Thursday, November 28, 2019
Irving Independent School District V. Amber Tatro Essay Example
Irving Independent School District V. Amber Tatro Paper Running Head: Irving Independent School District v. Amber Tatro Irving Independent School District v. Amber Tatro Warner University A child with disabilities is a major focus in todayââ¬â¢s education. Achieving my Bachelors in Special Education, I need to be aware of the need to ensure appropriate education for all children with disabilities. ââ¬Å"The education of children with disabilities is a top national priority. Our nationââ¬â¢s special education law, the Individuals with Disabilities Education Act (IDEA), sets high standards for their achievement and guides how special help and services are made available in schools to address their individual needs (National Dissemination)â⬠. This is my biggest challenge. I feel with the right tools and help with administration; my job will guarantee a bright future for my students with disabilities. I came across a case, Irving Independent School District v. Amber Tatro. The findings of this case gave me some insight on the statues and limitations that I as an educator have to abide by. But it also gave me hope that we the educators have the right to make such access meaningful to handicapped children. Amber Tatro was born with spina bifida. ââ¬Å"As a result, she suffers from orthopedic and speech impairments and a neurogenic bladder, which prevents her from emptying her bladder voluntarily. We will write a custom essay sample on Irving Independent School District V. Amber Tatro specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Irving Independent School District V. Amber Tatro specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Irving Independent School District V. Amber Tatro specifically for you FOR ONLY $16.38 $13.9/page Hire Writer Consequently, she must be catheterized (CIC), a procedure involving the insertion of a catheter into the urethra to drain the bladder, has been prescribed. The procedure is a simple one that may be performed in a few minutes by a layperson with less than an hourââ¬â¢s training (Irving)â⬠. If CIC is not performed every three to four hours, it could cause injury of the kidneys. In 1979, Amber Tatro was provided special education with an individualized education program under the requirements of the Education of the Handicapped Act. This provided Amber with special services while attending early childhood development classes. Amberââ¬â¢s individualized education program however, did not provide administrative remedies to secure CIC. ââ¬Å"In October 1979 respondents brought the present action in District Court against petitioner, the State Board of Education, and others. They sought an injunction ordering petitioner to provide Amber with CIC and sought damages and attorneyââ¬â¢s fees (Eric)â⬠. The courtââ¬â¢s found CIC to be a ââ¬Å"related serviceâ⬠allowing Amber to have a special education. The Court of Appeals affirmed and accepted the District Courtââ¬â¢s conclusion that state law permitted be required schools to hire trained personnel to help with the needs of handicapped children. This entitles an education for those children with special medical needs. ââ¬Å"A service that enables a handicapped child to remain at school during the day is an important means of providing the child with the meaningful access to education that Congress envisioned (Eric). â⬠ââ¬Å"The Petitionerââ¬â¢s view: First, to be entitled to related services, a child must be handicapped so as to require special education. In the absence of a handicap that requires special education, the need for what otherwise might qualify as a related service does not create an obligation under the Act. Second, only those services necessary to aid a handicapped child to benefit from special education must be provided, regardless how easily a school nurse or layperson could furnish them. Third, the regulations state that school nursing services must be provided only if they can be performed by a nurse of other qualified person, not if they must be performed by a physician (Eric). The resulting decision on this case was that yes, schoolââ¬â¢s are required to provide special medical needs for children with disabilities. What does this mean for education? It gives education and faculty the obligation to provide services that relate to both the health and educational needs of handicapped students (Eric). â⬠It allows them to correct undesirable behaviors by giving them support for a search when one is appropriate . It shows to the students and parents what could happen if you violate the rules of the school. It also encourages the students to leave certain nuisances that are not going to encourage their education at home. As for me as a professional, this case has given me some enlightment on what the rights of the students are. Irving Independent School District v Amber Tatro has opened up my eyes to the freedom children with disabilities have. No child will be left without an appropriate education. Works Cited ERIC Education Resources Information Center. ERIC ââ¬â Worldââ¬â¢s Largest Digital Library of Education Literature. Web. 19 May 2011.
