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How to Write a Wedding Speech: 13 Steps (with Pictures) - wikiHow
bumpy paper writing There are many reasons why some children. have difficulty learning how to form letters. and speech wedding, numbers, and how to write neatly. T here. Analysis Essay Assignment. are lots of fun ways to make this important. Learn about the handwriting curriculum that is being taught to speech help, your child at school. If your child is struggling, ask the teacher for. worksheets you can practice on rotman essay, at home. Letters in print should be written from writing help wedding top to bottom and from left to right. A multi-sensory approach to learning is a great approach for all children. Prepare a tray or baking pan with a shallow layer of any. Essay. impressionable substance (sand, sugar, salt, bird seed, rice, pudding, shaving cream, etc.) Practice forming letters and numbers. using the index (pointer) finger. Remember to form letters from top to bottom and from left to right.
Make raised letters on index cards to use for t rac ing with the index finger. Here 's how to make them : use glue to form the. letter, then cover it with sand or bird seed; puffy fabric paint; add food coloring to white glue and form letters in color . Speech Help Wedding. Make. sure to trace letters and numbers from controversy analysis essay top to bottom and from left to right. Pre-write letters on paper and have the child trace over them with glue (squeeze bottle type) form letters by gluing beans, rice, seeds, etc. on paper. form letters with putty, play doh, clay, modelling compound, etc. write letters with a vibrating pen; this additional sensory input will enhance the child's memory for letter formation. For letter recognition, have child read through a story at speech wedding his/her reading level and circle all of the a's or b's, etc. Write letters in the air with the pointer finger and thesis, large arm movements. Try it with eyes closed, then eyes open. Write letters on your child's back and see if he/she can guess what letter it is.
Write on each other's palms. Write capital letters and numbers within boxes that are rectangular, oriented to be tall rather then wide. U se the attributes of. the box as landmarks. For example, an H is speech formed starting at the top left corner to draw a line going down the thesis on political interest left side of the. box , then down the right side and finally a horizontal line across the middle (developed by the Handwriting Without Tears Writing letters from speech writing top to bottom (printing/manuscript) forming letters to write words in a consistent direction is the crucible essay choices most efficient way to write. For printing, the top-down method is. Review all of the Learning Letter activities above.
Emphasize starting at speech the top and working from left to right. On lined paper, in rotman video questions the left margin draw a simple house: the roof (a triangle) is within the speech writing wedding top half of the line, the house is a square. Rotman. within the bottom half, below the house is the basement. Remind the child to writing help wedding, start letters in the attic or roof if capitols, tall. lower case letters and video essay, numbers. Small letters stay in the house and start at speech help wedding the top of the box. Descending letters also start at. the top of the box and live in the basement.
Make up a song or a chant about starting letters at the type. The Handwriting Without Tears writing program has a CD filled. with songs about letter writing. Write letters in the air with the papers pointer finger and with large arm movements. Try it with eyes closed, then eyes open. Write letters on your child's back and see if he/she can guess what letter it is. Write on each other's palms. On a large chalk board or dry erase board, write large letters, always starting at the top.
Turn them into rainbow letters by. going over them with different colors. Write letters on paper that is placed over writing help, a textured surface, such as sandpaper, plastic craft canvas or rubbing plates. The. tactile feedback from the bumpy surface will enhance the child's memory for correct letter formation. Video Essay. Writing on Lines.
In many Kindergarten classrooms, children begin to write on paper without lines. Eventually lines are introduced, sometimes. around mid-year. If your child has difficulty using writing lines effectively, here are some strategies: Highlight the bottom half of the line. Instruct the child to stay in speech help wedding the yellow (or whatever colored was used) for all the small. Choices. letters; tall letters start at the top line and descending letters dive down from the middle. Darken the help lines to increase awareness; sometimes copying paper on the darkest setting will mak e the lines easier to see.
Create a raised base (bottom) line b y using glue once it's dry or Wikki Stix. Analysis. Use the clear color changing marker on the base line, then write with a color marker in the set. When the color has changed the. Writing Wedding. child knows he/she has reached the bottom line. There are a variety of phrases german, paper styles and modifications available for purchase. Speech Help. Talk to your child's therapist for recommendations. On lined paper, in the left margin draw a simple house: the roof (a triangle) is essay phrases within the top half of the line, the house is a square. within the bottom half, below the house is the basement. Tall letters start in the attic, short letters are inside the house and. descending letters go down to the basement.
Highlight the left margin to increase the child's awareness of where to begin and continue sentences. Highlight the right margin if the child tends to speech writing wedding, cram in words at the ends of the lines. Teach child to place a ruler at the left margin; remind him/her to return to the ruler to continue sentences. Highlight the left margin green (for go) and right margin red (for stop). Teach child to finger space: place his/her left index finger (if right handed) after each word he writes. For lefties, it's better to space with an object, such as a popsicle stick.
Have child make his/her own finger spacer: decorate a popsicle stick or tongue depressor, Call it a spaceman Have child place a dot with a stamp marker or highlighter after each word as a spacer, or to make a small dot with the pencil; later. he/she can erase the dots. Thesis Interest. It's better to have large exaggerated spaces, especially for young writers. Writing. Using 2 fingers to space may be a good way to start. Try graph paper, enlarge the boxes if necessary on a copy machine, and write one letter in each box with one box in between. Controversy Analysis Essay Assignment. Readispace paper, made by Mead, can be purchased at some WalMart stores or ordered directly from the Mead website: this. Speech Writing Wedding. has short vertical lines on each writing line for writing and writing, spacing letters evenly. To increase awareness and also f or fun, challenge your child to speech help wedding, read sentences that d on' t have spaces in between words. Have. him/her rewrite the sentences correctly. Letter and Number Reversals (writing backwards) Reversals of custom, numbers and upper case letters can be fixed by writing within boxes ( rectangular shaped and speech help wedding, oriented to be tall. rather th a n wide ). Use the features of the box as landmarks. Crucible Essay Choices. Add a sticker or draw a star at the top left corner of the box. (developed by speech the Handwriting Without Tears program , www.HWTears.com ) . For the number 5, for example, tell child to custom papers report, start. instructions for most numbers and letters. Lower case letter reversals are commonly seen with the letters b/d, p/q/g, w/m, j, s and z. For b/d, teach child to make your bed by speech writing wedding forming 2 thumbs up, touching knuckles together, the left hand forms a 'b', the right hand forms a 'd', pictured at right.
Talk to your child's therapist or teacher about worksheets with activities to help children. identify problematic letters. As examples, there are circle all the w's mixed within a field. of m's; coloring activities to color targeted letters, hidden pictures, and writing phrases, more. work on learning the directional terms right and left. Can your child identify his/her own right and left hands point to wedding, objects. on the right vs. left sides of his immediate environment? Try this fun dice game: called Left-Center-Right at http://www. Thesis Interest. form letters with putty, play doh, clay, modelling compound, etc. For letter recognition, have child read through a story at his/her reading level and circle all of the b 's or d 's, etc. Write letters in the air with the pointer finger and large arm movements. Try it with eyes closed, then eyes open. Write letters on your child's back and see if he/she can guess what letter it is. Write on each other's palms.
People hold pencils and other writing tools in a variety of ways. The most common grip is called a tripod grip. Speech Help Wedding. This involves. pinching the pencil between the pads of the thumb and index finger while the pencil rests on the side of the middle finger. Many. people use a quadrupod grip which is similar except two fingers are on top of the pencil opposing the thumb and the pencil rests on. the side of the ring finger. And there are many variations. For more information about optimal pencil grip, visit Thumb Opposition. and scroll down to information on web space. MOST PENCIL GRIPS DO NOT NEED TO BE CORRECTED.
It's important to. discuss this with your child's therapist. If you feel that your child's grip on the pencil is affecting his/her handwriting legibility, there are a number of activities to help. develop the correct muscles for holding. On Political. Refer to the section on Pincer Grasp for ideas. when coloring, drawing and writing use short writing and drawing tools such as broken crayons, golf pencils, Pip Squeak markers, short colored pencils or small bits of chalk. Discuss your conerns with your child's therapist. There are a variety of finger positioning devices available, if needed. Posture for Writing. Ideal sitting posture for writing is to be upright in the chair with the speech help wedding hips and knees at 90 degrees and diversity common, feet.
flat on the floor. The elbows should be bent at 90 degrees or less. When the writing wedding arms are straight down at the. sides, the desktop should be about halfway between the crucible choices shoulder and elbow or lower. The desk should be lowered (or the chair. Speech Writing Help Wedding. raised) if the crucible desktop is higher than this. Speech Writing Help Wedding. The head should be a reasonable distance from the paper, about rotman questions, 12 to writing wedding, 20 inches. When writing, the wrist should be in a neutral position or slightly extended (hand bent back). The best writing surface is a slanted one.
This helps to keep the head upright and supports the forearm and hand in the optimal. position for writing. Essay. Most school desks are not slanted but a simple modification is to use a wide 3-ring binder (3 to 4 inch spine)
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My Dream Job Essays and Research Papers. Essay: Dreams From My Father Barack Obama’s Dreams From My Father is exactly what it claims to be . by title, a story of speech writing, race and german, identity. Speech Writing Help Wedding! Barack Obama comes from a diverse background, which he explores throughout the essay phrases german book. Speech! Having a white American mother and essay choices, black Kenyan father, he has a different experience than the speech majority of people in no plagiarism society when it comes to race and identity, however still it seems similar to the experience of writing help wedding, many blacks as described in William E. Cross’s Black Psychological. African American , Barack Obama , Black people 1303 Words | 3 Pages. Presentation: Barack Obama Dreams from essay My Father Barack Obama – “ Dreams From My Father-A Story of Race and Heritance” Today I want to introduce you United States President . Barack Obama’s first memoir, dreams from my father. Wedding! It was first published in July 1995 as he was preparing to launch his political career and crucible essay, republished in August 2004. Help! Author: Since my book is an autobiography I won’t tell you everything about the author, I just will give some personal facts about him.
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It is through the thesis on political steady love of his family that allows Obama to truly find acceptance. African American , Ann Dunham , Barack Obama 841 Words | 3 Pages. Obama: Individual in the Community(Dreams of writing, My Father) Alyna Torres QU 101 Professor Matt Tortora September 29, 2010 Dreams from diversity essay app My Father There are many barriers one must . overcome, and to accomplish this, one must find their distinctiveness and take a key role in the community. Speech Help! Throughout the novel, Dreams from controversy my Father by our current president Barrack Obama, Barrack demonstrates the true meaning of speech writing wedding, being an individual. He is highly active in his community, despite the fact that he is part of the black community. Papers No Plagiarism! The economic, social, and. A Great Way to Care , Barack Obama , Dreams from speech writing help wedding My Father 1916 Words | 5 Pages. migration. Controversy Analysis Essay Assignment! To add on, I will inform you about he migration that occurred through out my relatives lives.
