blood Culture Test. Typhoid fever is caused by a harmful bacterium called Salmonella typhi (WHO, 2014). Considering the fact that he had visited West Africa, a tropical country, and the symptoms, it is clear that he must have contracted typhoid fever. The microscopic organisms that cause typhoid fever spread through polluted substances or water and sporadically through immediate contact with someone with the organism (Mayoclinic.org, 2014). Typhoid fever is a severe sickness associated with severe headache and is caused by the Salmonella typhi microscopic organisms. It can likewise be caused by Salmonella paratyphi, a related bacterium that normally prompts a less serious disease (Balentine, 2014). The bacterium that has infected the man is the Salmonella typhi since the symptoms shown were more severe than those associated with salmonella paratyphi. Laboratory testing is required to confirm the clinical diagnosis. To test for the disease, blood specimens and stool samples are required. Laboratory conclusion of typhoid fever requires separation and recognizable proof of salmonella enterica serotype Typhi. After samples are gathered, they are screened independently to distinguish the microbes. In order to

Marketing Plan for Product Line Essay Example | Topics and Well Written Essays - 1250 words

Marketing Plan for Product Line - Essay Example 1. How the Selected Small Appliance Supports Company G’s Mission Statement The small appliance supports Company G’s mission statement in several ways. In the first place, the appliances are made using very few materials and little energy. This will boil down to decreased cost of production, and eventually, helping clients purchase them at affordable rates. Beside the aforementioned advantage which will have clients saving their money, the pleasing visual features of design are also likely to excite the passions and happiness of the clients. This happiness is in fact a central part of client’s lives. B. Marketing Objectives 1. The target market for the company’s product is very broad, given that it incorporates all the areas that have undergone electrification. The veracity behind this postulation is elucidated by the fact that the new product can be used in a domestic setting. Given that America is entirely electrified, the whole of it serves as target mar ket. The rest of the developed world, such as the UK and Europe, can also serve as part of the target market, since globalization has become responsible for many multinationals. Multinationals, in turn, have the entire globe, continent, or a regional block serving as target market. 2. Four Selected Marketing Objectives for Company G and an Objective for Each of the Four Marketing Strategies (Product, Distribution, Price, and Promotion) Marketing objectives refer to the goals that an enterprise may wish to accomplish through marketing efforts. For Company G, they are: reaching the desired profit potential for the newly innovated small appliance; helping the appliance fit into the market effectively (introducing the brand to the market successfully); ensuring continuance of use by the market (fostering the demand of the product in the market); and improving the living standard of the market (by making the appliance as helpful, efficient, affordable and physically appealing as possible ). The objectives that Company G is intent on using are also four. The company is aiming at making favorable amounts of profit by tinkering with scientific innovation to deflate the cost of production. Secondly, Company G intends to introduce the brand to the market by making it as unique (helpful, efficient, affordable and aesthetically appealing) as possible. Similarly, the company intends to foster the demand for the same product in the market by promoting it, as a way of making both potential and prospective clients aware of the availability of the product in the market. Finally, by strengthening the attributes of the appliance, especially its affordability and efficiency, the company will have improved the living standards in the market. C. Competitive Situation Analysis 1. Classifying Company G’s Products Using the Three-Way Consumer Product Classification System (a) Convenience goods: the product will always be presented in the market as a commodity from which the like ly benefit from establishing cost and quality evaluation is believed to be less significant in regard to the time and effort of the consumer. (b) Shopping goods: The quality of company G’s product will enable the company to present it in the market to rationally make comparisons of the price, fashion, and suitability. This will be achieved by highlighting these qualities in ads targeted at likely and repeat consumers. (c)

The role if Integrated Management System in Developing Inventory Dissertation - 1

The role if Integrated Management System in Developing Inventory Management system in Government Sector - Dissertation Example The government sector in UAE is in the integrated management system primary poses for assisting their store division that effectively processes related tasks of operation.The integrated management system helps to developing and improving any existing gaps and weaknesses when the application is utilized to being tailored to each department process tasks. The gaps and issues related to safety, building developments, staff quality, and the transferring of data that meets international standards sets the level of needed achievement. The weaknesses in proficiency meeting internal practices with sufficient resources can continue the lack of productivity to transferring data or materials from one point to another. This can cause a risk associated to cost that without an integrated management system in place to monitor and detect failure to meeting standards and negatively hinder the organization for progressing. The pursuit for organizations relates to having proficiency in their integral m anagement system that prevents lapse of coverage to processing tasks within certain daily practices. The review of the company internal processes in select departments offers a vantage point of identified gaps, such as, safety issues, building development, staff quality, material requisitions, and material transfers. Thus, the defined element of concern to address such gaps of issues are notion to structure the integrated management system in a way that adapts to each department needs for proficiency. This is key to solving the problem identified of slow responses from the government store division to the targeted consumer, in the ability, to structuring the technology resources effectively that limits overall associated risks. The aim is the achievement of objectives that arise from its polices with reference to a specific sector of the business. Further, the mission of having a combination of processes and practices that are used within an organization to aid the implementation of the organization’s policies provides a lasting impression to business model for efficiency. The goal is in reviewing the slow responses of productive processing of tasks that are mirrored - to certain integral management systems capabilities in the delivering of objectives that arise from these policies, is known as Integrated Management System [Def.] In the identification of risks the business processes in Operational Risk [Def.] are categorized into four areas: 1. Quality- risk of supplying the customer with a different product or service 2. Safety- risk associated with the supply of an unsafe product/service, or workers getting injured during production 3. Environment- risk of producing a product that could be harmful for the environment and/or the consumer 4. Security- risk involved with being associated with criminal activity during the provision of a product The core investment in business relates to the managing the resources that improves the overall profitability of the organization. Therefore, the needs is to having a huge cash flow constraint is imperative for the organization to optimize inventory using the analytical and statistical methods applied by an integrated approach. Respectively, the optimizing inventory is an output of many inter-organizational processes that making it one of the major challenges can hinder on reaching a desired outcome. The pursuit for the organization to lower service levels often it has been noticed that company’

