Writing a Sample Application Diversity Essay

Writing a Sample Application Diversity EssayA sample application diversity essay may be one of the easiest ways to get an opportunity at a higher education or business. The reason is because of how easy it is to get access to them and how easy it is to write. Let's see what it takes to write the sample application.First, we must have an idea as to what diversity essay really is. It is basically a professional document that has something to do with the applicant's skills and experiences. It is in this document that we will state the applicant's objectives for their work. It is also used by employers to assess the potential employee as to why they are being given the job. If they feel that the applicant possesses certain qualities, they will give them the job and if not, the employer will prefer them because of the quality of their documents.As for writing the diversity essay, you don't need to be a trained or a professional writer. There are several online resources and other informat ion sources that will help you develop your writing skills. Also, you can consult an online article writer who can provide you with some basic information about article writing.Most likely, the diversity essay will have one important part to it, the introduction. The introduction is essentially an overview of the applicant's abilities and the reason for hiring them. This introduction may consist of one paragraph or two paragraphs which gives us a general idea about the qualifications of the applicant.The next part of the essay is the introduction section. This is where we give a brief description of the applicant's achievements and skills. If the applicant is a high school graduate, they will give more details on their academic achievements and skills.If the diversity essay is being applied for, they are to discuss their achievements and skill to others. Theyare also to give the reason for them getting the job. If it is a writing job, they should mention why they are successful in i t. If they feel that they are hardworking and have good communication skills, then they will include these skills in their application.Another good idea to follow when writing the diversity essay is to be honest with your application. This will make it easier for the hiring staff to evaluate you and the reasons for you getting the job.

Behavior Incentives and Classroom Rewards

Behavior Incentives and Classroom Rewards Classroom incentives, prizes, and punishments are part of a controversial topic for teachers. Many teachers see extrinsic material rewards as an appropriate and effective way to manage behavior in the elementary classroom. Other teachers dont want to bribe the kids to do work that they should be intrinsically motivated to do on their own. Should You Offer Classroom Incentives Early in the School Year? The idea of classroom rewards is an important concept to consider at the beginning of the school year. If you start off the year showering students with rewards, they are going to expect it and will most likely only work for the rewards. However, if you limit prizes from day one, you may find that you can get away from the material aspect a little bit and save yourself a significant amount of money in the long run.  Here is an example of what worked for me and thoughts about the concept of rewards. Rewards in First Classroom? In setting up my first classroom (third grade), I wanted to avoid rewards. I dreamed of my students working for knowledges sake. However, after trial and error, I found that kids respond to rewards well and sometimes you just have to use what works. The teachers before us most likely showered our current students with rewards, so they probably expect it by now. Also, teachers (and all employees) work for a reward - money. How many of us would work and try hard if we werent getting a salary? Money and rewards, in general, make the world go round, whether its a pretty picture or not. Timing When Incentives are Needed At the beginning of the year, I didnt do anything with rewards or behavior management because my kids started out the year quiet and hard working. But, around Thanksgiving, I was at the end of my rope and started introducing rewards. Teachers might want to try going as long as they can without rewards because the prizes start losing their effectiveness after awhile because the kids expect them or get used to receiving the rewards. It also works to change the rewards as the year progresses, just to add a little excitement and a boost to their effectiveness. Avoiding Material Rewards I dont use any material rewards in my classroom. I dont give out anything that costs money for me to buy. Im not willing to spend a lot of my own time and money to keep a store or prize box stocked for daily rewards. Good Work Tickets In the end, positive reinforcement of good behavior worked best for my students and me. I used Good Work Tickets which are just leftover scraps of construction paper (that would have been thrown away otherwise) cut up into little 1 inch by 1-inch squares. I have the kids cut them up for me after school or whenever they want. They love to do it. I dont even have to do that part. Involving Students in Giving Rewards When kids are working quietly and doing what they are supposed to be doing, I give them a good work ticket. They put their student # on the back and turn it into the raffle box. Also, if a child finished his or her work or has been working well, I let them pass out the good work tickets, which they love doing. This is a great thing to do with problem children; kids who are usually in trouble will love monitoring their classmates behavior. The students are usually more strict than I am with handing them out. Since they are free, it doesnt matter how many you give out.   Awarding Incentives On Fridays, I do a little drawing. The rewards are things like: Sit at the teachers desk for the day15 minutes playing an educational computer gameBe the caller for multiplication bingoMake up a math problem for the other children to solveGo to lunch 5 minutes early with a friendStay out for a longer recess with a friendChoose your seat for the dayRead out loud to the class You can tailor these rewards to what the cool things in your classroom are. I usually pick two  or three winners and then, just for fun, I pick one more, and that person is the Cool Person of the Day. The kids and I just thought that was a funny thing to do and a nice way to wrap up the drawing. Also, I keep a bag of candy in my cupboard for a quick reward (if someone catches a mistake I make, goes above and beyond the call of duty, etc.). Its a pretty cheap thing to have around just in case. Just throw candy to the kid and keep on teaching. Dont Overemphasize Rewards I didnt place a large emphasis on rewards. I tried to make learning fun, and my kids genuinely did get excited about learning new things. I had them begging me to teach them harder math concepts because they knew they could handle it. Ultimately, how you use rewards in your classroom is a personal decision. There are no right or wrong answers. Like everything in teaching, what works for one teacher may not work for another. But, it does help to discuss your ideas with other educators and see what others are doing in their classroom. Good luck!