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Prepared Remarks of President Barack Obama: Back to School Event. the whole speech, and pathos when he tells about his own experience and expresses how he feels on help this matter in the speech, which in general, makes it . easier to earn people's attention. “I know the feeling. When I was young my family lived in Indonesia for a few years, and my mother didn't have the money to send me where all the American kids went to school. So she decided to teach me extra lessons herself, Monday through Friday – at essay writing phrases german, 4:30 in speech writing wedding the morning.” Feelings are important to custom no plagiarism use, especially. 2008 Democratic National Convention , Barack Obama , Democratic Party 1117 Words | 3 Pages. why did Barack wrote a book for his father? Dreams for writing help, my father Barack Hussein Obama was born in 1961, in Honolulu, . Hawaii. Essay! His mother was a white American girl from wedding Kansas and his father a black man from Luo, a Kenyan tribe. At that time their union was unusual, so Barack had to essay common live with that combination of races. He grew up with his mothers family far from his father and speech, thus to his black origins. Barack had a hard time understanding his situation during his childhood.
He was lost. African American , Barack Obama , Democratic Party 823 Words | 2 Pages. Dreams from essay choices My Father: A Story of Race and Inheritance Summer . Reading Assignment 1. Help! Explain the papers no plagiarism author’s purpose for writing this book? The author of this book is Barack Obama, and the reason I believe he wrote this book is to speech writing wedding share his experience growing up and for people be able to understand his personal background. He shared experiences from being raised by diversity essay common app his mother and grandmother while his father was living in wedding Kenya. 2008 Democratic National Convention , Ann Dunham , Barack Obama 530 Words | 2 Pages.
Barack Obama: 'Dreams from crucible My Father' Personal Response Number One Title: Dreams from My Father ‘A Story of Race and Inheritance’ Author: Barack Obama Genre: . Autobiography, Life Memoir Before Barack Obama was a Politician he was an author. ‘ Dreams from writing My Father: A Story of Race and Inheritance’ is an Auto-Biography written by Barack Obama. The book describes Obama’s life in choices three parts, from his birth in Honolulu, Hawaii up to the final part of the book which includes his emotional and revealing trip back to his father’s homeland;. African American , Ann Dunham , Barack Obama 765 Words | 2 Pages. MY VACATION AT THE CITY I can still remember the time I went to the city with my family just to have a bit of relaxation since . we are over and done with our periodical examinations. Speech Writing Help Wedding! Hoping that we can spend some precious time together, I felt so excited while we are on our way. I expected a lot of jokes and laughter, and full of satisfaction when we get there. After a long journey on a muddy and terribly devastated nautical highway, we reach the app city, the speech writing help only city and the capital of app, our province. Barack Obama , Democratic Party , Dreams from speech writing My Father 773 Words | 2 Pages.
Life without Television When my family’s only assignment television set went to the repair shop the other day, my parents, . my sister, and I thought we would have a terrible week. Wedding! How could we get though the essay app long evenings in wedding such a quiet house? What would it be like without all the shows to keep us company? We soon realized, though, that living without television for a while was a stroke of papers no plagiarism report, good fortune. Help! It became easy for each of us to enjoy some activities alone, to complete some postponed chores. Anxiety , Barack Obama , Dreams from My Father 606 Words | 2 Pages. My Dream Job ? I believe that all of the controversy analysis men that contributed their story to Bob Greene’s “Cut” were affected by . rejection and humiliation as children.
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MDM SUPARNA [pic] My Dream Job Child’s Dream . Everyone has a dream . I too dream of controversy analysis, a job that will make me child’s dream comes true. My grandfather and father both traditional Chinese physician. They have excellent medical skill and lofty medical ethic. In China, The doctor is called ‘angles in writing help white’, People respect them. Writing Phrases German! I used to get sick in my childhood. My father always can cure my disease by speech writing help wedding traditional Chinese medical.
I think. Acupuncture , Chinese herbology , Health 838 Words | 4 Pages. ? In The Life You Imagined and Dreams From My Farther, Derek Jeter and Barack Obama use a . variety of writing strategies to convey their goals. Both texts describe their childhood dreams and goals, however each author uses different writing styles such as academic vocabulary, cause and essay, effect, colloquial vocabulary and figurative language. Derek Jeter and Barack Obama both used Figurative language and cause and.
Barack Obama , Dreams from My Father , High school 385 Words | 2 Pages. My Dream Job My first day in high school was so overwhelming. My heart was racing and . Speech! my legs were shaking. I was excited and nervous at the same time. I was so happy to see all my friends after what seem to rotman video questions be a very long, summer break.
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He worked there for three years from June 1985 to speech wedding May 1988. During his three years as the DCP's director, its staff grew from one to thirteen . and essay writing phrases, its annual budget grew from $70,000 to $400,000. His achievements included helping set up a job training program, a college preparatory tutoring program, and a tenants' rights organization in Altgeld Gardens. Obama also worked as a consultant and writing help, instructor for the Gamaliel Foundation, a community organizing institute. In mid-1988, he. Ann Dunham , Barack Obama , Columbia University 634 Words | 2 Pages. My Dream Job For many years since I was young I had the passion to thesis be a police officer, I wanted to be that hero . Speech! who I seen on television that saved everybody from danger and harm but little did I know it wasn’t as easy as television made it come out to be. As my school days passed I finally came to a conclusion of what I wanted my life to be like. High school was the german turning point where I no longer wanted to be a police officer anymore, I grew knowledge of better opportunities for me and being.
Bar association , Barrister , Corporate lawyer 1300 Words | 3 Pages. ongoing training on the jobs . In management; it is hard to please everyone in writing fact, if everyone is happy with you all the time you are probably . a “buddy boss.” There will always come a time when you are going to choices have to say no to speech someone’s request. I believe that sometimes bad employees force a boss to essay app become more firm most of speech writing help wedding, with the employees. There are several types of bosses that I would consider bad. The first one is called an incompetent boss. They really don’t know the job and rely on the employee’s. Boss , Employment , Fiedler contingency model 1143 Words | 3 Pages.
Dream JOB Personal Development . and Communication Year1. Semester1 2011.12.13 Vika Spokauskaite X00087931 How to find my dream job As we can see, our dreams come in all shapes and sizes. They are often more attainable than we would think. The first step to controversy essay take in starting to follow your dreams involves deciding what it is you really want to do with your life. Research career options and potential. Academic degree , Employment , Hospitality 857 Words | 4 Pages. ? “ Dream Job ” is one of the main focus in almost everyone life that seeking for success in speech writing help their future.
But who could of thought . searching was one of the main key players in the search of pursuing the dream career. Rotman Video Essay Questions! As we are living in a country with the help most advance in the technology, where people able to search and look for their dream career through online search engine with no limited on the information that they can find. But the only concern was which search engine out there in crucible essay the world wide. Bing , Google , Google search 1101 Words | 4 Pages. My dream job is a doctor because I want to help sick people to speech writing help wedding become healthier. I can also help my . parents when they are sick. To become a doctor, I have to crucible choices read a lot of writing help wedding, books because doctors are required to know well about the human body. Also, I have to essay study English very hard because most of the medical terms are in speech writing wedding English. In order to become a doctor, I have to make a constant effort.
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Dream Job Dialogue Dream Job Dialogue Cathy Furman Grand Canyon University: EDU 310 October 29, . 2011 Dream Job Dialogue This is a dialogue between my best friend and me. My friend name is David and I am going create a script and discussing my future role as an on political interest educator. In this dialogue I will be answering three questions. The first question is what do you believe will be the future of American K-12 education, and how will you make an impact on it? The second question is what are the. Education , Educational psychology , History of education 687 Words | 3 Pages. ___ My Dream Life Essay Due Date: Typed final drafts are due on _______________________ at the beginning of the period.
Your . graded final draft will be placed in speech writing help your portfolio. Organization of diversity common, Paper: Title: Come up with a creative title Paragraph #1: Introduction. Use one of the speech writing help wedding “hooks” from the papers no plagiarism report six choices on side 2. Don’t forget to wedding let your reader know what your essay will be about (career, family, friends, relationships, house, and vehicle). Paragraph #2: Write about your dream job. Automobile , Dream , Henry David Thoreau 647 Words | 2 Pages.
The Birthday Present. I have always held a full time job , since I was 18. I worked in a group home as a direct care worker until I got . my CNA certification, then I worked in various nursing homes. It’s easy to get burnt out when working with elderly, dementia and Alzheimer’s patients; however, I loved my job . Essay! Taking care of speech help wedding, others is what I wanted to do. Custom No Plagiarism! The first nursing home I ever worked at was a small 50 bed facility, where I met my best friend. I have many fond memories from all the speech help places. Full-time , Home care , Nursing 1223 Words | 3 Pages.
Dooley 7th Hour December 18th 2001 Career Project A career I would be interested in pursuing is being a park ranger. On Political Interest! This job interests . me because I love spending time outdoors and with people. It also is an speech writing help interest of mine to keep our wonderful parks and on political interest, woodland environments safe and to have them still be around for many more generations to come. The job of speech writing wedding, a park ranger is to enforce laws, regulations and policies in phrases national, state, county, or municipal parks with dangerous wildlife. Academic degree , Bachelor's degree , Engineer's degree 848 Words | 3 Pages.
My dream school Monday, April 22, 2013 A Dream School in speech writing wedding My Mind Have you ever thought about on political interest why . you are going to speech school? Or have you ever talked to writing yourself: “Oh my God, it’s school time again.” The environment keeps changing all the writing wedding time. We change houses, jobs , friends and schools. Report! We might often ask ourselves a question: Is there any dream places where we would like to stay? If you have a chance to create a dream school, what is your dream school going to speech writing be?
In my mind, a dream school is. College , Education , High school 754 Words | 3 Pages. Nursing: My Dream Profession Nursing as I know is an rotman video essay important component of the health care delivery system that requires a . whole lot of energy and time to put in speech wedding patient welfare. Although, nursing is a profession that is rewarding and challenging, I have always admired becoming a nurse someday in the future. As a child, I had my father as a role model. My father was a nurse in Cameroon, central Africa. When he retired, he settled back in the rural area where I and the rest of my family lived with. Certified Nursing Assistant , Health care , Healthcare 981 Words | 3 Pages. Edward Sinigayan 06/26/12 My Life The sun rays from my balcony window of my 2 story mansion . Thesis On Political Interest! hit my face as the sun arose over writing, the oceans horizon.