Betty Woodman Work of Art Research Paper Example | Topics and Well Written Essays - 500 words - 1

Betty Woodman Work of Art - Research Paper Example She has combined the artwork of ceramics into the functionality of day to day use and as pieces of art. Most of her works are colorful and varies in style. She would rather be eclectic that be identified by one style. Her work is not boring. It is diverse, interesting and shows influences that span different cultures. Her work cannot be said to come from one nation. She is an international artist. The two works chosen represent two complete opposites of her scope of artwork and to show her style is eclectic. In 2008-2009, she composed a series of Gauguin, Vase Diptyque for the Sevres Gallery. They are made of tender porcelain. It is interesting to understand why she called them Gauguin. She must have been influenced by his Double-Vase decorated with a Breton Figure, 1886-7. (History of ....) It is made of clay. He considered ceramics another form of sculpture and the Sevres Porcelain factory had ruined it with their development of porcelain. expressed in these vases come from the Baroque period of the 18th century by the sumptuous use of curves in furniture. This is a personal interpretation. These vases are wonderful in the use of white because they are so atypical of most of her works. They can been seen on the Sevres site listed in the "Works Cited". A similar representation of these vases can be seen on the American Academy in Rome Site. Last year until December 2010, she was showing at the American Academy in Rome. Her Roman Fresco/Pleasures and  Places was the premium work. It has a double interest as it shows her diversity in her work and represents her life that she spends in Italy. She has divided her life between the New York and near Florence where she has had her studio for the last 30 years. The Fresco is made of ceramic on canvas. She was strongly influenced by her time spent doing a fresco in the American Embassy in China in 2009 . She was able

Analysis of The Allegory of the Cave Essay Example | Topics and Well Written Essays - 750 words

Analysis of The Allegory of the Cave - Essay Example Glube’s analysis will be considered. The cave is incredibly dark since there is no adequate light inside it, making difficult, even for the inhabitants to see objects. Inside the cave, there are chained people on their feet and necks making it difficult to move. Equally, there is another world just out of the cave, which is separated by a wall. Numerous people walk on this wall causing reflection of the shadows into the cave, which the prisoners perceive as real. However, in actual sense, this is just an illusion. This scenario contrasts sharply with the outer world, which is characterized by light and visibility of everything (Grube, 112). This makes a prisoner released from the cave to dazzle in the light, however as he stays longer, he is acclimatized. He expresses sympathy to the prisoners in the darkness. He sees it better for one to be a prisoner in the other outer world. As a point of departure, the Allegory of the cave represents a dialogue between the protagonist Socrates and Glaucon, the interlocutor. The people in the cave are seen bound by chains and believing that the reality lies in the shadows of the artifacts. It is unbelievable how these people manage a life confined in darkness, because the fire represented is behind them. This is a metaphorical application, which gives a picture of their state while in the cave. Their senses are bound and they are confined to their sense of ignorance, which makes Socrates to wonder how these people will respond if they were â€Å"released from their bondage and cured of their ignorance† (Grube 187). Socrates believes that there is a possibility that, the prisoners will be confused to differentiate between the real artifact and its shadow. Accordingly, Grube notes that the primary intention of education as articulated by Plato is not to impart knowledge but to change the behavior and

Stem Cell Research Ethical Dilemma Essay Example | Topics and Well Written Essays - 1000 words

Stem Cell Research Ethical Dilemma - Essay Example The functionalities of stem cells allow the body to repair itself internally as they can divide through mitosis so as to replenish other cells. While dividing, stem cells can either remain as it is, that is a stem cell, or can develop into any other body cell such as nerve cell, white blood cell, red blood cell, or muscle cell. It is there unique qualities – as unspecialized cells as well as ones that can be induced to be specialized to perform certain functions – that they have attracted such attention and research from the scientific community. However, the extent to which these cells can be induced under particular conditions is arguable especially due to its association with ethical concerns. While many characteristics can be induced upon the cells by exposing it to different conditions without any harm, the fact that there is a potential danger from such exposition takes over progressive research on the subject. Also, several stem cell experiments on human embryoni c cells for IVF (in vitro fertilization) and somatic cells presents ethical concerns which is seen by many as ‘tinkering’. It is important to consider that science has forwarded and developed as a result of research. Since its early days, the various researches conducted by scientists and theorists have played a central roles in the advancement of scientific knowledge. However, this fact does not ignore the moral and ethical responsibilities of a scientific researcher while she or he is on his path to conduct experiments. Most stem cell research experiments are looked upon as essential discoveries that can lead to a transformation of the modern world. More researcher in the field can provide answers to several of the scientific questions and can also resolve problems associated with human reproduction. The debate revolving around embryonic stem cells is its position on the value of life which may considers an embryo as a person or otherwise. Since embryo is considered to be an early form