Free Essays on Competitive Strategies

Competitive Strategies Though unwritten, survival is perhaps the fundamental challenge for a business. With a lot of competitors out there, it’s a dog eat dog world out there. And as they say, eat or be eaten. To survive and stand out, companies should outperform their competitors. There’s a whole lot more to it than merely building satisfactory products. Building customers and focusing on relationship marketing is the challenge. While it is customary for business to focus on attracting customers, the emphasis nowadays seems to lean towards relationship marketing. This marketing task encompasses creating, maintaining, and enhancing strong relationships with customers and other stakeholders. Beyond designing strategies to gain new customers, companies are making efforts to retain their current customers and build profitable, long-term relationships with them. The key to building lasting relationships is creating superior customer value and satisfaction. This results to customer satisfaction when a company’s performance has fulfilled buyers’ expectations. To create customer value and satisfaction, and to retain customers, companies must manage their value chains and value-delivery networks in a customer-oriented way. And in order to prepare an effective marketing strategy, a company must consider its competitors as well as its customers. They need to identify their major competitors and assesses their objectives, strategies, strengths, and weaknesses, and reaction patterns in order to develop a strong competitive advantage over them. I personally agree that determining which competitive marketing strategy to use will depend on the position of the business in the market. A market leader, for example, has to focus on expanding their market, protecting their market share, and expanding their market share.... Free Essays on Competitive Strategies Free Essays on Competitive Strategies Competitive Strategies Though unwritten, survival is perhaps the fundamental challenge for a business. With a lot of competitors out there, it’s a dog eat dog world out there. And as they say, eat or be eaten. To survive and stand out, companies should outperform their competitors. There’s a whole lot more to it than merely building satisfactory products. Building customers and focusing on relationship marketing is the challenge. While it is customary for business to focus on attracting customers, the emphasis nowadays seems to lean towards relationship marketing. This marketing task encompasses creating, maintaining, and enhancing strong relationships with customers and other stakeholders. Beyond designing strategies to gain new customers, companies are making efforts to retain their current customers and build profitable, long-term relationships with them. The key to building lasting relationships is creating superior customer value and satisfaction. This results to customer satisfaction when a company’s performance has fulfilled buyers’ expectations. To create customer value and satisfaction, and to retain customers, companies must manage their value chains and value-delivery networks in a customer-oriented way. And in order to prepare an effective marketing strategy, a company must consider its competitors as well as its customers. They need to identify their major competitors and assesses their objectives, strategies, strengths, and weaknesses, and reaction patterns in order to develop a strong competitive advantage over them. I personally agree that determining which competitive marketing strategy to use will depend on the position of the business in the market. A market leader, for example, has to focus on expanding their market, protecting their market share, and expanding their market share....

Environmental ethics Essay Example | Topics and Well Written Essays - 1250 words

Environmental ethics - Essay Example r, some argue that a good way to do so would be to develop a non-anthropocentric ethical outlook that would taken into account rights of the animals and change the way people interact with nature. This paper will present how Islam can shape relationship between people and nature. By far the concept of oneness of God should be seen as an essential one in Islam. What is more important is that it is not found on theological level only, but is implemented on every other level. In other words, while Islam is a religious tradition, it also has some ideas that are relevant to the environment. It is estimated that the Quran has around 650 references to ecology (â€Å"Environmental Ethics in Islam†). However, one of the most important ones is the understanding that God is one and all environment belongs to Him. Therefore, people simply must not harm nature in any way. The most important thing about environmental ethics of Islam is that God Said in Quran: â€Å"And He has subjected to you whatever is in the heavens and whatever is on the earth - all from Him. Indeed in that are signs for a people who give thought† (Qurad 45:13). It is suggested that when God created everything in the world, He left different signs in His creation that would reflect his majesty and glory. That is why a true believer should look at the environment as a collection of signs that show how great God is. With this idea in mind, it is absolutely impossible to permit any kind of harmful actions towards the nature and that would be seen as a deliberate ruining of harmony which was established by God Himself. The Quran states that all things in the world are â€Å"created in proportion and measure† (Quran 54:49). That is why if a person makes any change in the environment, for example by making an entire species extinct, than this balance is broke once and for all. What is more important is that people do not possess wisdom to restore the balance; that is why they should never perform actions that have

Operations and Projects Management Essay Example | Topics and Well Written Essays - 2000 words

