Tuesday, December 31, 2019
Le Rosey The Most Expensive School in the World
Its no secret that private school is expensive. With many schools clocking in with annual tuition fees that rival the costs of luxury cars and middle-class household incomes, it can seem like a private education is out of reach. These large price tags leave many families trying to figure out how to pay for private school. But, it also leaves them wondering, just how high can tuition go? In the United States, this is often a tricky question to answer. When you refer to private school tuitions, youre not just including the stereotypical elite private school; youre technically referring to all private schools, including independent schools (who are independently funded through tuition and donations) and most religious schools, which typically receive funding from both tuition and donations, but also a third source, like a church or temple that offsets the cost of attending the school. That means, the average cost of private school will be considerably lower than you might expect: about $10,000 a year overall in the nation, but tuition averages also vary by state. So, where do all these astronomical price tags for private school education come from? Lets look at the tuition levels of independent schools, schools that rely solely on tuition and donations for funding. According to the National Association of Independent Schools (NAIS), in 2015-2016 the average tuition for a day school was about $20,000 and the average tuition for a boarding school was about $52,000. This is where we start seeing the annual costs that rival luxury cars. In major metropolitan areas, like New York City and Los Angeles, school tuitions will be even higher than the national averages, sometimes drastically so, with some day school tuitions exceeding $40,000 a year and boarding schools moving past the $60,000 a year price tag. Not sure what the difference is between private schools and independent schools? Check this out. What School is the Most Expensive In the World? To find the most expensive schools in the world, we need to venture out of the United States and across the pond. Private school education is a tradition in Europe, with many countries boasting private institutions hundreds of years before the United States. In fact, schools in England provided the inspiration and model for many American private schools today. Switzerland is home to several schools with some of the highest tuitions in the world, including the one that comes out on top. This country boasts 10 schools with tuition costs that exceed $75,000 a year according to an article on MSN Money. The title of the most expensive private school in the world goes to Institut Le Rosey, with an annual tuition of $113,178 per year. Le Rosey is a boarding school founded in 1880 by Paul Carnal. Students enjoy a bilingual (French and English) and bicultural education in a lovely setting. Students spend their time on two lavish campuses: one in Rolle on Lake Geneva and a winter campus in the mountains at Gstaad. The reception area of the Rolle campus is located in a medieval chateau. The roughly seventy-acre campus contains boarding houses (the girls campus is located nearby), academic buildings with about 50 classrooms and eight science laboratories, and a library with 30,000 volumes. The campus also includes a theater, three dining rooms where students dine in formal dress, two cafeterias, and a chapel. Each morning, students have a chocolate break in true Swiss style. Some students receive scholarships to attend Le Rosey. The school has also undertaken many charitable projects, including building a school in Mali, Africa, at which many students volunteer. On campus, the students are able to participate in activities as diverse as flying lessons, golf, horse riding, and shooting. The schools athletic facilities include ten clay tennis courts, an indoor pool, a shooting, and archery range, a greenhouse, an equestrian center, and a sailing center. The school is in the midst of building Carnal Hall, designed by renowned architect Bernard Tschumi, which will feature an 800-seat auditorium, music rooms, and art studios, among other spaces. The project reportedly costs tens of millions of dollars to construct. Since 1916, students at Le Rosey have spent January through March in the mountains in Gstaad to escape the fog that descends on Lake Geneva in the winter. In a fairytale-like setting in which students live in pleasant chalets, Roseans spend the morning in lessons and the afternoons enjoying skiing and skating in the fresh air. They also have use of indoor fitness centers and an ice hockey rink. The school is reportedly looking to relocate its winter campus from Gstaad. All students sit for the International Baccalaureate (IB) or the French baccalaurà ©at. Roseans, as the students are called, can study all subjects in French or English, and they enjoy a 5:1 student-to-faculty ratio. To ensure a truly international education for its students, the school will only take 10% of its 400 students, ages 7-18, from any one country, and about 60 countries are represented in the student body. The school educates some of the best-known families in Europe, including the Rothschilds and the Radziwills. In addition, the schools alumni include many monarchs, such as Prince Rainier III of Monaco, King Albert II of Belgium, and Aga Khan IV. Famous parents of students have included Elizabeth Taylor, Aristotle Onassis, David Niven, Diana Ross, and John Lennon, among countless others. Winston Churchill was the grandfather of a student at the school. Interestingly, Julian Casablancas and Albert Hammond, Jr., members of the band the Strokes, met at Le Rosey. The school has been featured in countless novels, such as Bret Easton Elliss American Psycho (1991) and Answered Prayers: The Unfinished Novel by Truman Capote. Article updated by Stacy Jagodowski
Monday, December 23, 2019
Analysis Of The Movie American Sniper - 1550 Words
The opening scene of the movie American Sniper, â€Å"which tells the story of Chris Kyle, a Navy SEAL who shot his way to 160 confirmed kills in Iraq,†(Buckley) starts out when Chris Kyle was just a child and him and his father are out in the forest shooting deer and him beating up a bully who was picking on his little brother at school. Later on into Kyle s young adulthood he made a decision to quit being a cowboy rodeo star and instead enlist with the Navy SEALS in 1998. During this time Kyle meets his future wife. Then, once after the trauma of 9/11, the war in Iraq puts Kyle to work as a sharpshooter, and the film shows his skills as frightening and strange. From this point, the arc of the film essentially follows Kyle across his missions as a sniper. An important element of the plot is his face-off with an enemy sniper Mustafa, A Syrian sniper who was a former Olympian rifleman, who Kyle does manage to take out near the end of the film. Kyle was shot and killed later on by a veteran who he was actually trying to help. Even though every Iraq citizen isn t a terrorist, American Sniper should be known for its stereotypes against race because the invisible norm of the white dominant culture and the display of the male body, white males in particular. Also to add to that the movie is showing the masculine spectacle and its collapse by portraying Iraq and how all they want to do is kill Americans. Palos 2 The invisible norm in the movie American Sniper shows the frequentShow MoreRelatedAnalysis Of The Movie American Sniper 1641 Words  | 7 Pageshorrors of terrorism on 9/11 he was ready to fight for his country and enlisted into the military. He goes on to fight in four tours and becomes the deadliest sniper in American history. After each tour, he felt that he had to go back. He had two goals that he couldn’t give up on; protecting his team and taking out the deadliest enemy sniper, Mustafa. Chris would not stop until he achieved his goals, when he finally did, he faced a new battle. He struggled with normal daily life, but even then heRead MoreAnalysis Of The Movie American Sniper 1733 Words  | 7 Pagesâ€Å"I’m willing to meet my creator and answer for every shot that I took†¦Ã¢â‚¬ (www.imdb.com). Kyle, in the movie American Sniper, says these exact words for a reason. Just like how Kyle had a specific reason for the words he said, Matt Taibbi, who wrote American Sniper Is Almost Too Dumb To Criticize, had a reason why he structured and presented the article the way he did; he has answers within the words to explain why he wrote what he did for the most likely audience of Rolling Stone. Not only does TaibbiRead MoreAnalysis Of The Movie American Sniper 1354 Words  | 6 PagesChris Kyle – American Sniper The film American Sniper chronicles the events of one of the most celebrated marksmen in the United States. Christopher Scott Kyle was born and raised in western Texas. He possessed a fondness toward firearms from an early age and frequently participated in hunting expeditions. According to Adam Bernstein, an obituary editor for the Washington Post, Kyle dreamed â€Å"†¦to be a cowboy and†¦to be in the military.†To fulfill the former, he attended Tarleton State UniversityRead MoreArchetypal Analysis : American Sniper1003 Words  | 5 PagesAmerican Sniper: An Archetypal Analysis The movie American sniper is produced by Bradley Cooper, Clint Eastwood, Peter Morgan, Robert Lorenz, Andrew Lazar. American Sniper was released in 2014, and America feels sympathy for this unfortunately true story. American sniper is about a Navy S.E.A.L, Chris Kyle, who is played by award winning Bradley Cooper. Chris Kyles is a confirmed sniper legend, taking on four tours in Iraq to protect his comrades. He faces much internal conflict in this time periodRead MoreAmerican Sniper : A Biographical War Drama Film Directed By Clint Eastwood1623 Words  | 7 PagesAmerican Sniper is a biographical war drama film directed by Clint Eastwood about the life of Chris Kyle. From a young age, Kyle was taught that as a sheepdog, it was his duty and honor to protect the sheep from the wolvesâ€â€a biblical reference to David’s account of when he defended his flock of sheep against fierce animals in 1 Samuel 17:34-36 (Cummings and Cummings). Upon being deeply moved after seeing the news coverage of the U.S. Embassy bombings in 1998, Kyle left his life as a rodeo cowboyRead MoreHow The Media Shapes The Public Discourse Of Crime1344 Words  | 6 Pages Hannah M. Lahodny March 6th, 2015 || CMJS 2003 Examples and Analysis of How the Media Shapes the Public Discourse of Crime Whether through social media, televised news, or newspapers, most people are exposed to some sort of news media every day. It is the responsibility of the media to inform the public about what is happening in the world around us, and more often than not, that includes reporting crime. If the media is the source of our information, they have the power toRead MoreCriminal Profiling And The Law Enforcement2100 Words  | 9 Pagesthe law enforcement and the government agencies to pursue unknown perpetrators. It objectively seeks to identify the major personality and the behavioral characteristics of the serial offenders based on a thorough analysis of the crimes committed. It includes the combination of the analysis of the physical and the behavioral evidence. This study aims at analyzing criminal profiling on the basis of its basic elements and its use in law enforcement. The documented history of criminal profiling is tracedRead More Saving Private Ryan Essay1053 Words  | 5 Pagesweapons and injuries true to their time, the film’s portrayal of war goes a lot deeper than that. The expressions and feelings of soldiers along with their morals and ideology are depicted unifyingly with the horror of war. The lives and deaths of American soldiers in the immediate part of the invasion of Normandy are illustrated more realistically than ever before. Saving Private Ryan captures the â€Å"harsh reality of war as authentically as possible†. The films historical accuracy of the Omaha beachRead MoreThe Analysis of Saving Private Ryan by Steven Spielberg Essay1583 Words  | 7 PagesThe Analysis of Saving Private Ryan by Steven Spielberg Analyse he methods used to make the opening sequence of ‘Saving Private Ryan’ both shocking and realistic, and discuss its effectiveness as an opening to a film The film ‘Saving Private Ryan’ was released on September 11th 1998; the film was directed by Steven Spielberg, and was produced by Paramount pictures along with DreamWorks. Steven Spielberg has directed manyRead MoreSacrifice And Saving Private Ryan4254 Words  | 18 Pagesresponse. The last scene is of an American flag flying over the cemetery. Literature Review During my research for the analysis of this paper my research was focused on finding article that dealt mostly with the theme of sacrifice. While I did find many articles that wrote on the subject of the film Saving Private Ryan not one talked specifically about the theme of sacrifice; which I feel is a major theme of the film. A. Susan Owen’s article called â€Å"Memory, War and American Identity: Saving Private Ryan
Sunday, December 15, 2019
Bshs 402 Free Essays
string(111) " differences and similarities of case management in the community setting and in the managed care environment\." Course Syllabus BSHS/402 CASE MANAGEMENT Course Start Date: 10/30/2012 Course End Date: 12/3/2012 Please print a copy of this syllabus for handy reference. Whenever there is a question about what assignments are due, please remember this syllabus is considered the ruling document. Copyright Copyright  ©2009 by University of Phoenix. We will write a custom essay sample on Bshs 402 or any similar topic only for you Order Now All rights reserved. University of Phoenix © is a registered trademark of Apollo Group, Inc. in the United States and/or other countries. Microsoft ©, Windows ©, and Windows NT © are registered trademarks of Microsoft Corporation in the United States and/or other countries. All other company and product names are trademarks or registered trademarks of their respective companies. Use of these marks is not intended to imply endorsement, sponsorship, or affiliation. Edited in accordance with University of Phoenix © editorial standards and practices. Course Description This course covers principles, practices, and issues in case management. The diagnosis and treatment of developmental, psychological, and psychiatric roblems and treatment resources in the lease restrictive and most cost effective settings will be examined. Course Topics amp; Objectives Week One: Case Management Overview, Clientele, and Practice Models  ·Ã‚        Understand the basic definition and application of the case management function and process.  ·Ã‚        Delineate the concepts of case man agement as they apply to the needs of various special populations.  ·Ã‚        Describe the components of an integrated delivery model of case management. Week Two: Implementation of the Case Management Process         Describe the role and practice framework of case management.  ·Ã‚        Identify the differences and similarities of case management in the community setting and in the managed care environment. You read "Bshs 402" in category "Papers" Week Three: Case Management Skills: Interpersonal and Information Gathering Skills, Goal Setting, Intervention, and Evaluation  ·Ã‚        Demonstrate the interpersonal skills necessary to build rapport in the early stages of case management.  ·Ã‚        Understand the integration of assessment to problem identification and goal setting.  ·Ã‚        Examine the connection between interven tion planning and resource utilization. Week Four: Case Management Skills: Counseling, Therapy, and Linking of Clients to Services  ·Ã‚        Examine the personal helping interventions that can have positive effects on behavioral patterns of vulnerable clients.  ·Ã‚        Understand the case manager’s role in developing formal and informal linkages to benefit the client. Week Five: Case Management Skills: Reassessment, Outcome Monitoring, Advocacy, and General Case Management Problems  ·Ã‚        Understand the correlation of reassessment, monitoring, and outcome evaluation to the prevention of future problems. Course Materials                                                                                                               Rothman, J. , ;amp; Sager, J. S. (1998). Case management: Integrating individual and community practice (2nd ed. ). Boston: Allyn and Bacon. All electronic materials are available on your student Web site. Point Values for Course Assignments                                                                           ASSIGNMENTS| Points| Individual (75%)|  | All WeeksParticipation and Discussion Questions| 200| Week Two Individual Assignment: Special Populations Paper| 150| Week Three Individual Assignment: Textbook Quiz| 200| Week FiveIndividual Assignment: Final Examination| 200| Learning Team (25%)|  | Week TwoLearning Team Charter| 25| Week ThreeCase Manager Interview Questions| 25| Week FourLearning Team Assignment: Informal Networks Paper| 100| Week FiveLearning Team Assignment: Case Manager Interviews Presentation| 100| Total| 100| Week One Case Management Overview, Clientele, and Practice Models         Understand the basic definition and application of the case management function and process.  ·Ã‚        Delineate the concepts of case management as they apply to the needs of various special populations.  ·Ã‚        Describe the components of an integrated delivery model of case management. Course Assignments 1. Readings  ·Ã‚        Read the Appendix and Ch. 1, 2, ;amp; 10 of C ase Management.  ·Ã‚        Read this week’s Electronic Reserve Readings. 2. Learning Team Instructions  ·Ã‚        Review the Week One objectives and discuss insights and questions you may have.         Prepare for the Case Manager Interviews Power Point Presentation. ?                                       Create a plan for how the case manager interviews will be selected and conducted and adding any new ideas. ?                                       Discuss the areas that each of you wishes to pursue, who to contact, and how to contact likely interviewees. ?                                       Start your search NOW to find a case manager to interview for your LT project. Each student is required to interview a case manager. You cannot interview someone where you work and you cannot interview you own case manager if you have one. Your case managers must have either a BA or MA degree. ?                                       Start thinking about questions you will ask your case manager. Working with your team members, start discussing possible questions you will ask the case managers during the interview.  ·Ã‚        Information obtained from these interviews will combined and synthesized into a Power Point presentation in Week Five about how case managers function in the real world.         Search online for articles on case management for special needs populations. Each person can choose their own population to write on for the Week Two Special Population paper; this is an exercise to help each team learn about various special populations. ?                                       Divide the various disability populations and conduct an online search for articles on each student’s specific population. ?                                       Review the articles found and focus on the similarities and differences in services to the various populations.                                        Conduct a group discussion in which you review the similarities and differences in case management practices between special needs populations. 3. Discussion Questions  ·Ã‚        There is a difference in goals that are set by the client, and goals that a provider may wish for the client to achieve. Compare client-driven goals and provider-given goals.  ·Ã‚        As we’ve learned from this week’s reading, there are many different forms of advocacy. Discuss the role of advocacy in case management. What are some examples of ways we as case managers can appropriately advocate for our clients? Weekly Reminders Discussion Questions Discussion question responses will not count towards the class participation requirement. Only Posts to the Main forum will count towards participation. All Week: Remember to participate in the class discussions 4 out of 7 days during the week. Summary of Week 1 Deliverables Assignment| Individual or Learning Team| Location| Due|  Participation| Individual| Main| Ongoing – 4 days per week| Bio| Individual| Chat Room| Tuesday| Check-In| Individual| Main| Wednesday| Discussion Question (DQ) #1| Individual| Main| Wednesday| DQ #2| Individual| Main| Friday| Check-In to the Learning Team | Learning Team| Learning Team| Monday| Week Two Implementation of the Case Management Process  ·Ã‚        Describe the role and practice framework of case management.  ·Ã‚        Identify the differences and similarities of case management in the community setting and in the managed care environment. Course Assignments 1. Readings  ·Ã‚        Read Ch. 3 ;amp; 4 of Case Management.  ·Ã‚        Read this week’s Electronic Reserve Readings. 2. Learning Team Instructions  ·Ã‚        Prepare for the Textbook Quiz in Week Three by reviewing Ch. –4 of Case Management as a group. Create and Submit the Learning Team Charter to the Learning Team Forum. There is a Learning Team Charter located in the Materials Forum that should be used for this exercise.  ·    Diversity Issues Exercise oÂ Â Â Â Â à ‚  Form dyads or triads and discuss with your teammate(s) your differences in sex, race, culture, politics, and religion. After you have completed your discussion, talk to each other about what you found hard to discuss, what you found easy, and whether or not what you experienced relates to your work with clients. Discuss your experiences with the rest of the Learning Team. 3. Individual Assignment: Special Populations Paper  ·Ã‚        Resource: University of Phoenix Material: Criteria for Preparing Individual Paper on Special Populations (It will say that it is due Week Four, but it is due Week Two)  ·Ã‚        Review the material gathered on your chosen special population for the Week One Learning Team discussion. The materials should include at least two scholarly sources.  ·Ã‚        Write a 3- to 5-page paper in which you explain the following:  ? What populations have you reviewed and which one have you selected? ?                                       How and why have you selected this population? How was this area of interest formed? ?                                       What do you bring to the field of helping that would benefit this specific population? ?                                       How would you use case management to help this population? ?                                       What limitations and strengths do you bring to this chosen field? H ow would you use the strengths and overcome the limitations?                                        Are there likely to be multicultural issues to be addressed as you work with this population? How would you address those? ?                                       What local resources did you find in your Internet search for this population? Format your paper according to APA standard. This is a scholarly paper, requiring at least two scholarly sources, and citations of all information that is not common knowledge. Additionally, it should NOT be written in first person. Be creative! 4. Discussion Questions Discuss the importance of boundaries for both the client and practitioner in case management. Describe the role played by managed care in case management. Weekly Reminders Discussion Questions Discussion question responses will not count towards the class participation requirement. Only Posts to the Main forum will count towards participation. Participation All Week: Remember to participate in the class discussions 4 out of 7 days during the week. Summary of Week 2 Deliverables Assignment| Individual or Learning Team| Location| Due|  Participation| Individual| Main| Ongoing – 4 days per week| LT Charter| Learning Team| Assignments link| Tuesday| DQ #3| Individual| Main| Wednesday| DQ #4 | Individual| Main| Friday| Special Populations Paper| Individual| Assignments Link| Sunday| Week Three Case Management Skills: Interpersonal and Information Gathering Skills, Goal Setting, Intervention, and Evaluation * Demonstrate the interpersonal skills necessary to build rapport in the early stages of case management. * Understand the integration of assessment to problem identification and goal setting. * Examine the connection between intervention planning and resource utilization. Course Assignments . Readings  ·Ã‚        Read Ch. 5 ;amp; 6 of Case Management.  ·Ã‚        Read this week’s Electronic Reserve Readings. 5. Individual Assignment: Textbook Quiz –    The Quiz will be posted prior to Day 1 of Week Three.  ·Ã‚        Complete the quiz on Ch. 1–4 of Case Management. 6. Learning Team Instructions  ·Ã‚        Discuss progress being made toward locating appropriate interviewees for the case management interviews, including any difficulties anyone is facing or experiencing, and solve problems as a team to overcome the difficulties.       Working as a team, prepare 12 interview questions (2 questions for each principle) in which the following are demonstrated: ? Assessment and reassessment ?        Establishing a relationship ?        Fostering client participation and empowerment ? Monitoring ?        Advocacy ?        Evaluation (system used to prevent problems in the future) These twelve questions are the core that each team member will be asking the case managers and presenting in full for the Case Managers Interview PPT. They should be submitted in the assignment link by the due date indicated. 7. Discussion Questions Using a case study provided by your instructor as an example, address one of the following two questions:  ·Ã‚        List the components of an intake interview. In other words, what do you need to find out?  ·Ã‚        List the components of assessment. Describe how you would assess the seriousness of each problem and the steps you might take to address them. Using a case study provided by your instructor as an example, address one of the following two questions:  ·Ã‚        Describe the process of setting goals.  ·Ã‚        Describe formal and informal support systems and how you might use them for your case study. Weekly Reminders Discussion Questions Discussion question responses will not count towards the class participation requirement. Only Posts to the Main forum will count towards participation. Participation All Week: Remember to participate in the class discussions 4 out of 7 days during the week. Summary of Week 3 Deliverables Assignment| Individual or Learning Team| Location| Due|  Participation| Individual| Main| Ongoing – 4 days per week| DQ #5| Individual| Main| Wednesday| DQ #6| Individual| Main| Friday| Textbook Quiz| Individual| Assignments Link| Sunday| Case Manager Interview Questions| Learning Team| Assignments Link| Monday| Week Four Case Management Skills: Counseling, Therapy, and Linking of Clients to Services * Examine the personal helping interventions that can have positive effects on behavioral patterns of vulnerable clients. * Understand the case manager’s role in developing formal and informal linkages to benefit the client. Course Assignments 8. Readings  ·Ã‚        Read Ch. 7 amp; 9 of Case Management.  ·Ã‚        Read this week’s Electronic Reserve Readings. 9. Learning Team Instructions          Review textbook material as a group from Weeks One through Four in preparation for the Final Examination in Week Five.  ·Ã‚        Continue preparing for the completion of the Case Manager Interviews Power Point Presentation due in Week Five. 10. Learning Team Assignment: Informal Networks paper ?        Write a 4- to 5-page paper using the following criteria:  Research: As a team, find two peer reviewed articles or other scholarly sources (not including the textbook) in the UOP Library related to informal support networks. Every member of the team needs to read the articles.         Use information from the articles, your personal experiences if you so choose (1-2 paragraphs only of personal experiences in the paper – not 1-2 paragraphs of personal experiences for each member of the Learning Team), and ideas from the group discussion about the special population in your article. Be sure to read and follow the rubric posted in your Materials forum. ?        Be sure to give a description of the special population served in the article. Include information on the race, age, economic status, culture, and family structure of the special population.         Submit your Informal Social Network assignment through the Assignment Link. * 11. Discussion Questions  ·Ã‚        Explain the difference between counseling and therapy. What do case managers do? *  ·Ã‚        Explain the differences between empowering and enabling clients and give examples of each. * Weekly Reminders Discussion Questions Discussion question responses will not count towards the class participation requirement. Only Posts to the Main forum will count towards participation. Participation All Week: Remember to participate in the class discussions 4 out of 7 days during the week. Summary of Week 4 Deliverables Assignment| Individual or Learning Team| Location| Due| Participation| Individual| Main| Ongoing – 4 days per week| DQ #7| Individual| Main| Wednesday| DQ #8| Individual| Main| Friday| Informal Networks Paper| Learning Team| Assignments Link| Monday| Week Five Case Management Skills: Reassessment, Outcome Monitoring, and Advocacy, and General Case Management Problems * Understand the correlation of reassessment, monitoring, and outcome evaluation to the prevention of future problems. Course Assignments 13. Readings  ·Ã‚        Read Ch. 8 of Case Management.  ·Ã‚        Review Ch. 1–9 of Case Management.         Read this week’s Electronic Reserve Readings. 14. Individual Assignment: Final Examination  ·Ã‚        Complete the Final Examination. 15. Learning Team Assignment: Case Manager Interviews – Power Point Presentation  ·Ã‚        Submit the information compiled by the team’s research and interviews on case managers in a Power Point Slide Presentation through the Assignment Link. There are NO maximum or minimum number of slides required. A word doc (. doc or docx) copy of all speaker’s notes is REQUIRED and should be entered into the assignment link separately. Failure to do so will result in a loss of points. 16. Discussion Questions  ·Ã‚        In case management, the term â€Å"monitoring†has a specific meaning. Describe its definition and purpose within this context. Be sure to include the role of client involvement in your discussion. *  ·Ã‚        During monitoring and reassessment, clients may encounter various barriers. Describe one such barrier and what you as the case manager might do to help your client overcome it. Weekly Reminders Final Week Requirements Discussion question responses and participation will be required during the final week of the course. Discussion question responses will not count towards the class participation requirement Only Posts to the Main forum will count towards participation. Participation All Week: Remember to participate in the class discussions 4 out of 7 days during the week. Summary of Week 5 Deliverables Assignment| Individual or Learning Team| Location| Due| Participation| Individual| Main| Ongoing – 4 days per week| DQ #9| Individual| Main| Wednesday| DQ #10| Individual| Main| Friday| Final Exam| Individual| Assignments Link| Sunday| Learning Team Evaluations| Individual| Individual| Monday| Case Manager Interviews – Power Point Presentation| Learning Team| Assignments Link| Monday| How to cite Bshs 402, Papers
Friday, December 6, 2019
Dream home free essay sample
My dream home would be located in the Caribbean along the beaches of Jamaica with a panoramic view of the ocean. The house would be pretty big but not to big that you would get lost in it. I would want to have a four car garage to store all of my luxury transportation. Even with the ocean steps away I would still like to have an indoor pool, bowling alley and a basketball court. I would also like a huge backyard that led onto the beach so I could Just walk out on the beach anytime I felt the need. My backyard would include a hot tub with a water fall feature. A built in barbeque pit where I could have family and friends over to eat delicious food beach side with the sweet sounds of reggae playing all night long. Also we would have a screen in porch Just to protect us from all the bugs. We will write a custom essay sample on Dream home or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Inside my home would include an elevator for my lazy days. There would be plasma TV throughout the house. I would want to have a state of the art gym where I can invite a trainer over to keep me in good shape. Also, would have heated floors this is a must I dont like wearing shoes or having cold feet. I would like the smell of the Caribbean sprayed automatically over the entire home. I would want a really nice kitchen with granite table tops and nice cooking supplies along with a cook to order chef. I would also like a nice washer and dryer along with a butler working for me to help me keep my estate together. I would also need a top of the line security system to be safe. I would also need a speaker system throughout the house so I can always hear music and know whats going on around me I would have a house that is awesome and great and has good style and texture to it. I would have a custom designer come and decorate my house to look nice and modern. This is my dream home that I would want to live in forever.