Health Care Transparency Essay Example for Free

Health Care Transparency Essay Healthcare transparency has been defined by the Institute of Medicine (IOM) as making available to the public, in a reliable and understandable manner, information on the health care system’s quality, efficiency and consumer experience with care, which includes price and quality data, so as to influence the behavior of patients, providers, payers and others to achieve better outcomes (American College, 2010). Transparency allows consumers to make better informed decisions. It also helps health facilities convey information to the public. With more information in the open, there will be less overall confusion. People will be better equipped and facilities will know how they compare to other facilities. In the past transparency has been affected by lawsuits. With the risk of being sued, many physicians and hospitals did not want to divulge private information. Of course, this attitude is beginning to change. In the video â€Å"Healthcare Transparency† Dr. Patrick Cawley expresses that transparency in the future will be greatly increased (Dr. Cawley, P., 2009). More information will lead to better patient care. Eventually a patient will be able to review how well a hospital or physician is able to provide care. Everything from infection rates to waiting times will all be accessible to the public. I agree with all forms of medical transparency. Access to wait times will better prepare potential patients for their visits to a hospital. Knowledge of infection rates will affect how the public perceives a health institute. If infection rates are high, most likely public opinion will be able to change this. No longer will things of this nature be shrugged off as typical health care. If a facility is providing less than optimal care, people will be aware of this and know to avoid the facility. This means that poor health care facilities will rightfully fail, while prominent effective health  facilities remain active and prosperous. Thus means overall better patient care. If only the best health care facilities are able to thrive, more people will be able to receive optimal care. Patient satisfaction surveys will also help potential patients understand the environment they are about to enter. If a staff is rude and curt than the public will have access to this. Essentially, this will encourage health care providers to give optimal quality of service to each and every patient. Of course, it’s important that a patients expectations are not too grand. Nothing in life is perfect and people should understand this. Busy hours and numerous patients can cause fatigue. After all, health care providers are still human. Perhaps if all physicians were machines then we could expect them all to be perfect. Performance of medical procedures will enlighten a patient of how well a hospital is able to provide a service. This in turn will allow consumers to make the best choice when selecting a facility for providing care. Someone needing back surgery should be able to locate and choose a facility right for them. If a facility performs poorly with back surgeries, the public has a right to know so that they can avoid this. People have the right to make the most well informed decision. Facility treatment of patients should definitely be transparent. If a facility is trying to hide something it can’t be good. People have the right to know how well a facility treats their patients. This also encourages a facility to always do their best. Ultimately, everyone wants the best health care possible. With expanded information more people will be properly informed of all their choices. Transparency means freedom for consumers. It means more access to information, and more freedom to select the best choice. Without transparency health care is more of a guessing game. Does the facility perform well with back surgery? Who knows guess you’ll have to find out on your own. Of course, that’s risky. But why risk, when you can be informed? At least with information the public can make better decisions. Better decisions will ultimately lead to the best health care. The strong will survive, while the weak will perish. Poor health facilities will fail as more and more people choose the best facilities. As the best facilities succeed the health community will become stronger as a whole. A strong health community will lead to an overall better equipped public community. References American College of Physicians. (2010). Health Transparency. Retrieved from http://www.acponline.org/advocacy/current_policy_papers/assets/transparency.pdf Dr. Cawley, P. (2009). Health Care Transparency. Retrieved from https://portal.phoenix.edu/medialibrary/videodetails.05V130128092014044.html

Southwest Airlines Essay Example for Free

Southwest Airlines Essay Background Summary Southwest Airlines based in Dallas was founded in 1967 by Rollin King and Herb Kelleher. It is one of the major domestic airliners which provides carrier and transportation service. This company has 35,499 employees and it runs over 500 Boeing 737 aircraft in 67 cities in the US. Southwest’s principal values are: Providing low-fare and short haul service. Offering the highest quality of customer service. Putting a lot of importance on the fair treatment to its customers. Building friendly relationship between its customers and employees.   Southwest Airlines has achieved a great position in the airline industry by adopting five important strategies. First, using the minor league airports which have helped the company to reduce traffic delays and increase passenger convenience. Second, flying one kind of aircraft has helped it to achieve lower training cost. Third, reducing turn-around time by using point-to-point strategy, has avoided the use of complicated reservation process system. Forth, not offering assigned seating and preferential treatment on frequent fliers, has led the company to have better ticket price. Lastly, emphasis on building good relationship between passengers and attendants has been a well valuable factor. Southwest uses a different kind of reward programs. For instance, the reward for frequent fliers includes free flights according to the number of flights; which means if you fly eight round trips or sixteen one way trips, you will get one free round trip ticket. In addition the company offers free drink coupons, toll-free reservations phone numbers, and credit with a preferred partner, which means if you take fifty round trips in a year, you can designate one person to travel with you for one year. Southwest Airlines main competitors are: Continental Airlines, USAir ways, Delta, United airlines, and American Airlines. As you can see in the table below, the current days have been really challenging for the industry. However Southwest has been able to increase its operating revenues. Southwest decided to go public in 1977 with the ticker symbol LUV. The company gained $11,023 million in 2008, and today its stock price reaches $9.83. Its strategy as an egalitarian company has let the company achieve success. However some frequent passengers have raised some questions about the policy of avoiding preferential treatment for its loyal customers. Major problem The Southwest Airlines major problem is the threat to lose some of its frequent customers. The case illustrates two opposite kinds of frequent passengers: The first one is William Mark, who loves almost everything that Southwest provides such as: the opportunity to come earlier and have a great seat, the absence of meals, and the ticket prices. The other one is Liz Bast, who loves the policy of using minor league airports, but has complaints related to the ways of seat assignment, the rules about upgrading restricted tickets, and she wishes to have preferential treatment, especially because she flies more than 100.000 miles per year. The customers like Liz Bast might be looking for another airliner company. Therefore, Southwest needs to figure out one strategy which helps to avoid this problem. Contributing Factors: The threat to lose some of Southwest’s frequent customers is caused by five factors: Recheck-in baggage: Passengers with connected flight who are going to switch to another airline have to pick up their checked baggage and recheck-in with the next airline. No assigned seats for passengers: Southwest used first-come first-served system in seats assignment, which means people who arrived first will get the better seats. This is an issue because passengers might easily change their preferences and fly with other airlines. For example, Liz Bast is a frequent customer of Southwest Airlines, but because she is always busy she comes late to her flights and the company cannot offer her the seat she wanted. Liz’s problem will be solved if she could book a specific seat and this service is not valid at Southwest Airlines. Rewards count on trips number: there is no credit given to passengers on how many miles they flew, but free flights are offered according to the number of trips taken. Therefore, customers could choose Southwest Airlines for only short flights because the length of flight is not a factor in the company reward system. Restricted fare tickets: Passengers with restricted fare tickets cannot use their tickets if they missed the flight without paying the difference even if they were  frequent customers. This strict policy gives the customers a feeling that the company does not value their business. High competition in the industry: 2001 was so difficult for airlines industry, the Southwest’s competitors might be thinking of attracting its loyal customers for their benefits. Advantages and Disadvantages of Potential Solutions First Solution: Southwest Airlines makes an advertisement campaign, which emphasizes not only its low fare but also high quality customer service. Advantages: It will help increase the company’s image and awareness. If the company construct a good advertisement campaign, it will increase its sales and that will lead to increase the company’s revenue It will be a good communication tool for the company to reach out to its costumers and let them know about the company’s value. Disadvantage: The campaign might increase sales, but it would not give what frequent customers really want. The campaign will be costly and it is possible for Southwest to spend a fortune on it and get a little profit. Second Solution: Southwest changes its policies on seat assignment and ticket restrictions in two ways: By paying $25 extra fee, the customers can choose their seat. For frequent customers, who have flown more than five times per year, there will be no charge on their restricted fare tickets if they miss their flight. Advantage: Using this strategy we think that Southwest might retain costumers who expected to be treated with some priorities or differentiation. Likewise, we consider that with this strategy the company might increase its incomes, and also attract some clients of its competitors. Disadvantage: The company identity will be changed from an egalitarian company to a privilege one. Therefore, this policy might confuse clients about what the  real target is. Recommendation: We suggest the second solution, which is to change the company’s policies on seat assignment and ticket restrictions, for five reasons: First, the main problem will be solved by giving clients, such as Liz Bast, the opportunity to decide their seats with extra fee. In addition, this solution will keep the company’s customers more satisfied and at the same time increasing their loyalty. Second, solution number two will increase the company’s revenues. According to The Wall Street Journal1, by receiving extra fee on assigning seats, Southwest could add seven hundred fifty million dollars ($750.000.000) in its year revenues. Third, if you take a look at first solution, you can see that it will increase the awareness of the company products, offers, and strengthen the company’s image. However, it will bring more costs to the company by spending more money on its advertising campaign Forth, it is a long-term solution. By giving an advantage to the customers who make their reservation earlier, Southwest will strengthen its position among competitors, and the major problem will be solved. Finally, with the second solution, Southwest airlines should focus more on its customers reward system and improve it. Moreover, in a very competitive sector where Southwest operates, it must rely on customer’s loyalty and with such reward system it should attract more customers.