Operations and Projects Management - Essay Example The quality of service to a customer is paramount in any service firm, and the Bank of Muscat has not underrated this fact. It is one of the banks offering the best quality of banking services in Oman. The bank has a strong believe in quality leadership that seeks to challenge everything the bank does. Such an approach helps the bank maintain and improve the quality of services offered. The bank’s quality policy is pegged on building and maintaining a good reputation and image by offering the best quality in services and products to customers (Ilin, 2010). The bank targets both international and international markets and boasts more about offering products that exceed the needs of their customers. On quality, the bank pursues the following objectives; Govindarajo & Kalyani, (2013, p. 569) Conducted a study to examined how the bank uses relationship marketing to deliver quality service to its customers. They found that the quality of services was measured in terms of responsiveness, ambience, trust and assurance. Bank Muscat has done very well in delivering quality service through the quality management system that ensures responsiveness to customer queries and complaints, their banking halls are designed to offer the latest and more comfortable service thereby creating the required ambience (Bank Muscat, 2013). Customers are served almost as soon as they appear on the bank. This has helped the bank to gain trust since customers are assured of the best service. The bank employees are specially trained to handle customers by offering the best services. The design of the banking facilities is one of the best in Oman as technology has been used to improve customer experience and delivery of service (Ilin, 2010). The bank is better pl aced because its services and products are based on Islamic beliefs, which are the fundamental religion in the area. The bank has designed its products to cover both individuals and

Targeted Drug Delivery for Sex Dependent Cancers

Targeted Drug Delivery for Sex Dependent Cancers Occurring cancer in any part of the human body such as lung, kidney, skin and etc. has a different incidence ratio between men and women. sex dependent cancers have seen just in male or female which is dependent to sex hormones and specific sex organs such as prostate cancer in male and Ovary and endometrial cancers in female, breast cancer is seen in both sex with 5% incidence in male. Despite of a self-explaining differentiation between the sex organs, since these organs functions are regulated by same hypothalamic gonadotropin-releasing hormone similarities in cell signaling and pathways via molecular interactions are highlighted for cancer studies and targeted therapy. Targeted drug delivery for sex dependent cancers has been studied for many years, but exploring similarities of sex-dependent cancers targeting could provide an opportunity for future targeted drug delivery of these cancers simultaneous effects analysis. Breast Cancer: Breast cancer (BC) is the most common cancer and cause of death among women worldwide during the past decades. To improve diagnosis, therapy and prevention of BC, molecular developments provide various techniques for scientist to study and differentiate BC cell lines as well as observe different phenotype of BC. They classified BC to three main subtypes: estrogen/progesterone receptor (ER) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC). Estrogen/progesterone receptor (ER) positive: In BC subtypes of ER+, the overexpression of estrogen receptors on breast cells and nucleus membranes cause the over uptake of estrogen [1]. Many studies showed that estrogen receptors could be targeted for anti-cancer delivery to breast cells. Some estrogen receptor targeted drugs now use in clinical therapy like tamoxifen from the family of SERMs (selective estrogen receptor modulators) which are competitive agonist of the estrogen receptor [2]. Arimidex, Fareston (Toremifene), Anastrozole, Exemestane, anastrozole, letrozole [3], [4],[5]  Fulvestrant [6]  are now in market. Other estrogen receptor targeted drug is a family of aromatase Inhibitors (AI) that suspend the estrogen production. The third-generation aromatase inhibitors are classified into irreversible steroidal inhibitors and they have shown high potential to replace tamoxifen in postmenopausal women such as Exemestane, anastrozole, letrozole[2,4 ,5]. SERDs (selective estrogen receptor down-regulators) is another estrogen targeted that only drug with FDA approved is fulvestrant on the name of Faslodex used in metastatic hormone positive breast cancer [6]. HER2 positive: This breast cancer subtype is referred to overexpression of erbB2 (HER2) from the epidermal growth factor receptor family on breast cells membranes [7]. Anti HER2 agent has studied for targeted therapy of this subtype. Recombinant humanized monoclonal antibodies such as trastuzumab and pertuzumab are widely used for HER2 positive breast cancer and any other HER2 positive cancers [8],  [9],  [10]. Some monoclonal antibodies are under further clinical trials studies like ertumaxomab and margetuximab  [11]  .Her2 Vaccine is now under further studies [11]. Triple Negative breast cancer (TNBC): These subtype tumors do not express receptors for estrogen or progesterone and not overexpress the HER2 receptor. TNBC is a malignant cancer with the high rate of incidence in younger age and it grows faster with the high potential of metastasis in early stage while it is unlikely to be seen on annual mammogram [12]. Not only patients with TNBC almost show poor prognosis compare to other subtypes, but also during therapy they are at the higher risk of relapse, metastasis, and survival [13]. Since the clinical trial of some designed drug were not successful, no commercialized drug and therapy for this subtype still exists. Endometrial Cancer: Endometrial Cancer (EC) begins in the uterus cells of the endometrium layer. Mostly surgery including hysterectomy (removal of the uterus) and removal of ovaries and lymph nodes is the only way to cure the EC if biopsies show that cancer has not spread, no other treatment is needed. According to clinic pathological characteristics, EC is classified to two subtype. Estrogen-dependent endometrioid and estrogen-independent non-endometrioid carcinoma. [14],  [15]. Estrogen-independent EC shows p53 and p16 mutations, overexpression of HER2 and E-cadherin loss [16]. Most of the diagnosed EC tumor are estrogen-dependent that express estrogen receptor and hormonal therapy with progestron is a primary line [17]. Since EC Type I express estrogen receptor the like ER+ BC mentioned previously, targeted therapies for EC are SERM, AI and GnRH inhibitors. Tamoxifen (as SERM) and anastrazole (as AI) commonly used. Anti-angiogenesis drugs are efficiently used for EC like Aflibercept, Abitrexate (Methotrexate) is an only trial drug for EC. Prostate Cancer: Prostate cancer is derived from the specific epithelial of secondary sex organs. Todays, the prostate cancer strategies of treatment is mostly based on suppressing testosterone level by anti-androgenic, gonadorelin agonist or antagonists [18]. Despite of the unknown active mutation in oncogenic pathways in prostate cancers subsets, some molecules express specifically in prostate epithelial cells which have been studied as therapeutic targets including; cell surface prostate-specific membrane antigen (PSMA), the secreted protease prostate-specific antigen (PSA), and the enzyme prostatic acid phosphatase (PAP). PSMA targeting: PSMA is an integral cell surface membrane protein and specifically over-expressed in advanced prostate cancers. PSMA has been studied in phase II trial as a targeted therapy via monoclonal antibody (J591) conjugated with radio and chemical compounds [19]. PSA: The prostate-specific antigen (PSA) mostly use as an indicator for primary diagnosis of prostate cancer. Gonadorelin antagonists can suppress testosterone and PSA, by then Degarelix (Firmagon) is now using for treatment in prostate cancer patients. ARN-509 antiandrogen is only used for prostate cancer with high level of PSA indication. PAP: Prostatic acid phosphatase (PAP) is an enzyme produced by prostate and the amount increased in prostate cancer cells. In clinical studies PAP mostly used as an antigen for anti-tumor vaccines [20]. Ovarian Cancer: Ovarian Cancer is a 5th cause of cancer related death among women worldwide [21].Ovarian cancer has not yet been classified. It is poor diagnosed in stage I and in stage II,III,IV diagnosed by metastasis to other organs  [22]. Surgery and aggressive chemotherapy are currently the only way to treat the ovarian cancer. Many studies on targeted therapy for ovarian cancer by nano-carriers are undergoing. Although, in market there is nano-carriers like liposome that carried chemotherapeutic agents like doxorubicin; DOXIL (Doxorubicin Hydrochloride Liposome), Evacet (Doxorubicin Hydrochloride Liposome) [23]. Novel Targeted therapy: As previously has been mentioned, these cancers are mostly depended on sex hormones level, HER2 expression and other individual molecular marker indications. Almost all chemotherapy regiment have cytotoxic effect on non-cancer cells and caused the chemotherapy side effects. If these chemotherapy regiment could be conjugated with marker to specific targets of cancer cells the result would be cytotoxicity of drug just for cancer cells and no more side effects for healthy cells. This conjugation can be followed by protein based interactions like antigen- antibody mechanism or ligand-receptor affinity. Today novel therapeutical aims are trying to conjugate monoclonal antibodies with drugs which is called antibody-drug conjugated (ADC). Other novel targeted therapy is to conjugate the peptide or protein with drug (PDC). Both ADC and PCD are the subtype of protein drug conjugated approach. The result of covalent conjugation of drug with antibody or peptide is another novel strategy of prod rug in which after delivered to cells would be cleaved by an enzyme and release active drug [24]. For targeted drug delivery for any drugs two main subjects should be considered; Carrier and Targets: Carriers: Antibody: In past decades, targeted drug delivery has been improved by development of antibodies against any identified targeted antigen. Not only antibodies can induce uptake of conjugated drug in targeted cells, but also they can enhance the role of complement-dependant cytotoxicity system to invade targeted cells. The potential of making almost any antigen as a target is an interesting properties of ADCs, however, just few of the human antibodies have shown a longer proper half-lives like IgG1, IgG2, and IgG4. Nearly 40 monoclonal antibodies (mAb) have been approved and develop not only for cancer but also for some autoimmune disease [25]. While antibodies have shown low loading capacity of drug, on molecule of antibodies are capable to conjugate with less than 3 molecules of drug, for improve ADCs efficacy drug should be highly potent. As mentioned previously, HER2 is overexpressed in breast, prostate, ovarian and endometrial cancer that the anti-HER2 antibody can be used for targeted drug delivery. Antibody-drug conjugates (ADC) for HER2 positive is a conjugation of trastuzumab as an antibody and emtansine as cytotoxic compound and commercialized as TDM1. Other cytotoxic compound in conjugation with antibody is under further studies and clinical trial process like defucosylated trastuzumab [26],[27]. Lapatinib is commercialized drug from the family of Receptor tyrosine kinase inhibitors (RTKI) that target the intracellular binding site of HER and EGFR family [28]. In breast cancer antibodies of Anti-LIV1 mAb (hIgG1), Anti-GPNMB mAb (hIgG2), Anti-cripto mAb (hIgG1) in conjugation with drug Auristatin E and DM4 (maytansine) are now clinical Phase I. Anti-HER2 mAb (hIgG1) in conjugation with Emtansine-DM1 (maytansine) has been approved in early 2013 and used for metastatic breast cancer. Anti-TROP-2 mAb (mIgG1) in conjugation with SN-38 (irinotecan metabolite) is under further studies for triple negative breast cancer in Phase II clinical [29]. In prostate cancer Anti-PSMA mAb (hIgG1) in conjugation with Auristatin E (auristatin) is still on phase I clinical [30]. IgG1 ADC targets Folate receptor is in Phase 1 studies for ovarian cancer [31]. Protein/Peptide-drug conjugated (PDC): Proteins are sequences of amino acids with 3D or 4D structures that have vital responsibility in all alive cells. Protein has been studied as a carrier for drug due to its stability, longer half-life, biodegradability and easy modification for carry drug with no effect on its desirable function [32]. Protein which are widely used as for drug delivery are Transferrin and Albumin [33], Zein [34],  Elastin and Gelatine  [35], Gliadin and Legumin [36]. The conjugation of albumin with methotrexate has been studied preclinical for many cancers but it had shown effect on just bone and prostate cancer [37]. Conjugation of transferrin with N-alkylisatin derivatives had shown 10 times more efficient on breast cancer tumor in vivo [38]  and also conjugation with Artemisinin shown high toxicity for breast cancer in rat [39]. Gelatin conjugation with Gallic acid has been studied on prostate cancer [40]. Abraxane is an albumin conjugated with paclitaxel in phase I trial for metastatic breast cancer, prostate and ovarian cancer [41]. Peptide usually refers to a sequence of amino acids (up to 50) with just up to secondary structure [42]. Peptide ligand can be used for targeted receptors. However, peptides have short half-life and poor stability in serum as they can be degraded by protease, but peptides are smaller than antibodies and can easily penetrate the targeted cells and overcome biological barriers that the result would be the fast uptake of drug by targeted cells and also peptides have shown high drug loading potential  [43]. Acyclic RGD4C as peptide c(Cys-Phe-Cys-Asp-Gly-Arg-Cys-Asp-Cys) in conjugation with doxorubicin has been shown higher antitumor activity on metastatic breast cancer in vivo than doxorubicin alone [44]. Targets: Gonadotropin hormone receptor targeting: The overexpression of luteinizing hormone releasing hormone (LHRH) receptors has been well reported on many cancer tumors specially breast, ovary, endometrial and prostate cancer [45],[46]. LHRH analog is widely used as a supplementary drug in order to bind to the LHRH receptor [47]. LHRH agonist induce downregulation of LHRH and suppress sex steroid hormone. While, LHRH antagonist block the LHRH receptors and suppress LHRH and sex steroid releasing immediately [48],[49].  Prostate cancer drug in market like Degarelix (Firmagon) (ANTAGONISTS), Lupron, Leuprolide Acetate, Zoladex (Goserelin Acetate) are LHRH analog [50]. LHRH and its analogue as a peptide with a sequence of 10 amino acids have been studied as a targeted drug carrier. AEZS-108 (formerly known as AN-152) is an LHRH agonist conjugation with doxorubin which is shown anti-cancer activity in phase II clinical trial of gynaecological cancers and a promising result for prostate cancer [51]. LHRH also has been studied for carry cisplatin encapsulated in dextran nano-particle to breast cancer cells [52]. Compound uptake via an interaction between LHRH and its receptor and then endocytosis by cell membrane. As normal cells with no overexpression of LHRH receptor could not uptake the drug, side effects of toxic drug significantly has been reduced36. Growth factor targeting: Growth factor refers to substances that stimulate cells proliferation and differentiation by binding to their receptors which is tyrosine kinase activate other cell pathways. Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) and their receptors are two class of growth factors that have been studied for targeted therapy: Angiogenic pathway targeting: In all cancers, tumor growth and metastasis depend on angiogenesis pathway which activated by vascular endothelial growth factors. VEGF family and their receptors (VEGFR) have been studied for inhibition of tomur growth and metastasis as their overexpression had been seen in most of the malignant cancers [53]. The stimulation of VEGF not only induces cells mitosis and abort apoptosis, but also caused the chemotherapy and radiotherapy resistance [54]. On the other hand, chemotherapy and radiotherapy could induce VEGF in tumor cells [55]. Hereby, today anti-VEGF drug have been added to chemotherapy regiment. Ovarian cancer cell lines has shown overexpress of VEGFR as well as breast cancer cell line like MDA-MB-453, and MDA-MB-231,T-47D,and MCF7  [56]. Studies on triple negative breast cancer cell lines; MDA-MB-453; have shown that overexpression of VEGF protected cancer cells from apoptosis and improved cell mitosis and invasion [57]. Treatment of MDA-MB-453 and MDA-MB-231 with anti-sense oligonucleotide inhibition of VEGF has shown over 50% decrease in invasion by Martigel assay [58]. Targeting VEGF has been studied in Phase I and II clinical by designing monoclonal anti-body directly against VEGF that shown suppressing metastasis relapsed in patients with breast cancer [59],  [60],  [61]. Now, Bevacizumab (Avastin ®) is a monoclonal anti-body that bind to VEGF that has studied in phase III trial for metastasis breast cancer. Successful result has been released in phase III trial studies E2100, AVADO, RIBBON-1 that have Bevacizumab as a supplement and chemotherapy regiment like paclitaxel, docetaxel, anthracycline-based as a first line treatment respectively  [62],  [63],  [64]. Epidermal growth factor targeting: Epidermal growth factor (EGF) is a factor that induce cell growth, proliferation, differentiation, and survival by binding to its receptor (EGFR) with tyrosine kinase activity. The EGFR from ErbB family (also known as HER) has shown overexpression in cell surface of many cancers, especially breast, prostate, and ovarian cancer. HER2 is a receptor with three domains of extracellular for ligand, transmembrane domain, and cytoplasmic domain with tyrosine kinase activity. The excess of HER2 on cell membrane and high tyrosine kinase activities induce the downstream signalling pathways like PI3K/AKT/mTOR as well as JAK/STAT pathways which suppress apoptosis and promote proliferation and survival. HER2 is overexpressed in 15-30% of invasive breast cancers [65],  [66],  [67]. Cetuximab (Erbitux) and panitumumab (Vectibix) are the two most advanced monoclonal anti-bodies targeting the extracellular domain of the receptor and inhibit ligand-receptor interaction and tyrosine kinase activity [68],  [69]. But an abnormal form of HER2 which has the lack of extracellular domain, known as P95, is still active but resistance to drug and antibodies that target the extracellular domain[70]. Antibody-drug conjugates (ADC) for HER2 positive is a conjugation of trastuzumab as an antibody and emtansine as cytotoxic compound and commercialized as TDM1. Other cytotoxic compound in conjugation with antibody is under further studies and clinical trial process like defucosylated trastuzumab26,[71]. Lapatinib is commercialized drug from the family of Receptor tyrosine kinase inhibitors (RTKI) that target the intracellular binding site of HER and EGFR family [72]. References: [1] Garcia-Becerra R, Santos N, Diaz L, Camacho J. Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance. Int J Mol Sci. 2012;14(1):108-45. [2] Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998;339(22):1609-18. [3] Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol. 2000;18(22):3758-67. [4] Mouridsen HT. Letrozole in advanced breast cancer: the PO25 trial. Breast Cancer Res Treat. 2007;105 Suppl 1:19-29. [5] Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008;26(30):4883-90. [6] Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002;20(16):3386-95. [7] Menard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER2 as a prognostic factor in breast cancer. Oncology. 2001;61 Suppl 2:67-72. [8] Baselga J, Albanell J, Molina MA, Arribas J. Mechanism of action of trastuzumab and scientific update. Semin Oncol. 2001;28(5 Suppl 16):4-11. [9] Gennari R, Menard S, Fagnoni F, Ponchio L, Scelsi M, Tagliabue E. Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res. 2004;10(17):5650-5. [10] Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014;32(33):3753-61. [11] Toss A, Cristofanilli M. Molecular characterization and targeted therapeutic approaches in breast cancer. Breast Cancer Res. 2015;17:60. [12] Jamdde VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N. Therapeutic targets of triple-negative breast cancer: a review. Br J Pharmacol. 2015;172(17):4228-37. [13] Mustacchi G, De Laurentiis M. 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[19] Fernandez-Garcia EM, Vera-Badillo FE, Perez-Valderrama B, Matos-Pita AS, Duran I. Immunotherapy in prostate cancer: review of the current evidence. Clin Transl Oncol. 2014;339-57. [20] Becker JT, Olson BM, Johnson LE, Davies JG, Dunphy EJ, McNeel DG. DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer. J Immunother. 2010;33(6):639-47. [21] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer. 2010; 127:2893-2917. [22] -Bast RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9:415-28. [23] Delie F, Allemann E, Cohen M. Nanocarriers for ovarian cancer active drug targeting. J Drug Deliv Sci Technol. 2012;22(5):421-6. [24] Hamada Y. Recent progress in prodrug design strategies based on generally applicable modifications. 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How Far Does Luck Explain the Rise and Fall of Napoleon Bonaparte Essay

How far does luck explain the rise and fall of Napoleon Bonaparte? Napoleon Bonaparte like many others rose to prominence during the turbulent times of the French revolution- he was therefore lucky to have been born at such a time in to justify his advancing position. However his reputation as a skilled tactician and strategist enabled him to initially capitalize on the reforms of the French Revolution to improve the lives of French citizens. Napoleon Bonaparte emerged as an important figure for re-establishing order in France and initially gained the trust and support of his countrymen, winning many great military victories against the nations of Europe. But over time, Napoleon’s lust for power overcame his good economic, political and military accomplishments, and his transformation into a selfish dictator led to his fall. To say he was unlucky at this point is an understatement. Napoleon’s upbringing is one that could be considered unconventional (at first) for a successful ruler of France. Napoleon was the son of a middle class Corsican family, at a time when Corsica had not even been French for long. Being formerly subject to Genoa, the Corsican people did not speak French but a dialect of Italian. They were, and are, a fiercely independent Mediterranean people, with a Mediterranean temperament. Napoleon was always self-conscious about his humble origins and provincial background. He came from a mediocre family and went to a mediocre military academy, where his schoolmates made fun of his thick Corsican accent. Despite this however he was lucky in a sense that his noble background afforded him more opportunities than were available to a normal Corsican at the time. In January 1779, Napoleon was enrolled at a religious school in Autun, mainland France, to learn French. In May he was admitted to a military academy at Brienne-le-Chateau. He excelled in various subjects including mathematics and was viewed by one examiner as a candidate for an â€Å"excellent sailor†. Napoleon was the first Corsican to graduate from the Ecole Militaire, a testament to his intellectual abilities in the field. Of course his application to maths determined his specialisation as an artillery officer. This can be considered a stroke of luck in his favour, – one of many that he benefited from – inasmuch as the artillery was the most prestigious branch of the army under the old regime. But the biggest stroke of luck Napoleon had was to be born when he was – in the age of the French Revolution. Napoleon, like many others, was made by the Revolution. The Revolution turned the whole world upside down and presented an ambitious young man (he was always ambitious – a consequence of his resentment at his inferior status) with new and vast opportunities. Looking again at the perspective of Napoleon’s capabilities as a man rather than his luck during his ascension we must also consider his fluidity. Despite his early one sidedness and his view of himself as a devout Corsican, he was ostracized by his countrymen when trying to attempt to instil himself as the head of the Corsican national government. The Corsican nationalists were inclined to reactionary and monarchist ideas and distrustful of the ideals of the Revolution. They were also distrustful of Napoleon, who had the misfortune of being seen as a Corsican provincial to the French and a French interloper to the Corsicans. Rejected by his compatriots, Napoleon abandoned all his nationalist ideals. He later became transformed from an ardent Corsican patriot to a fervent advocate of French centralism. In a sense it was luck that Napoleon now saw France as an area would he could advance to power, but there nothing surprising about this sudden turnabout. Napoleon never had any fixed principles about anything, except his own advancement. His early Republican sympathies may have been genuine but they were certainly tempered with a heavy dose of opportunism. He specialised in currying favour with his superiors in order to climb the ladder of careerist advancement. When it was advantageous to appear as a Jacobin, he donned the tricolour, but later he swung against the Jacobins with equal alacrity when their star waned. Napoleon’s big opportunity came in 1794 at the siege of Toulon. This key Mediterranean port had declared for the English and allowed British forces to occupy it. England was the real bulwark of reaction and bankrolled the wars against revolutionary France that others fought. Napoleon saw his chance to make a mark and did so by conspicuous bravery and a high degree of skill in the use of artillery, which decided the battle in France’s favour. His rapid rise to fame and success had begun. His next big military success came with the invasion of Italy in the strategic campaign against Austria. It was at this point Napoleon demonstrated excellent qualities as a tactician and a politician. Napoleon vetoed the idea of the Directory atheists to march on Rome and dethrone the Pope as he reasoned this would create a power vacuum which would be exploited by the Kingdom of Naples. Instead, in March 1797, Bonaparte led his army into Austria and forced it to negotiate peace. The resulting Treaty of Leoben gave France control of most of northern Italy and the Low Countries, and a secret clause promised the Republic of Venice to Austria. Bonaparte marched on Venice and forced its surrender, ending 1,100 years of independence; he also authorised the French to loot treasures such as the Horses of Saint Mark. His application of conventional military ideas to real-world situations effected his military triumphs, such as creative use of artillery as a mobile force to support his infantry. He referred to his tactics thus: â€Å"I have fought sixty battles and I have learned nothing which I did not know at the beginning. Look at Caesar; he fought the first like the last. † His decision to record his exploits through two newspapers he founded for the army and circulation in France earned him wide critical acclaim. But again he was known to sacrifice military glory in favour of preserving his position, as shown by negotiations in Austria and the treaty of Campio Formio in response to Barras and the French republican allies in control of the French government becoming dependent on Bonaparte following the Coup of 18 Fructidor in order to depose the French royalists who feared Napoleon was becoming a dictator. It was not unlucky that this happened, as Napoleon handled the situation effectively and was able to continue his quest for power. His capacity as a strategist in military campaign against nations hostile to France continued to shine when he conceived an expedition into Egypt in order to seize it and thereby undermine Britain’s access to it’s trade interests in India. Although this invasion failed, mostly due to his loss in the battle of the Nile against Horatio Nelson, Napoleon- unlike his later years was able to take defeat well, speeding up the retreat by poisoning plague stricken men- this supposed act of fratricide was deemed necessary by his supporters given the continued harassment of stragglers by Ottoman forces, and indeed those left behind alive were tortured and beheaded by the Ottomans. Back in Egypt, on 25 July, Bonaparte defeated an Ottoman amphibious invasion at Abukir. The coup of Brumaire in 1799 while being the main event for Napoleon’s ascension to ruler of France largely defines how far his luck went in his rise to power. The reasons for General Bonaparte’s coup may have lain more in his defeats than by his victories. In November 1799, France was suffering the effects of military reverses brought on by Bonaparte’s adventurism in theMiddle East. The looming threat of opportunistic invasion by the Second Coalition had provoked internal unrest, with Bonaparte stuck in Egypt. When he returned he stormed into the chambers escorted by grenadiers. At this point his ineptitude at speechmaking failed to impressed the dissolutioned directory, and he was heckled out and even assaulted at the council of Five Hundred. It was only by the intervention of his brother Lucien that he was spared great injury or death, and lucien’s skill at organising the troops to expel the violent deputies from the chamber shouting â€Å"kick ‘em all out! † and dispersing the council. This spelled the end of the directory and the establishment of the consulate. Napoleon had hoped that the his French empire would last for centuries, but the reality was much more disconcerting. His downfall however was not so much attributed to bad luck as it was his ego and complacency due to his earlier military successes. Two main things contributed to his downfall, Economics and Military failure. In the Treaty of Tilset, Napoleon established the continental system which basically was a boycott of selling and buying of goods with the British. He realized that England depended heavily on other countries to buy from and sell to. However Napoleon underestimated the fact that England could trade with the U.  S and controlled India (even though he tried to stop British Trade with India in his invasion of Egypt) and was not limited to Prussia, Russia and Austria. The continental system did not hurt England as much as he had hoped, but it hurt other countries because they loved English goods and got them any way they could. This was also just another reason for the Austrians, Prussians and Russians to rebel against him. Napoleon tended to try and get his way in negotiations by shouting at those who didn’t agree with him, and on one occasion physically assaulted an Austrian diplomat who disagreed with his demands. Napoleon believed military dominance was sufficient to impose his will on Europe, but this necessitated constantly keeping a large army in the field, which strained French finances and alienated the ordinary population of Europe, as French troops lived off the country when campaigning or stationed abroad. His failure to compromise through diplomacy after military victories meant he was never able to consolidate his gains long term and confirm them through any prolonged period of subsequent peace. Napoleon was never accepted as ‘one of them’ by other European rulers. His practice of dethroning monarchs and replacing them with members of his own family, who had no right to them and who were certainly no better as rulers, scared all other European monarchs, who were afraid they might be next. Napoleon didn’t really understand seapower, nor its importance and how to use it effectively. The French navy got few resources-manpower and money being directed mainly to the army. This left the French fleet underequipped, undermanned, and undertrained, which led to a drop in morale and its easy defeat in battle. No attempt was made to rebuild the French fleet after Trafalgar, global naval supremacy being left wholly in British hands. Napoleon didn’t realize that this would have long term economic effects as well as military ones. In the Treaty of Tilset, Napoleon established the continental system which basically was a boycott of selling and buying of goods with the British. He realized that England depended heavily on other countries to buy from and sell to. However Napoleon in a moment of political ineptitude underestimated that though was that England could trade with the U.  S and and controlled India (even though he tried to stop British Trade with India in his invasion of Egypt) and was not limited to Prussia, Russia and Austria. The continental system did not hurt England as much as he had hoped, but it hurt other countries because they loved English goods and got them any way they could. This was also just another reason for the Austrians, Prussians and Russians to rebel against him. Instead of crippling the British economy, it crippled that of much of Europe. Britain had responded with Orders in Council, a close blockade of Europe’s major ports that cut off all foreign seaborne trade to continental Europe. This impoverished many people, denied Europe’s aristocracy luxury goods, and led to endemic smuggling that undermined the economy of France and other European states. When Napoleon created the Continental System, Portugal refused to comply with a treaty that would severely weaken its trade. Promptly, the French marched in with their armies and overran Spain and Portugal. The Spanish people feared that the Catholic Church would be thrown aside by the French, causing unrest. In addition, Napoleon further humiliated the Spanish by deposing their king, to whom the Spaniards were loyal, instead putting his brother on the throne. This was the spark that would set off the true Peninsular War with constant guerrilla warfare that would end with Napoleon losing 300,000 troops by 1813, after 5 years of fighting. Harsh treatment of the population, in particular atrocities committed by French troops against any resistance by the peasantry, led to a opular Spanish uprising against French occupation forces in 1808. A British army sent to Portugal invaded Spain in support of the uprising,and its operations in conjunction with Spanish guerrillas caused the so called â€Å"Spanish ulcer† which diverted troops and resources away from Napoleon’s main army and forced France into a war on 2 fronts. But possibly the greatest blunder of Napoleon was his decision to invade Russia. Under pressure from important nobles who were losing money, the Tzar withdrew from the Continental System. Napoleon determined to invade Russia in 1812 so as to force Russia back in. ossibly due to his inflated ego in becoming the superior leader and incessant wanting of more land, he was convinced that Moscow was the heart of Russia and was determined to march there directly and take control. Napoleon was overconfident in that he allowed himself only nine weeks to defeat Russia and return to Italy and so did not provide cold weather gear for his soldiers nor frost nails for his horses. At the point of his expedition he was initially unlucky that the Russian army did not decide to fight face to face, although their initial retreat and the Russian Autumn inticed Napoleon too much, and he was lured deeper into Russia. The Russians instead implemented a scorched earth policy, destroying and burning anything worthy of supply and nourishment for Napoleon’s men, stretching the French emperor’s supply lines still further and demoralising his army. When the French and Russians finally met head on at the Battle of Borodino on 7 September, it was the largest and bloodiest single-day action of the Napoleonic Wars; it involved more than 250,000 soldiers and resulted in at least 70,000 casualties. The French captured the battlefield, but failed to destroy the Russian army. Moreover, the French could not replace their losses whereas the Russians could replace theirs. Napoleon was caught out by the Russian tactics, but could not adapt to them effectively due to his overreliance on previous tried and tested techniques, thinking he could still win the war on his standard strategy, he was badly wrong. Napoleon entered Moscow on September 14, after the Russian Army had again retreated. But by then the Russians had largely evacuated the city and even released criminals from the prisons to inconvenience the French; furthermore, the governor, Count Fyodor Rostopchin, ordered the city to be burnt. Alexander I refused to capitulate and the peace talks that Napoleon initiated failed. In October, with no clear sign of victory in sight, Napoleon began his disastrous Great Retreat from Moscow, during the usual autumn Russian mud season. Napoleon at this point found himself amongst a disorganised militant force that could only retreat via a single route easily blocked by the Russian army thanks to inadequate maps and intelligence gathered on the Russian geography and Topography: the aforementioned mud made the retreat slow and bloody, with better clothed Cossack troops able to strike with impunity against the confused French army. In the following weeks, the Grande Armee underwent catastrophic blows from the onset of the Russian Winter, the lack of supplies and constant guerilla warfare by Russian peasants and irregular troops. When the remnants of Napoleon’s army crossed the Berezina River in November, only 27,000 fit soldiers remained; the Grand Armee had lost some 380,000 men dead and 100,000 captured. Napoleon then abandoned his men and returned to Paris to protect his position as Emperor and to prepare to resist the advancing Russians. This disaster encouraged the formation of the Sixth Coalition, Prussia and Austria quickly joining Russia and Britain in arms against Napoleon. The strain of fighting a multi front war became apparent to him The Peninsular War (known to the French as the Spanish ulcer) combined with the Russian disaster of 1812 to weaken him so much that he was exiled, for the first time. When he returned in the Hundred Days, Napoleon’s downfall was that he did have so much power. He promised peace to the other European Powers if they let him have the throne. However, no-one could bear to see the man who once ruled most of Europe in power again, so it was off to war. This conflict led to Waterloo, and his final exile. In conclusion it was a combination of luck based on skill and merit that allowed Napoleon to ascend to power from such a foreign position leading the French to establish great military successes In his early years. The great French military leader Napoleon Bonaparte had initially capitalized on the reforms of the French Revolution to improve the lives of French citizens. However his focus on conquering Europe had eventually overridden his economic and military accomplishments. His previous successes exacerbated his ego to the point at which he became complacent with his standard tactics both on the battlefield and in the council. A sequence of poor diplomacy and belief that he could hold the European countries together by sheer force led to European countries rising in vengeance, such as the Spanish ulcer. Napoleon’s failure o deal with these threats and subsequent failing to enforce the ill fated continental system meant his empire was being dismantled piece by piece. Another reason for his downfall was his war tactic of constant Napoleonic Warfare. His main goal was to completely destroy the enemies army to the point where they no longer had the men to fight. But, this also caused heavy causualities on his side. Also, during his Invasion of Russia, he was hurt by the infamous Russian winters. When he retreated from Russia, almost all of his men got left behind (along with Michael Ney) and were completely annihilated by the enemy forces. After this, he suffered because of his army, or lack thereof. The resultant strain of fighting a multi front war against the united European forces was more failure of effective leadership than simple bad luck. Although he successfully returned from exile in the Hundred Days, his military defeat at Waterloo was the final nail in his coffin.