Monday, November 25, 2019
The 10 Most Frequently Looked-Up Words
The 10 Most Frequently Looked-Up Words The 10 Most Frequently Looked-Up Words The 10 Most Frequently Looked-Up Words By Mark Nichol According to Merriam-Websterââ¬â¢s website, these are the ten most frequently search terms on the site- not what is trending now, but the words that consistently rank among the top searches. 1. Affect/Effect This double entry is not surprising; the confusion between affect and effect is one of the most common among homophones (words that sound alike but are spelled differently) and near homophones. Merriam-Webster advises that writers can use a simple rule in mind when determining which word to use- affect is usually a verb and effect is usually a noun- but exceptions in which the reverse is true are frequent enough to render this advice scarcely useful. Another mnemonic to help you distinguish the two is that to affect is to have an effect, and an affect leads to an effect. Affect usually means ââ¬Å"have an effect or influence,â⬠as in ââ¬Å"Will not completing this assignment affect my grade?â⬠while an effect is something that is the result of a causative phenomenon (hence the phrase ââ¬Å"cause and effectâ⬠), as in ââ¬Å"Will not completing this have an effect on my grade?â⬠But note that affect can also serve as a noun meaning ââ¬Å"aspect of an emotionâ⬠or ââ¬Å"evidence of an emotion.â⬠In psychology, to say that one presents a flat affect is to express that the person exhibits little or no emotion. In addition, effect is sometimes used as a verb meaning ââ¬Å"bring about,â⬠as in ââ¬Å"Our goal is to effect a change in policy.â⬠One can also say, ââ¬Å"Our goal is to affect a change in policy,â⬠but that means that one merely wishes to have an impact; to effect a change is to deliberately create the change. As a verb, affect also means ââ¬Å"create the appearance of,â⬠as when one affects a sophisticated manner to conceal humble origins, or ââ¬Å"pretend,â⬠as when one affects not to know about something that one is actually aware of. Either sense implies deception. The adjective affective means ââ¬Å"emotionalâ⬠or ââ¬Å"expressing emotion,â⬠while affecting, as an adjective, means ââ¬Å"evoking a strong emotional response.â⬠Effective means ââ¬Å"producing a decisive or desired effectâ⬠and pertains to being actual, operative, or ready (and rarely, as a noun, denotes one who is effective), while effectual means ââ¬Å"producing, or able to produce, a desired effect.â⬠2. Albeit This archaic-seeming word means ââ¬Å"even thoughâ⬠; one would write, for example, ââ¬Å"The jacket was expensive, albeit a practical necessity in cold weather.â⬠It is one in a category of compound words combined to serve as an adverb, such as notwithstanding and nevertheless, or a conjunction such as the rare word howbeit or the common term whereas. 3. Ambiguous Ambiguous means ââ¬Å"doubtful or uncertainâ⬠or ââ¬Å"unexplainable,â⬠but usually it denotes something that can be understood in two distinct ways, as when one exclaims, ââ¬Å"Iââ¬â¢ve never seen anything like it,â⬠which does not inform the listener about whether the speaking is commenting positively or negatively. The first element, ambi-, meaning ââ¬Å"bothâ⬠or ââ¬Å"on both sides,â⬠is also seen in ambivalent (with which it is often confused, though that word means ââ¬Å"having contradictory feelingsâ⬠) and ambidextrous. The noun form of ambiguous is ambiguity. 4. Apathetic Apathetic is an adjective meaning ââ¬Å"indifferentâ⬠or ââ¬Å"uncaringâ⬠; the noun form, apathy, literally means ââ¬Å"lack of feeling.â⬠(This post discusses this and other words formed from the root pathos, meaning ââ¬Å"feelingâ⬠or ââ¬Å"suffering.â⬠) 5. Conundrum Conundrum refers to complex, difficult problems or, more informally, a mystery or puzzle (or a riddle with a punning answer). The word is, ironically, itself a mystery, with an unknown etymology, although one theory is that hundreds of years ago, an Oxford University student coined the word to parody Latin; indeed, more than one spelling among various forms used in the wordââ¬â¢s early years began with qu-, often a sign of Latin origin. 6. Cynical A cynical person is one skeptical of othersââ¬â¢ motives or convinced that people always put their own interests before those of others. The word derives from the name of a Greek school of philosophy, whose adherents were called Cynics (from the Greek term kynikos, meaning ââ¬Å"like a dogâ⬠); one with a cynical attitude is a cynic, and the quality of being cynical is called cynicism. 7. Integrity Integrity is the quality of being fair and honest (said of a person) or of being complete or sound (said of an object), as in the notion of structural integrity of something constructed. 8. Love Love is the most curious entry in this list, as it is a deceptively simple word. Love, however, can- as a noun or a verb- express a passion for anything (ââ¬Å"I love that movie!â⬠) as well as romantic and sexual feelings or behavior, in addition to religious passion. Loving and lovable are adjectival forms, and one who loves is a lover. 9. Pretentious Someone who has an exaggerated sense of importance or worth is pretentious; such a person is said to have pretensions, even if only one category of pretension exists, and a pretense is a deception (as in the redundant but idiomatic phrase ââ¬Å"false pretensesâ⬠). The word is derived from the Latin verb praetendere, which literally means ââ¬Å"stretch in frontâ⬠; pre means ââ¬Å"before,â⬠and tendere, meaning ââ¬Å"stretch,â⬠is the basis of tender (as in ââ¬Å"tender oneââ¬â¢s resignationâ⬠) and tendon, the term for connective tissue that stretches between muscles and bones. (Tender in the sense of ââ¬Å"sensitiveâ⬠or ââ¬Å"loving,â⬠among other meanings, is unrelated.) By extension, the notion of literal stretching gave way to the meanings ââ¬Å"stretching the truthâ⬠or ââ¬Å"acting as if something not true is true,â⬠and one who acts pretentiously is a pretender. 10. Ubiquitous Something widespread is ubiquitous; the quality of something existing everywhere or being encountered often is ubiquity. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Vocabulary category, check our popular posts, or choose a related post below:Is She a "Lady" or a "Woman"?Dawned vs. Donned50 Words with Alternative Spellings
Thursday, November 21, 2019
Business Plan for Car Hire Company Essay Example | Topics and Well Written Essays - 1250 words
Business Plan for Car Hire Company - Essay Example These factors include the income and expenditure of the people, the availability of the market and the effects of the global financial issues on the location of the business. The city of New York is one of the major financial hubs in the world. For this reason it is set to be susceptible to changes in the economic conditions, say fluctuations in currency. This and many others will most definitely have an effect on the spending habits of the consumers and this will trickle down to the financial performance of the business.Ã The major headache that comes up when developing any particular business is when it comes to setting up. This is the time the proprietor asks the question of whether it is in order to develop a new establishment altogether or just purchase and refurbish what has already been in existence. The cheaper alternative is the one which is to be sought. After this issue has been sorted out the next thing to deal with will be the availability of inputs and whether the se rvices will be timely. The car hire business can be a tricky one because there are some factors which may be beyond the control of the people involved. One such factor is the case of being stuck in traffic. This is something that can happen at any one time and it cannot be controlled by the car driver or the owner of the business.Aside from the issues dwelling on finances and the availability of the target market there are certain issues which may bring down the functionality market.... The P.E.S.T. analysis is the best way of getting to know of these traits in the environment of operation. This analysis will try and point out the effect which the political situation has on the business and its operations. At the same time it will point out the economic factors that influence the performance of a business. These factors include the income and expenditure of the people, the availability of the market and the effects of the global financial issues on the location of the business. The city of New York is one of the major financial hubs in the world. For this reason it is set to be susceptible to changes in the economic conditions, say fluctuations in currency. This and many others will most definitely have an effect on the spending habits of the consumers and this will trickle down to the financial performance of the business. The major headache that comes up when developing any particular business is when it comes to setting up. This is the time the proprietor asks th e question of whether it is in order to develop a new establishment altogether or just purchase and refurbish what has already been in existence. The cheaper alternative is the one which is to be sought. After this issue has been sorted out the next thing to deal with will be the availability of inputs and whether the services will be timely. The car hire business can be a tricky one because there are some factors which may be beyond the control of the people involved. One such factor is the case of being stuck in traffic. This is something that can happen at any one time and it cannot be controlled by the car driver or the owner of the business. Aside from the issues
Wednesday, November 20, 2019
Citibank IN New Countries for Futures Markets Development Essay
Citibank IN New Countries for Futures Markets Development - Essay Example Furthermore, the projected customer base also determines the market entry approach that best fits that target market. In the case of Chile, the country illustrates an ideal market size approximated at 17.4 million citizens, and with the main degree of economic freedom. In this regard, the best market entry approach for Chile is the improvement of customer engagement and satisfaction through more relevant ad timely communications. This is mainly because of the large projected customer base that in turn requires for additional attention. The real-time relationship between the customers and the bank backed by the timely communications offers in-depth customer insights through each interaction point (Czinkota 512). The turning of customerââ¬â¢s insights into automated and operational brilliance further paves way for the new banking service in Chile thus leading to realization of higher profits. This approach also suits Chile as it incorporates the research evidencing the deficiency of banks to provide value to their customers. Countering this pre-existent condition, this approach enhances the customerââ¬â¢s records using key insights such as their lifestyle and banking behavior. As a result, there exists a more relevant and effective distribution of value to all segments of the customer base. Subsequently, factors such as high ranking in World Bankââ¬â¢s income groups of 2012 and lower middle economy characterize Bolivia. Furthermore, the similarity between Bolivia and Chile as illustrated by the cultural dimensions calls for an entering approach that depicts slow customer attrition while building stronger relationships (Carlton 252). This approach ensures minimal dissatisfaction of customers thus preventing loss of established customer bases to competitors. Through creation of early warning systems, this approach identifies the customersââ¬â¢ turning points prior to their occurrence thus providing a chance to address the customers at risk. In other wor ds, this approach ensures continuous productivity through active implementation of retention measures through shaping the services according to the customerââ¬â¢s preferences. On the other hand, Slovenia illustrates a collective society whose members exchange adherence and loyalty. With a reduced market size, Slovenia calls for a real time customer growth initiative. This approach propels take cross-sell and up-sell to new heights by triggering the target marketââ¬â¢s readiness to open new accounts and enjoy the services offered. Through development of cross-sell and up-sell programs, identification of customerââ¬â¢s readiness to create, change or start utilizing on-line services becomes predictable. As a result, the bank gains control over the sale of certain products and services through studying customer behavior. Foreign direct investment actively participates to the growth of global business through provision of new markets and applicable marketing channels (Graham & S paulding 1). Furthermore, it contributes to provision of cheaper production facilities in a country like Chile where the population is relevantly high. Furthermore, licensing accrues for significantly higher returns through engagement into relatively risky markets such as Bolivia. Following to extreme competition, foreign direct investment facilitates provision and effective utilization of new technology, products and skills. On the other hand, these aspects aid the development of a strong forward
Monday, November 18, 2019
UKs Land Use Planning Essay Example | Topics and Well Written Essays - 1250 words
UKs Land Use Planning - Essay Example This responsibility is vested with the Office of the Deputy Prime Minister in England, in Wales and Scotland the Welsh Assembly Government and the Scottish Executive respectively. In addition these departments have to develop national planning policy guidance within which local authorities have to function (British Geological Survey, n.d.). The endeavour of the Planning Practice Standard is to develop the environmental impact assessment, EIA, as a planning tool in order to promote the objectives of town and country planning. "This PPS updates the RTPI Practice Advice Note 13, published in 1995, to reflect the requirements of the amended EIA Regulations, which came into effect in 1999". In order to implement the European Directive 85/337/EEC, as amended by the Directive 97/11/EC, legislation on environmental impact assessment has been introduced in the UK. Section 71A of the Town and Country Planning Act 1990, contains the requirement to carry out EIA of certain planning proposals. (The Royal Town Planning Institute, 2001). The use of land determines irrevocably the fate of natural and semi-natural ecosystems and consequently, sustainable development is ably assisted by Nature conservation policies and their relations with land use exemplify the importance being accorded to planning. This process makes it essential to establish fundamental links between developments in particular localities and environmental changes on a world - wide basis. This methodology requires the adoption of a strategic approach to the conservation and enhancement of biodiversity (Cowell and Owens 2002). The basic human responsibility to protect and improve the environment for the benefit of present and future generations was expressed on the global level as early as 1972, in principle 1 of the Stockholm Declaration, but the Aarhus Convention is the first international legal instrument to extend this concept to a set of legal obligations (Stec and Casey - Lefkowitz 2000). Land-use planning is concerned not only with site protection but of late; it is proving of immense relevance in the adoption of a proactively strategic approach to the conservation of nature. This approach must not only concentrate on preservation of what has survived but more importantly, it has to address itself to the problem of habitat restoration and enhancement. In the UK this change is visible in legislation and in the guidance being provided to the local planning authorities from government, statutory agencies and non-governmental organisations, for ensuring the protection of the biodiversity. Planning and nature conservation policy have been influenced to a great extent by the latest interpretations of sustainable development, especially those which involve the concepts of environmental capital and capacity. The role of land use planning has been highlighted by European legislation and in particular the Habitats Directive, which aims to conserve European species and habitats . This Directive, enjoins upon national governments the requirement to nominate Special Areas of Conservation (SACs), which are to be provided with stringent protection. That there are limitations to this approach is borne out by the fact that, despite their protected status, many sites have been lost or damaged as a result of land-use change. The major culprit in this aspect has been development as defined in town and country planning legislation, which has
Friday, November 15, 2019
Fe-AZT and Pd-AZT Synthesis and Effects
Fe-AZT and Pd-AZT Synthesis and Effects Synthesis and Effects of Fe-AZT and Pd-AZT on Viability of Human Hepatocytes and Hepatocellular Carcinoma Cells Submitted by: Anna Harutyunyan Introduction Cancer is one of the major causes of mortality in the world. In 2015, according to the National Cancer Institute, over 1.6 million new cases of cancer were reported in the United States. The estimated cancer deaths for the year of 2015 were over 500,000. According to the National Cancer Institute projections, in 2016 an estimated 1.7 million new cases of cancer were diagnosed in the United States and 595,690 people will die from the disease (National Cancer Institute). Although new cancer treatments and therapies are designed and implemented every year, cancer is still the number two cause of mortality in the United States, therefore developing and testing new effective anticancer agents is crucial. Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancers (Venook et al., 2010). The overall 5-year survival rate of HCC is less than 17%, making HCC the fastest rising cause of cancer related death in the United States (American Cancer Society 2016; Mittal and El-Serag, 2013). The annual age-adjusted incidence rates of HCC increased from 1.4 per 100,000 individuals in 1975-77 to 4.8 per 100,000 in 2005-07. An estimated 39,230 new cases of liver cancer (including intrahepatic bile duct cancers) were expected to occur in the US during 2016, approximately three-fourths of which would be hepatocellular carcinoma. An estimated 27,170 liver cancer deaths were expected in 2016 (American Cancer Society 2016). In 80-90% cases HHC occurs with and after cirrhosis. HCCs major risk factors are Hepatitis B and C viruses, cirrhosis, non-alcoholic fatty liver disease (NAFLD), overconsumption of alcohol and exposure to other carcinogenic substances (Mittal and El-Serag, 2013). Liver ca ncer is the sixth most common neoplasm and the third leading cause of cancer-related deaths, accounting for approximately 600,000 deaths annually (Venook et al., 2010). Because of early metastasis and progression, HCCs treatment is difficult, and traditional chemotherapy has shown limited success (Sabokrough et al, 2014). A research study published in 2015 suggested that an organometallic complex of platinum (II) azidothymidine (Pt (II)-AZT) has an antitumor effect on rat hepatocellular carcinoma cells. It was shown that this complex was significantly more effective in tumor suppression than the AZT without platinum (Sabokrough et al., 2014). Several organometallic complexes of AZT (with Zinc, Cobalt, Copper and Iron) were synthesized and characterized previously. The Iron complex of AZT (Fe-AZT) was shown to be the most stable (Shirvastav et al.) and have antimicrobial activity against 4 groups of bacteria. Electron rich ligands like AZT effectively bind and interact with metal ions producing metallodrugs which offer promising therapeutic application in terms of combating the drug-resistant strains of pathogens. It is also logical that a metal ion can influence the biological activity and therapeutic efficacy of the bio-molecule they bind (Shirvastav et al.) Thus it is useful to investigate the effect of a metal ion on the efficacy and mode of action of AZT in suppressing malignant cells and inducing apoptosis. To date, no research has been published regarding synthesis of Pd-AZT the inhibitory effect of both Fe-AZT and Pd-AZT on malignant cells. The aim of this research project is to synthesize Fe-AZT and Pd-AZT, confirm their structure and molecular mass and test their effects on viability of human hepatocellular carcinoma cells and normal human hepatocytes. Background Normal cell cycle In order to understand the biology of cancer it is crucial to understand the cell cycle of normal cells and cancerous cells. All cells in a given organism are under strict control of multiple regulatory agents, such as RB or p53 that control cell growth and keep the proliferative index stable. If there is a need for the cell to divide, the proliferative genes will turn on, or the suppressor genes that keep proliferation from occurring will be shut down, which will result in cell division (Hardin et al., 2014). The normal cell cycle consists of the following phases: G1, S, G2, M. During the G1 phase duplication of organelles, membrane systems and other important components happens. There is an important checkpoint at the end of this phase referred to as the restriction checkpoint, which verifies that DNA synthesis was successful and no errors have been detected. Next is the S phase during which the cell duplicates each chromosome. During the G2 the rest of the components that were not synthesized in the G1 phase are synthesized. A checkpoint after this phase makes sure the cell is ready to divide, and no errors in chromosome duplication were made. Mitosis is the next phase, when the cell physically divides (cytokinesis) making two identical daughter cells. A checkpoint during this phase checks if both of the daughter cells received the correct number of chromosomes. After division, the cell may remain in its silent G0 phase, when it does not divide, but continues to function. If any errors are detected on any of the checkpoints, the cell cycle is put on hold and the cell will undergo apoptosis. This process is governed my many enzymes and complexes, and theoretically, malfunction of any of these enzymes may result in uncontrolled cell division/proliferation. This can be the onset of carcinogenesis. Figure 1. The cell cycle phases with their checkpoints. Cancer cell cycle It is important to note that the normal cell cycle is under control of thousands of regulatory elements that are coded for by different genes. If mutations occur in the genes that code for the key elements keeping cell proliferation at bay, one level of control over the cell cycle is lost. There are cell signaling mechanisms through which immune cells detect faulty cells, send them death signals and the faulty cell undergoes apoptosis. It takes more than one mutation for a normal cell to start behaving like a cancer cell. Usually it is either the loss of the function of suppressor genes, or overexpression of proliferative genes that result in uncontrolled cell proliferation. When the cell becomes malignant, it loses the ability to respond to death signals, thus does not undergo apoptosis. The malignant cell cycle is slower than the normal cell cycle, however, since the cancer cells keep dividing and do not die, their number grows exponentially resulting in tumors (Weinberg, 2014). There is distinct cytological difference between normal and cancer cells (Figure 2). A normal cell has a smaller, regularly shaped nucleus, a low nucleus/cytoplasm ratio, is well differentiated and has well defined borders. Cancer cells have larger, irregularly shaped nucleus, high nucleus/cy toplasm ratio, are less differentiated and have irregular borders. In contract with normal cells that adhere to each other, cancer cells are less adhesive and break away from each other (Weinberg, 2014). Figure 2. The comparison of the cytology of normal cells and cancer cells. Azidothymidine (AZT), Fe(III)AZT, Pd(II)AZT Azidothymidine (AZT, Zidovudine) is a thymidine derivative in which the 3-hydroxy group is replaced by an azido group (Figure 3). It has been shown to have antitumor effects on different animal carcinoma cells both in vitro and in vivo through inhibition of telomerase activity and by causing cell cycle arrest (Gomez et al., 2012; Hadizadeh et al., 2014, Cooper and Lovett, 2011; Matteucci et al., 2015). Figure 3. Thymidine (left), Azidothymidine (right). Since cancer cells have higher proliferation rate than normal cells, their thymidine turnover rate is higher, which could contribute to their increased sensitivity to AZT. Several studies conducted by Fang et al., have shown that a hepatocellular carcinoma cell line (HepG2) is significantly more sensitive to AZT toxicity as compared to the normal hepatocyte (THLE2) sensitivity (Fang et al., 2014; Fang and Beland, 2009). The current hypothesis on how AZT affects the cell suggests that AZT is phosphorylated intracellularly yielding AZT-triphosphate and AZT-monophosphate. The AZT-monophosphate can be incorporated into the DNA structure instead of thymidine due to its similar molecular structure and shape. However, in contrast with thymidine, AZT lacks the 3 hydroxyl group which is the group that forms phosphodiester bonds between nucleotides in the DNA backbone structure. This means, wherever the AZT phosphate is incorporated in one of the DNA strands during DNA replication, the elongat ion of that strand halts (Figure 4). This is one of the mechanisms through which AZT causes damage to DNA (Fang et al, 2014). The commercial name of AZT is Zidovudine, and it is the basis of AIDS treatments. AZT blocks the replication of HIV-1 virus by competitively inhibiting the viral reverse transcriptase (RT). In other words, HIV RT prefers AZT to normal nucleotides. As described above, AZT is phosphorylated to AZT-triphosphate and is incorporated into viral DNA, halting nucleotide chain elongation. It is also known that AZT-triphosphate can be incorporated into eukaryotic DNA, although its affinity for DNA polymerases is lower than that for RT (Gomez et al, 2012). It was shown that Pt(II)-AZT is more effective in suppressing cancer cells than AZT, thus it has been suggested that having a transition metal bound to the central nitrogen atom of the azido group increases the complexs affinity for G-C and A-T base pairs and the P-backbone of DNA (Das and Pitre, 2007; Sabokrouh et al, 2015). Materials and Methods Fe-AZT and Pd-AZT synthesis To carry out the synthesis of Pd and Fe complexes, solid AZT and a standard ion solution of each metal (iron nitrate nonahydrate (Fe(NO3)3Ãâà ·9H2O and palladium chloride (PdCl2)) will be purchased from Sigma Aldrich (St. Louis, MO). Synthesis will be performed according to the protocol by Das and Pitre (2007). A 1:1 molar ratio of aqueous solution of AZT and metal ion will be refluxed for 3 hours. The volume of the reaction mixture will be reduced by 75% in order for the complex to precipitate. The solid product will be vacuum filtered, washed twice with ice-cold water, recrystallized and air-dried overnight. Infrared absorbance spectra will recorded for the AZT, Fe-AZT and Pd-AZT complexes. In the experiment conducted by Das and Pitre (2007) the comparison of IR spectra of pure AZT and its complex with Fe, the spectrum indicated a shift in bands from 2170 to 2150 cm-1 due to complexation through N atom of azido group. A similar band shift in the IR spectrum of Fe-AZT and Pd-AZT is expected. A Matrix Assisted Laser Ioniation/Distortion Time-of-Flight (MALDI TOF) mass spectrometry analysis will be performed for the Fe-AZT and Pd-AZT to determine the molar mass and the stoichiometry of the complexes. The matrix for analysis will be composed of 1:1 saturated Anthranilic Acid and Nicotinic Acid (Sigma Aldrich, St. Louis, MO). The samples and matrix will be dissolved in 45% acetonitrile: 55% water (van Kampen et al., 2004). Cell cultures HepG2, THLE2. Liver carcinoma cell line HepG2 and normal human liver cell line THLE2 will be obtained from American Type Culture Collection (Manassas, VA). The standard protocol recommended by ATCC will be used for establishing and maintaining hepatic cell lines. The cell lines will be plated at a density of 5 x 103 cells/cm2. HepG2 cells will be cultured in DMEM with 10% fetal bovine serum and antibiotics (penn/strep). THLE2 cells will be cultured in LHC-8 medium with 70ng/ml phosphoethanolamine, 5ng/ml epidermal growth factor, 10% fetal bovine serum and antibiotics (Fang et al., 2009). After ensuring sufficient cell growth and several passages of each cell line, the two cell lines will be divided into 4 groups each: control (no treatment) and treated with each drug: AZT, Fe-AZT and Pd-AZT (Table 1). Table 1. The experimental setup of the control and experimental groups of cells. Control 1 (C1) THLE2 cell line (no treatment) Control 2 (C2) HepG2 cell line (no treatment) Experimental 1 (E1) THLE2 cell line+AZT Experimental 2 (E2) HepG2 cell line+AZT Experimental 3 (E3) THLE2 cell line+Fe-AZT Experimental 4 (E4) HepG2 cell line+Fe-AZT Experimental 5 (E5) THLE2 cell line+Pd-AZT Experimental 6 (E6) HepG2 cell line+Pd-AZT The cells in the treated groups will be further categorized by the concentrations of the drug. HepG2 cells will be incubated with 2, 20 or 100 Ãâà µM aqueous solution of AZT, Fe-AZT or Pd-AZT for 14 days. THLE2 cells will be incubated with 50, 500 or 2500 Ãâà µM aqueous solution of AZT, Fe-AZT or Pd-AZT for 14 days. Each group of cells will be seeded at 5 x 103 cells/cm2 density in 6-well plates. The cells will be passaged weekly during the two-week treatment period. The dosage and incubation time were chosen based on a similar study (Fang et al., 2013; Matteucci et al., 2015; Sabokrouh et al., 2015). Cell viability assay After 14-day treatment period, 103 106 cells from each group will be seeded in a 96-well plate, incubated for 4 hours, and treated with MTT reagent, followed by a 8-12 hours incubation at 37Ãâà °C. After the incubation with MTT, when the cells have metabolized the yellow tetrazolium dye (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) to purple formazan, the cells will be treated by a detergent to release the formazan into the solution, and the absorbance will be measured at 570nm using an ELIZA reader. The number of metabolically active cells will be determined using a previously made calibration curve. The statistical differences will be calculated using a Two-Way ANOVA and Tukeys Post-Hoc Test. Anticipated outcomes. The expected mass-to-charge ratio from mass spectrometry analysis of Fe-AZT complex is 323.1, that of Pd-AZT is 373.6. Based on the published literature and the adopted hypothesis, all three drugs are expected to decrease cell viability. The concentration of either drug should have positive correlation with decrease in cell viability. Based on previous observations, it is expected that the HepG2 cells will be significantly more sensitive to both complexes, thus will be significantly less viable after the treatment compared to the THLE-2 cells. Study Participants and Timeline Anna Harutyunyan is the primary author of this study. She is currently a senior biology and chemistry major at Wilson College. This project will serve as Annas senior research project. She will conduct the research and present the results with the supervision of her advisors Dr. Deborah S. Austin (Sponsoring PAS member) and Dr. M. Dana Harriger (PAS Member). The research study began in September 2016 and will be completed by April 2017. Annas research findings will be analyzed and written as her senior thesis. Anna will also present her findings at the 2017 Pennsylvania Academy of Science meeting and at the Wilson College research colloquium. Budget Item Price MTT Assay Kit (ThermoFisher) $235.00 Zidovudine (Sigma) $124.00 LHC-8 medium (Gibco) $140.00 Total $499.00 Facilities and Equipment The MALDI TOF mass spectrophotometer will be provided by Pennsylvania State College of Medicine Mass Spectrometry Facility under supervision of Bruce Stanley, PhD. All materials, other instruments, and equipment not listed, including cell culture media and supplies, will be provided by the Department of Physical and Life Science of Wilson College. References à à American Cancer Society. Cancer Facts Figures 2016. Atlanta: American Cancer Society; 2016. Bilsland AE, Stevenson K, Liu Y, Hoare S, Cairney CJ, Roffey J, et al. (2014) Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms. PLoS Comput Biol 10(2): e1003448. doi:10.1371/journal.pcbi.1003448 BIOL2060 Cell Cycle [Photograph found in Department of Biology Memorial University of Newfoundland]. (2015). In Hardin Bertoni (Authors). Retrieved March 30, 2016, from http://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-19/CB19.html Chen, Yi-Bin. Liver Cancer Hepatocellular Carcinoma: MedlinePlus Medical Encyclopedia. U.S National Library of Medicine. U.S. National Library of Medicine, 1 Aug. 2015. Web. 10 Apr. 2016. Cooper, D. L., Lovett, S. T. (2011). Toxicity and tolerance mechanisms for azidothymidine, a replication gap-promoting agent, in Escherichia coli. DNA Repair, 10(3), 260-270. http://doi.org/10.1016/j.dnarep.2010.11.007 Das, R., Pitre, K. S. (september 2007). Bioinorganic studies on Fe (II)- zidovudine (azt) complex. Indian Journal of Chemical Technology, 14, 526-528. Retrieved February 20, 2016. Fang, J.-L., Beland, F. A. (2009). Long-Term Exposure to Zidovudine Delays Cell Cycle Progression, Induces Apoptosis, and Decreases Telomerase Activity in Human Hepatocytes. Toxicological Sciences, 111(1), 120-130. http://doi.org/10.1093/toxsci/kfp136 Fang, J., Han, T., Wu, Q., Beland, F., Chang, C., Guo, L., Fuscoe, J. (2014). Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Archives Of Toxicology, 88(3), 609-623. doi:10.1007/s00204-013-1169-3 Gomez, D. E., Armando, R. G., Alonso, D. F. (2012). AZT as a telomerase inhibitor. Frontiers in Oncology, 2, 113th ser. Retrieved March 11, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434370/ Hadizadeh, S., Najafzadeh, N., Mazani, M., Amani, M., Mansouri-Torshizi, H., Niapour, A. (2014). Cytotoxic Effects of Newly Synthesized Palladium(II) Complexes of Diethyldithiocarbamate on Gastrointestinal Cancer Cell Lines. Biochemistry Research International, 1-9.doi:10.1155/2014/813457 Hardin, J., Bertoni, G., Kleinsmith, L. J., Becker, W. M. (2014). Beckers world of the cell (8th ed.). Boston: Benjamin Cummings. Harrington, J. A., Reardon, J. E., Spector, T. (1993). 3-azido-3-deoxythymidine (AZT) monophosphate: an inhibitor of exonucleolytic repair of AZT-terminated DNA. Antimicrobial Agents and Chemotherapy, 37(4), 918-920. van Kampen Jeroen J.A., Fraaij Pieter L.A., Vishal Hira, van Rossum Annemarie M.C., Hartwig, Nico G., de Groot Ronald, Luider Theo M.. A new method for analysis of AZT- triphosphate and nucleotide-triphosphates. Biochemical and Biophysical Research Communications, Volume 316, Issue 3, 9 April 2004, 151-159] Matteucci, C., Minutolo, A., Marino-Merlo, F., Grelli, S., Frezza, C., Mastino, A., Macchi, B. (2015). Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB. Life Sciences, 127, 90-97. doi:10.1016/j.lfs.2015.01.038 Mittal, S., El-Serag, H. B. (2013). Epidemiology of HCC: Consider the Population. Journal ofClinical Gastroenterology, 47(0), S2-S6.http://doi.org/10.1097/MCG.0b013e3182872f29 National Cancer Institute. (n.d.). Surveillance, Epidemiology, and End Results Program. Retrieved February 16, 2016, from http://seer.cancer.gov/statfacts/html/all.html Neto, V. (2013, January). AZT action [Photograph found in Organic Chemistry]. Retrieved April 1, 2016, from http://wwwblogvine.blogspot.com/2013/01/azt-was-originally-intendedto- treat.html (Originally photographed 2013, January 20) Normal And Cancer Cells Structure [Photograph found in Cells or Tissue Abnormal Cells or Tissue Cells or Tissue Normal Cells or Tissue Historical Graphics, National Cancer Institute]. (2001, January 1). In P. Kenny (Illustrator). Retrieved April 1, 2016, from https://visualsonline.cancer.gov/details.cfm?imageid=2512 (Originally illustrated 1990, April) Pichard, L., Raulet, E., Fabre, G., Ferrini, J. B., Ourlin, J. C., Maurel, P. (2006, February). Human hepatocyte culture. Retrieved March 11, 2016, from https://www.researchgate.net/publication/7063976_Human_hepatocyte_culture Sabokrouh, A., Vaisi-Raygani, A., Goodarzi, M. T., Khatami, S., Taghizadeh-jahed, M., Shahabadi, N., à ¢Ã¢â ¬Ã ¦ Shakiba, Y. (2015). Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma. Avicenna Journal of Medical Biotechnology, 7(2), 50-56. Sabokrouh, A., Goodarzi, M. T., Vaisi-Raygani, A., Khatami, S., Taghizadeh-Jahed, M. (2014). Effects of Treatment with Platinum Azidothymidine and Azidothymidine on Telomerase Activity and Bcl-2 Concentration in Hepatocellular Carcinoma-Induced Rats. Avicenna Journal Of Medical Biotechnology, 6(4), 200-209. Telomere Shortening Determines the Proliferative Lifespan of Human Diploid Fibroblasts. 2001. Nature Reviews. By Nicole F. Mathon and Alison C. Lloyd. Web. 21 Mar. 2016. ThermoFisher Scientific. (n.d.). MRNA Extraction. Retrieved March 11, 2016, from https://www.thermofisher.com/us/en/home/life-science/dna-rna-purification-analysis/rna- extraction/rna-types/mrna-extraction.html Venook, A. P., Papandreou, C., Furuse, J., De Guevara, L. L. (2010). The Incidence and Epidemiology of Hepatocellular Carcinoma: A Global and Regional Persprective. The Oncologist, 4(15), 5-13. Retrieved March 11, 2016, from http://theoncologist.alphamedpress.org/content/15/suppl_4/5.long Weinberg, Robert A. The Biology of Cancer. 2nd ed. New York, NY: Garland Science, 2014. Print.