Mechanisms drug resistance to cancer chemotherapy

Mechanisms drug resistance to cancer chemotherapy Introduction Cancer is one of the major causes of death in the developed world and statistics show that one in three people will be diagnosed with cancer during their lifetime [1]. Cancers are malignant tumours and can be distinguished from normal cells by four characteristics; uncontrolled proliferation, dedifferentiation and loss of function, invasiveness, and ability to metastasise [2]. These characteristics are caused by altered gene expression, as a result of genetic mutations that inactivate tumour suppressor genes and / or activate oncogenes. Most cancer chemotherapeutic drugs affect only one characteristic aspect, which is uncontrolled proliferation [3]. In many cases the antiproloferation action is caused by damage to DNA, which initiates apoptosis and cell death [4]. As their main target is cell division, they affect all rapidly dividing cells, including normal cells. This produces general toxic effects, such as myelosuppression, alopecia, damage to gastrointestinal epithelium, sterility and severe nausea and vomiting. Besides the toxic effects of chemotherapy, another major problem is chemoresistance [5]. Resistance to chemotherapy is when the cancer cells do not respond to the drugs. It can be inherented, as a genetic mutation, or it can be acquired, as a cellular response to drug exposure. Mechanisms of resistance include: increased efflux or decreased influx of cytotoxic drugs; insufficient activation of the drug; increased inactivation of the drug; increased concentration of target enzyme; rapid repair of DNA lesions; or mutations in various genes. When patients develop resistance, multiple drugs with different pathways of entry and different cellular targets are used. However, cancer cells can become multidrug resistant, a phenomenon due to cells expressing mechanisms that cause simultaneous resistance to many different, structurally and functionally, unrelated drugs [6]. Multidrug resistance, generally, results from over expression of ATP-dependent efflux pumps [5]. These pumps have broad drug specificity and belong to a family of ATP-binding cassette (ABC) transporters, of which P-glycoprotein (PGP) is one of the most important members. Increased drug efflux, via these transporters, lowers intracellular drug concentration, allowing cancer cells to escape the toxic effects of the drugs. PGP inhibitors are being developed to overcome multidrug resistance and two that have reached clinical trials are varapamil, a calcium channel blocker, and cyclosporin A, an immunosuppressant [7]. The remainder of this review will focus on the different chemotherapeutic agents currently being used for the treatment of cancer and their mechanism of action. Also the main mechanism of resistance to these drugs will be explored, particularly focusing on the role of P-glycoprotein and how it can be modulated to reverse drug resistance. Drugs used in cancer chemotherapy Drugs used in the treatment of cancer are summarised in table 2. They are grouped into: cytotoxic drugs, which preferentially but not exclusively target rapidly dividing cancer cells; hormone therapy, which is a more specific form of treatment used for tumours derived from hormone sensitive tissues; and miscellaneous agents, which include a number of recently developed drugs such as monoclonal antibodies. Cytotoxic drugs Cytotoxic drugs can be further divided into the following; alkylating agents, which act by forming covalent bonds with DNA and impeding replication; antimetabolites, which block one or more of the metabolic pathways involved in DNA synthesis; cytotoxic antibiotics, which are of microbial origin and prevent cell division by directly acting on DNA; and plant derivertives, which affect microtubule function and hence the formation of the mitotic spindle. Alkylating agents Alkylating agents form carbonium ions, which are highly reactive and interact instantaneously with nucleophilic sites such as N7 of guanine in DNA [8]. They are bifunctional, which means they have two alkylating groups, and can cause intra- or inter-chain cross-linking between DNA strands. This prevents strand separation for DNA synthesis or transcription. They can also cause base mispairing between strands, which interferes with the progression of the replication fork [3]. These actions block DNA synthesis, causing a block at G2 phase and subsequently apoptotic cell death. Alkylating agents currently being used in chemotherapy primarily belong to the following families: nitrogen mustards (Cyclophosphamide, Chlorambucil, Melphalan, Ifosfamide, Busulfan); nitrosoureas (Carmustine, Lomustine, Fotemustine); aziridines (Thiotepa); Dacarbazine and platinum compounds (Cisplatin, Carboplatin, Oxaliplatin) [9]. Nitrogen mustards, nitrosoureas and aziridines are believed to kill tumour cells by inducing DNA inter-strand cross-links, while platinum compounds induce intra- and inter-strand cross-links, as well as DNA-protein cross-links under certain circumstances [8]. Resistance to these drugs can develop as a result of cancer cells rapidly repairing drug induced lesions [10], which will be discussed in detail later. Antimetabolites Antimetabolites interfere with the metabolic pathways involved in DNA synthesis. An example of an antimetabolite is Methotrexate, which is a folate antagonist [11]. Folates are essential for the synthesis of purine nucleotides and thymidylate, which in turn are essential for DNA synthesis and cell division. Folates are actively taken up into cells by the reduced folate carrier (RFC), where they are converted to polyglutamates. Polyglutamate folates are then reduced to tetrahydrofolate (FH4) by the enzyme dihydrofolate reductase (DHFR). Methotrexate exerts its action by being taken up into cells by the follate carrier, and like folate being converted to the polyglutamate form. It has a higher affinity for DHFR than the endogenous folate and thus inhibits the enzyme, depleting intracellular FH4, and therefore hindering DNA synthesis. Another example of an antimetabolite is Fluorouracil, which is a pyrimidine analogue [12]. It interferes with DTMP synthesis by forming a ternary complex with thymidylate synthetase (TS); the