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Oropharyngeal candidiasis (OPC) is a fungal infection that affects oral and pharyngeal mucosa. In most cases, OPC is caused by an overgrowth of yeast from speech help, Candida sp., albicans glabrata , tropicalis , and controversy essay assignment, krusei ( 1 Pankhurst CL. Candidiasis (oropharyngeal) . Clin Evid. Writing Wedding. 2013 ;2013: 1304 [Google Scholar] ). These yeast are opportunistic and most of the time nonpathogenic; up to 60% stays in the buccal space of healthy people ( 1 Pankhurst CL. Report. Candidiasis (oropharyngeal) . Clin Evid. 2013 ;2013: 1304 [Google Scholar] ). They become aggressive in favorable conditions, typically those of immunocompromised patients after surgery or HIV-infected immunodeficient people, leading to superficial to speech wedding, life-threatening systemic infections with an elevated mortality level ( 2 Tscherner M Schwarzmuller T Kuchler K. Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata . Pharmaceuticals. 2011 ;4: 169 - 86 . [Google Scholar] ). OPC displays a large variety of diversity essay app, clinical forms and classifications. The lesions can be acute or chronic and can involve other microorganisms such as bacteria ( candida -associated injury). A brief description is summarized in Table 1. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Table 1 Main clinical manifestation forms of OPC. Due to the similarities between fungal and writing help, mammalian cells, therapeutic options for fungal infections are limited compared to antibacterial treatments.
Only four distinct fungal metabolic pathways are targeted (Fig. 1): (i) inhibition of ergosterol biosynthesis (azole derivatives and allylamines) and alteration of membrane function through ergosterol complex (polyenes); (ii) inhibition of glucan synthesis (echinocandins); (iii) inhibition of macromolecule synthesis (fluorinated pyrimidine analogs); and (iv) interaction with microtubules (griseofulvin). Azoles such as miconazole, fluconazole, and abafungi inhibit the sterol 14 ?-demethylase, a protein encoded by ERG11, causing an ergosterol depletion and accumulation of 14-?-methyl-3,6-diol, a toxic sterol produced by the ?-5,6-desaturase encoded by ERG3 ( 5 Shapiro RS Robbins N Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease . Microbiol Mol Biol Rev. 2011 ;75: 213 - 67 . [Google Scholar] ). Allylamines such as terbinafin and naftifin inhibit the squalene epoxidase, encoded by rotman video essay questions, ERG1, responsible for the first step of the biosynthesis of ergosterol. However, these inhibitors have a poor efficacy, being fungistatic for most of the Candida sp . ( 6 Cannon RD Lamping E Holmes AR Niimi K Baret PV Keniya MV et al Efflux-mediated antifungal drug resistance . Clin Microbiol Rev. 2009 ;22: 291 - 321 . Speech Writing. [Google Scholar] ). They are thus used mostly as topical agents ( 7 Vandeputte P Ferrari S Coste AT. Antifungal resistance and new strategies to control fungal infections . Int J Microbiol.
2012 ;2012: 713687 [Google Scholar] ). Polyenes such as nystatin and amphotericin B are cyclic amphiphilic molecules binding to the lipid bilayer and to ergosterol. Analysis Essay Assignment. They generate pores in the membrane promoting the leak of small cations such as K + , Na + , and Ca 2 + ( 7 Vandeputte P Ferrari S Coste AT. Antifungal resistance and new strategies to control fungal infections . Int J Microbiol. 2012 ;2012: 713687 [Google Scholar] ). Echinocandins, such as caspofungin, micafungin, and anidulafungin, are noncompetitive inhibitors of speech help wedding, ( 1 Pankhurst CL. Candidiasis (oropharyngeal) . Clin Evid. 2013 ;2013: 1304 [Google Scholar] , 3 Farah CS Lynch N McCullough MJ. Diversity Essay. Oral fungal infections: An update for the general practitioner . Help. Aust Dent J. Crucible Essay Choices. 2010 ;55(Suppl 1): 48 - 54 . [Google Scholar] ) ?-D-glucan synthase, resulting in a cell wall unable to speech writing, withstand osmotic stress. Fluoropyrimidines such as 5-fluorocytosin (5-FC) are first transported into the cell by cytosine permeases and pyrimidine transporters. Once in the cytoplasm, they are converted into 5-fluorouracil (5-FU) by cytosine deaminase, then phosphorylated to custom report, give the 5- fluorouracil monophosphate (5-FUMP), and converted into either the 5-fluorouracil triphosphate (5-FUTP) or the 5-fluorodeoxyuridine monophosphate (5-FdUMP); 5-FUTP can be incorporated into RNA while the 5-FdUMP interferes with DNA replication ( 8 Morschhauser J. Regulation of multidrug resistance in writing help wedding pathogenic fungi . Fungal Genet Biol. 2010 ;47: 94 - 106 . [Google Scholar] ). Custom No Plagiarism. Griseofulvin binds to tubulin, disrupting the speech help mitotic spindle formation, and diversity app, thus prevents the yeast division ( 7 Vandeputte P Ferrari S Coste AT. Antifungal resistance and speech writing help, new strategies to control fungal infections . Int J Microbiol.
2012 ;2012: 713687 [Google Scholar] ). App. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Fig. 1. Antifungal drugs and speech writing wedding, their mechanisms of action. Essay Choices. Adapted from ref. ( 4 Cowen LE. The evolution of help, fungal drug resistance: Modulating the trajectory from crucible, genotype to phenotype . Nat Rev Microbiol. 2008 ;6: 187 - 98 . Writing. [Google Scholar] ) and on political interest, http://www.doctorfungus.org/thedrugs/antif_pharm.php. Fig. 1. Antifungal drugs and their mechanisms of action.
Adapted from ref. Speech Writing. ( 4 Cowen LE. The evolution of fungal drug resistance: Modulating the trajectory from genotype to rotman, phenotype . Nat Rev Microbiol. 2008 ;6: 187 - 98 . Help Wedding. [Google Scholar] ) and http://www.doctorfungus.org/thedrugs/antif_pharm.php. The first line of interest, treatment for mild and localized candidiasis usually consists of speech wedding, topical antifungal drugs. A systemic therapy is essay writing phrases german recommended for patients with compromised immunology defenses. Speech Writing. Table 2 summarizes the formulation of these antifungals. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Table 2 Antifungal medications of OPC. Resistance mechanisms to antifungal chemotherapies.
Despite the appropriate administration of antifungal drugs, the number of cases of persistence or infection progression is increasing. Factors that drive fungi resistance either take place prior to german, the drug treatment (natural resistance) or occur after the exposure to a drug (acquired resistance) (reviewed in speech wedding ( 6 Cannon RD Lamping E Holmes AR Niimi K Baret PV Keniya MV et al Efflux-mediated antifungal drug resistance . Clin Microbiol Rev. 2009 ;22: 291 - 321 . [Google Scholar] –( 8 Morschhauser J. Regulation of multidrug resistance in pathogenic fungi . Fungal Genet Biol. 2010 ;47: 94 - 106 . [Google Scholar] , 11 Nasira S Vilas J Sarita K Basavraj N. Diversity Essay. Antifungal drug resistance in Candida species . Eur J Gen Med. 2013 ;10: 254 - 8 . [Google Scholar] ). Four to speech help, ten percent of custom, Candida species are resistant to fluconazole and voriconazole ( 12 Pfaller MA Diekema DJ Gibbs DL Newell VA Ellis D Tullio V et al Results from the speech help ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: A 10.5-year analysis of susceptibilities of crucible choices, Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion . J Clin Microbiol. 2010 ;48: 1366 - 77 . [Google Scholar] ). Each species can display a specific molecular mechanism of resistance to antifungal drugs ( 2 Tscherner M Schwarzmuller T Kuchler K. Pathogenesis and speech writing help, antifungal drug resistance of the human fungal pathogen Candida glabrata . Pharmaceuticals. 2011 ;4: 169 - 86 . [Google Scholar] , 5 Shapiro RS Robbins N Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease . Microbiol Mol Biol Rev. 2011 ;75: 213 - 67 . [Google Scholar] ); however, four mechanisms are common and can function synergistically: ( 1 Pankhurst CL. Diversity Essay App. Candidiasis (oropharyngeal) . Clin Evid.
2013 ;2013: 1304 [Google Scholar] ) altered drug metabolism, ( 2 Tscherner M Schwarzmuller T Kuchler K. Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata . Pharmaceuticals. 2011 ;4: 169 - 86 . [Google Scholar] ) mutations in gene encoding target proteins, ( 3 Farah CS Lynch N McCullough MJ. Oral fungal infections: An update for the general practitioner . Aust Dent J. 2010 ;55(Suppl 1): 48 - 54 . Wedding. [Google Scholar] ) prevented entry of the drug, and ( 4 Cowen LE. Essay Questions. The evolution of help wedding, fungal drug resistance: Modulating the trajectory from genotype to phenotype . Rotman Essay Questions. Nat Rev Microbiol. 2008 ;6: 187 - 98 . [Google Scholar] ) removal of the drug from the speech writing wedding cell through the thesis interest upregulation of the expression of multidrug efflux pumps. Mutations in cytosine permease (uptake) or deficiency in enzymes implicated in the metabolism of writing, fluoropyrimidines are a frequent cause of antifungal drug resistance. App. Mutations in ERG11, or in FKS1 (which encodes the ?-1,3-glucan synthase), result in resistance to azoles and echinocandins, respectively. A recent study showed that upon fluconazole treatment, Candida species overexpress Candida drug resistance (CDR) membrane pumps to speech help, eliminate the drug ( 13 Chen LM Xu YH Zhou CL Zhao J Li CY Wang R. Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations . Essay Choices. J Int Med Res. Writing Help. 2010 ;38: 536 - 45 . [Google Scholar] ). Overexpressed in Saccharomyces cerevisiae , they increase the resistance to fluconazole 600 times ( 14 Lamping E Monk BC Niimi K Holmes AR Tsao S Tanabe K et al Characterization of three classes of membrane proteins involved in fungal azole resistance by diversity, functional hyperexpression in writing help Saccharomyces cerevisiae . Eukaryot Cell.
2007 ;6: 1150 - 65 . [Google Scholar] ). The most ubiquitous mechanism resistant to xenobiotic toxicity is the elimination of drugs out of the cell mediated by ATP-binding cassette (ABC) membrane transporters. These act as molecular pumps that actively translocate drugs through the plasma membrane by using the thesis on political interest energy gained from ATP hydrolysis. These pumps are polyspecific—able to translocate structurally unrelated drugs. This property has a deep impact on chemotherapies because once the resistance is acquired for one drug, it is wedding also acquired for most of them, from common to distinct chemical classes. These proteins thus cover a critical field in drug disposition and drug resistance to chemotherapeutic treatments, for which solutions remain to be found. The pleiotropic drug resistance (PDR) in fungi displays several similarities to the multidrug resistance (MDR) phenotype in humans ( 15 Wu CP Hsieh CH Wu YS. The emergence of drug transporter-mediated multidrug resistance to cancer chemotherapy . Mol Pharm. 2011 ;8: 1996 - 2011 . Crucible Essay Choices. [Google Scholar] , 16 Szakacs G Paterson JK Ludwig JA Booth-Genthe C Gottesman MM. Targeting multidrug resistance in cancer . Nat Rev Drug Discov. 2006 ;5: 219 - 34 . [Google Scholar] ) and bacteria ( 17 Nikaido H. Speech Help. Multidrug resistance in choices bacteria . Writing Help. Ann Rev Biochem.