Wednesday, November 13, 2019
The Radical Changes Resulting from the American Revolution Essay
All of us alive today have grown up learning about the American Revolution. Although it contains the word ââ¬Å"revolutionâ⬠in its name, there are many who donââ¬â¢t consider the American Revolution a real revolution. After considering the definition of a revolution ââ¬â a radical change of an entire system, usually by war, resulting in a change of the way of life of the people involved ââ¬â and the American society before and after the American Revolution, it is obvious that those who donââ¬â¢t consider the American Revolution a revolution are mistaken. Among the many aspects of colonial society affected by the American Revolution, those most greatly affected by the revolution were the attitude towards slavery, the role of women, and the role of trade. The Civil War, as well as events associated with it, being a large part of our history, is taught to all children in America at an early age. Growing up, we are taught the evils of slavery and how slaves were treated poorly. The evils about which weââ¬â¢ve been taught were actually occurring prior to the American Revolution. Over the course of the revolution, the attitude toward and treatment of slaves changed. Before the American Revolution, many people, though not all, thought of slaves as ââ¬Å"subhumanâ⬠or as animals. Even among those who gave the slaves the good treatment they deserved, there was still a feeling that the whites were better than the slaves. How many black people did could have been seen living in their nice house with a few white slaves? None; that sight was non-existent. The few black people who were free had little money. Had they been wealthy, there was still no way they ever would have found a white person who would have been their slave. Nor would that have been allowed. ... ...heir own laws about trade (once the Constitution was written). The colonies, not Britain, could decide who they traded with and what taxes they charged; they had complete control over the system of trade. The term ââ¬Å"revolutionâ⬠requires a radical change of an entire system that changes peopleââ¬â¢s lives. Slavery, the attitudes toward women, and the trade system were only a few parts of the entire system that changed during the American Revolution. Not to mention the change in government from a Monarchy to a Democracy! Peopleââ¬â¢s lives have been different ever since the American Revolution. Had the colonists never broken away from Britain, we wouldnââ¬â¢t be studying American history. Rather, weââ¬â¢d be studying British history. The large step of breaking away from England has radically changed the way the colonists lived and has had a huge influence on the way we live today. The Radical Changes Resulting from the American Revolution Essay All of us alive today have grown up learning about the American Revolution. Although it contains the word ââ¬Å"revolutionâ⬠in its name, there are many who donââ¬â¢t consider the American Revolution a real revolution. After considering the definition of a revolution ââ¬â a radical change of an entire system, usually by war, resulting in a change of the way of life of the people involved ââ¬â and the American society before and after the American Revolution, it is obvious that those who donââ¬â¢t consider the American Revolution a revolution are mistaken. Among the many aspects of colonial society affected by the American Revolution, those most greatly affected by the revolution were the attitude towards slavery, the role of women, and the role of trade. The Civil War, as well as events associated with it, being a large part of our history, is taught to all children in America at an early age. Growing up, we are taught the evils of slavery and how slaves were treated poorly. The evils about which weââ¬â¢ve been taught were actually occurring prior to the American Revolution. Over the course of the revolution, the attitude toward and treatment of slaves changed. Before the American Revolution, many people, though not all, thought of slaves as ââ¬Å"subhumanâ⬠or as animals. Even among those who gave the slaves the good treatment they deserved, there was still a feeling that the whites were better than the slaves. How many black people did could have been seen living in their nice house with a few white slaves? None; that sight was non-existent. The few black people who were free had little money. Had they been wealthy, there was still no way they ever would have found a white person who would have been their slave. Nor would that have been allowed. ... ...heir own laws about trade (once the Constitution was written). The colonies, not Britain, could decide who they traded with and what taxes they charged; they had complete control over the system of trade. The term ââ¬Å"revolutionâ⬠requires a radical change of an entire system that changes peopleââ¬â¢s lives. Slavery, the attitudes toward women, and the trade system were only a few parts of the entire system that changed during the American Revolution. Not to mention the change in government from a Monarchy to a Democracy! Peopleââ¬â¢s lives have been different ever since the American Revolution. Had the colonists never broken away from Britain, we wouldnââ¬â¢t be studying American history. Rather, weââ¬â¢d be studying British history. The large step of breaking away from England has radically changed the way the colonists lived and has had a huge influence on the way we live today.
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