enzyme that produces DTMP. DTMP is required for the synthesis of DNA and purines, so the irreversible inhibition of the enzyme by fluorouracil results in is inhibition of DNA but not RNA or protein synthesis. Fludarabine is a purine analogue, which is another group of antimetabolites [13]. It is metabolised to its triphosphate form, which inhibits DNA polymerase. As well as the general side effects associated with chemotherapy, patients may develop resistance to antimetabolites; due to a decreased amount of drug uptake [14] or altered concentration of target enzymes [15], which will be discussed later. Cytotoxic antibiotics Cytotoxic antibiotics, such as the anthracyclines (Doxorubicin, Idarubicin, Daunorubicin, Epirubicin, Aclarubicin, Mitoxantrone) bind to DNA and inhibit both DNA and RNA synthesis [16]. Their main cytotoxic action is mediated through an inhibitory effect on topoisomerase II, the activity of which is markedly increased in proliferating cells. During DNA replication, reversible swivelling needs to take place around the replication fork in order to prevent the daughter DNA molecule becoming inextricably entangled during mitotic segregation [17]. The swivel is produced by topoisomerase II, which nicks both DNA strands and subsequently reseals the breaks. Doxorubicin intercalates in the DNA, and its effect is in essence, to stabilise the DNA-topoisomerase II complex after the strands have been nicked, thus halting the process at this point [18]. Dactinomycin is also a cytotoxic antibiotic, which intercalates in the minor groove of DNA, interfering with the movement of RNA polymerase along the gene and thus preventing transcription [19]. Bleomycins are a group of metal-chelating glycopeptide antibiotics that degrade preformed DNA, causing chain fragmentation and release of free bases [20]. This action is thought to involve chelation of ferrous iron and interaction with oxygen, resulting in the oxidation of iron and generation of superoxide and/or hydroxyl radicals. They are most effective in the G2 phase of the cell cycle and mitosis, but are also active against non-dividing cells, that is cells in the G0 phase. This class of drugs cause resistance by altered activity of topoisomerase II, aswell as reduced uptake of the drugs [21]. Plant derivatives One sub group of plant derivatives is the vinca alkaloids, which includes Vincristine, Vinblastine, Vindesine and Vinorelbine [22]. They bind to tubulin and inhibit its polymerisation into microtubules. This prevents spindle formation in dividing cells, which causes arrest at metaphase. They also inhibit other cellular activities that involve microtubules, such as leucocyte phagocytosis, chemotaxis and axonal transport in neurons. They are relatively non-toxic in comparison to the previously mentioned cytotoxic drugs. Another group of plant derivatives is the taxanes, which include Paclitaxel and Docetaxel [23]. They act on microtubules by stabilising them, in effect freezing them in the polymerised state, which achieves a similar effect to that of the vinca alkaloids. Campothecins is another group of plant derivatives and include Irinotecan and Topotecan [24]. They bind to and inhibit topoisomerase I; high levels of which occur throughout the cell cycle. Hormone therapy Tumours derived from hormone sensitive tissues may be hormone dependent [25]. This is due to the presence of steroid receptors in the malignant cells. Their growth can be inhibited by agents with apposing actions, hormone antagonists or drugs that inhibit the endogenous hormone synthesis. The most important group of drugs used to treat cancer are the steroids, namely the glucocorticoids (Prednisolone and Dexamethasone), oestrogens (Diethylstilbestrol and Ethinyloestradiol) and gonadotrophin-releasing hormone analogues (Octreotide and Lanreotide), as well as agents that antagonise hormone action (Tamoxifen, Toremifene and Fulvestrant). Such drugs rarely act as a cure but do mitigate the symptoms of the cancer and thus play an important part in the clinical management of sex-hormone-dependant tumours. Miscellaneous agents Crisantaspase Crisantaspase is a preparation of the enzyme asparaginase and therefore, like asparaginase, can break down asparagine to aspartic acid and ammonia [26]. It is active against tumour cells, such as those of acute lymphoblastic leukaemia, which have lost the capacity to synthesise asparagine and therefore require an exogenous source. As most normal body cells are able to synthesise asparagine, the drug has a fairly selective action and very little suppressive effect on the bone marrow, the mucosa of the gastrointestinal tract or hair follicles. Monoclonal Antibodies Antibodies are immunoglobulins that react with defined target proteins expressed on cancer cells. This activates the hosts immune response, which kills cancer cells by complement-mediated lysis or by killer cells. Monoclonal antibodies can also attach to and activate growth factor receptors on cancer cells, thus inhibiting the survival pathway and promoting apoptosis. Rituximab is a monoclonal antibody that is licensed (in combination with other chemotherapeutic agents) for treatment of certain types of lymphomas [27]. It lysis B lymphocytes by binding to the calcium- channel forming CD20 protein and activating completment. It also sensitises resistant cells to other chemotherapeutic drugs. Trastuzumab (Herceptin) is a humanised murine monoclonal antibody that binds to a protein termed HER2 (the human epithelial growth factor receptor 2); a receptor with integral tyrosine kinase activity [28]. It induces the host immune response as well as inducing the cell cycle inhibitors p21 and p27. Imatinib Mesylate Imatinib is an inhibitor of signalling pathway kinases [29]. It inhibits the platelet-derived growth factor (PDGF); a receptor tyrosine kinase, and the Bcr/Abl kinase; a cytoplasmic kinase. These are considered to be unique factors in the pathogenesis of chronic myeloid leukaemias. Imatinib is licensed for the treatment of this tumour when it has proved to be resistant to other therapeutic strategies, as well as for the treatment of some gastrointestinal tumours that are not susceptible to surgery. Resistance to Anticancer Drugs As mentioned previously patients