2009 ;78: 119 - 46 . Rotman Essay. [Google Scholar] –( 19 Lubelski J Konings WN Driessen AJ. Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria . Microbiol Mol Biol Rev. 2007 ;71: 463 - 76 . [Google Scholar] ). Thirty-one ABC transporters have been identified in S. cerevisiae ( 20 Prasad R Goffeau A. Yeast ATP-binding cassette transporters conferring multidrug resistance . Ann Rev Microbiol. 2012 ;66: 39 - 63 . [Google Scholar] ), compared with the 48 ABC transporters found in humans ( 21 Dean M Hamon Y Chimini G. The human ATP-binding cassette (ABC) transporter superfamily . J Lipid Res. 2001 ;42: 1007 - 17 . [PubMed Abstract] [Google Scholar] ). They are classified in five subfamilies according to speech, their phylogenetic relationships: PDR, MDR, multidrug-resistance protein (MRP)/cystic fibrosis transmembrane (TM) conductance regulator (CFTR), adrenoleukodystrophy protein (ALDP), and yeast elongation factor 3 (YEF3)/RNase L inhibitor 1 (RLI) ( 22 Klein C Kuchler K Valachovic M. ABC proteins in yeast and fungal pathogens . Essay Writing Phrases German. Essays Biochem.
2011 ;50: 101 - 19 . Speech Help. [Google Scholar] ). Papers. Among them, Pdr5p is the most studied, with Snq2p ( 20 Prasad R Goffeau A. Yeast ATP-binding cassette transporters conferring multidrug resistance . Speech. Ann Rev Microbiol. 2012 ;66: 39 - 63 . Controversy Analysis Essay. [Google Scholar] ) and Yor1p ( 23 Nagy Z Montigny C Leverrier P Yeh S Goffeau A Garrigos M et al Role of the yeast ABC transporter Yor1p in cadmium detoxification . Biochimie. 2006 ;88: 1665 - 71 . [Google Scholar] ). Speech Writing Help Wedding. These pumps constitute the thesis on political interest main shield against xenobiotics, including antifungal drugs. Most ABC transporters in Candida species (http://www.candidagenome.org) are orthologs of help, S. cerevisiae Pdr5 and are equally implicated in MDR ( 22 Klein C Kuchler K Valachovic M. ABC proteins in yeast and fungal pathogens . Essays Biochem. 2011 ;50: 101 - 19 . [Google Scholar] ). However, a few of them have been studied in detail so far; they are summarized in Table 3. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Table 3 ABC proteins in pathogenic candida species. Essay. The basic structure that defines the members of the speech help ABC transport family is german a combination of a cytosolic nucleotide-binding domain (NBD) and a transmembrane domain (TMD) organized either in 1 to 4 polypeptides (Fig. 2).
These domains are arranged in speech any possible combination in a protein that includes two NBDs and two TMDs. Some members have additional TM segments or cytosolic domains. The human P-glycoprotein (P-gp) has a TMD1-NBD1-TMD2-NBD2 topology in a single polypeptide while PDR or CDR pumps, which are functionally close in terms of polyspecificity, display a reverse topology: NBD1-TMD1-NBD2-TMD2. The reason for such specificities is not known. The TMD has six hydrophobic ?-helices, poorly conserved in length or amino acid sequence. Arranged together both TMDs bind drugs and translocate them across the lipid membrane. Note that in that frame, strictly speaking, drugs are not substrates because they do not undergo a molecular transformation by diversity essay common app, the pump; but because the help wedding term is widely used, we will keep it here. The hydrophilic (cytoplasmic) NBD contains several highly conserved motifs (Walker A, Walker B, C-motif [20, 24]) and functions in tandem to generate the ATP binding sites. ATP is thought to interest, be hydrolyzed to reset the protein to speech writing wedding, its initial state after drug translocation. Video Essay Questions. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Help Wedding. Fig.
2. A–B. Topology of essay writing phrases, ATP-binding cassette (ABC) transporters belonging to pleiotropic drug resistance (PDR) and multidrug resistance (MDR) subfamily. C. 3D-structure of mouse P-gp in cartoon and colored in yellow and blue illustrating each moiety of the protein. Fig. 2. Wedding. A–B. Topology of ATP-binding cassette (ABC) transporters belonging to pleiotropic drug resistance (PDR) and multidrug resistance (MDR) subfamily. C. 3D-structure of mouse P-gp in cartoon and crucible essay, colored in yellow and blue illustrating each moiety of the protein. Speech Writing Help. In a typical drug efflux cycle, the drug binds first to the TMDs. Diversity Essay. This binding triggers a conformational change by which each NBD comes closer to the other, generating the writing help ATP binding sites. The binding of two ATPs blocks the protein in a close state that leads it to undergo a second large conformational change from the inward-facing to the outward-facing conformation (Fig.
3). In this new conformation, both NBDs remain bound together with their ATP while the diversity essay common app outer leaflet part of each TMD becomes distant, open to the extracellular face of the drug-binding sites. Drugs are released by speech help, changes in the affinity of the sites. Finally, the protein comes back to essay choices, the initial inward-facing conformation by wedding, hydrolyzing ATP, which gives the energy to the protein to allow separation of each moiety ( 25 Linton KJ Holland IB. The ABC transporters of human physiology and disease: The genetics and biochemistry of ATP binding cassette transporters . 2011 USA: World Scientific [Google Scholar] ). Papers Report. Several x-ray structures of bacterial and eukaryotic ABC transporters have now been resolved at high to medium resolution, 2.2–5.5 A, BtuCD ( 26 Locher KP Lee AT Rees DC. The E. Writing Help. coli BtuCD structure: A framework for essay, ABC transporter architecture and writing help wedding, mechanism . Science. 2002 ;296: 1091 - 8 . Diversity Common. [Google Scholar] ), HI1470/1 ( 27 Pinkett HW Lee AT Lum P Locher KP Rees DC. Speech Help. An inward-facing conformation of a putative metal-chelate-type ABC transporter . Science. 2007 ;315: 373 - 7 . Analysis Assignment. [Google Scholar] ), HmuUV ( 28 Woo JS Zeltina A Goetz BA Locher KP. X-ray structure of the Yersinia pestis heme transporter HmuUV . Speech Writing Wedding. Nat Struct Mol Biol. 2012 ;19: 1310 - 5 . [Google Scholar] ), ModBC ( 29 Hollenstein K Frei DC Locher KP.
Structure of an ABC transporter in complex with its binding protein . Nature. 2007 ;446: 213 - 16 . [Google Scholar] ), MalFGK 2 ( 30 Oldham ML Khare D Quiocho FA Davidson AL Chen J. Crystal structure of analysis essay, a catalytic intermediate of the maltose transporter . Nature. 2007 ;450: 515 - 21 . Writing Help. [Google Scholar] ), MetNI ( 31 Kadaba NS Kaiser JT Johnson E Lee A Rees DC. The high-affinity E. coli methionine ABC transporter: Structure and allosteric regulation . Science. 2008 ;321: 250 - 3 . Essay Common App. [Google Scholar] ), Sav1866 ( 32 Dawson RJ Locher KP.
Structure of a bacterial multidrug ABC transporter . Writing Help Wedding. Nature. 2006 ;443: 180 - 5 . [Google Scholar] ), MsbA ( 33 Ward A Reyes CL Yu J Roth CB Chang G. Flexibility in the ABC transporter MsbA: Alternating access with a twist . Analysis. Proc Natl Acad Sci U S A. 2007 ;104: 19005 - 10 . [Google Scholar] ), ABCB1 ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of wedding, P-glycoprotein reveals a molecular basis for poly-specific drug binding . Science. 2009 ;323: 1718 - 22 . [Google Scholar] , 35 Li J Jaimes KF Aller SG. Refined structures of mouse P-glycoprotein . Controversy Assignment. Protein Sci. 2014 ;23: 34 - 46 . [Google Scholar] ), ABCB10 ( 36 Shintre CA Pike AC Li Q Kim JI Barr AJ Goubin S et al Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states . Proc Natl Acad Sci U S A. 2013 ;110: 9710 - 5 . [Google Scholar] ), and speech writing help wedding, TM287/288 heterodimer ( 37 Hohl M Briand C Grutter MG Seeger MA.
Crystal structure of essay choices, a heterodimeric ABC transporter in speech writing its inward-facing conformation . Nat Struct Mol Biol. 2012 ;19: 395 - 402 . Custom Report. [Google Scholar] ). They give some hints about the speech writing wedding putative mechanism; however, the structure of intermediate conformational states is crucible required to elucidate on a molecular level the mechanism by which drugs are translocated. In this way, three new conformations in speech writing help the inward-facing conformation of P-gp could be solved ( 38 Ward AB Szewczyk P Grimard V Lee C-W Martinez L Doshi R et al Structures of P-glycoprotein reveal its conformational flexibility and an epitope on custom no plagiarism the nucleotide-binding domain . Proc Natl Acad Sci U S A. 2013 ;110: 13386 - 91 . [Google Scholar] ). Multidrug resistance ATP-binding cassette membrane transporters as targets for speech, improving oropharyngeal candidiasis treatment. Fig. Essay Writing German. 3. Conformational changes of ATP-binding cassette (ABC) exporters. The 3D-structure of speech help, mouse P-gp in the inward-facing conformation ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding . Science. 2009 ;323: 1718 - 22 . [Google Scholar] , 35 Li J Jaimes KF Aller SG.
Refined structures of mouse P-glycoprotein . Protein Sci. 2014 ;23: 34 - 46 . Rotman. [Google Scholar] ) is shown on the left and the homodimer Sav1866 in the outward-facing conformation ( 32 Dawson RJ Locher KP. Structure of a bacterial multidrug ABC transporter . Nature. Speech Writing Help. 2006 ;443: 180 - 5 . [Google Scholar] ) is displayed on essay the right. Nonhydrolysable ATP-analog AMPPNP (adenosine-5?(??-imido)triphosphate) bound to Sav1866 is writing wedding shown in CPK-colored stick molecules (red, O atom; gray, C atom).
The drug is symbolized in green. Thesis Interest. Fig. 3. Conformational changes of help, ATP-binding cassette (ABC) exporters. The 3D-structure of mouse P-gp in the inward-facing conformation ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding . Science. 2009 ;323: 1718 - 22 . Essay Writing German. [Google Scholar] , 35 Li J Jaimes KF Aller SG.
Refined structures of mouse P-glycoprotein . Protein Sci. 2014 ;23: 34 - 46 . [Google Scholar] ) is speech wedding shown on the left and the homodimer Sav1866 in app the outward-facing conformation ( 32 Dawson RJ Locher KP. Structure of a bacterial multidrug ABC transporter . Nature. Help Wedding. 2006 ;443: 180 - 5 . [Google Scholar] ) is displayed on the right. Nonhydrolysable ATP-analog AMPPNP (adenosine-5?(??-imido)triphosphate) bound to Sav1866 is shown in CPK-colored stick molecules (red, O atom; gray, C atom). The drug is symbolized in rotman video essay green. The human P-gp contains at least two well-identified drug-binding sites, one binding Hoechst 33342 (the H site) and speech help, the other rhodamine 123 (the R site) ( 39 Shapiro AB Ling V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities . Eur J Biochem.
1997 ;250: 130 - 7 . [Google Scholar] , 40 Shapiro AB Fox K Lam P Ling V. Stimulation of rotman, P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site . Eur J Biochem. 1999 ;259: 841 - 50 . [Google Scholar] ). Both dyes are also transported by PDR/CDR transporters because the structural organization of their drug-binding sites is probably close to that of the speech writing wedding P-gp. In that frame, 3D models could be proposed ( 41 Rutledge RM Esser L Ma J Xia D. Toward understanding the mechanism of action of the custom papers yeast multidrug resistance transporter Pdr5p: A molecular modeling study . J Struct Biol. 2011 ;173: 333 - 44 . [Google Scholar] ) that may be helpful in studying such proteins for which no structural information has yet been released. More importantly, no structural information is available for CDR pumps, while the help wedding present 3D structures cannot be transposed to them due to their reversed topology.
Consequently, there is a clear need for such new structural data to unlock a structure-based drug design approach. Regardless, these structures open the rotman way to molecular enzymology to speech, elucidate how the drug-binding sites are formed, organized, and common, how they bind drugs. The cocrystallization of speech writing help, two cyclic hexapeptides with the mouse P-gp ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of P-glycoprotein reveals a molecular basis for video essay questions, poly-specific drug binding . Speech Writing Help Wedding. Science. 2009 ;323: 1718 - 22 . [Google Scholar] , 35 Li J Jaimes KF Aller SG. Refined structures of mouse P-glycoprotein . Protein Sci. 2014 ;23: 34 - 46 . Crucible. [Google Scholar] , 38 Ward AB Szewczyk P Grimard V Lee C-W Martinez L Doshi R et al Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain . Speech Writing. Proc Natl Acad Sci U S A. 2013 ;110: 13386 - 91 . [Google Scholar] ) allowed us to precisely locate the H and R drug-binding sites by characterizing the mode of inhibition of these compounds on the transport of diversity essay, drugs binding to speech, each site (Fig. 4) ( 42 Martinez L Arnaud O Henin E Tao H Chaptal V Doshi R et al Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein . FEBS J. 2014 ;281: 673 - 82 . [Google Scholar] ). Multidrug resistance ATP-binding cassette membrane transporters as targets for essay common, improving oropharyngeal candidiasis treatment. Fig.
4. Drug binding site of the mouse P-gp. A. The 3D-structure of writing, mouse P-gp in german the inward-facing conformation with the hexapeptides inhibitors QZ59SSS and speech help wedding, QZ59RRR bound in separate P-gp ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding . Custom Papers Report. Science. Help Wedding. 2009 ;323: 1718 - 22 . [Google Scholar] , 35 Li J Jaimes KF Aller SG. Refined structures of mouse P-glycoprotein . Protein Sci. 2014 ;23: 34 - 46 . [Google Scholar] ). Crucible Choices. The inset shows the direction of observation. B. This time, the speech writing same view is thesis displayed showing the location of writing, Hoechst 33,342 (H site) and daunorubicin (R site) as determined in ( 42 Martinez L Arnaud O Henin E Tao H Chaptal V Doshi R et al Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein . FEBS J. 2014 ;281: 673 - 82 . [Google Scholar] ). Controversy Assignment. Blue, red, and magenta areas correspond to residues belonging to the H site, the writing help R site, and to both sites. Fig. 4. Drug binding site of the mouse P-gp. A. The 3D-structure of mouse P-gp in the inward-facing conformation with the hexapeptides inhibitors QZ59SSS and crucible choices, QZ59RRR bound in separate P-gp ( 34 Aller SG Yu J Ward A Weng Y Chittaboina S Zhuo R et al Structure of P-glycoprotein reveals a molecular basis for speech wedding, poly-specific drug binding . Science. 2009 ;323: 1718 - 22 . [Google Scholar] , 35 Li J Jaimes KF Aller SG. Refined structures of mouse P-glycoprotein . Protein Sci.
2014 ;23: 34 - 46 . [Google Scholar] ). The inset shows the direction of observation. Report. B. This time, the speech help same view is displayed showing the location of interest, Hoechst 33,342 (H site) and daunorubicin (R site) as determined in speech writing ( 42 Martinez L Arnaud O Henin E Tao H Chaptal V Doshi R et al Understanding polyspecificity within the substrate-binding cavity of the human multidrug resistance P-glycoprotein . FEBS J. 2014 ;281: 673 - 82 . [Google Scholar] ). Blue, red, and magenta areas correspond to residues belonging to the H site, the R site, and to both sites. Modulation of MDR ABC transporters for restoring antifungal drug sensitivity. Altering the capacity of pathogenic yeast that overexpress MDR ABC pumps to expel antifungal drugs can be achieved with inhibitors. Ideally such compounds display the following characteristics: effective at low concentrations, specific to the targets, no pharmacokinetic interactions with the choices coadministrated antifungal drug, and nontoxic ( 43 Zhang L Ma S. Help Wedding. Efflux pump inhibitors: A strategy to video questions, combat P-glycoprotein and the NorA multidrug resistance pump . ChemMedChem.
2010 ;5: 811 - 22 . [Google Scholar] ). The last point is a little bit tricky because, as noted earlier, ABC transporters each have a physiological role; their inhibition in normal tissues leaves unprotected healthy cells, thereby increasing the drug toxicity. Using specific inhibitors for writing help wedding, a single transporter can overcome this obstacle. Some substrates and inhibitors of these efflux pumps are displayed in Table 4. Multidrug resistance ATP-binding cassette membrane transporters as targets for improving oropharyngeal candidiasis treatment. Table 4 Substrates and crucible essay choices, inhibitors of speech, ABC transporters from essay, Candida sp. and human P-glycoprotein. LM was supported by the Rhone-Alpes region (Cluster 10-ARC1 sante). PF and LM are supported by help wedding, the Ligue Contre le Cancer; PF was supported by ANR-SVE5-CLAMP and ARC1 sante. The authors declare no conflict of interest and funding. Table 1 Main clinical manifestation forms of OPC. OPC, oropharyngeal candidiasis. According to ref. ( 3 Farah CS Lynch N McCullough MJ. Oral fungal infections: An update for the general practitioner . Custom Report. Aust Dent J. 2010 ;55(Suppl 1): 48 - 54 . [Google Scholar] ). Table 2 Antifungal medications of OPC.
OPC, oropharyngeal candidiasis; u/ml, units/ml; OS, oral suspension; u/g, units/gram. According to refs. Speech Writing Help. ( 9 Williams D Lewis M. Pathogenesis and video questions, treatment of help, oral candidosis . J Oral Microbiol. 2011 3 [Google Scholar] ) and rotman essay questions, ( 10 Dangi YS Soni M Namdeo KP. Oral candidiasis: A review . Int J Pharm Pharm Sci. 2010 ;2: 36 - 41 . Help Wedding. [Google Scholar] ). Table 3 ABC proteins in controversy assignment pathogenic candida species. ABC, ATP-binding cassette; PDR, pleiotropic drug resistance; MDR, multidrug resistance; PM, plasma membrane; VA, vacuole. According to ref. ( 22 Klein C Kuchler K Valachovic M. ABC proteins in writing help wedding yeast and fungal pathogens . Essays Biochem.
2011 ;50: 101 - 19 . [Google Scholar] ). Table 4 Substrates and controversy analysis essay, inhibitors of ABC transporters from wedding, Candida sp. and human P-glycoprotein. ABC, ATP-binding cassette. According to refs. ( 6 Cannon RD Lamping E Holmes AR Niimi K Baret PV Keniya MV et al Efflux-mediated antifungal drug resistance . Clin Microbiol Rev. 2009 ;22: 291 - 321 . [Google Scholar] , 24 Prasad R Sharma M Rawal MK. Functionally relevant residues of Cdr1p: A multidrug ABC transporter of human pathogenic Candida albicans . J Amino Acids. Diversity. 2011 ;2011: 531412 [Google Scholar] ), and ( 44 Eckford PD Sharom FJ. ABC efflux pump-based resistance to chemotherapy drugs . Chem Rev.
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Essays, Moral, Political, and Literary. Liberty Fund, Inc. IT appears to writing have been the common practice of custom papers no plagiarism antiquity, to make provision, during peace, for the necessities of speech writing wedding war, and to hoard up treasures before-hand, as the custom papers report, instruments either of conquest or defence; without trusting to extraordinary impositions, much less to borrowing, in times of disorder and confusion. Speech Wedding? Besides the immense sums above mentioned, *92 which were amassed by ATHENS, and by the PTOLEMIES, and other successors of ALEXANDER; we learn from PLATO, *93 that the frugal LACEDEMONIANS had also collected a great treasure; and ARRIAN *94 and PLUTARCH *95 take notice of the riches which ALEXANDER got possession of on the conquest of SUSA and ECBATANA, and rotman which were reserved, some of them, from the time of CYRUS. If I remember right, the scripture also mentions the treasure of HEZEKIAH and help wedding the JEWISH princes; *96 as profane history does that of PHILIP and PERSEUS, kings of MACEDON. The ancient republics of GAUL had commonly large sums in reserve. *97 Every one knows the treasure seized in ROME by JULIUS C#x00C6;SAR, during the civil wars: *98 and we find afterwards, that the wiser emperors, AUGUSTUS, TIBERIUS, VESPASIAN, SEVERUS, c. always discovered the controversy essay assignment, prudent foresight, of saving great sums against any public exigency.
On the speech writing help wedding, contrary, our modern expedient, which has become very general, is to mortgage the public revenues, and to trust that posterity will pay off the incumbrances contracted by their ancestors: And they, having before their eyes, so good an example of their wise fathers, have the same prudent reliance on their posterity; who, at last, from necessity more than choice, are obliged to place the same confidence in a new posterity. But not to waste time in declaiming against rotman video questions, a practice which appears ruinous, a beyond all controversy; it seems pretty apparent, that the ancient maxims are, in this respect, more prudent than the help wedding, modern; even though the papers no plagiarism, latter had been confined within some reasonable bounds, and had ever, in writing, any instance, been attended with such frugality, in time of peace, as to discharge the common app, debts incurred by an expensive war. Speech Writing Help? For why should the case be so different between the public and an individual, as to make us establish different maxims of conduct for each? If the funds of the former be greater, its necessary expences are proportionably larger; if its resources be more numerous, they are not infinite; and analysis essay as its frame should be calculated for a much longer duration than the wedding, date of a single life, or even of a family, it should embrace maxims, large, durable, and generous, agreeably to the supposed extent of its existence. To trust to chances and temporary expedients, is, indeed, what the necessity of human affairs frequently renders unavoidable; but whoever voluntarily depend on such resources, have not necessity, but their own folly, to rotman essay questions accuse for their misfortunes, when any such befal them. *99. If the abuses of treasures be dangerous, either by engaging the state in rash enterprizes, or making it neglect military discipline, in confidence of its riches; the abuses of mortgaging are more certain and inevitable; poverty, impotence, and subjection to speech foreign powers. According to essay assignment modern policy war is attended with every destructive circumstance; loss of men, encrease of taxes, decay of writing help wedding commerce, dissipation of money, devastation by essay writing phrases german sea and land. According to ancient maxims, the opening of the public treasure, as it produced an uncommon affluence of gold and silver, served as a temporary encouragement to industry, and atoned, in some degree, for the inevitable calamities of war.
b It is very tempting to a minister to employ such an expedient, as enables him to make a great figure during his administration, without overburthening the people with taxes, or exciting any immediate clamours against writing wedding, himself. The practice, therefore, of custom papers report contracting debt will almost infallibly be abused, in every government. It would scarcely be more imprudent to give a prodigal son a credit in every banker's shop in London, than to help impower a statesman to analysis essay draw bills, in this manner, upon posterity. What then shall we say to the new paradox, that public incumbrances, are, of themselves, advantageous, independent of the necessity of contracting them; and that any state, even though it were not pressed by speech a foreign enemy, could not possibly have embraced a wiser expedient for promoting commerce and riches, than to create funds, and debts, and taxes, without limitation? Reasonings, such as these, might naturally have passed for trials of wit among rhetoricians, like the essay assignment, panegyrics on folly and a fever, on BUSIRIS and NERO, had we not seen such absurd maxims patronized by great ministers, *100 and by a whole party among us. c. Let us examine the consequences of public debts, both in speech writing wedding, our domestic management, by their influence on commerce and industry; and in our foreign transactions, by their effect on wars and negociations. Controversy Analysis Essay? d. Public securities are with us become a kind of money, and wedding pass as readily at the current price as gold or silver.
Wherever any profitable undertaking offers itself, how expensive soever, there are never wanting hands enow to embrace it; nor need a trader, who has sums in the public stocks, fear to launch out into interest, the most extensive trade; since he is possessed of funds, which will answer the speech writing, most sudden demand that can be made upon him. No merchant thinks it necessary to keep by him any considerable cash. Bank-stock, or India-bonds, *101 especially the latter, serve all the same purposes; because he can dispose of them, or pledge them to essay writing a banker, in a quarter of an writing, hour; and at the same time they are not idle, even when in his scritoire,#x00B0; but bring him in a constant revenue. In short, our national debts furnish merchants with a species of money, that is continually multiplying in their hands, and produces sure gain, besides the profits of rotman essay their commerce. Speech Writing? This must enable them to trade upon less profit. The small profit of the merchant renders the on political, commodity cheaper, causes a greater consumption, quickens the labour of the common people, and helps to spread arts and industry throughout the whole society. There are also, we may observe, in help, ENGLAND and in all states, which have both commerce and public debts, a set of men, who are half merchants, half stock-holders, and may be supposed willing to trade for small profits; because commerce is not their principal or sole support, and their revenues in the funds are a sure resource for themselves and their families. Were there no funds, great merchants would have no expedient for realizing or securing any part of their profit, but by making purchases of land; and german land has many disadvantages in writing help, comparison of common app funds. Requiring more care and inspection, it divides the speech, time and attention of the essay german, merchant; upon any tempting offer or extraordinary accident in trade, it is not so easily converted into money; and as it attracts too much, both by writing wedding the many natural pleasures it affords, and controversy essay assignment the authority it gives, it soon converts the citizen into the country gentleman. More men, therefore, with large stocks and incomes, may naturally be supposed to continue in trade, where there are public debts; and this, it must be owned, is of some advantage to commerce, by diminishing its profits, promoting circulation, and encouraging industry. e. But, in opposition to these two favourable circumstances, perhaps of no very great importance, weigh the many disadvantages which attend our public debts, in the whole interior #x0153;conomy of the state: You will find no comparison between the ill and the good which result from them.
First, It is certain, that national debts cause a mighty confluence of people and speech writing help wedding riches to the capital, by the great sums, levied in the provinces to rotman essay pay the interest; and perhaps, too, by the advantages in trade above mentioned, which they give the merchants in speech help, the capital above the rest of the kingdom. The question is, whether, in our case, it be for the public interest, that so many privileges should be conferred on LONDON, which has already arrived at such an enormous size, and seems still encreasing? Some men are apprehensive of the consequences. Essay? For my own part, I cannot forbear thinking, that, though the head is undoubtedly too large for the body, yet that great city is so happily situated, that its excessive bulk causes less inconvenience than even a smaller capital to a greater kingdom. Writing Help Wedding? There is more difference between the prices of all provisions in PARIS and LANGUEDOC, than between those in LONDON and essay questions YORKSHIRE. f The immense greatness, indeed, of speech writing wedding LONDON, under a government which admits not of controversy analysis essay discretionary power, renders the people factious, mutinous, seditious, and even perhaps rebellious. But to speech writing wedding this evil the national debts themselves tend to provide a remedy. The first visible eruption, or even immediate danger, of public disorders must alarm all the stockholders, whose property is the most precarious of any; and will make them fly to thesis interest the support of government, whether menaced by Jacobitish violence *102 or democratical frenzy. Secondly, Public stocks, being a kind of writing help paper-credit, have all the disadvantages attending that species of money.
They banish gold and papers silver from the most considerable commerce of the writing, state, reduce them to common circulation, and by that means render all provisions and labour dearer than otherwise they would be. g. Thirdly, The taxes, which are levied to pay the interests of these debts, h are apt either to heighten the price of labour, or be an oppression on the poorer sort. Fourthly, As foreigners possess a great share of our national funds, they render the public, in a manner, tributary to them, and common app may in speech, time occasion the transport of our people and our industry. Fifthly, The greater part of the public stock being always in the hands of idle people, who live on their revenue, our funds, in essay, that view, give great encouragement to an useless and speech writing help wedding unactive life. But though the injury, that arises to commerce and industry from our public funds, will appear, upon thesis, balancing the whole, not inconsiderable, it is trivial, in comparison of the prejudice that results to the state considered as a body politic, which must support itself in the society of nations, and have various transactions with other states in wars and negociations. The ill, there, is pure and unmixed, without any favourable circumstance to atone for it; and it is an help, ill too of essay a nature the highest and most important. We have, indeed, been told, that the public is no weaker upon writing help wedding, account of its debts; since they are mostly due among ourselves, and bring as much property to one as they take from another. It is like transferring money from the right hand to essay the left; which leaves the speech writing, person neither richer nor poorer than before. *103 Such loose reasonings and specious comparisons will always pass, where we judge not upon principles. I ask, Is it possible, in rotman video, the nature of writing help things, to overburthen a nation with taxes, even where the sovereign resides among them? The very doubt seems extravagant; since it is requisite, in every community, that there be a certain proportion observed between the laborious and the idle part of it.
But if all our present taxes be mortgaged, must we not invent new ones? And may not this matter be carried to essay common a length that is ruinous and speech help destructive? In every nation, there are always some methods of levying money more easy than others, agreeably to the way of living of the people, and the commodities they make use of. In GREAT BRITAIN, the excises upon malt and beer afford a large revenue; because the operations of malting and brewing are tedious, and are impossible to be concealed; and at the same time, these commodities are not so absolutely necessary to life, as that the raising of their price would very much affect the poorer sort. No Plagiarism Report? These taxes being all mortgaged, what difficulty to find new ones! what vexation and speech writing ruin of the poor! Duties upon consumptions are more equal and questions easy than those upon possessions. Speech Writing Help Wedding? What a loss to the public, that the former are all exhausted, and that we must have recourse to the more grievous method of crucible levying taxes! Were all the proprietors of land only stewards to the public, must not necessity force them to speech help wedding practise all the arts of oppression used by stewards; where the rotman video questions, absence or negligence of the proprietor render them secure against enquiry? It will scarcely be asserted, that no bounds ought ever to be set to national debts; and that the public would be no weaker, were twelve or fifteen shillings in the pound, land-tax, mortgaged, with all the speech, present customs and excises. There is something, therefore, in the case, beside the essay common app, mere transferring of help wedding property from the one hand to another.
In 500 years, the posterity of custom no plagiarism those now in the coaches, and of those upon the boxes,#x00B0; will probably have changed places, without affecting the public by speech help these revolutions. i Suppose the public once fairly brought to rotman video essay that condition, to which it is hastening with such amazing rapidity; suppose the land to speech help be taxed eighteen or nineteen shillings in the pound; for custom it can never bear the whole twenty; suppose all the speech writing help, excises and customs to be screwed up to the utmost which the nation can bear, without entirely losing its commerce and industry; and suppose that all those funds are mortgaged to perpetuity, and that the invention and wit of all our projectors can find no new imposition, which may serve as the foundation of a new loan; and let us consider the necessary consequences of this situation. Though the imperfect state of our political knowledge, and the narrow capacities of men, make it difficult to fortel the effects which will result from any untried measure, the seeds of ruin are here scattered with such profusion as not to escape the eye of the most careless observer. In this unnatural state of society, the only persons, who possess any revenue beyond the immediate effects of their industry, are the stock-holders, who draw almost all the rent of the land and houses, besides the custom papers, produce of all the customs and excises. These are men, who have no connexions with the state, who can enjoy their revenue in any part of the globe in which they chuse to speech wedding reside, who will naturally bury themselves in the capital or in great cities, and who will sink into the lethargy of a stupid and pampered luxury, without spirit, ambition, or enjoyment. Adieu#x00B0; to thesis on political all ideas of nobility, gentry, and family. The stocks can be transferred in an instant, and being in such a fluctuating state, will seldom be transmitted during three generations from father to son.
Or were they to writing remain ever so long in one family, they convey no hereditary authority or credit to the possessor; and by this means, the several ranks of men, which form a kind of independent magistracy in a state, instituted by the hand of nature, are entirely lost; and every man in diversity, authority derives his influence from the commission alone of the sovereign. No expedient remains for writing preventing or suppressing insurrections, but mercenary armies: No expedient at all remains for resisting tyranny: Elections are swayed by bribery and video essay corruption alone: And the middle power between king and people being totally removed, a grievous despotism must infallibly prevail. The landholders, despised for their poverty, and writing hated for their oppressions, will be utterly unable to make any opposition to it. Though a resolution should be formed by custom no plagiarism report the legislature never to impose any tax which hurts commerce and discourages industry, it will be impossible for men, in subjects of such extreme delicacy, to speech wedding reason so justly as never to be mistaken, or amidst difficulties so urgent, never to be seduced from their resolution. The continual fluctuations in writing, commerce require continual alterations in the nature of the taxes; which exposes the legislature every moment to the danger both of wilful and involuntary error. And any great blow given to trade, whether by speech writing help wedding injudicious taxes or by other accidents, throws the whole system of government into confusion. But what expedient can the public now employ, even supposing trade to on political continue in the most flourishing condition, in order to speech help support its foreign wars and enterprizes, and to defend its own honour and interests, or those of its allies? I do not ask how the public is to exert such a prodigious power as it has maintained during our late wars; where we have so much exceeded, not only our own natural strength, but even that of the greatest empires. This extravagance is the abuse complained of, as the source of all the dangers, to which we are at common app, present exposed. But since we must still suppose great commerce and opulence to speech writing help wedding remain, even after every fund is mortgaged; these riches must be defended by proportional power; and whence is the public to derive the revenue which supports it?
It must plainly be from a continual taxation of the annuitants, or, which is the same thing, from mortgaging anew, on every exigency, a certain part of their annuities; *104 and thus making them contribute to their own defence, and to that of the nation. But the difficulties, attending this system of policy, will easily appear, whether we suppose the king to have become absolute master, or to be still controuled by national councils, in which the annuitants themselves must necessarily bear the principal sway. If the prince has become absolute, as may naturally be expected from this situation of affairs, it is so easy for him to encrease his exactions upon the annuitants, which amount only to common the retaining money in his own hands, that this species of property would soon lose all its credit, and the whole income of every individual in the state must lie entirely at the mercy of the sovereign: A degree of despotism, which no oriental monarchy has ever yet attained. If, on the contrary, the speech, consent of the annuitants be requisite for every taxation, they will never be persuaded to contribute sufficiently even to the support of government; as the rotman video essay, diminution of their revenue must in that case be very sensible, would not be disguised under the appearance of a branch of excise or customs, and writing would not be shared by any other order of the choices, state, who are already supposed to be taxed to the utmost. There are instances, in some republics, of a hundredth penny, and sometimes of the fiftieth, being given to the support of the state; but this is always an extraordinary exertion of power, and can never become the foundation of speech a constant national defence.
We have always found, where a government has mortgaged all its revenues, that it necessarily sinks into a state of languor, inactivity, and impotence. Such are the inconveniencies, which may reasonably be foreseen, of this situation, to essay common app which GREAT BRITAIN is visibly tending. Not to mention, the numberless inconveniencies, which cannot be foreseen, and which must result from so monstrous a situation as that of making the public the chief or sole proprietor of land, besides investing it with every branch of customs and excise, which the fertile imagination of speech writing help wedding ministers and controversy essay projectors#x00B0; have been able to invent. I must confess, that there is a strange supineness, from long custom, creeped into all ranks of men, with regard to speech wedding public debts, not unlike what divines so vehemently complain of with regard to their religious doctrines. We all own, that the most sanguine imagination cannot hope, either that this or any future ministry will be possessed of video such rigid and help steady frugality, as to make a considerable progress in the payment of our debts; or that the situation of foreign affairs will, for any long time, allow them leisure and controversy analysis essay assignment tranquillity for such an undertaking. j What then is to become of writing help us?
Were we ever so good Christians, and ever so resigned to Providence; this, methinks, were a curious question, even considered as a speculative one, and what it might not be altogether impossible to form some conjectural solution of. The events here will depend little upon the contingencies of battles, negociations, intrigues, and factions. There seems to be a natural progress of things, which may guide our reasoning. As it would have required but a moderate share of crucible prudence, when we first began this practice of mortgaging, to have foretold, from the nature of men and of ministers, that things would necessarily be carried to the length we see; so now, that they have at last happily reached it, it may not be difficult to guess at the consequences. It must, indeed, be one of these two events; either the nation must destroy public credit, or public credit will destroy the nation. It is impossible that they can both subsist, after the speech writing wedding, manner they have been hitherto managed, in papers no plagiarism, this, as well as in some other countries. There was, indeed, a scheme for the payment of our debts, which was proposed by an excellent citizen, Mr.
HUTCHINSON, *105 above thirty years ago, and which was much approved of by some men of sense, but never was likely to take effect. He asserted, that there was a fallacy in imagining that the public owed this debt; for that really every individual owed a proportional share of it, and paid, in his taxes, a proportional share of the interest, beside the expence of levying these taxes. Had we not better, then, says he, make a distribution of the writing help, debt among ourselves, and each of us contribute a sum suitable to his property, and by that means discharge at once all our funds and public mortgages? He seems not to have considered, that the laborious poor pay a considerable part of the essay, taxes by their annual consumptions, though they could not advance, at writing help wedding, once, a proportional part of the sum required. Not to mention, that property in money and stock in trade might easily be concealed or disguised; and that visible property in lands and houses would really at last answer for the whole: An inequality and oppression, which never would be submitted to. But though this project is not likely to take place; it is not altogether improbable, that, when the nation becomes heartily sick of their debts, and is cruelly oppressed by them, some daring projector may arise with visionary schemes for their discharge. And as public credit will begin, by that time, to be a little frail, the least touch will destroy it, as happened in FRANCE during the regency; *106 and in this manner it will die of the doctor. k. But it is more probable, that the breach of national faith will be the necessary effect of wars, defeats, misfortunes, and public calamities, or even perhaps of victories and conquests. I must confess, when I see princes and states fighting and quarrelling, amidst their debts, funds, and public mortgages, it always brings to diversity essay app my mind a match of cudgel-playing#x00B0; fought in a China shop.
How can it be expected, that sovereigns will spare a species of property, which is pernicious to themselves and to the public, when they have so little compassion on writing help, lives and properties, that are useful to both? Let the time come (and surely it will come) when the new funds, created for the exigencies of the year, are not subscribed to, and raise not the video essay questions, money projected. Suppose, either that the cash of the nation is exhausted; or that our faith,#x00B0; which has hitherto been so ample, begins to fail us. Suppose, that, in writing help wedding, this distress, the nation is threatened with an invasion; a rebellion is suspected or broken out at home; a squadron cannot be equipped for want of pay, victuals, or repairs; or even a foreign subsidy cannot be advanced. What must a prince or minister do in such an controversy essay assignment, emergence? The right of self-preservation is unalienable in every individual, much more in every community. Speech Writing? *107 And the custom papers, folly of our statesmen must then be greater than the folly of those who first contracted debt, or, what is more, than that of those who trusted, or continue to trust this security, if these statesmen have the means of safety in their hands, and do not employ them. The funds, created and mortgaged, will, by speech wedding that time, bring in essay, a large yearly revenue, sufficient for the defence and security of the nation: Money is perhaps lying in the exchequer,#x00B0; ready for speech wedding the discharge of the quarterly interest: Necessity calls, fear urges, reason exhorts, compassion alone exclaims: The money will immediately be seized for the current service, under the essay choices, most solemn protestations, perhaps, of being immediately replaced.
But no more is requisite. The whole fabric, already tottering, falls to writing help wedding the ground, and buries thousands in its ruins. Analysis? And this, I think, may be called the natural death of wedding public credit: For to this period it tends as naturally as an animal body to its dissolution and destruction. l So great dupes are the report, generality of mankind, that, notwithstanding such a violent shock to public credit, as a voluntary bankruptcy in ENGLAND would occasion, it would not probably be long ere credit would again revive in as flourishing a condition as before. Writing Help? The present king of FRANCE, during the questions, late war, *108 borrowed money at lower interest than ever his grandfather did; and as low as the speech help, BRITISH parliament, comparing the natural rate of thesis interest interest in both kingdoms. And though men are commonly more governed by wedding what they have seen, than by what they foresee, with whatever certainty; yet promises, protestations, fair appearances, with the allurements of present interest, have such powerful influence as few are able to resist. Mankind are, in all ages, caught by the same baits: The same tricks, played over and over again, still trepan#x00B0; them. The heights of popularity and diversity essay patriotism are still the beaten road to power and writing help wedding tyranny; flattery to treachery; standing armies to arbitrary government; and the glory of God to the temporal interest of the clergy. The fear of an everlasting destruction of essay german credit, allowing it to be an evil, is a needless bugbear.#x00B0; A prudent man, in reality, would rather lend to the public immediately after we had taken a spunge to our debts, than at present; as much as an help wedding, opulent knave, even though one could not force him to pay, is a preferable debtor to an honest bankrupt: For the former, in order to carry on controversy essay, business, may find it his interest to discharge his debts, where they are not exorbitant: The latter has it not in his power. The reasoning of TACITUS, *109 as it is eternally true, is very applicable to our present case. Sed vulgus ad magnitudinem beneficiorum aderat: Stultissimus quisque pecuniis mercabatur: Apud sapientes cassa habebantur, qu#x00E6; neque dari neque accipi, salva republica, poterant.
The public is a debtor, whom no man can oblige to pay. The only speech writing help check which the controversy essay assignment, creditors have upon writing, her, is the interest of preserving credit; an interest, which may easily be overbalanced by a great debt, and by a difficult and extraordinary emergence, even supposing that credit irrecoverable. Not to custom no plagiarism report mention, that a present necessity often forces states into measures, which are, strictly speaking, against their interest. These two events, supposed above, are calamitous, but not the most calamitous. Thousands are thereby sacrificed to the safety of millions. But we are not without danger, that the contrary event may take place, and that millions may be sacrificed for ever to the temporary safety of thousands. *110 Our popular government, perhaps, will render it difficult or dangerous for a minister to venture on help, so desperate an expedient, as that of essay a voluntary bankruptcy.
And though the house of Lords be altogether composed of proprietors of land, and the house of Commons chiefly; and writing help consequently neither of them can be supposed to have great property in the funds. Yet the connections of the members may be so great with the controversy analysis assignment, proprietors, as to writing wedding render them more tenacious of public faith, than prudence, policy, or even justice, strictly speaking, requires. And perhaps too, our foreign enemies m may be so politic as to discover, that our safety lies in despair, and rotman may not, therefore, show the danger, open and barefaced, till it be inevitable. The balance of power in EUROPE, our grandfathers, our fathers, and we, have all deemed too unequal to writing wedding be preserved without our attention and assistance. But our children, weary of the struggle, and fettered with incumbrances, may sit down secure, and see their neighbours oppressed and conquered; till, at last, they themselves and their creditors lie both at the mercy of the conqueror. And this may properly enough be denominated the violent death of our public credit.
These seem to be the events, which are not very remote, and which reason foresees as clearly almost as she can do any thing that lies in the womb of time. And though the ancients maintained, that in analysis, order to speech wedding reach the gift of prophecy, a certain divine fury or madness was requisite, one may safely affirm, that, in essay choices, order to deliver such prophecies as these, no more is necessary, than merely to speech writing help wedding be in diversity essay common, one's senses, free from the influence of popular madness and delusion.
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Free Information Technology essays. In this article we will investigate whether or not the speech writing wedding statement ‘IT doesn’t matter’ applies to 3 semi government agencies in the Netherlands. The research is based on the concepts of resource based theory. In this article, the hypothesis is tested that the resources of IT lack the essay german characteristics that give sustainable competitive advantage for writing help, semi government agencies. Interviews are conducted at the agencies among decision makers to get their opinion on the characteristics of the IT resources in custom papers report, relation to competitive advantage. Summary IT doesn’t matter by Nicholas Carr. In his article in the Harvard Business Review of 2003 Carr argues that IT has lost its strategic value. His argument is based on the assumption that in the early days companies could get a strategic advantage, but that nowadays IT cannot give those advantages anymore.
IT has become a commodity. And by speech writing help wedding, nature a commodity doesn’t provide competitive advantage. It has become an infrastructural technology that is easily acquired and copied. The increasing affordability of IT functionality has destroyed one of the diversity essay most important potential barriers to competitors. As a consequence, the way to writing help approach IT investment and management will need to change dramatically. The resource based theory is based on research within the field of strategic management. It stipulates that the competitive advantage of a firm lies primarily in the application of thesis interest, a set of wedding, tangible and intangible resources at the disposal of an organization. In order to have a sustained competitive advantage, these resources should be heterogonous in nature and not perfectly mobile. Barney (1991) added that these valuable resources should not be perfectly imitable or substitutable without great effort. If these conditions hold, competitive advantage may be achieved.
In their meta analysis of strategic resources and performance, Crook et al (2008) have proven that there is strong evidence that supports the essay common resource based theory. Wade Hulland (2004) investigated the speech writing help use of the resource based theory in video, information systems research. They distinguish between resources as assets and help wedding as capabilities. Assets are defined as anything tangible or intangible the firm can use in its processes for creating, producing and /or offering its products to a market. In contrast, capabilities transform inputs into outputs of greater worth. Capabilities can include skills, such as technical or managerial ability, or processes, such as systems development or integration. In this research the resources as defined by Wade Hulland are used as well as the characteristics which apply to Information Systems. This investigation is crucible, a qualitative research among semi government agencies. Speech Help Wedding. As we investigate the diversity opinions of decision makers on IT and writing help wedding the relation between IT and sustainable competitive advantage, this investigation is by nature a research on the subjective world of mental states. The opinions of the decision makers on IT and the relationship with sustainable competitive advantage are important.
It makes a big difference in choices, the way they make their decisions whether they regard IT as a strategic resource or as a commodity. As we apply the theory of the resource based view, this is writing wedding, a world 2-3 research. The research stands in the interpretivist tradition. A case study approach among three semi government agencies is used. Such a case study sheds light on the rationales of decision makers on essay questions, IT. Before discussing the speech help wedding research question a proper definition of ‘IT’ and ‘sustainable competitive advantage’ is required. Definition of ‘IT ‘ and ‘sustainable competitive advantage’
As mentioned Wade Hulland make a distinction between assets and capabilities. Both are resources as meant in the resource based theory. In accordance with the article by Wade Hulland (2004) the following IT resources define IT : a. Outside-in resources: 1. Manage external relationships: the ability to manage relations between the IS function and stakeholders outside the firm; 2. Market responsiveness: the essay app collection of help wedding, information from external sources and diversity essay common app dissemination of speech writing wedding, a firm’s market intelligence and the organization’s response to custom papers no plagiarism that learning; b. Spanning resources: 3. IS- business partnerships (manage internal relationships): processes of alignment between the IS function and other departments; 4. IS planning and change management: capability to plan, manage and use appropriate technology architectures and standards;
c. Inside-out resources: 5. IS infrastructure. 6. IS technical skills. 7. IS development. 8. Cost effective IS operations.
We will use these resource aspects in order to define what IT is about. So we confine the scope of IT, as used by Carr in his article, to the resources as mentioned above. In a sense we use a scope for IT that is writing, broader than Carr’s as it also involves the management of information systems and the management of external relationships. The theory states that the crucible choices characteristics of the resources as such are necessary conditions for competitive advantage. Writing Help. Furthermore in this theory there is a difference between the crucible essay resources that help the firm gain a competitive advantage and that help the speech writing firm to sustain that advantage.
These characteristics to gain competitive advantage are: 1. Valuable ‘ a resource must enable an organization to conceive or implement strategies that improves its efficiency and custom no plagiarism report effectiveness (Barney, 1991); 2. Rare ‘ To be of speech help wedding, value , a resource must be rare by definition. Crucible Essay Choices. If a valuable resource is controlled by only one firm it could be a source of competitive advantage; 3. Appropriability: the writing wedding advantage may not benefit a firm, if the firm is unable to appropriate the returns accruing form the advantage. Characteristics to sustain the advantage are: 4. Inimitable ‘This advantage could be sustainable if competitors are not able to duplicate this. 5. Non-substitutable ‘ Even if a resource is rare, potentially value creating and imperfectly imitable, an equally important aspect is lack of substitutability. 6. Mobility- In addition the resources must have a low tradability and imperfect mobility to diversity essay app give a sustained competitive advantage. The definition of ‘Sustained competitive advantage’ in a semi government is a difficult one: being part of the government means that there is no market ( for public goods) or there is a monopoly by law. Semi government is characterized by provisioning of services , for which these organizations get a fee in return.
This means that the writing help wedding term competitive advantage has to be redefined: in this investigation we reformulate ‘competitive advantage’ as achieving the public goals as defined by law and Government-regulations in the best way possible and the degree in which they succeed in generating revenue in a profitable way (i.e. with the lowest costs) by the provision of services. In fact ‘sustained competitive advantage’ in this case study is interpreted as sustainable goal achievement in the best possible way. In short the research question is ‘IT doesn’t matter’: The eight resources of IT don’t lead to sustainable competitive advantage. In the research the attributes of the IT resources are investigated (valuable, rare, appropriability, inimitability, non-substitutable, inmobility) as well as their relation with sustained goal achievement. When, in the opinion of the thesis on political decision makers, there is no relation between the resources and writing wedding sustainable goal achievement, the following statement is falsified: As mentioned, we confine this research to the semi government in custom papers report, the Netherlands. They have the same complex environment and many different stakeholders. Furthermore, they depend for a significant part of their revenue on help wedding, the fees they get for essay common app, the provision of information services. Three semi government agencies in the Netherlands apply for this: The Netherlands’ Cadastre, Land Registry and Mapping Agency, RDW (a public service provider in the mobility chain), and the Chamber of Commerce.
These organizations have an arrangement with the Dutch government for speech writing help wedding, levying fees in return for rotman video essay questions, the services provided. They are therefore similar in speech writing, kind in assessing the goal achievement of their organization (the reformulation of the term ‘sustainable competitive advantage’). In order to have a good understanding of the organizations involved, official and internal documentation, including the essay decision making on IT by the Board of Directors or Steering Committees, are reviewed. On basis of this review a selection of the relevant decision makers in the agencies is made. This is verified in contact with the agencies themselves. Writing Wedding. The interview will be conducted with at least two decision makers of the agency, e.g. the CEO and the CIO.
Selection of the decision makers depends in last resort on the decision making structure in the agency. The questions of an open interview are prepared, based on the literature of the resource based theory. The open interview is tested with an expert-collegea of the University of Tilburg. An interview protocol is formulated. Thesis Interest. Within one month the interviews are conducted. They consist of three interviews with the decision makers of the agencies involved. Well in advance of the interview, they receive the information on the subject of the interview and the duration. The agency gets an abstract of the results of the interview of writing help, their agency in return and is promised the no plagiarism report report of the results of the investigation. The interview consists of an writing, introduction to break the ice and rotman video essay questions get a relation with the interviewees The interview is speech writing wedding, conducted with two researchers.
The researchers stress the importance of the knowledge and perspectives of the interviewees. Essay Questions. If permission is speech writing, given, the interview will be taped. During the rotman questions interview, the researchers give a brief explanation of the speech IT resources, which are in controversy essay assignment, scope and their characteristics. Additionally information is given on speech help, the term ‘goal achievement’. In open questions, the opinion of the decision makers is recorded. Afterwards the results of the interview are analyzed. The analysis results in a report of the agency, in which the opinions of the decision makers are listed.
The listings include all the 8 resources and their characteristics and their relation to the goal achievement of the organization (the reformulation of the term ‘sustainable competitive advantage’). The investigation results in three reports (one per agency); they report the IT resources and crucible choices the characteristics in relation to the goal achievement of the organization. Speech Writing Help. From these lists, conclusions can be drawn whether the IT resources with the desired characteristics lead to goal achievement. A possible outcome might be that some IT resources have a positive relation with sustainable goal achievement while others have not. Validity and conclusion. This study has a low external validity as the scope is confined to 3 semi government agencies in the Netherlands, which provide for a considerable part of their revenue by fees for writing german, their information services. The study is more based on internal validity: whether the relations between the IT resources, their characteristics and goal achievement hold in the opinion of the decision makers. To assure the validity and reliability of the instrument of the open interview, the instrument is tested beforehand. The interview is carried out by speech writing, two interviewers in order to avoid subjectivity in the interpretation of the answers as much as possible. During the rotman video interview, examples are supplied for the eight IT-resources as well as a definition of the attributes.
The valuation of the attributes of the IT-resources is by writing wedding, nature subjective. After all the decision makers indicate how they value these attributes. Barney, J.B., (1991), Firm Resources and Sustained Competitive Advantage. Journal of Management; 17, (1), pp.99’120. Barney, J.B., (2001), Is the essay phrases german Resource-Based Theory a Useful Perspective for Strategic Management Research? Yes. Academy of Management Review; 26, (1), pp. 41’56. Carr, N.G., IT doesn’t matter (2003), Harvard Business Review (2003)
Crook, T. R., Ketchen Jr., D. J., Combs, J. G., Todd, S. Y. (2008). Speech Writing Help. Strategic resources and essay choices performance: A meta-analysis. Strategic Management Journal; 29, pp. 1141’1154. Wade, M and Hulland, J. (2004), The Resource-Based View and Information Systems Research: Review, Extension, and Suggestions for Future Research. MIS Quarterly, Vol. 28, No. Writing Help Wedding. 1 (Mar., 2004), pp. 107-142.
Appendix Table of results per agency. Search our thousands of essay questions, essays: If this essay isn't quite what you're looking for, why not order your own custom Information Technology essay, dissertation or piece of coursework that answers your exact question? There are UK writers just like me on hand, waiting to help you. Each of us is qualified to a high level in wedding, our area of expertise, and we can write you a fully researched, fully referenced complete original answer to your essay question. Just complete our simple order form and you could have your customised Information Technology work in your email box, in as little as 3 hours.
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