Friday, November 29, 2019
Minute to Midnight free essay sample
The new Linkin Park album â€Å"Minutes to Midnight†is what I am doing by review on. Linkin Park has really been known to be a lot of hard rock music. That is what there first two albums â€Å"Hybrid Theory†and â€Å"Meteora†where like, which they sold a lot of. Many people like there style the way it is right now. Now having heard there new music on the new â€Å"Minutes to Midnight†album, they have really matured in there music. Songs that they are making have a lot more deep thought to them and are calmer in a lot of ways. Having always been a huge fan of there music, I still am even after this softer kind of rock that they are playing. Most of there music is deep and enjoyable to listen to. More people will be able to sit and enjoy this new album better then there last few because there are a lot of people that dont like screaming that they did in there last albums. We will write a custom essay sample on Minute to Midnight or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Linkin Park will be getting a lot of new fans and I am very impressed with this new album. It is unlike any elses band because they defiantly have there own style of music.
Monday, November 25, 2019
Free Essays on Management
In order to answer the question, is management an art, a science or both, a person must understand the definitions of all three terms. Management can be thought of as the process of working with people to accomplish a set of goals or objectives for a specific company or organization. According to Zimmerman (2001), management is the act or art of managing. A manager carries out activities such as directing, conducting, administrates, provide guidance, and controls all aspect of their organization. Nordwall (1998) stated that the term science is the collection of information gained through experimentation, observation and studying. The purpose for science is to understand/seeing how things behave and interact through observation and comparison. Some sources define art as an advanced expertise that you can learn by studying, practice and observation (Princeton, n.d.). Some people believe that management/leadership is innate but it is something that can be learned. Customarily, McN amara (1999) stated, management is thought of by four general activities which include planning, organizing, leading and coordinating of resources. There are many areas of knowledge and skills that are required in order to carry out the main functions of management. McNamara (1999) stated that â€Å"managers work toward the organization’s goals using its resources in an effective and efficient manner.†This definition is true in all forms of management, whether it’s in the corporate world or in healthcare. Levin (2001) stated that healthcare management teams are â€Å"tasked with crafting strategic direction and deciding upon major initiatives their organization needs to implement to maintain strategic advantage in the healthcare marketplace.†These managers must practice existing goals of the organization, study to improve those goals and make observation for future goals or plans for their organization. Today’s managers must be politically savvy , flex... Free Essays on Management Free Essays on Management The dictionary describes it as, the duration of one’s life; the hours and days which a person has at his disposal. How we dispose of that time is time management. It’s the way we spend our time to organize and execute around our priorities. Remember just because time is intangible doesn’t mean that it is not valuable. Styles and How To Use Them There are many different types of time management, some are simpler and some are more complex, but all are useful. We must each find a style that we’re compatible with and implement it into our lives. Even if the style you choose is not the most effective one, you must use it everyday to help better manage your time. Before you begin to manage your time you must realize that it is not a short-term project, but a life long commitment. Getting and Staying Organized This is a system that’s purpose is to save you a few hours a day by showing you how to organize. The goal of this style of time management is to get organized so that you can convert time that you’ve wasted during a normal day into time that can be used more efficiently and effectively. This style of time management is directed on business in general, but I feel it can still be applied to every day life. It gives us simple easy to do tips on how we can become organized. The first tip is to separate the things that are importance from the things that are not. Then throw away what’s not important. Next tip is to place the important stuff in order that it needs to be done by creating a master list. A master list is the concept of writing everything down in an orderly, meticulous way, so that you can do a better job of staying on top of things. Another tip is to write everything down on paper. The reasoning behind this is that because you are saved from having to rem ember lots of information, you’ll have more brainpower for more important things. This system seems to focus on the short-term and is really basic. It may w... Free Essays on Management A Plethora of Management Problems†In the article â€Å"Bridge project is put on hold due to construction problems†there are clearly many problems besides just construction. Along with basic delays in construction there are also a number of managerial problems for Essex and Union County to overcome. The main problems with the new bridge construction are that the project lacks the basic managerial functions such as planning, controlling, organizing and leadership. Problems with the initial phase of construction have halted the project indefinitely. I believe this is because of improper planning and conceptual skills. As of now, there has not been a date set for completion of the permanent bridge indicating a lack of decision making and organization. No one involved in this project did any contingency planning in case of unforeseen circumstances. I think a solution to getting this project restarted would be to have some rational decision making and planning. Someone needs to formulate a plan to get the bridge up and moving again and some one needs to make some decisions on who is going to do the construction properly and needs to implement a set of alternatives to the plans, should anything go wrong again, they would have a back up plan. Another problem associated with the delay is the company they chose to do the construction on the bridge. The county chose the company based on the lowest bid and didn’t choose the contractor most capable of coordinating this project. They had non-union workers who lacked the knowledge and skills to complete this job. They should have picked the construction company with the most experience with this type of project. I don’t believe they used rational decision making in choosing the construction company. A place that this project lacks is in the strategical plan for completing the project and the strategy implementation of the plan. The plan that was designed for this bridge ... Free Essays on Management The majority of a manager’s job involves communicating with the people in his or her organization as well as individuals in other organizations. This interaction can have positive and negative outcomes, such as need satisfaction, social support and conflict. As many of you already know, communication is the process of transmitting information. No matter what level of management an individual is in, he or she will use different communication techniques on a daily basis. The two techniques that managers use most often are verbal and written communication. Some advantages of verbal communication are it’s easy to use and it generates immediate feedback between individuals. Some disadvantages are that it can be difficult to choose the correct words to convey an idea, it leaves little time for the individual to respond and there is no written record of the communication. On the other hand, written communication has an advantage because it is usually more precise than verbal communication. Also, written communication can be tracked. A few disadvantages are that it can inhibit feedback between the individuals and it take more time and effort to prepare than verbal communication. There are several barriers to the communication process. Some individual barriers are related to personal characteristics and the manager’s predisposition to the individual he or she is communicating with. Examples of those predispositions may be age, race, gender or religion. Organizational barriers within the workplace also affect communication. The armed forces is a good example of organizational barriers. As with any corporation, there is a chain of command that employees must follow. However, in the military, that chain of command is very strict and heavily enforced and this can inhibit communication between a supervisor and subordinate. This lack of communication can lead to problems in the workplace, such as decreased motiv... Free Essays on Management In order to answer the question, is management an art, a science or both, a person must understand the definitions of all three terms. Management can be thought of as the process of working with people to accomplish a set of goals or objectives for a specific company or organization. According to Zimmerman (2001), management is the act or art of managing. A manager carries out activities such as directing, conducting, administrates, provide guidance, and controls all aspect of their organization. Nordwall (1998) stated that the term science is the collection of information gained through experimentation, observation and studying. The purpose for science is to understand/seeing how things behave and interact through observation and comparison. Some sources define art as an advanced expertise that you can learn by studying, practice and observation (Princeton, n.d.). Some people believe that management/leadership is innate but it is something that can be learned. Customarily, McN amara (1999) stated, management is thought of by four general activities which include planning, organizing, leading and coordinating of resources. There are many areas of knowledge and skills that are required in order to carry out the main functions of management. McNamara (1999) stated that â€Å"managers work toward the organization’s goals using its resources in an effective and efficient manner.†This definition is true in all forms of management, whether it’s in the corporate world or in healthcare. Levin (2001) stated that healthcare management teams are â€Å"tasked with crafting strategic direction and deciding upon major initiatives their organization needs to implement to maintain strategic advantage in the healthcare marketplace.†These managers must practice existing goals of the organization, study to improve those goals and make observation for future goals or plans for their organization. Today’s managers must be politically savvy , flex...
Thursday, November 21, 2019
Nitrogen removal from wastewater using anaerobic ammonium oxidation Term Paper
Nitrogen removal from wastewater using anaerobic ammonium oxidation (Anammox) process - Term Paper Example Generally, this bacterial can be found almost everywhere. Findings have shown that the contribution of this bacterium on the removal of nitrogen in the environment can be immense. The process, said to be chemolithrophic, is a very new loop in the biogeochemical nitrogen cycle hitherto unknown to engineering (Dong & Sun, 2007). While there is very little, that is known about the ecology, genetics, or even the physiology of the bacteria, this research project will be very important in shedding some light on the community structure of the Anaerobic Ammonium Oxidation bacterial and all their involvement in environmental parameters that include nitrate, ammonium, and the salinity levels. This project discusses the effects of pH and salinity on the anammox process with results showing that the salinity is among the few factors that are really affecting the effectiveness of the whole process. My thanks go to Mr. XXXX through whose guidance I have learned molecular techniques used for the investigation of bacteria. It is due to his patient and undying support that pushed this study through. A good and encouraging attitude and his excitement about this work encouraged me to explore deeper into learning as much as possible in the process. I wish to also thank Ms. YYYY who also made this research a success through teaching me about the most fundamental and traditional microbiology techniques. Mr. QQQQ introduced the isotope ratio mass spectrometer to me. He was also very encouraging and it was through his words of wisdom that the concept behind stable isotope geochemistry became one that I can handle well, and with ease. This research owes its completion to WWWW who collected the sediment samples from XXX Estuary. All the other members of the microbiology laboratory were very helpful throughout my visits to the lab. It was their long, well-informed discussions that made the research a success, and I will forever cherish such
Wednesday, November 20, 2019
Describe the theories, arguments and evidence used in your four Essay
Describe the theories, arguments and evidence used in your four subject readings. What do the readings tell you about the study - Essay Example In the fourteenth century the Roman law gave the above mentioned privileges whereas a century later English authorities granted the similar rights to the parents. Yet the intellectual evolution kicked in and by seventeenth century scholars initiated to view children as an important part of the society and supported the notion of facility settlement for their training (Peck 2008). Based on the above paragraph, it can be assumed that the tendency and the power of evolution are embedded within the fabric of humanity and humans are gifted with an unexplainable energy to overcome resistance to change. Historically the females were not considered humans and in the present they are recognized as equals to the male population. All of the instances demonstrate the fact that humans kept on growing intellectually in the past and therefore their behavior also became better with the passage of time. In the process of intellectual growth old concepts were challenged and replaced with new and more practical ones. Corporate professionals in the past were only concerned with the maximization of the profit. However nowadays businessmen are getting more and more attached to the concepts of job autonomy, modern training and prevention of environmental degradation. Literature Review Modern thinking started to be accepted and praised when it challenged the concept of capitalism. The state socialism evolved around the premise of accumulation of wealth within few hands and therefore causing serious financial inequalities in the West as it is mentioned in the book that â€Å"State socialism attempts as far as possible to substitute central planning for the working of economic market†(Hall 1992 pp 54). However, the neo-classic economic experts stated that the country should and must use its natural and human resources efficiently in order to maximize their utility to the society. The Marxism, an important economic theory holds on to the point that there are no notable difference s in social classes regarding their needs and wants. Nevertheless the true message of the theory is that all humans should be treated equally in the eyes of economics and there should be negligible impact of social boundaries on the commitment of the resources it is written in the book â€Å"State power could caretaker of the existence (Hall 1992 pp 32). Thus, the state will have the ultimate responsibility of fulfilling the needs and wants of the citizens. According to Marx’s viewpoint â€Å"the presence of politics in the society is a representation of classes and their goals and objectives†(Hall 1992 pp 31) and the above mentioned economic authority is having an unconstructive view of politics in general. But in a more practical sense the model of politics presented by Marx is supporting dictatorship as there is no provision for public opinion. Furthermore the Marxist ideas about political activities were implemented by the Soviet Union in the form of State govern ed Socialism The profound failure of the above mentioned political system supports that democracy has a tendency to prevail under adverse situation because it is more accommodating towards the human nature as it supports freedom of speech and choice. However socialism thrives on the idea of protecting the capital so that it can be used for the greater good of the society. But in this kind of system people starve by the millions because the state never
Monday, November 18, 2019
Emotional and Behavior Disorders Assignment Example | Topics and Well Written Essays - 1500 words
Emotional and Behavior Disorders - Assignment Example This study stresses that emotional or behavioral disorders are classified into three groups, namely: internalizing factors, low incidence disorder and externalizing. Behavior disorders can also be inherited through an individual’s genes or because of a chemical imbalance in one’s brain because of an injury sustained in the brains. Youth exposed to violence, death of a family member(s), abuse and extreme stress are also prone to suffering from behavior and emotional disorders. 8 emotional and behavioral disorders Characteristics/Traits Commonly Used Medications Recommended Therapeutic Interventions Recommended Educational Interventions Disorder Name: Attention Deficit Hyperactive Disorder (ADHD)   From this paper it is clear that the affected child is unable to pay attention to anything. The affected child is easily distracted and not constantly active. The child is not still. The use of stimulant and non-stimulant medications like atomoxetine are normally recomm ended. Induced psychosis in methylphenidate is also recommended as medication. Lisdexamfetamin, Dextroamphetamine, Amphetamine-Dextroamphetamine are also the common medication. The Team Approach should be effectively used in which the parents, therapist, psychologist, teachers and the school, and physician should work together to focus on interventions, like consistent use of reward systems, techniques and schedules to help in mastering of skills. People should be made aware of the causes of these conditions and preventive measures put in place to prevent occurrence. Treatment should also be sought as early as possible for people who are affected. Disorder Name: Severe Depression   Loss of concentration in normal activities. The affected child experiences changes in appetite and feels hopeless. Lack of value towards life which may lead to destructive behaviors and suicide. Various antidepressants are used in the treatment of depression and conditions related to depression. T hey include Tricyclic antidepressant, Monoamine Oxidase Inhibitors, Selective Serotonin Inhibitors reuptake inhibitors and Serotin & norepinephrine Inhibitors. Interpersonal Therapies and cognitive behavioral therapies should be used in the treatment of severe depression. People should be made aware of the causes of these conditions and preventive measures put in place to prevent occurrence. Treatment should also be sought as early as possible for people who are affected. Disorder Name: Eating Disorders  Â
Saturday, November 16, 2019
Supply Chain Risk Management
Supply Chain Risk Management A global supply chain is subject to various types of supply and demand uncertainties existing at different nodes of the supply chain giving rise to a variety of risks that can lead to disruption. Companies that stay on top of supply chain risk make their businesses more resilient. They can enhance the companys competitive position, support growth and produce measurable returns. Many companies have recognized this and are now undertaking supply chain risk management programs This research paper reviews published approaches to supply chain risk management and tries to understand how the risks differ in two major industries-electronics and pharmaceuticals. For managers, it provides knowledge of the types of risks that may be present in their supply chain and presents a variety of strategies for identifying and managing the same. Introduction Globalisation, multiple channels to market, the pressure to run lean supply chains extending beyond traditional organisational boundaries, and the need to embrace external parties such as contract manufacturers and logistics service providers, have left the modern supply chain increasingly vulnerable to risk and to possible disruption. Economic disruptions including currency fluctuations, commodity price volatility, and sudden downturns in demand and ownership or investment restrictions imposed by governments have become more frequent and more visible since the financial crisis of 2008. Despite significant growth in international trade, cross-border movements are vulnerable to customs regimes, tariff and non-tariff barriers, quota systems, security concerns and infrastructure bottlenecks. All these risks can be clubbed into- macroeconomic, extended value chain, operational and functional risks. Almost two-thirds of the respondents to a global survey conducted by Mckinsey consisting of executives, say that the risks to their supply chain have increased over the past years. A significant of them also agreed to the fact their companies dont take any steps to mitigate these risks. (Source: September 2006 Mckinsey Quarterly global survey of business executives) Thus there is a clear need to review risk management practices as they pertain to both long-term strategic and short-term tactical decision-making. Organizations should review their risk exposure against objective, transparent criteria, with costs balanced against the benefits of potential methods for mitigating risk. . There are two sides to supply chain risk management: Risk assessment and mitigation Response to supply chain disruption Both are necessary components to an effective supply chain risk management strategy. With strong risk mitigation strategies in place a company is ready to face a given supply chain event. However, not all events may be anticipated. When these events occur, accompany must be prepared to respond quickly and effectively or risk suffering financial and customer service losses. Both the quantitative and qualitative risks will be covered through this paper. A step by step approach to tackle SCRM is proposed:- Assessing risk To assess risk, an inventory of key risks is build, along with the effects and probabilistic likelihood of each risk. A supply chain probability and impact matrix needs to be built. Designing a framework to manage the supply chain Once assessed, supply chain risks need to be managed via a framework that integrates all the key risk capabilities required. Implementing supply chain risk mitigation Companies need a robust action plan funded with the appropriate resources to address the core of the risk issues and implement treatment. The objective of this paper is to propose a comprehensive risk management and mitigation model for global supply chains. The model is intended to equip managers with a step-by-step procedure to identify, assess, and manage risks in their global supply chains, and guide future research. The paper reviews various risk mitigation techniques proposed in different papers in this subject and tries to understand its significance in the electronics and pharmaceutical industry. Literature Review Manuj and Mentzer (2008) say that due to demanding customers and competitive pressures, businesses today are restructuring themselves to operate on a global basis to take advantage of the international product, factor, and capital markets. There are several concerns in operating globally, including economic, political, logistical, competitive, cultural, and infrastructure. Typically, a firm operating internationally is part of a complex supply chain. Global supply chains require highly coordinated flows of goods, services, information, and cash within and across national boundaries. Maximizing profits in a multi-national environment include sourcing from locations that offer the lowest total procurement cost, manufacturing and assembling products in least cost countries, and marketing in high potential demand centres. But Wright and Datskovska (2012) are of the opinion that through lean processes and the geographical concentration of production, most executives would probably say tha t their supply chains and transport networks have become more efficient. These advances in efficiency, however, have also changed the risk profile for their supply chains. Janat Shah (2009) proclaims that lean techniques have created chains with longer paths and shorter clock speeds resulting in more opportunities for disruption and a smaller margin for error for a disruption to take place. Lengthy supply chains are increasingly proving to be a source of concern in the face of disruptions in sourcing, production and distribution of goods and services. As a result, many organizations need to take a hard look at supply chain risk and to review their plans and procedures for dealing with a broad range of new contingencies. Supply chain risk classification Wagner and Bode (2008) describes a supply chain risk as the combination of (1) an unintended, anomalous triggering event that materializes somewhere in the supply chain or its environment, and (2) a consequential situation which significantly threatens normal business operations of the firms in the supply chain. We can describe a five step approach to supply chain risk management- Risk Identification, Risk Assessment and Evaluation, Selection of Appropriate Risk Management, Implementation of Supply Chain Risk Management Strategy and Mitigation of Supply Chain Risk. Different authors have described various classifications of risk sources. Various supply chain risks can be divided as Supply, Operational, Demand, Security, Macro, Policy, Competitive and Resource risks. Chopra and Sodhi (2004) classify them as Disruption, Delay, Forecast, Systems, IP, Procurement, Receivables, Inventory and Capacity risks. Juttner, Peck and Christopher (2004) simplifies the classification to environmenta l risk sources, network-related risk sources and organisational risk sources. Risk assessment Pramod Kumar Mishra (2011) says that decisions on supply risks can be taken only when the impact of risks on the companys business can be evaluated. This can be quantitative or qualitative depending on the resources available. Risk assessment involves exploring what if scenarios like those below can help groups identify, understand and prioritize risks, a key prerequisite to tailoring effective risk-mitigation strategies. Manuj talks of two methods-probabilistic choice and risk analysis methods depending on the repeatability of events. Janat Shah has described constructing a probability and impact matrix to assess risk. Historical data may be used to understand the behaviour of risk probability distributions. However, there are many instances when there is none, inadequate, or unreliable historical data. In such cases, techniques such as the Delphi method may be used to assign probabilities. But Iyer(2008) says that this exercise is challenging because the relationships between risk factors are not static. One decision or risk factor may impact other risk factors. Risk mitigation Risk management is focused on identifying and assessing the probabilities and consequences of risks, and selecting appropriate risk strategies to reduce the probability of, or losses associated with, adverse events. Basically risk mitigation strategies can be classified primarily into seven categories: avoidance, postponement, speculation, hedging, control, sharing/transferring, and security. Hult, Craighead and Ketchen (2010) have suggested real options based method. Janat Shah has created a matrix with investment required for mitigation and risk score as the axis to decide the mitigation plan. Juttner, Peck and Christopher (2004) in there paper have defined an approach based on avoidance, control, cooperation and flexibility. Avoidance is through dropping product lines, markets, supplier or partners. They define a control approach through increasing stockpiling and buffer inventory, maintaining excess capacity and imposing contractual obligations. Cooperation is mentioned to be thr ough joint efforts in information sharing and preparing continuity plans. Flexibility can be through multiple sourcing and localised sourcing. Blos, Wee and Yang (2009) have devised a framework based on business continuity planning. Depending on the demand and supply uncertainty, the authors have also defined a matrix aligning the strategic objectives of the firm with the supply chain objective and the mitigation plan to be followed. An efficient, responsive, risk hedging and agile supply chain each have different plans. There are also devised methods for continous risk monitoring-stress testing and Tailoring Risk Management approaches. Trade-off The biggest challenge companies face is mitigating supply-chain risks without eroding profits. Juttner, Peck and Christopher (2004) summarised the trade-off decision as (1) Repeatability versus unpredictability, ie trading the benefits of repeatable processes against the cost of a lack of flexibility; (2) the lowest bidder versus the known supplier; (3) centralisation versus dispersion decisions in production and distribution; (4) collaboration versus secrecy, ie while sharing more information on e.g. the results of risk audits would better place organisations to manage supply chain risks, it could also deter potential customers or weaken the bargaining position; (5) redundancy versus efficiency, ie managing the conflict between excess capacity in a supply chain and the efficiency-focused lean paradigm aiming at the elimination or reduction of waste. A final, maybe paramount supply chain trade-off decision is between managing risk and delivering value. This is the trade-off between t he extra costs related to most of the mitigating strategies and the total costs of supply as a main principle of contemporary supply chain management. Risks in Pharmaceutical industry Enyinda, Mbah, Ogbuehi (2010) reports on the empirical findings of the quantification of risks that decision makers consider most important when deciding on a risk portfolio to mitigate and the manner in which risks are prioritized according to their importance in the pharmaceutical sector. The empirical findings suggest that decision makers attached great importance to counterfeit, Food and Drugs Board, and exchange-rate fluctuations. With respect to risk-mitigation strategies, risk reduction is considered most important, followed by risk avoidance. Dynamic sensitivity analysis with respect to a change (increase) in the Food and Drugs Board did not result in any change in the ranking of risk policy options, while a change (increase) in counterfeit resulted in a change in the ranking between risk reduction and risk avoidance. Risk avoidance ranked number one, followed by risk reduction. The paper leverages the analytic hierarchy process (AHP) to quantify risk mitigation. Greg Brandyberry (2010) reports five important trends in risk management practices in the pharmaceutical industry. Sensible cash-flow management: With the changing environment of increased regulation, price controls, generic-drug competition, and longer and more expensive research and development cycles, pharmaceutical and biotechnology companies have become much more focused on supply-chain cash-flow management strategies (following the lead of other industries that began implementing these strategies as many as 25 years ago). These strategies consist of a combination of programs that strive to better balance cash inflows versus cash outflows. Better balance of low cost versus low risk. Global supply chains have been under development across pharmaceutical industry since decades. Outsourcing, combined with low-cost country sourcing, is even riskier. The US Food and Drug Administrations recall of heparin in 2008 due to contamination of lots produced in China is another example. In this heparin recall, the drug was oversulfated as Chinese heparin manufacturers were unethically cutting the medication with chondroitin sulfate to cut down on manufacturing costs. This incident had devastating impacts on those who had chosen to use this Chinese supplier. FDA reported that there were hundreds of serious adverse reactions and scores of deaths among patients that had taken the heparin (2). The hard lessons learned from this incident have made it important for companies to revaluate their low-cost country sourcing strategies. They are evaluating risk versus cost and rebalancing their supply strategies to less riskier profiles. Comprehensive strategic-procurement initiatives Strategic sourcing is a pragmatic and structured procurement process. This process is conducted over several steps and includes: rigorous internal and external analysis; development of multiple strategic options weighted for risk and cost; strategy selection made collaboratively with business stakeholders; well-orchestrated negotiation; and detailed implementation planning, supplier selection, and ongoing supplier management, including continuous-improvement activities. Sustainability When it comes to embracing sustainability and green behaviour in manufacturing and product specifications, several large corporations such as GlaxoSmithKline (London), Proctor Gamble (Cincinnati), Diageo (London), and Unilever (London) achieved material cost savings, enhanced brand image, and generated increased demand for their products through innovative changes in primary and secondary packaging components. Risk in electronics industry Frank Zwibler and Marco Hermann (2012) have suggested that most supply chains in the electronics industry are global networks consisting of a single OEM, an A-supplier, and several small and medium supply companies (SME). These networks are characterized, firstly, by the dominance of the OEM or the A-supplier and, secondly, by the volatile electronics market and its strong fluctuations in demand, short product life cycles, and tremendous potential for technical innovation. Supply chain mapping, brain-writing method and stress, resilience and expense portfolio have been described as successive steps of risk identification. The Failure Mode and Effects Analysis (FMEA) technique has been used for risk assessment. After assessing the different parameters, the so-called risk priority number (RPN) can be determined. Risk measures to control are similar to earlier described mitigation plans. Sodhi(2005) has outlined a process to manage this risk by suggesting two risk measures for demand- a nd inventory-related risk respectively and two linear-programming (LP) models: one for allocating the plants replenishment schedule among the customers and the other to guide the request to plants for replenishment over the horizon. Research lacunae There is an immense need for action in industry to implement supply chain risk management systems. Each industry differs in their management of supply chain risks. Not only that supply chain risk management is not evenly applied throughout the different sectors, there are also great differences in the use and the implementation of supply chain risk management. A study comparing sector wise supply chain risk management is of immense scope. Research Methodology Mainly secondary research from peer reviewed journals, articles, websites and proceeds. Analysis The supply chain risk management process can be summarised as Figure : Supply Chain Risk Management Framework Electronics Industry More than ever before, electronics manufacturers are facing harsh realities. With further dismantling of trade barriers, globalization is now enabling companies to enter new markets each with its own standards and regulations creating fragmented product lines and distributed networks of suppliers and vendors. Product innovation is receiving greater emphasis as global competitors turn up the heat and product lifecycles continue to shrink. The entire nature of demand has changed, placing traditional forecasting weak. The fact is, long-range planning and demand forecasting are increasingly and inherently losing their ability to guide manufacturers as the recent inventory crisis in electronics showed all too clearly. With the introduction of partners such as electronics manufacturing services (EMS) providers, component suppliers and distributors, original design manufacturers (ODMs), contract design manufacturers (CDMs), and other participants, it becomes more challenging to control that network of suppliers. Although original equipment manufacturers (OEMs) still have direct design relationships with the semiconductor. Suppliers, the purchasing relationship comes about through the OEMs partners, making inventory ownership ambiguous, blurring inventory visibility across the supply chain, and creating unstructured processes among partners for managing supply chain execution. Figure Electronics Supply Chain (Source: QAD White Paper: Successful Risk Management in the Electronics Supply Chain) Critical risks Inventory Risk This is the greatest risk for supply chains getting caught holding inventory when a product becomes obsolete or demand shifts unexpectedly. With the highly volatile demand of electronics manufacturing, companies that rely heavily on demand-forecast accuracy face unnecessary inventory risks. Supply-Interruption Risk Conversely, no company wants to experience materials shortages that impact their ability to supply finished product to their customers. Supply interruptions are the ultimate opportunity cost for manufacturers. Capacity Risk In the cyclical electronics industry, most profits arise from new orders during a peak cycle coinciding with price premiums. Too little capacity presents significant opportunity costs. Conversely, excess capacity can negate the profits gained in the peak period. (Frank Zwibler and Marco Hermann (2010)) Risk Mitigation Inventory Visibility Faster Information Lead Times Sales and Operations Planning Managing Key Performance Indicators Managing Inter-Enterprise Business Processes Lean Manufacturing Service and Support Management An IT backbone enabling Supporting a pull-based manufacturing and replenishment environment Achieving inventory visibility across fragmented supply chains including multiple tiers and component suppliers and contract manufacturers Minimizing supply interruptions by reducing information lead time Comprehensive sales and operations planning (SOP) to optimize inventory at various points in the supply chain Monitoring supply chain KPIs including supplier and contract performance Managing outsourcing operations Supporting lean manufacturing and lean supply chain strategies Creating aggregated supply plans to drive strategic sourcing This ability to assess the impact and exposure from sources of risk made a big difference to the fortunes of Nokia and Ericsson, which were leading cell phone vendors in 2000. In March 2000, a fire broke out at their common supplier Phillips NVs semiconductor plant in New Mexico, forcing the plant to remain shut down for several months. The difference in outcomes between the two companies was dramatic-Nokia came out of the disruption stronger and gained market share, while a substantially weakened Ericsson lost more than à ¢Ã¢â‚¬Å¡Ã‚ ¬400 million that year and ultimately exited the cell phone market in 2001. This difference was primarily due to Nokias comprehensive supply chain risk management program, which helped the company immediately-and accurately-estimate the impact of the shutdown on its business, and then react accordingly. Nokia switched orders to other Phillips plants and to Japanese and American suppliers, and redesigned chips to reduce its reliance on Phillips products. By comparison, Ericsson was unable to assess the potential impact of the fire on its business and could not respond quickly to the incident. Pharmaceutical Industry Figure : Pharmaceuticals Supply Chain (Source: Chartered Quality Institute Guide) Critical Risks Counterfeit Drugs As pharmaceutical supply chains worldwide continue to experience increased risk levels, led by counterfeit risk, the WHO reports (1998) that 10% of all drugs distributed worldwide are counterfeits, with a disproportionate 60% rate in the developing countries. Pharmaceutical counterfeits can impose tremendous costs on both the pharmaceutical industry and patient safety. The costs through the actions of counterfeiters and diverters include more sick patients, loss of life, erosion of public health confidence, loss of brand image, reduced profit and reduced shareholder value. These costs are compounded by the costs of product recalls and the growing threat of counterfeiting and diversion. Compromised or untrustworthy drug value chains can create uncertainty , decrease investment, and decrease in research and development. Food and Drugs Board Compliance norms for pharmaceuticals can make or break a drug. Regulators are becoming much stricter about quality issues, increasing the size and frequency of mandatory product recalls. The number of drug recalls by the FDA increased by more than 28 percent in 2009 to 2010, for example Exchange-rate fluctuations Foreign exchange rates can fluctuate dramatically over the course of a supply agreement and it is important to consider their impact upfront. Clinical trial risk This is a risk specific to the pharma supply chain arising as a result of the drug development process. The empirical findings from Enyindas research using Saatis AHP indicate that counterfeit risk (0.453) is considered more important, followed by FDB (0.264), exchange rate (0.112) and other risks. This helps in inferring the ranking of the risks in the sequence presented above. Risk mitigation for Counterfeits Usage of technology is the only means to curb the menace of counterfeit drugs. Sophisticated pack design and labelling using special inks Holograms Tags and tamper-evident seals Field agents actively investigating instances of counterfeit product Consumer Awareness Programs Enyinda Szmerekovsky(2010) have proposed that U.S. pharmaceutical firms must turn to SR supply chain to better track and trace prescription drugs. And the key enabler to SR supply chain is RFID technology that has been touted as the holy grail. Because of the significant promise that RFID has, FDA recommended its adoption by the pharmaceutical industry in order to achieve and meet the electronic pedigree requirement and compliance. Effective risk management requires the ability of the decision maker to rank and prioritize a portfolio of risk factors involved in the supply chain. Managing the risk throughout the supply chain now means taking a systemic view. The goal is to build a system that can detect and work around any major supply-chain weaknesses. Discussion Hypothesis H0: All industries face similar supply chin risks. H1 :All findustries do not face same supply chain risks. Analysis of the risks shows that each of the industrys pharmaceuticals and electronics has critical risks which are quite unique to it in the case of the former. Firstly, Counterfeit risks are an inherent risk in the pharmaceutical sector with irreparable damage and life threatening implication as a result. This can tarnish the company with a huge blow to its brand and spoil its top line in the short term. They have a higher potential of damage to the company in terms of plausible revenue losses because of the inseparability in their appearance as compared to the original. This is not the same case with electronics where, there are ample amount of duplicates in the market but their appearance and performance can be easily scrutinized to arrive at a decision to buy. And they rarely have life threatening consequences. Secondly, pharmaceutical industry is controlled by the FDA who is a strict watchdog of the practices in the industry. New drugs receive extensive scrutiny before FDA approval in a process called a New Drug Application or NDA. The FDA reviews and regulates prescription drug advertising and promotion. After approval of an NDA, the sponsor must review and report to the FDA every patient adverse drug experience of which it learns. In electronics there is CEA, but they are not that a controllable authority as that FDA puts on pharmaceuticals. Thirdly, clinical trials done during drug development are very unique to the pharmaceutical research developing new drugs. Thus these particular risks are not a part of electronics industry and the generalised risk framework wont do for the same.They require specialised risk mitigation plans as discussed. Conclusion and Managerial Implications Supply Chain risk management will be a key success factor for companies in a globalized world if they have implemented a risk management process in their organizational structure. We have briefly reviewed several published literatures on supply chain risks. An effort has been made to define critical risks followed by its classification for electronics and the pharmaceutical industry. Several models of risk assessment from published sources have been reviewed .After this, several strategies of risk management is being presented. Supply chain risk management is thus a growing and challenging area with lot of research potential to be explored further. A future research scope would be to quantify the impact of various risks on each industry through primary research. Both pharmaceutical and electronic supply-chain risks are often related to a lack of information visibility or deviations in the information and physical flows from upstream to downstream, increased knowledge of essential risk management procedures and structures can significantly improve the ability of decision makers in implementing appropriate mitigation treatments for identifiable risk portfolios.
Wednesday, November 13, 2019
Gender and Equality in the Workforce in the USSR Essay -- Equality Emp
Gender and Equality in the Workforce in the USSR For every person, different reasons exist to go out and seek employment. These reasons, however, stem from the type of government that people are ruled by. In Russia, during the period that will be discussed, a Socialist government ruled the USSR. It was under this government, that everyone was to have a job and unemployment was to be kept at a minimum. During this socialist regime, the attitudes to working will be taken from the perspectives of three related women. The first woman, Mela Krul, was born in 1932 and is the mother of Alla Veitsman and Helen Krul Zlatkin. Alla Veitsman is the oldest sister and was born in 1954. Although her work experience under the socialist government is brief, it shows signs of the progress that women made during the middle to late 1900s. Helen Zlatkin, born in 1962, had no work experience in the former USSR, but her personal account demonstrates the types of choices that women made in order to have both family and work. Mela Krul was the only one who had extensive work experience in the USSR, but she was able to see the changes and progress that women underwent through the daily activities and choices that both of her daughters made. As these three women came to the United States of America, along with their families, they faced a democratic government where employment was not guaranteed and women did have to face the hardships of unemployment, and more importantly, inequality. It would be the values and traditions that both Alla and Helen believed in that allowed them to be successful and relatively unaffected by inequality. In the time period that the three women lived in the USSR, society was ruled by socialism (communists did exist, but were not the majority). Under this theory of government, everyone worked; it was believed to be a disgrace if a person simply sat at home and did not participate in the labor force. The goal was to have every citizen in the USSR working; there was little focus on quality or productivity, "Early Soviet policies rested on the assumption that genuine equality and independence for women depended on full economics participation." (Lapidus 168) People were encouraged to work, not to meet their potential in the workplace. In order to receive their monthly pay in rubles, the workers had a quota to meet. The workers rarely met this quota --... ...to a certain age group desire these things -- but she did not take into account immigrants. No matter when a certain immigrant woman is born, once she has arrived into the United States she wants a job and a family -- a career comes later. For an immigrant woman, it is never a question between a family or a job, you have both -- you must have a job to keep the family healthy and in need of nothing. For an immigrant woman coming from a socialist government where benefits were nonexistent, jobs in America that do offer benefits do not advocate inequality, but advocate progress and an opportunity to support one's family by fully participating in the labor market. Immigrant families never lose sight of the importance of family and the support that they can offer you. Society is constantly changing and new and better things are always improving, but the help of one's family members can never be overlooked -- some traditions promote modernization and progress. The authors of the econom ic models discussed try to fit people into categories without taking into account very important exceptions -- personal values will never fit into categories and will always promote equality and progress.
Monday, November 11, 2019
Ebay Case Study
Characteristics of digital media that support eBay is storage. Data is one of the most important assets to any business same goes to storage that eBay needs to save their customer data. If they lack of storage they will face the problems such as lost product data, high technology security that help eBay to keep their information save. Due to its absolute volume, how and where eBay store this ever-growing pool of data has become more important than ever. The IT infrastructure must be able to scale with growth and continue to provide consistent levels of performance for the sake of eBay. Storing data is not just about how and where, but also the speed in which it can be accessed, manipulated, and presented where it can ease eBay's customer. Next characteristic of digital media that support eBay is community. Community media can play an important role in helping eBay to use storytelling to communicate and advance eBay's mission. Community media canters provide community members entree to the tools and training they need to produce digital stories. There are three ways community media can help use storytelling to start a meaningful dialogue and create modification. First, use storytelling as a community development strategy. It is through judicious storytelling that community media can help turn a community's shared experiences and concerns into a big picture. This big picture lays the foundation for an effective community development strategy for eBay. Secondly, use storytelling as an instrument for citizen empowerment. Personal stories facilitate deeper connections between people. Storytelling reaches the heart of decision-makers who often forget the predicament of the people; this is where storytelling begins to create power and empowerment. And lastly, use storytelling to build social capital. Social capital refers to personal relationships people have developed over time that enable them to influence human capital, policy-making or community initiatives. Other than that, digital communication also one of the characteristic of digital media that support eBay. Digital conversation is a powerful medium for delivering the data. In virtual global, visible communication is a perfect style of conveying your brand info by means of the use of the image, video, or minimal texts. Digital conversation may be a drawing, a commercial, a poster or any visible fabric you could find on line on social media structures. These days, the net is occupied by way of visible content and everything is revealed with the help of visual media. In addition, the characteristics of digital media that support eBay also include data. The sheer volume of data coupled with the improved analysis skills to be had these days approach that groups now have the potential to get a higher information of the way their customers behave within the beyond and present in addition to probable the future. This veritable wealth of records can be mined and manipulated into actionable information which could help remedy key business issues, promote extra products or services, and the entirety in between. Facts analytics has emerge as a vital aggressive differentiation from which most any enterprise can advantage. Lastly, ratings and reviews also one of the characteristics that include in eBay's. Ratings and reviews are the maximum essential assets of information during the customer buying process. Users are eager to verify their purchase decisions, and strive to do so using social media and real-time feedback from other users as their primary source. Good ratings and reviews will instantly create a sign of trust to others customer. The five characteristic of eBay was the most important to growth their income.
Saturday, November 9, 2019
Professional Issues in Information Technology essays
Professional Issues in Information Technology essays Professional Issues in Information Technology Dont they say first impressions last ... well, heres my first impression on: 1. the relevance of this subject to my course and; So where do I start - well how about I start with you because once Ive made my first impression on you, based on my first impressions about this subject, then I can justify the second point. It seems clear to me that I am supposed to be writing not based on what I dont know but on what I do know. Well thats easy, not a great deal, so I will be completely honest and say I havent researched any of the content in this essay and it is only based on my own understanding. So here are the key words youve given me to trigger some potential ideas in my head (a) ethics, (b) computer ethics, (c) professional ethics. My initial thought is shit however I cant say that! But why not? Im only expressing the way I feel ... is that right or wrong? a) Hang on, is that ethics? Questioning the notion of what is right or wrong and attempting to justify it through our opinions. Ive got a feeling Im warm however I cant be completely sure. What I am sure of, is you cannot pin ethics down and there is no absolute right or wrong answer. However many people and society in general will subscribe to what is considered right or wrong. Obvious examples include refrain from rape, stealing, murder, assault, slander, and fraud. And in society this is enforced through law which often based on circumstance or evolution can fall over and bring us to question what is written down as right or wrong and the issue becomes one of an ethical debate. Personally I dont believe in absolute right or wrong which is probably similar to the ideas of a Zen Buddha. A step further would have me saying I dont be ...
Wednesday, November 6, 2019
Tumor-Stroma Interaction †Biology Research Paper
Tumor-Stroma Interaction – Biology Research Paper Free Online Research Papers Tumor-Stroma Interaction Biology Research Paper Abstract Matrix metalloproteinases (MMPs) are metal-dependent endopeptidases that play pivotal roles in tumor disease progression. In many solid tumors, MMPs are indeed produced by tumor stromal cells, rather than by tumor cells. This expression pattern is, at least in part, regulated by tumor-stroma interaction via tumor cell-associated extracellular matrix metalloproteinase inducer (EMMPRIN). In vitro, recombinant EMMPRIN dose-dependently stimulated MMP-1 production by primary human fibroblast cells. Interestingly, in addition to stimulating MMP expression, EMMPRIN also induced its own gene expression. To further explore this potential positive feedback regulatory mechanism, we generated human breast cancer cells expressing different levels of EMMPRIN. Coculture of EMMPRIN-positive tumor cells with fibroblast cells resulted in a concomitant stimulation of MMP-2, MMP-9, and EMMPRIN production. This induction was EMMPRIN dependent, was further enhanced by overexpression, and was reduced by antisense suppression of EMMPRIN expression in tumor cells. Increased expression of membrane-associated EMMPRIN was accompanied by an MMP-dependent generation of a soluble form of EMMPRIN representing a proteolytic cleavage product lacking the carboxyl terminus. On the basis of these findings, we propose a model in which tumor cell-associated EMMPRIN stimulates MMPs, as well as EMMPRIN expression in tumor stroma. Increased MMP activity in tumor local environment results in proteolytic cleavage of membrane-associated EMMPRIN, releasing soluble EMMPRIN. Soluble EMMPRIN in turn acts in a paracrine fashion on stroma cells that are both adjacent and distant to tumor sites to further stimulate the production of MMPs and additional EMMPRIN, which consequently contributes to tumor angiogenesis, tumor growth, and metastasis. Introduction Degradation of basement membrane by matrix metalloproteinases (MMPs) is one of the most critical steps in various stages of tumor disease progression, including tumor angiogenesis, tumor growth, as well as local invasion and subsequent distant metastasis (1–3). MMPs are a family of more than 25 endopeptidases that are metal dependent and share a common modular domain structure. MMPs are overproduced in tumor local environment. Collectively, these enzymes are capable of cleaving all of the extracellular matrix components of the parenchymal and vascular basement membranes, normally mechanical barriers to tumor cell migration and invasion. High levels of MMPs have been correlated with increased tumor invasion capacity both in vitro and in vivo (4, 5). Clinically, elevated levels of MMPs detected in the body fluids of cancer patients correlate with adverse prognosis in various cancers (6, 7). Imbalances in the production of MMPs and their endogenous inhibitors, tissue inhibitors o f metalloproteinases (TIMPs), result in tumor angiogenesis and metastasis (2, 3, 8–12). Interestingly, recent studies of clinical tumor specimens provided evidence that most MMPs are generated by peritumoral fibroblasts in the stromal compartment, instead of by tumor cells themselves. Peritumor stromal cells are indeed responsible for the production of tumor-associated interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), stromelysin-3 (MMP-11), and gelatinase A (MMP-2), in breast, colon, lung, skin, and head and neck cancers (13–16). The induction of MMP production is, at least in part, mediated by tumor-stromal cell interaction via a tumor cell surface glycoprotein, extracellular matrix metalloproteinase inducer (EMMPRIN; 17, 18). EMMPRIN was originally purified from the plasma membrane of cancer cells as a glycoprotein of Mr 58,000, and was designated tumor collagenase stimulating factor (TCSF) because of its ability to stimulate fibroblast synthesis of collagenase-1 (MMP-1; 19, 20). Subsequent studies further demonstrated that EMMPRIN also induced fibroblast synthesis of MMP-2, MMP-3, as well as the membrane-type 1 MMP (MT1-MMP) and MT2-MMP that function as endogenous activators of MMP-2 (17, 21, 22). Therefore, EMMPRIN functions as an upstream modulator of MMP production in tumor local environment. EMMPRIN-positive tumor cells stimulate neighboring fibroblast cells to express MMPs and therefore facilitate tumor invasion and metastasis. This rationale for the function of EMMPRIN has been supported by results from several clinical studies that demonstrated high levels of EMMPRIN expression in tumor compartments as compared to peritumoral stromal tissues. These tumors include the lung (16), breast (16), bladder (23, 24), and glioma (25). Examination of EMMPRIN expression in these clinical samples by a variety of means, including Northern blot, in situ hybridization, and immunostaining, revealed that in most cases, EMMPRIN is expressed by tumor cells, but not by the neighboring stromal cells. In contrast, MMPs are expressed by peritumoral stromal cells. The biological significance of increased expression of EMMPRIN in tumor cells was investigated by in vitro studies using recombinant EMMPRIN or native EMMPRIN purified from tumor cells. EMMPRIN has been shown to stimulate the expression of various MMPs produced by fibroblasts (17, 18). The induction occurred at the transcription level and is at least in part mediated by a mitogen-activated protein kinase (MAPK) p38 kinase signaling pathway (18). The role of EMMPRIN in tumor growth and metastasis was directly illustrated using EMMPRIN-overexpressing human breast cancer cells. MDA MB 463 cells are normally slow-growing cells when they are implanted into nude mice. However, when these cells were transfected with EMMPRIN, they adopted a more aggressive growth pattern, with both accelerated growth rate and metastatic phenotypes (26). To further study the interplay between tumor cell-associated EMMPRIN and fibroblast cells, we used recombinant engineering to generate MDA MB 231 human breast cancer cells expressing different levels of EMMPRIN. We discovered a novel positive feedback regulatory mechanism controlling the interaction between tumor and fibroblast cells. Our results demonstrate that EMMPRIN positively regulates its own gene expression, in addition to stimulating MMP expression. Furthermore, we also detected generation of soluble EMMPRIN in the coculture of tumor and fibroblast cells that occurs via an MMP-dependent cleavage. On the basis of these new findings, we propose a new model in which the interplay between tumor and stromal compartments is regulated by both tumor cell surface EMMPRIN, as well as by soluble EMMPRIN, generated from MMP-dependent cleavage. Results Induction of MMP-1 Expression by Soluble Recombinant Human EMMPRIN in Primary Fibroblast Cells The stimulatory effects of EMMPRIN on cultured fibroblast cells were studied using a soluble recombinant EMMPRIN protein (srEMMPRIN) corresponding to the extracellular portion of the molecule. srEMMPRIN was added at different concentrations to primary normal human fibroblast cells in culture. Serum-free media conditioned by these cells were collected at 1 or 3 days after EMMPRIN stimulation. MMP-1 production in response to EMMPRIN stimulation was determined by assaying MMP-1 activity secreted into the conditioned medium. EMMPRIN dose-dependently stimulated MMP-1 production by normal human lung fibroblast (NHLF) cells (Fig. 1 ). The stimulation of MMP-1 production by srEMMPRIN also occurred on the transcription level as determined by TaqMan analysis (Fig. 2A ). FIGURE 1. Induction of MMP-1 expression by soluble recombinant human EMMPRIN in human primary lung fibroblast cells. srEMMPRIN dose-dependently stimulated MMP-1 production by NHLF cells. Ten thousand NHLF cells (passage 1) were plated in each well of a 96-well cell culture plate. Cells were challenged with different concentrations of EMMPRIN. After 1 day and 3 days, conditioned medium was collected from each well and MMP-1 activity was determined. Points, mean values of duplicates from three independent experiments; error bars, SDs. FIGURE 2. Induction of EMMPRIN expression by soluble recombinant human EMMPRIN in primary fibroblast cells. Primary normal human fibroblast cells of the lung were challenged with 5 Â µg/ml of srEMMPRIN. A. Total RNA was collected from untreated cells or at 4, 24, and 48 h after EMMPRIN treatment. EMMPRIN and MMP-1 gene expression level was determined by quantitative TaqMan analysis and was expressed as percentage to that in untreated cells, which was designated as 100%. B. Western blot analysis of EMMPRIN expression in fibroblast cells in response to stimulation with recombinant EMMPRIN. Cell lysate containing 50 Â µg of total protein was loaded into each lane, G361 high EMMPRIN-expressing melanoma cells (lane 1), fibroblast cells treated with EMMPRIN (lane 2), and unstimulated fibroblast cells (lane 3). Positive Feedback Regulation of EMMPRIN Gene Expression in Primary Fibroblast Cells Interestingly, when we examined the expression level of EMMPRIN in fibroblast cells after stimulation with 5 Â µg/ml EMMPRIN, we observed a substantial increase in EMMPRIN gene expression in these cells. As determined by quantitative TaqMan analysis, a 2.2-fold increase in EMMPRIN gene expression was induced at 4 h after cells were stimulated with EMMPRIN (Fig. 2A). EMMPRIN gene expression continuously increased to 4.6-fold at 24 h and 3.7-fold at 48 h after treatment. On EMMPRIN stimulation, MMP-1 gene expression level also increased (Fig. 2A). This induction occurred more rapidly and transiently, with a peak expression of a 3.3-fold increase at 4 h, and dropped to near pretreatment level at 48 h. When EMMPRIN protein expression in fibroblast cells treated with EMMPRIN was examined with Western blot analysis, we observed a strong increase in EMMPRIN protein expression (Fig. 2). In contrast, only minimal levels of EMMPRIN protein were detectable in unstimulated fibroblast cells. Tak en together, these results suggest that in addition to increased expression of MMP-1, fibroblast cells also respond to EMMPRIN stimulation by up-regulating EMMPRIN gene expression. Generation of MDA MB 231 Tumor Cells Expressing Different Levels of EMMPRIN To further explore the potential regulatory mechanism of EMMPRIN gene expression in fibroblast cells, especially in the context of tumor-fibroblast cell-cell interaction, we used recombinant DNA engineering technology to generate cancer cells that express different levels of EMMPRIN. As described in Materials and Methods, MDA MB 231 human breast cancer cells were transfected with expression vectors harboring the full-length coding region of human EMMPRIN in either sense or antisense orientations. Stably transfected cells were cloned and EMMPRIN expression level in these cells was determined by Western blot analysis. As shown in Fig. 3 , EMMPRIN protein expression in one of sense transfected cell clones S1-3 was approximately 2-fold higher as compared to that of wild-type control cells. In contrast, EMMPRIN protein expression was substantially inhibited in two antisense transfected cell clones, AS1-5 and AS2-5, to only 47% and 62% of that in wild-type cells. Changes in EMMPRIN protein expression in these engineered cells were also independently confirmed by ELISA analysis (Fig. 4 ). In addition, changes in EMMPRIN protein expression also occurred on cell surface in sense and antisense transfected cells, respectively, as determined by fluorescence-activated cell (FAC) analysis (data not shown). FIGURE 3. Generation of MDA MB 231 tumor cells expressing different levels of EMMPRIN. A. Western blot analysis of EMMPRIN protein in cell lysates. Samples containing 20 Â µg of total protein from each cell type were loaded in duplicates, MDA MB 231 wild-type cells (lanes 1 and 2), S1-3 cells (lanes 3 and 4), AS1-5 cells (lanes 5 and 6), and AS2-5 cells (lanes 7 and 8). A single EMMPRIN protein band of approximately Mr 52,000 was detected in all of the samples. B. Quantitative determination of EMMPRIN expression by scanning densitometry. EMMPRIN Western blot was scanned and the pixel density of each band was determined by scanning densitometry. EMMPRIN expression level in each cell type was expressed as the percentage of density of that in wild-type cells (lane 1), which was designated as 100% error bars, SDs. FIGURE 4. Stimulation of both cell-associated and soluble EMMPRIN expression in coculture of tumor cells and fibroblast cells. EMMPRIN protein concentration was determined by ELISA analysis in total cell lysate (A) or in conditioned medium (B) of breast cancer cells expressing different levels of EMMPRIN either in monoculture or in coculture with NHDF cells. All concentrations were normalized to total protein amounts. WT, wild-type MDA MB 231 human breast cancer cells; S1-3, sense transfected EMMPRIN-overexpressing cells; AS1-5 and AS2-5, antisense transfected cells. Columns, representative of two independent experiments; error bars, SDs. We next used these cells with different levels of EMMPRIN protein expression to address the role of tumor cell-derived EMMPRIN in regulating its own expression during tumor-fibroblast cell interaction. Stimulation of Both Cell-Associated and Soluble EMMPRIN Expression in Coculture of Tumor Cells and Fibroblast Cells In monoculture of tumor cells or fibroblast cells, only low levels of EMMPRIN protein were detected in cell pellets or conditioned medium by ELISA analysis. Transfection with sense or antisense expression constructs resulted in substantial changes in cell-associated EMMPRIN expression, with an increase from 3.32 ng/ml in wild-type to 7.2 ng/ml in sense transfected S1-3 cells, and a decrease to 0.85 and 1.43 ng/ml in antisense transfected AS1-5 and AS2-5 cells, respectively (Fig. 4A). Only low levels of soluble EMMPRIN were detected in conditioned medium of these cells in monoculture. Transfection of tumor cells with sense and antisense expression constructs resulted in only minor changes in soluble EMMPRIN protein levels (Fig. 4B). The expression of cell-associated EMMPRIN was readily induced when tumor cells were cultured together with fibroblast cells. In coculture, EMMPRIN was detected at 10 ng/ml as compared to 0.8 ng/ml in fibroblast cells and 3.32 ng/ml in wild-type tumor cells in monoculture (Fig. 4A). This increase in EMMPRIN expression in coculture was mediated by tumor cell-associated EMMPRIN. When EMMPRIN expression in tumor cells was inhibited by antisense transfection in AS1-5 and AS2-5 cells, the increase in EMMPRIN expression stimulated by coculture was concomitantly reduced to minimal levels (Fig. 4A). It is known that coculture of EMMPRIN-positive tumor cells with fibroblast cells stimulates MMP expression (22, 27). These MMPs can in turn cleave cell surface proteins to generate soluble proteins. We therefore postulated that there may be an increase in soluble EMMPRIN protein level in conditioned medium of these cells in coculture. In monoculture, the levels of soluble EMMPRIN were extremely low in conditioned medium of fibroblast cells (0.31 ng/ml) and wild-type tumor cells (0.53 ng/ml; Fig. 4B). However, coculture of tumor cells with fibroblast cells induced the release of substantial amounts of soluble EMMPRIN, 7.48 ng/ml by wild-type and fibroblast coculture and 10.39 ng/ml by S1-3 and fibroblast coculture (Fig. 4B). Similar to cell-associated EMMPRIN, the increase in soluble EMMPRIN expression was also correlated with the degree of EMMPRIN expression in tumor cells. Inhibition of EMMPRIN expression by antisense transfection virtually abolished the generation of soluble EMMPRI N in coculture (Fig. 4B). Taken together, these results demonstrate a positive feedback regulatory mechanism of EMMPRIN gene expression during tumor-fibroblast cell-cell interaction. In addition to stimulating EMMPRIN expression and MMP expression, tumor cell-associated EMMPRIN also mediates the release of soluble EMMPRIN during tumor-fibroblast cell interactions. MMP-Dependent Generation of Soluble EMMPRIN in Coculture of EMMPRIN-Positive Tumor Cells and Fibroblast Cells Western blot analyses using antibodies against different regions of EMMPRIN were performed to further characterize soluble EMMPRIN generated in the coculture of tumor cells and fibroblast cells. Antibodies against the extracellular portion of EMMPRIN molecule detected a single band of approximately Mr 52,000, consistent with the size of intact protein, in total cell lysates. Meanwhile, this same antibody detected a slightly smaller molecule in the conditioned medium from coculture, indicating a loss of a portion of EMMPRIN protein (Fig. 5A ). Interestingly, antibodies specific to the carboxyl terminus of EMMPRIN only detected EMMPRIN in total cell lysates, but failed to detect any EMMPRIN protein in conditioned medium (Fig. 5A). Taken together, these data suggest that soluble EMMPRIN secreted into coculture medium of tumor and fibroblast cells is likely a cleaved product of the full-length transpanning form of membrane EMMPRIN. FIGURE 5. Soluble EMMPRIN in coculture of EMMPRIN-positive tumor cells and fibroblast cells- proteolytic cleavage products generated in an MMP-dependent fashion. A. Western blot analyses of cell lysates or conditioned medium of coculture of wild-type MDA MB 231 human breast cancer cells and fibroblast cells. Membranes with 50 ng recombinant EMMPRIN extracellular domain (lane A), cell lysates of 50 Â µg total protein (lanes B and D), and conditioned medium of 50 Â µg total protein (lanes C and E) were blotted with antibodies that recognize extracellular domain (lanes A–C) or intracellular carboxyl terminus (lanes D and E). B. Soluble EMMPRIN concentration in conditioned medium from coculture of tumor cells and fibroblast cells was determined using ELISA analysis. 1,10 phenanthroline was included in the study from 0.1, 0.5 to 1.0 Â µM to inhibit MMP enzymatic activity. WT, wild-type MDA MB 231 human breast cancer cells. Columns, representative of two independent experiments; error bars, SDs. , NHDF; , WT; , WT + NHDF; , WT + NHDF + 0.1 Â µM 1,10 PA; , WT + NHDF + 0.5 Â µM 1,10 PA; , WT + NHDF + 1.0 Â µM 1,10 PA; *, P < .05 compared to WT + NHDF. Because the generation of soluble EMMPRIN occurred concomitantly with increased production of MMP in coculture of tumor and fibroblast cells, we speculated that the release of soluble EMMPRIN might be mediated by MMP-dependent proteolytic cleavage. To further explore the mechanism of soluble EMMPRIN generation, 1,10 phenanthroline (1,10 PA) a general metalloproteinase inhibitor, was used at noncytotoxic concentrations to inhibit the enzymatic activity of MMPs. As shown in Fig. 5B, inhibition of MMP activity by 1,10 PA resulted in significant decreases in the level of soluble EMMPRIN in a dose-dependent fashion. These results demonstrate that the generation of soluble EMMPRIN stimulated by tumor fibroblast cell-cell interactions is the result of proteolytic cleavage of membrane-associated EMMPRIN by increased MMP activities in coculture. Discussion It is now known that the microenvironment of the tumor-host interface plays a proactive role during malignant disease progression, including the transition from carcinoma in situ to invasive cancer, tumor cell proliferation, and tumor cell dissemination and metastasis (28). On the host side, the stromal compartment is comprised of a variety of cell types, including immune cells, inflammatory cells, muscle and myofibroblast cells, and vascular cells. Tumor cells express molecules, either secreted or presented on cell surface, to interact with surrounding stromal cells. In the current study, we have demonstrated that EMMPRIN exists in both soluble and membrane-bound forms. Generation of soluble EMMPRIN resulted from tumor-fibroblast cell interaction in an EMMPRIN-dependent fashion, and was mediated by MMP proteolytic activities. These novel findings suggest a positive feedback regulatory mechanism of EMMPRIN expression that occurs at tumor-host interface. EMMPRIN is normally expressed as a glycoprotein on tumor cell surface that migrates at an apparent molecular size of Mr 58,000 (19). The domain structure of EMMPRIN consists of an extracellular portion which contains two immunoglobulin-like domains, a transmembrane domain, and a short cytoplasmic domain (19). It has been suggested that tumor cell-associated EMMPRIN exerts its MMP stimulatory effects on fibroblast cells via close cell-to-cell contact. However, the production of soluble EMMPRIN by tumor cells has recently been indicated in several studies (29, 30). In these studies, tumor cells affect fibroblast cells in the absence of physical contact in an EMMPRIN-dependent fashion, resulting in increased MMP-2 expression and activation (29), or enhanced cell migration or invasion (30). In addition, soluble full-length EMMPRIN has been purified from concentrated culturing medium of breast cancer cells, presumably secreted in shed vesicles (31). However, secreted soluble EMMPRIN in ca ncer cell monoculture is estimated to account for only 2–3% of EMMPRIN produced by these cells (31). In the present study, we have demonstrated the release of a substantial amount of soluble EMMPRIN into cell culture medium of cocultured tumor and fibroblast cells. Because fibroblast cells respond to EMMPRIN stimulation in producing increased levels of EMMPRIN, it is likely that the soluble EMMPRIN detected in coculture is derived from both tumor and fibroblast cells. In addition, the soluble EMMPRIN generated in coculture lacks the intracellular carboxyl terminus as determined using an antibody against the intracellular region of the molecule. In contrast, this carboxyl terminal region was preserved in cell-associated EMMPRIN. More interestingly, generation of soluble EMMPRIN in coculture could be efficiently blocked via inhibiting MMP activity. Therefore, this soluble EMMPRIN likely represents the proteolytic product of membrane-associated EMMPRIN. The generation of soluble EMMPRIN at the interface of tumor-host interaction may have profound biological significance. The soluble EMMPRIN could diffuse away from local tumor invasion site and stimulate stromal cells at distant sites. We and others have shown that soluble EMMPRIN consisting of only the extracellular portion of the molecular is functional in stimulating MMP expression in fibroblast and endothelial cells (17, 32). Increased MMP activity in the stromal compartment in turn promotes tumor invasion and angiogenesis. The receptor on fibroblast cells that is responsible for EMMPRIN-mediated stimulation of MMP production has remained elusive (17, 21). It has been suggested that EMMPRIN may serve as its own counter-receptor in cancer cells, thus stimulating MMP via a homophilic interaction (33). One could speculate that EMMPRIN on fibroblast cells could also serve as counter-receptors for tumor cell-associated EMMPRIN in stimulating MMP expression. However, this hypothesis is not supported by the fact that only extremely low levels of EMMPRIN expression could be detected in normal fibroblast cells. Our finding of a novel positive feedback regulatory mechanism of EMMPRIN expression provides an alternative explanation for the potential role of EMMPRIN as its own counter-receptor in fibroblast cells. When fibroblast cells were exposed to EMMPRIN stimulus, EMMPRIN expression is up-regulated in these cells. Newly synthesized EMMPRIN could then be presented on the cell surface and serves as the counter-re ceptor for EMMPRIN-dependent signaling between tumor and fibroblast cells. This novel regulatory mechanism is supported by recent findings of EMMPRIN mRNA expression in peritumoral fibroblasts in ovarian carcinoma (34). However, this homophilic interaction likely only accounts for EMMPRIN-mediated tumor-host interaction in some tumors because EMMPRIN expression has not been detected in the stroma of many other tumors including melanoma (35), or lung and breast cancer (16). In these samples, despite of a lack of EMMPRIN expression in stromal tissue, MMP expression is stimulated in stromal tissues adjacent to EMMPRIN-positive tumor cells, suggesting that there might be an unknown receptor(s) on stromal cell surface mediating these interactions. In conclusion, we have identified a novel positive feedback regulatory mechanism of EMMPRIN expression in fibroblast cells and discovered a soluble form of EMMPRIN. These findings suggest an amplification of EMMPRIN-mediated, MMP-dependent signaling events at the tumor and host interface, as well as at distant sites (Fig. 6 ). FIGURE 6. Proposed model for signal loops between EMMPRIN and MMP and tumor cells and host cells. Tumor cells use cell surface EMMPRIN to initiate contact with surrounding fibroblast cells (1), signaling fibroblast cells to synthesize MMPs (2). MMPs secreted by fibroblast cells subsequently cleave cell surface EMMPRIN and generate soluble EMMPRIN (sEMMPRIN; 3). These sEMMPRIN molecules, in turn, act on cells either in local tumor environment or diffuse away to act on distant cells (4) to further stimulate MMP and EMMPRIN expression (5) and augment the migration and invasion potential of tumor cells (6). Materials and Methods Cell Culture MDA MB 231 human breast carcinoma cells were purchased from American Type Culture Collection (Manassas, VA) and were cultured under recommended conditions. Briefly, cells were cultured in DMEM containing 10% fetal bovine serum (Life Technologies, Inc., Grand Island, NY). NHLF or normal human dermal fibroblast (NHDF) cells were obtained from Clonetics (Walkersville, MD) and were cultured in fibroblast growth medium containing 1 Â µg/ml human recombinant fibroblast growth factor (hFGF), 5 mg/ml insulin, 50 mg/ml gentamicin, and 50 mg/ml amphotericin B, at 37Â °C, 5% CO2. For coculture experiments, 100,000 cancer cells (MDA MB 231, MDA MB 231 S1-3, MDA MB 231 AS1-5, or AS2-5) were cultured together with 200,000 NHDF cells in a six-well cell culture plate in complete DMEM culturing medium. After 24 h, culturing medium was replaced with fresh serum-free DMEM and cells were cultured for 2 days. Culture medium was then replaced with 1.0 ml of fresh serum-free DMEM. Conditioned medium was collected 3 days later and secreted EMMPRIN protein concentration was determined using ELISA. Cells were lysed with 200 Â µl lysis buffer [50 mM Tris (pH 7.8), 150 mM NaCl, and 1% NP40] to determine cell-associated EMMPRIN concentrations. Cell Treatment and MMP-1 Activity Assay Recombinant EMMPRIN corresponding to the extracellular domain of human EMMPRIN protein was produced in NSO cells (RD Systems, Minneapolis, MN). MMP-1 activity in serum-free medium conditioned by fibroblast cells treated with different amounts of recombinant EMMPRIN protein was quantitatively determined using an MMP-1 Activity Assay Kit according to product manual (RD Systems). Briefly, MMP-1 contained in 150 Â µl of standards or samples was captured by anti-MMP-1 antibodies immobilized on the bottom of assay wells. Captured MMP-1 was subsequently activated by 4-aminophenylmercuric acetate (APMA). MMP substrate added into each well was cleaved by activated MMP-1 and the resulting fluorescence was determined using SpectraFluor Plus Plate Reader (TECAN, Research Triangle Park, NC) with the following parameters: excitation wavelength at 320 nm and emission wavelength at 405 nm. Generation of Sense and Antisense Expression Constructs and Establishment of Stable Transfectants To study the function of EMMPRIN in mediating tumor and stromal fibroblast cell interaction, the cDNA sequence corresponding to human EMMPRIN open reading frame (ORF) was PCR amplified and subcloned into pcDNA3.1TOPO vectors (Invitrogen, Carlsbad, CA). The EMMPRIN open reading frame was cloned in both sense and antisense orientations for cytomegalovirus promoter-driven expression in mammalian cells. Transfection of MDA MB 231 human breast carcinoma cells was performed using Effectene transfection reagents according to manufacturer's recommendations (Qiagen, Valencia, CA). Stably transfected cells were selected using Genicitin at 1000 Â µg/ml (Life Technologies). Individual transfectant colonies were established by cloning antibiotic-resistant cell colonies. Effects of sense and antisense transfection on EMMPRIN protein expression were determined using Western blot analysis and ELISA. RNA Sample Preparation and TaqMan Quantitative Reverse Transcription-PCR Total RNA was extracted from cells using RNeasy Kit (Qiagen) following manufacturer's instructions. Five micrograms of total RNA were used in the reverse transcription (RT) reactions which were carried out in a 50-Â µl total volume using Superscript First-Strand Synthesis System for RT-PCR kit following manufacturer's instructions (Invitrogen). Briefly, RNA samples were mixed with 0.5 Â µg/Â µl Oligo(dT), 0.4 mM dNTP mix in a total volume of 25 Â µl and were incubated at 65Â °C for 5 min, followed by quick cooling on ice for 2 min. The tubes were spun briefly and added with 5 Â µl 10x RT buffer, 10 Â µl 25 mM MgCl2, 2 Â µl 0.1 M DTT, 1 Â µl RNaseOUT, 1 Â µl (50 units) of Superscript II RT, and 6 Â µl nuclease-free water. The tubes were gently mixed and incubated at 42Â °C for 50 min. The reaction was terminated at 70Â °C for 15 min followed by quick cooling on ice for 2 min. The tubes were spun briefly and 1 Â µl of RNase H was added and incubated for 20 min at 37Â °C before proceeding to amplification of the target gene. Real-time PCR analyses were performed in 50 Â µl volume containing 2x TaqMan Universal PCR Master mix (Perkin-Elmer, Norwalk, CT), appropriate amounts of cDNA or genomic DNA, and 200 nM of TaqMan primers and 400 nM of TaqMan probes. Primer pairs and probes used in the study were designed using Primer Express software (Perkin-Elmer), with sequences listed in Table 1. Probes were labeled at the 5'-end with fluorescent reporter dye Fam and at the 3'-end with fluorescent quencher dye Tamra by Synthegen (Houston, TX) to allow direct detection of PCR products. Real-time PCR amplification and detection were performed in 96-well optical plates using ABI 7900HT sequence detector (PE Biosystems, Norwalk, CT). PCR conditions included thermal cycles of 30 s of 95Â °C for denaturing, 30 s of 60Â °C for annealing, and 60 s of 68Â °C for elongation. Relative gene copy numbers were calculated using a standard curve generated using PCR standards, serially diluted human genomic DNA (Clontech, Palo Alto, CA). Protein Electrophoresis and Western Blot Analysis Stably transfected cells were lysed in cell lysis buffer containing 50 mM Tris (pH 7.8), 150 mM NaCl, and 1% NP40. Protein concentration of cell lysate or conditioned medium was determined using the MicroBCA method (Pierce, Rockford, IL). Equal amount of proteins was loaded onto 4–15% gradient gels and was separated by SDS-PAGE under reducing conditions. Resolved proteins were electrophoretically transferred to nitrocellulose membranes (Invitrogen). The membranes were blocked with 5% low fat dry milk in TBS-T [10 mM Tris (pH 7.2), 50 mM NaCl, 0.5% Tween 20] for 1 h at room temperature, followed by incubating with primary antibody at 4Â °C overnight. Anti-EMMPRIN monoclonal antibody purchased from Research Diagnostics Inc. (Flanders, NJ) recognizes the extracellular portion of the protein. C-19 polyclonal antibody from Santa Cruz Biotechnology (Santa Cruz, CA) was raised against peptides of the carboxyl terminus of EMMPRIN protein. Blots were extensively washed with TBS-T and incubated with 1:5000 dilution of horseradish peroxidase (HRP) conjugated secondary antibody (Vector Laboratories, Burlingame, CA) diluted in TBS-T for 1 h at room temperature. Labeled proteins were visualized with Western Blotting Luminol Reagent (Santa Cruz Biotechnology). Pixel density of protein bands on Western blot was determined using Un-Scan-It software (Silk Scientific Corporation, Orem, UT). EMMPRIN ELISA EMMPRIN protein concentration in conditioned medium was determined using EMMPRIN ELISA. Briefly, 96-well Nunc Immuno Plates (Nunc, Denmark) were coated overnight at 4Â °C with 50 Â µl of anti-EMMPRIN antibody (RD Systems) at 5 Â µg/ml in buffer A (pH 7.4, 20 mM Tris-HCl, 150 mM NaCl, 1 mM CaCl2, 1 mM MgCl2, and 10 Â µM MnCl2). After one wash in buffer A, nonspecific binding sites were blocked with 150 Â µl of blocking buffer [3% bovine serum albumin (BSA) in buffer A] for 1 h at 37Â °C. Wells were then rinsed two times with binding buffer (buffer A with 0.3% BSA and 0.2% Tween 20). Either recombinant human EMMPRIN or conditioned medium was added into each well and was incubated at 37Â °C for 2 h. After three washes with binding buffer at RT, plates were blocked with 150 Â µl of blocking buffer (3% BSA in buffer A) at 37Â °C for 1 h. Fifty microliters of 1:5000 diluted biotin-conjugated anti-EMMPRIN antibodies (RDI-147, Research Diagnostics) were added into each well and incu bated at 37Â °C for 2 h. After three washes with binding buffer, 50 Â µl of horseradish peroxidase-conjugated streptavidin 1:10,000 diluted in binding buffer were added into each well, and were incubated at 37Â °C for 1 h. After three washes with binding buffer at RT, 50 Â µl of developing buffer (1 mg/ml O-phenylenediamine, 0.1 M citric acid, 0.2 M sodium phosphate, 0.01% H2O2) were added to each well and incubated at RT until color develops. Colorimetric reactions were stopped by adding 25 Â µl of 4 N H2SO4. ELISA data acquisition was performed using VersaMax Tunable MicroPlate Reader (Molecular Devices, Sunnyvale, CA) at 490 nm. Data were analyzed using Softmax Pro 3.1 software (Molecular Devices). 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