can develop resistance to many chemotherapeutic agents. This can be caused by a number of mechanisms, which are summarised in figure 1. A decrease in the amount of drug taken up by the cell Resistance can develop as a result of decreased drug uptake. This can be due to the loss of transporter function, for example RFC [30]. Decreased influx of Methotrexate in tumour cells has been widely associated with decreased RFC gene expression. Down-regulation of the transporter protein is due to alterations in the transcription and translation factors. Transcriptional factors, such as the Sp1 family, CREB (cyclic AMP-response element binding protein) and p53, regulate RFC gene expression [31]. Therefore loss of function of these transcription factors cause silencing of the RFC gene, which results in reduced protein level. Also post-translational modifications of transcription factors alter phosphorylation patterns, which abolishes Sp1 and CREB function thereby resulting in loss of RFC gene expression and subsequently resistance [32]. Mutations in the human RFC gene can also decrease drug influx. Jensen et al (1998) have reported a mutation that causes marked changes in the kinetic properties of RFC mediated transport of folates [14]. The structurally altered RFC was functionally characterized by a 9- and 31-fold increased affinity for transport of reduced folate cofactors and folic acid, respectively. This allowed the accumulation of intracellular folates, which sustained cell growth and DNA replication, allowing cancer cells to escape the cytotoxic effects of antifolate drugs. Altered concentration of target enzyme Increased expression of target enzyme is a common mechanism of acquired resistance. For example Methotrexate resistance can develop as a result of DHFR gene amplification and subsequent enzyme overexpression [15]. Gene amplification is thought to occur as a consequent of antifolate inhibitors binding to DHFR, which causes a conformational change that alters the translational autoregulatary negative feedback mechanism, wherein DHFR protein specifically interacts with its own mRNA and negatively controls translational efficiency. The drug concentration will be limited to the dose administered, which will not be able to block the additional enzyme that is synthesised, resulting in cancer cells overcoming the inhibitory effect of the drug. Insufficient activation of the drug Some drugs require metabolic activation to manifest their antitumour activity for example Cytarabine has to undergo catalytic conversion, by the action of deoxycytidine kinase, to an active form [33]. So under expression or mutation of this drug-metabolising enzyme can reduce drug efficacy and cause resistance. Another example of resistance due to insufficient activation of the drug is Mercaptopurine, which is a prodrug [34]. Mercaptopurine is activated by hypoxanthine guanine phosphoribosyl transferase (HGPRT) and mutations that reduce the activity of this enzyme will allow the cancer cells to escape the toxic effects of the drug. Increase in inactivation Resistant to Mercatopurine can also develop as a result of increased inactivation of the drug [35]. The mechanism behind this is thiopurine s-methyltransferase (TPMT), which inactivates Mercaptopurine and thereby prevents the formation of the active drug. Mutations in the TPMT gene will alter its activity and may cause resistance. Rapid repair of drug-induced lesions Patients can develop resistance as a result of cancer cells recognizing DNA lesions and rapidly initiating repair pathways [9]. This is the main cause of resistance to alkylating agents as their mechanism of action is DNA damage There are several repair pathways and include the Direct Repair (DR) pathway, Base Excision Repair (BER) pathway, Nucleotide Excision Repair (NER) pathway, Homologous Recombination (HR) pathway and Non-Homologous End Joining (NHEJ) pathway. The DR pathway is mainly mediated by the DNA repair protein: O6-alkylguanine DNA alkyltransferase (AGT) [36]. AGT transfers the alkyl adducts from the nucleotides to the cysteine residue within its active site, independently from other proteins and without causing DNA strand breaks. The BER pathway recognizes and accurately removes bases that have been damaged by alkylation [37]. A damaged base is removed by a damage-specific DNA glycosylase, leading to the formation of a potentially cytotoxic apurinic or apirimidinic site intermediate. This is then processed by an AP endonuclease (APE1), which generates a strand break that is further processed by Poly ADP-Ribose Polymerase (PARP), DNA polymerase b (Polb) and ligase III to restore the damage. The NER pathway deals with the repair of bulky DNA lesions formed by DNA-alkylating agents such as Cisplatin, which distort the DNA double helix and block DNA replication and transcription [38]. Two major mechanisms of DNA repair have been recognized in this pathway: the transcription-coupled repair, which specifically targets at and removes lesions that block the progression of RNA polymerase II, and the global genome repair, which deals with lesions in the rest of the genome. Generally, nucleotide repair is a complex multi-step process that sequentially deploys a group of proteins to reorganize the lesion, remove the damage, and support new DNA synthesis. The HR and NHEJ pathways are involved in the repair of DNA double strand breaks, commonly considered to be the most lethal of all DNA lesions. Double strand breaks are induced by chemotherapeutic agents such Bleomycin, and Etoposide. In the HR pathway, ATM (ataxia talagiectasia mutated kinase) and its related ATR proteins sense the severe DNA lesions, and are mobilized to phosphorylate a wide range of substrate proteins [39]. Also a number of regulatory proteins, including BRCA1, BRCA2 and p53, are recruited to coordinate the DNA repair. The NHEJ pathway involves the alignment of the broken ends followed by recruitment and activation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and DNA ligase IV to complete the ligation step [40]. Mutations Mutations in various genes can give rise to resistant target molecules, for example the p53 gene [41]. The p53 protein is an important regulator of the cell cycle and is sensitive to any DNA damage caused during replication. Following DNA damage it will normally induce G1 arrest and/or apoptosis to prevent the production of defective cells. Mutations in this gene will cause the loss of p53 function, which will allow cells with damaged DNA to continue replicating, resulting in resistance to DNA damaging drugs. Other genes, such as h-ras and bcl-2/bax, involved in the apoptotic pathway, have also been implicated in resistance [42]. Resistance due to mutations in genes will affect a wide range of anticancer drugs as all cells contain the same genetic material. It also potentially increases the proportion of surviving mutant cells, which leads to greater tumour heterogeneity. Increased expression of efflux pumps Resistance to natural hydrophobic drugs, such as vinca alkaloids and taxanes, as well as the cytotoxic antibiotics, such as anthracyclines and Dactinomycin, occurs due to the over expression of ATP-dependent efflux pumps in cancer cells [5]. These pumps belong to a family of ATP-binding cassette (ABC) transporters, which are divided into eight distinct subfamilies, shown in table 1. Of these subfamilies PGP, also known as MDR1, has a broad drug specificity, which explains the cross-resistance to several chemically unrelated compounds. It is a multidrug efflux pump that has 12 transmembrane regions, which bind hydrophobic drug substrates that are either neutral or positively charged [6]. It also has two ATP-binding sites, as hydrolysis of two ATP molecules are needed for the transport one drug molecule [43]. Binding of substrate to the transmembrane regions stimulates the ATPase activity of PGP, causing a conformational change that releases substrate to the extracellular space. Hydrol ysis at the second ATP site is required to re-set the transporter so that it can bind substrate again, completing one catalytic cycle. Increased expression of the PGP transporter in cancer cells increases the amount of catalytic cycles that occur, which increases the amount of drug effluxed [5]. This lowers the intracellular drug concentration below a cell-killing threshold, which results in resistance. Not all multidrug-resistant cancer cells express PGP. Resistance in these cells was discovered to be linked with the expression of the multidrug-resistance-associated protein 1 (MRP1) [44]. MRP1 is similar to PGP in structure (table 1) but, unlike PGP, it recognizes neutral and negatively charged hydrophobic natural products, and transports glutathione and other conjugates of these drugs, or, in some cases, such as for Vincristine, co-transports unconjugated glutathione. Some anticancer drugs, such as Mitoxantrone, are poor substrates for PGP and MRP1. Mitoxantrone resistance is due to a more distant member of the ABC transporter family, MXR (Mitoxantrone-resistance gene) [45]. This transporter is thought to be a homodimer of two half-transporters, each containing an ATP-binding domain at the amino-terminal end of the molecule and six transmembrane segments (table 1). Resistance can also develop as a result of increased expression of ABC transporters in the apical membrane of the gastrointestinal tract [46]. ABC transporters play a key physiological role, where they extrude toxins thus forming a protective mechanism and a first line of defense. Increased expression of these transporters decreases drug uptake and therefore decrease drug bioavailability. Examples of chemotherapeutic agents that develop resistance by this mechanism include antimetabolites, such as Methotrexate and Fluorouracil, and alkylating agents, such as Cisplatin. Also water-soluble drugs that piggyback on transporters and carriers or enter by means of endocytosis can fail to accumulate as they will not be able to enter the body. Additionally, PGP actively secretes intravenously administered drugs into the gastrointestinal tract [47]. Resistance due to increased levels of PGP transporters in the gastrointestinal tract is illustrated by MDR1a/MDR1b-knockout mice, which have shown to have increased tissue concentrations of PGP substrates. Studies have also shown increased tissue absorption of PGP substrates, following oral administration, when co-administered with a PGP inhibitor. Reversal of drug resistance in cancer Ways to overcome multidrug resistance due to the over expression of ABC transporters are being researched. Some of the main approaches include developing PGP inhibitors, antibodies against the PGP transporter, antisense oligonucleotides and liposome-encapsulated drugs. Drugs that can reverse multidrug resistance, such as PGP inhibitors, could be useful interventions to improve bioavailability, by increasing oral uptake of anticancer drugs and decreasing drug excretion, thereby reducing dosing requirements [7]. Two inhibitors that are used in the laboratory and in clinical trials that attempted to reverse drug resistance are the calcium channel blocker, verapamil and, the immunosuppressant, cyclosporin A. Another method that can be used to inhibit PGP is by competitive inhibition [48]. PGP binds many different hydrophobic compounds so any drug that interacts with the substrate-binding region is likely to be a competitive inhibitor of other drugs. Thus, two drugs that are transported by PGP will compete for this transport, resulting in increased oral absorption of both, decreased excretion, and redistribution. This kind of drug interaction can be used to inhibit the multidrug transporter, when the inhibitor drug has little or no other pharmacologic e ffect. Monoclonal antibodies (MAbs) against PGP have been used to kill multidrug resistant cells [49]. MAbs are of therapeutic use as they can activate the immune response, which results in complement mediated lysis or antibody dependent cellular cytotoxicity of the cells. An example of a MAb is MRK-16, which has shown selective toxicity towards tumours that are over expressing PGP. Molecules, which are normally involved in signal transduction on T and B cells can also be targeted for antibody therapy [50]. Such molecules include CD19, which is a membrane receptor involved in signal transduction and potentiates the response of B cells to antigens. MAbs directed against CD19 can induce cell-cycle arrest due to negative growth signals that cross-link immunoglobulin M and CD19. Antisense drugs work by down regulating gene expression [51]. This occurs by sequence-specific blinding of either DNA or RNA, which inhibits transcription or translation, respectively. Different antisense-oligodeoxynucleotides have been reported to chemosensitize resistant tumour cells to anticancer drugs through down regulation of PGP expression and thus increasing the intracellular accumulation of anticancer drugs in the cancer cells. The efficiency of a synthetic oligodeoxynucleotide (ODN) in regulating gene expression in living cells depends on its thermodynamic stability, resistance toward nucleases and cellular uptake [52]. A number of studies indicate that a synthetic ODN coupled with a DNA intercalator such as acridine, naphthyl imide, psoralen or pyrene might act to increase stability. Novel drug delivery systems such as liposome-encapsulated drugs have also been developed to overcome multidrug resistance [53]. Liposome formulations contain a small fraction of polyethylene glycol (PEG)-derivatised phospholipid, which has been shown to dramatically alter the pharmacokinetic properties of certain anticancer drugs. These pharmacokinetic alterations include long elimination half-life and small volume of distribution. Another formulation developed to bypass PGP transporters is anionic liposomes, which are internalised by certain cells and are able to provide drug release in intracellular compartments. Conclusion Cancer is prevalent in the western world and much research is dedicated to produce effective chemotherapy. Current chemotherapy includes alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivertives, hormone therapy and monoclonal antibodies. However the efficacy of these chemptherapeutic agents is limited to patients developing multidrug resistance. This is mainly due to the over expression of ABC transporters, particularly the PGP transporter, as they have broad drug specificity so can bind many structurally unrelated drugs [5]. Techniques to reverse multidrug resistance are being developed and include co-administration of PGP inhibitors, which prevent the binding of anticancer drugs the transporter [7], the use of antibodies, which kill cells over expressing the PGP transporter [49], antisense oligonucleotides that down regulate PGP expression [51] and liposome-encapsulated drugs, which alter the pharmacokinetic properties of anticancer drugs [53]. A better understanding of the mechanism by which ABC transporters efflux chemotherapy and further analysis, in clinical trials, of known mechanisms of multidrug resistance would increase the development of agents that reverse multidrug resistance. Also improved imaging techniques used in clinic to screen cancer cells would enhance the ability of practitioners to prescribe individualised treatment according to the patients level of resistance. One approach that can be developed is to produce fluorescent antibodies against all 48 human ABC transporters and use them in conjunction with a specialised fluorescent microscope to monitor the levels of ABC transporters in cancer cells. References Office for National Statistics (2005) Cancer Statistics registrations: registrations of cancer diagnosed in 2006, England. http://www.statistics.gov.uk/downloads/theme_health/MB1-37/MB1_37_2006.pdf [accessed December 2009] Weinberg RA (1996) How Cancer Arises. Scientific American; 275: 42-48 Lawley PD and Phillips DH (1996) DNA adducts from chemotherapeutic agents. Mutation Research; 355: 13-40 This article is not included in your organizations subscription. However, you may be able to access this article under your organizations agreement with ELowenthal RM and Eaton K (1996) Toxicity of Chemotherapy. Hematology/Oncology Clinics of North America; 10: 967-990 Gottesman MM (2002) Mechanisms of cancer drug resistance. Annual Review of Medicine; 53: 615-627 Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual Review of Pharmacology and Toxicology; 39: 361-398 Ferry DR, Traunecker H and Kerr DJ (1996) Clinical trials of P-glycoprotein reversal in solid tumours. European Journal of Cancer ; 32A: 1070-1081 Lawley PD and Brookes P (1967) Interstrand cross-linking of DNA by difunctional alkylating agents. Journal of Molecular Biology; 25: 143-160 Zhu Y, Hub J, Hu Y and Liu W (2009) Anti-Tumour Treatment Targeting DNA repair pathways: A novel approach to reduce cancer therapeutic resistance. Cancer Treatment Reviews; 35: 590-596 Bouziane M, Miao F, Ye N, Holmquist G, Chyzak G and OConnor TR (1998) Repair of DNA alkylation damage. Acta Biochim Pol; 45:191-202 Schweitzer BI, Dicker AP and Bertino JR (1990) Dihydrofolate reductase as a therapeutic target. FASEB Journal; 4: 2441-2452 Spiegelman S, Nayaak R, Sawyer R, Stolfi R and Martin D (1980) Potentiation of the antitumor activity of 5-FU by thymidine and its correlation with the formation of (5-FU)RNA. Cancer; 45: 1129-1134 Nabhan C, Gartenhaus RB and Tallman MS (2004) Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia: dawn of a new era. Leukemia Research; 28: 429-442 Jansen G, Mauritz R, Drori S, Sprecher H, KathmannI, Bunni M, Priest DG, Noordhuis P, Schornagel JH, Pinedo HM, Peters GJ and Assaraf YG (1998). A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance. Journal of Biological Chemistry; 273: 30189-30198 Tai N, Schmitz JC, Chen TM and Chu E (2004) Characterization of cis-acting regulatory element in the proteincoding region of human dihydrofolate reductase mRNA. Biochemical Journal; 378: 999-1006 Zunino F and Capranico G (1990) DNA topoisomerase II as the primary target of antitumor anthracyclines. Anti-Cancer Drug Design; 5: 307-317 Wang JC (1996) DNA Topoisomerases. Annual Review of Biochemistry; 65: 635-692 Kasahara K, Fujiwara Y, Sugimoto Y, Nishio K, Tamura T, Matsuda T and Saijo N (1992) Determinants of Response to the DNA Topoisomerase II Inhibitors Doxorubicin and Etoposide in Human Lung Cancer Cell Lines. Journal of the National Cancer Institute; 84: 113-118 Chen AY, Yu C, Gatto B, and Liu LF (1993) DNA minor groove-binding ligands: A different class of mammalian DNA topoisomerase I inhibitors. Procedings of the National Academy of Sciences of the USA; 90: 8131-8135 Povirk LF (1996) DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzi