Instructions:Go to ONET ONLINESearch your Career by typing it in the top right corner under Occupation Quick SearchLook for your career from the generated listDo you see a SUN symbol next to it?Do you see a GREEN LEAVE symbol next to it?Assignment:Write me a short paragraph on your findings and let me know if your career has a bight outlook or not and if it’s part of the green economy or not. Knowing this, does it change anything about your plans and goals? If you haven’t made up your mind on your career goal, chose something you like or considering or you may end up pursuing. The paragraph should be around 100 words.
Public Relations and Child Development Careers Discussion
THE INGREDIENTS OF A SUSTAINABILITY PLAN“We can have real impact on the ground.”—Roland Weening, president of coffee, Mondelēz InternationalAs one of the world’s largest snack food companies, Mondelēz International operates in more than 80 countries, sourcing ingredients for coffee products from such countries as Vietnam, Indonesia, and Brazil and cocoa for chocolate from Côte d’Ivoire, Ghana, India, and the Dominican Republic. Mondelēz, which is headquartered in the Chicago suburb of Deerfield, Illinois, is committed to promoting sustainability throughout its supply chain and such initiatives as its Cocoa Life and Coffee Made Happy programs are designed to ensure that agricultural supplies are sustainably sourced.In its “2013 Call for Well-Being Progress Report,” for instance, Mondelēz announced that with 10 percent of its cocoa supply sustainably sourced, the company is on target to reach its longer-term goals. In order to reach those goals, Mondelēz plans to spend $400 million over 10 years to train cocoa farmers in better agricultural and business practices and to provide them with access to planting materials. “We’re investing in much more than farming,” explains Bharat Puri, president of global chocolate and candy. “It’s about empowering cocoa communities as a whole so cocoa-farming villages become places where people want to live.”President of coffee division Roland Weening agrees: “Together with our partners,” he says, “we can help farmers solve challenges and secure a more sustainable coffee supply.” For Mondelēz, then, working closely with communities of growers is not simply a matter of improving supply-chain efficiency: It also reflects the principle that the power of a big company to contribute to global sustainability can be harnessed most effectively when it’s extended to the activities of the smaller organizations with which it does business. “We can have real impact on the ground,” says Weening.As of 2013, Weening’s division was sustainably sourcing 56 percent of its coffee and was well on its way to its goal of 70 percent by 2015. As a matter of fact, Mondelēz is big on goal settingin all of its sustainability initiatives. In wheat, for example, which is a core ingredient in the company’s line of biscuits, Mondelēz established the Harmony Charter, a partnership with members of its wheat supply chain designed to encourage “more respectful agricultural practices, which include wheat variety selection, soil management, limiting fertilizers and pesticides, and smart water use.” The company has set a goal of using Harmony wheat in 75 percent of its total biscuit volume by 2015. According to its 2013 report, it has reached a volume of 44 percent and is on target to meet that goal.Mondelēz is also a member of the Roundtable on Sustainable Palm Oil (RSPO), which was established in 2004 to promote the production of sustainable oil palm products through the certification of industry practices. The company set a goal of having 100 percent of its palm oil supply RSPO certified by 2015, and in 2013, Mondelēz announced that the goal had been reached two years ahead of schedule. Now that the goal has been attained, says Dave Brown, VP of global commodities and strategic sourcing, we recognize the need to go further, so we also challenged our palm oil suppliers to provide transparency on the levels of traceability in their palm oil supply chains. Knowing the sources of palm oil supplies is an essential first step to enable scrutiny and promote improvements in practice on the ground.Not surprisingly, Mondelēz set a goal for ensuring acceptable levels of supply-chain traceability—the ability to trace an ingredient through every stage of production and distribution. The company plans to review suppliers’ traceability practices and then publish an action plan for giving priority to suppliers whose practices are consistent with companywide sustainability principles. The goal is to eliminate all supplies that don’t meet standards by 2020.To understand how Mondelēz wants to coordinate the entire range of its sustainability efforts, we might take a look at one of its most recent initiatives. In 2014, Mondelēz Ireland announced a partnership with Bord Bia Origin Green, a nationwide Irish food-related sustainability program, to promote sustainability throughout the country’s food sector. “We have already achieved significant positive change in Ireland,” explains Patrick Miskelly, manufacturing director of Mondelēz Ireland, “but we have a lot more goals to achieve,” and the company sees the Origin Green partnership as the means of taking its sustainability plans to the next level.These plans revolve around the three manufacturing plants that Mondelēz operates in Ireland, and the immediate focus will be on the supply chain—in particular, the sourcing of raw materials. The company is already committed to local sourcing. At one plant, for example, 37 percent of all raw materials originate locally; another plant uses 21 million gallons of milk from local cooperatives that have adopted sustainable farming practices. Origin Green will add independent verification of farmers’ and food suppliers’ success in setting and achieving measurable sustainability goals.Sustainable sourcing, however, is only one aspect of Mondelēz Ireland’s sustainability strategy. In terms of organizational planning, sustainable-sourcing programs reflect a set of carefully developed tactical plansdesigned to further a larger strategic plan. Sustainability goals, for example, also include the protection of Ireland’s rich natural resources and a reduction of the company’s overall environmental impact. Between 2005 and 2010, the company reduced waste at all three Irish plants by 42 percent, and the largest of the three has already met its goal of diverting all of its waste from Irish landfills by 2014.Mondelēz Ireland also plans to reduce carbon emissions from natural gas consumption by 15 percent by 2016, and like most sustainability-conscious organizations, Mondelēz International regards its various sustainability plans as part of an overarching strategy to reduce its carbon footprint—the total of greenhouse gas (GHG) emissions for which it’s responsible. Between 2005 and 2010, the company reduced GHG emissions by 18 percent and then set a goal of another 15 percent reduction by 2015. As of 2013, it had attained a 9 percent reduction and considered itself on target. As for reducing energy use, Mondelēz admits that “more improvement is needed” if it’s to meet its goal of a 15 percent reduction by 2015; as of 2013, it had cut energy use by only 6 percent. On the upside, the company has exceeded its 2015 goal of reducing manufacturing waste by 15 percent, having achieved a 46 percent reduction by 2013.CASE QUESTIONSHere are a series of Mondelēz’s publicly announced objectives for enhancing sustainability:Reducing production waste to landfill sites by 60 percentReducing our energy and GHG in manufacturingEducating employees to reuse water and improve processesReducing the impact of our operationsAddressing child labor in the cocoa supply chainReducing packaging materialEliminating 50 million pounds of packaging materialBuying certified commoditiesWhich of these are best considered strategic plans? Tactical plans? Operational plans? Which ones might qualify as programs? Projects? Policies? Be sure to explain your reasoning for each item.“Our business success,” says Mondelēz chairman and CEO Irene Rosenfeld, “is directly linked to enhancing the well-being of the people who make and enjoy our products and to supporting the communities where we grow our ingredients.”Assume that you’re a Mondelēz representative who’s been asked to give a presentation to students in an introductory management class. Explain Rosenfeld’s reasoning or her “philosophy” of “business success.” Be sure to give some examples of how and why this approach works at Mondelēz (which, remember, is a global snack food company).Explain—hypothetically—how the following might emerge as barriers to sustainability planningat Mondelēz:Inappropriate goalsAn improper reward systemA dynamic and complex environmentResistance to changeConstraintsAccording to a 2014 McKinsey & Co. survey of executives, 36 percent included reputation management—building, maintaining, or improving corporate reputation—among the top three reasons for addressing sustainability. Explain how the following management strategies can help to enhance both sustainability and reputation:Setting aggressive internal goals for sustainability initiativesAdopting a unified sustainability strategy with clearly articulated prioritiesBuilding a broad leadership coalition in shaping sustainability strategyEnsuring that everyone in the organization understands the financial benefits of sustainability
Management at Work Strategic plans Food Industry Discussion
Introduction To The James Bond Character
James Bond was born by the hands of English writer Ian Fleming, father of the world most famous secret agent novels. Codename 007, double 0 for the license to kill, James bond is a charming British special agent with the talent to solve the twisted machination of rich and powerful evil’s minds. HISTORY OF THE CHARACTER After rising to the rank of commander in the British navy, Bond Joined MI6, becoming one of the few agents “licensed to kill”. His role is to track down those who seek world domination and the destruction of Western civilization. Nothing stops him in battle with ultimate evil. (2) Inside the MI6, who occupies a bureaucratic office is designated by a letter; among all, M is the direct boss of James Bond, Q is the technological section and is involved in the creation of all the essential gadgets for James Bond missions. At last but not least miss Moneypenny, James Bond’s secretary, and all the so called ” bond girl” that are one of the fundamental feature for the series (feature also accused of sexism and machismo) THE AUTHOR Ian Lancaster Flaming was born in Mayfair, London, May 28, 1908. His family was part of the English aristocracy: his grandfather was the wealthy scottish banker Robert Fleming and his father, Valentine Fleming, was a conservative member of parliament, service-oriented land owner in Oxfordshire. Ian was only 9 years old when the father was killed in the first world war. He begins his studies in 1921 at Eton college, and complete them with some difficulties, but he was one of the best athletes of the institute. Young Ian is exuberant, loves beautiful women and sports cars, and is not ashamed to be seen as a heavy drinker. To correct the behavior of the boy, the mother enrols him at the military academy. Disappointed, his mother sends him in Austria, in a British family who runs a guesthouse for students. In a free and stimulated environment, different from the English one, Ian improves his profits. Thanks to this environment Ian become passionate about climbing and skiing; and this same panorama, recurs in his novels. He continued his studies by attending courses in Foreign Policy at the Universities of Geneva and Monaco. Undertake the profession of journalist for the Reuters agency. His eccentric passions are reflected in the founding of the club “Le Cercle”, dedicated to the cult of gastronomy and gambling; (in the movie “license to kill”, the first appearance of James Bond is right inside the club “The Cercle”). In the 1939 he joined the secret service of the British Navy: spending those years conducting a series of operations that will form the basis of the experience that give credibility, life and substance to the character of James Bond. In 1952 he married Geraldine Anne Rothermere, Countess of Charteris. During the Honeymoon he wrote Casino Royale, his first book with James Bond. Will end up writing a total of twelve novels and two collections of shorts stories on 007, a book inquiry on the international traffic of diamonds and a surreal novel titled “Chitty Chitty Bang Bang”. In the saga’s most famous secret agent in the world, Ian Fleming used many episodes of his personal and professional life. In 1964, Fleming suffered a severe debilitating chest cold, which combined with pleurisy, forcing a slow recovery. That summer his mother died, leaving behind her small fortune from Valentine Fleming’s trust. By this time, Fleming had already earned his own fortune, created his own identity, and ruled his own literary empire. His doctors advised him he was too ill to attend his mother’s service, but he went anyway. Fleming tried to force his recovery, dictating letters in protest of his condition, as if by sheer will, Fleming could regain his health. In August went to St. Georges to meet with the golf committee. His heart failed him, and the night of August 11, Ian Fleming began to bleed to death from within. At 1 a.m. on August 12, 1964, Ian Fleming died at the age of 56. He is buried in Sevenhampton, near Swindon not too far from the Welsh border. His wife Anne died in 1981. Fleming’s only child, Casper, died from a suicidal drug overdose in 1975. Both are buried beside Ian beneath a simple obelisk monument in the shadow of the local stone church. (3) THE ARMY TODAY Royal Navy The United Kingdom is an island nation. The sea has always been a vital factor in its history. It has been a means of people arriving from overseas, a barrier to invaders, a highway for trade and the basis for a once global empire. After the second World war the Royal Navy sees a great transformation in technology, roles and society. The strategic impact of the Royal Navy was transformed introducing nuclear power and nuclear armed submarines that changes the strategic nuclear deterrent of Britain; ships design was transformed; the Navy first guided missile armed destroyer was completed in 1962; officer entry at schoolboy age was replaced by the mid-1950s, by entry at eighteen. (4) Royal Marines Ethos “The ethos of the Royal Marines refers to our role and the way we fulfil it. Since the Second World War, we have developed a specific function as a commando and amphibious force, undertaking operations in harsh environments be they mountain, jungle, cold weather or desert. This difficult and unique task requires certain personal characteristics, which are nurtured at the Commando Training Centre during training and then maintained and developed during our subsequent service. It is because of these individual qualities that we are able to fulfil our collective role successfully; combined, these two key elements form our ethos”. (5) MI6 The Secret Intelligence Service (SIS), is the espionage agency of Great Britain. It’s more commonly known as the Military Intelligence section 6 (MI6). It was founded in 1909 as the foreign section of the Secret Service Bureau. It provides the British Government whit a global covert capability to promote and defend the national security and economic well – being of the United Kingdome. Ian Fleming worked for the MI6 during the second world war, for the secret services of the Royal Navy. (6) WHAT WE CAN LEARN FROM JAMES BOND James Bond Movies and novels, changed the collective imaginary He is the central character in one of the best-selling series of popular novels in literary history, and the hero of the most successful and enduring cycle of films ever produced. His critics accused him of racism, sexism, and snobbery. His fans see him as cultured, seductive, and discerning. He is agent 007, licensed to kill. First appearing with the publication of Ian Fleming’sng’s Casino Royale in 1953 and crossing over to the big screen with the film adaption of Dr No in 1962, James Bond emerged at a turning point in British post-war history, a moment of profound cultural change that saw Britain’s decline as a superpower and its reinvention as a swinging mecca for music, fashion, shopping and youth culture. As a fictional character who perpetuated British fantasies of global influence while simultaneously glamourizing an affluent lifestyle based on brand-name consumerism, exotic travel, and sexual conquest, bond novels and films have reminded at the forefront of popular culture, continuously modernizing the 007 formula to reflect – and often anticipate – changing social attitudes, major developments in world politics, and shifting trends in popular fiction and cinema culture. (1) ( “The James Bond phenomenon, A critical reader”; Christoph Lindner; Univerisity of Wales, Aberystwyth; Manchester University Press; 2003) The bond look: The way James Bond present himself to the world – his “look” – provides a number of telling insights his personality. As befits his public persona of a successful businessman for Universal Exports, his style is undemonstrative and classically tailored, suggesting a man at ease with himself and in control of his life. He favors lightweight suits in muted shades for most occasions, and a tuxedo for formal events. Shoes, shirts, and ties are of the best quality. Everything fits, nothing is left to chance – he transcends the whims of fashion. Bond in love: For James Bond a beautiful woman, especially in independent, free-spirited woman, is an irresistible challenge – the ultimate prize of a life lived as if there were no tomorrow. Love never lasts long in Bond World. As Paris Carver, a former lover, once remarked with tragic foresight: “this job of yours – it’s murder on relationship”. So Bond keeps moving, from romance to romance. Yet one name will always linger his memory – the name of his murdered bride, Tracy di Vincenzo. ( “James Bond the secret world of 007”; Alastair Dougall; Dorling Kindersley Publishing, London, New York, Munich, Melbourne, and Delhi; 2006 ) ( http://www.klast.net/bond/flem_bio.html; Jhon Cork (email@example.com); Ian Fleming Foundation, 1995 [online]; accessed on 03/05/2010 ) (3) ( http://www.royalnavy.mod.uk/history/historical-periods/1945-2000/ [online] accessed on 04/05/2010 ) (4) (http://www.royalnavy.mod.uk/royalmarines/history-and-ethos/ethos-beliefs/ [online ] accessed on 04/05/2010) (5) ( http://www.sis.gov.uk/output/sis-home-welcome.html; [online]; accessed on 04/05/2010 ) (6)
Analysis of GATA3 ChIP-seq in the Four Cells
python assignment help Analysis of GATA3 ChIP-seq in the Four Cells. Analysis of GATA3 ChIP-seq data in A549ã€MCF-7ã€T-47D and SK-N-SH cells Highlights: There was 4839 common GATA3 target genes among the four cells The common GATA3 target genes were mainly enriched in pathway related with cancer. The GATA3 target genes were identified, including ER1, FOXA1, AKR1C1 and LGALS1. “GAT” motif was significantly enriched in the four motif of GATA3 binding site. Abstract: Objective: To investigate regulatory mechanism of GATA3 on different tumor cells. Methods: We downloaded fastq file of GATA3 ChIP-Seq data from ENCODE project. The GATA3 ChIP-Seq data was from human lung adenocarcinoma epithelial cells (A549), human hormone-dependent breast cancer cells (T47-D and MCF7), and bone marrow cells in neuroblastoma patients (SK-N-SH). Then GATA3 ChIP-Seq data was subjected to pairwise comparison and identification of GATA3 binding site. The GATA3 target gene in the four tumor cells was further subjected to pathway enrichment analysis, Gene ontology enrichment analysis and motif identification. Results: We found a strong similarity for GATA3 ChIP-Seq in MCF and T47-D cells. GATA3 ChIP-seq data in T47-D cells was strongly similar with that in A549 cells. Analyzing GATA3 binding site in the four tumor cells, we identified 21,507 peaks in A549, 120,057 peaks in MCF-7, 141,332 peaks in SK-N-SH and 69,153 peaks in T-47D, respectively. And there was4839 common GATA3 target genes among the four tumor cells. In addition, 4 GATA3 target genes were identified, including common gene ER1, MCF-7 and T47-D common gene FOXA1, A549-specific gene AKR1C1, and SK-N-SH-specific gene LGALS1. Motif analysis showed significant enrichment of “GAT” motif in the four motif of binding site, and with varying bases sequences around “GAT” motif. Conclusion: We obtain some genes which may play an important role in regulatory action of GATA3 on tumor model, including ER1, FOXA1, AKR1C1, and LGALS. And this may provide scientific basis for detection regulatory mechanism of GATA3 on tumor model. Key words: GATA3, ChIP-seq data, Human lung adenocarcinoma epithelial cells (A549), Human hormone-dependent breast cancer cells (T47-D and MCF7), Bone marrow cells in neuroblastoma patients (SK-N-SH) Introduction GATA family is a zinc finger transcription factor family and contains 6 members, and it binds the DNA sequence (A/T)GATA(A/G) via a DNA binding domain containing one or two zinc-finger domains . GATA3 (GATA binding protein 3 to DNA sequence [A/T]GATA[A/G]) as one member of GATA family plays an important role in promoting and directing cell proliferation, development, and differentiation in many tissues and cell types [2, 3], such as mammary-gland , luminal cell of the mammary gland , T lymphocytes , thymocyte  and so on. Many researchers have reported over-expression of GATA3 in breast carcinomas [7-9]. Low GATA3 expression has also been suggested to correlate with poor prognosis in breast cancer . GATA3 expression is highly correlated with estrogen receptor α (ERα) in human breast tumors [10, 11]. In addition, one research have showed GATA3 could inhibit breast cancer metastasis by the reversal of epithelial mesenchymal transition . Furthermore, aberrant expression of GATA3 has been reported in other cancers except breast cancer, such as pancreatic cancer , prostatic carcinoma , neuroblastoma tumors . However, the mechanism of GATA3 in the progression of tumor remains unclear and it need further research. In this study, in order to investigate regulatory mechanism of GATA3 on different tumor cells, we used GATA3 ChIP-Seq data for human lung adenocarcinoma epithelial cells (A549), human hormone-dependent breast cancer cells (T47-D and MCF7), and bone marrow cells in neuroblastoma patients (SK-N-SH). Then, we performed pairwise comparison of GATA3 ChIP-Seq data and identified GATA3 binding site. The GATA3 targets gene among the four tumor cells were further subjected to pathway enrichment analysis, Gene ontology (GO) enrichment analysis and motif identification. Material and methods GATA3 ChIP-Seq data GATA3 ChIP-Seq data for A549, T47-D and MCF7, and SK-N-SH was used in this study. Although both T47-D 47D and MCF7 are human hormone-dependent breast cancer cells, they had different proteomic profiles . The fastq file of ChIP-Seq data was downloaded from ENCODE (Encyclopedia of DNA Elements) project (https://www.encodeproject.org/). The ENCODE project is aimed to identify all functional elements in the human genome sequence. Reads preprocessing Before read mapping, low quality sequences need be removed from the reads by multiple rounds of trimming and cleaning. Initial cleaning and trimming was accomplished with trimmomatic (version 0.22)  with the default values. Reads Mapping Read mapping was performed with bowtie2 (version 2.0.1) . Reads were mapped to the hg19 human genome using bowtie2. Bowtie2 allows mismatch and gap, and could make alignment very fast and memory-efficient. Pairwise comparison of ChIP-Seq data in the four cells We performed pairwise comparison of GATA3 ChIP-Seq data in the four tumor cells by calculating the Pearson correlation coefficient of the overlapping GATA3 ChIP-Seq data. Pearson correlation coefficient were normalized for peak width and height, the number of total peaks and the number of peaks in the four cells. The higher Pearson correlation coefficient means that the overlapping ChIP-Seq data was almost coincident in the two different tumor cells. Identification of GATA3 binding sites MACS (Model-based Analysis of ChIP-Seq)  and CisGenome  are two different peak detection algorithms in predicting transcription factor binding sites in ChIP-seq data. We firstly used MACS (version126.96.36.19930712) to find ChIP peaks in GATA3 binding sites, with bandwidth of 200 and the other default values. FDR (false discovery rate) < 0.05 was identified. Then, CisGenome was used to identify regions with peaks (-1000, 2000), regions at FDR < 0.05 was identified. Pathway enrichment analysis In order to obtain the pathway associated with GATA3 target gene in the four tumor cells, we used a web-based toolset for functional interpretation of gene lists g: Profiler  for pathway annotation and enrichment analyses with P value < 0.01. Gene ontology enrichment analysis of the GATA3 target-gene DAVID (database for annotation, visualization, and integrated discovery)  is an analytical tools aimed at systematically extracting biological meaning from large gene/protein lists. We used the DAVID to analyze the functions of the GATA3 target gene in the four tumor cells and defined significant function enrichment of these genes in multiple GO categories with P value < 0.01. Motif identification Among highly expressed transcripts, the top 100 peaks with the lowest FDR in the four cells were selected for motif search. The highest point in a peak was used and extended on both sides with either 50 bp. To identify motifs of binding site, the MEME (Multiple EM for Motif Elicitation)-ChIP software  was used with the default values. Random genomic sequences were used as background. Motifs with a P-value of 0.001 were called enriched. Then, the motifs identified in the four tumor cells were compared with the existing motifs using the database of human motifs . Results Comparison of GATA3 ChIP-seq data in the four cells As shown in Table 1, We observed a strong similarity for GATA3 ChIP-seq data in MCF and T47-D cells (pearson correlation = 0.61). However, GATA3 ChIP-seq data in T47-D cells was strongly similar with that in A549 cells (pearson correlation = 0.72). There was no similarity between GATA3 ChIP-seq data in SK-N-SH cells and that in the other three tumor cells. Identification of GATA3 binding site The numbers of peaks and genes annotation information were shown in Table 2, we identified 21,507 peaks in A549, 120,057 peaks in MCF-7, 141,332 peaks in SK-N-SH and 69,153 peaks in T-47D, with FDR < 0.05. In addition, the lowest number of peaks was detected in T46-D cells, and the lowest number of annotated genes was in A549 cells. As shown in Figure 1, 41.7ï½ž47.96 percentage peaks were located within intron region, 41.39ï½ž48.12 percentage peaks (< 2kb or within genes) were not annotated. Most of the peaks in exon region was located in the first exon region. For the peaks near transcriptional start site (TSS), the distance between most of the peaks and TSS was less than 500 kb. There was no apparent significance in distribution of peak in gene binding site among the four cells. As shown in Figure 3, there was 4839 common GATA3 target genes among the four tumor cells. Pathway enrichment analysis of the common GATA3 target genes in the four tumor cells To explore whether 4839 GATA3 target genes share specific pathway, we performed pathway enrichment analysis using g: Profiler. As shown in table 3, there were 15 KEGG (kyoto encyclopedia of genes and genomes) pathways relevant with the common GATA3 target genes. 6 of 15 KEGG pathways were related with cancer. Two other KEGG pathways were involved in focal adhesion and adherens junction, respectively. In addition, the common GATA3 target genes were also enriched in and ubiquition mediated proteolysis pathways.The ubiquition mediated proteolysis pathway was relevant with cell cycle  and the remaining three pathways were related with cell migration [26-28]. Gene ontology enrichment analysis of the GATA3 target gene Table 4 and Table 5 shows the specific GO categories and pathways in each tumor cells, respectively. As shown in Table 5, only GATA3 target genes in A549 cells shared specific pathway enrichment. The GATA3 target genes in A549 cells, UGT1A9ã€UGT2A3 and UGT2B28, were uridine glucuronyl transferas, and were enriched in metabolic process and hormone biosynthesis. The GATA3 target genes in MCF-7 cells were mainly enriched in process relevant to cell differentiation. The GATA3 target genes in SK-N-SH cells were mainly enriched in process relevant to positive regulation of I-kappaB kinase/NF-kappaB cascade. The GATA3 target genes in T47-D cells were mainly enriched in process relevant to cell adhesion. Distribution of GATA3 binding sites in relation to genome annotation In order to investigate the distribution of GATA3 binding site in relation to genome annotation in the four tumor cells. We detected the binding signal ofthe known GATA3 target estrogen receptor alpha gene (ER1) region. As shown in Figure 4(A), it was detected GATA3 could bind to ER1 region in the four tumor cells with great difference in binding site. There were 34 peaks, 21 peaks, 2 peaks and 10 peaks observed for MCF-7, T47-D,A549 and SK-N-SH cells, respectively. Furthermore, GATA3 in MCF-7 and T47-D cells might bind to many ER1 regions including promoter and intron regions. GATA3 in A549 and SK-N-SH cells only bind to 3’-intron region. Then, we detected binding signal of 3 tumor-specific GATA3 target genes (MCF-7 and T47-D common target gene FOXA1 (forkhead box A1), A549-specific gene AKR1C1 (human aldo-keto reductase), and SK-N-SH-specific gene LGALS1 (Lactose-binding lectin 1)) to investigate distribution of GATA3 binding site. As shown in Figure 4(B), the credible binding signal was detected at 5’-upstream in MCF-7 and T47-D cells, and none of peaks was detected inA549 and SK-N-SH cells. However, there was a slight difference in peaks of binding site between MCF-7 and T47-D cells. For T47-D cells, an apparent peak was observed at FOXA1 3’UTR region, but there was no peaks observed at the same position in MCF-7 cells. In addition, because AKR1C1 and LGALS1 was specific GATA3 target gene for A549 and SK-N-SH cells, respectively, peaks for the specific GATA3 target gene could only be detected in corresponding cells. As shown in Figure 4(C) and 4(D), there were apparent peaks detected for AKR1C1 in A549 cells and for LGALS1 in SK-N-SH cells, respectively, and there was no apparent peak observed in other cells. Motif analysis Top 100 peaks with the lowest FDR were used for motif search, and further were compared with the known motif. However, there was no motifs with a P-value of 0.001 enriched in top 100 peaks in A549 cells. Thus, top 200 peaks in A549 cells were used for motif search, and motifs with a P-value of 0.001 were selected successfully. As shown in Figure 5, there was slight difference in motifs of GATA3 binding site identified among the four cells, in good agreement with known motif of GATA3 binding site. In addition, we find significant enrichment of “GAT” motif in the four motifs of GATA3 binding site, and with varying bases sequences around “GAT” motif. Discussion In this study, to explore the regulatory mechanism of GATA3 on different tumor cells, we compared the GATA3 ChIP-Seq data in the four tumor cells (A549,T47-D, MCF7 and SK-N-SH). A total of 1,507 peaks were identified in A549, 120,057 peaks in MCF-7, 141,332 peaks in SK-N-SH and 69,153 peaks in T-47D, and most of the peaks in the four cells were located in intron region. We also identified 4839 common GATA3 target genes in the four tumor cells. Pathway enrichment analysis revealed that the common GATA3 target genes were enriched in pathways related with cancer, cell cycle and cell migration, which indicated that these common GATA3 target genes might be the core node of tumor progression related with GATA3. In addition, the common target gene ER1 and 3 tumor-specific target genes were identified, including MCF-7 and T47-D common target gene FOXA1, A549-specific gene AKR1C1, and SK-N-SH-specific gene LGALS. Motif analysis revealed that significant enrichment of “GAT” motif was identified in GATA3 binding site among the four tumor cells. ESR1 encodes oestrogen receptor alpha, a transcription factor that enhances the response to diverse stimuli, including oestrogen and growth factors, in various tissue types . Researchers have reported that GATA3 transcription factor stimulates ESR1 transcription through multiple binding sites in the ESR1 gene promoter . In this study, we found great difference in binding site of ESR1 and GATA3 in the four tumor cells. Thus, we could suggest GATA may affect ESR1 transcription activity by altering binding site with ESR1 in different cells. FOXA1 encodes forkhead box A1, a forkhead family transcription factor that could enhance the interaction of ERα with DNA by interacting with cis-regulatory regions of heterochromatin . Many researches have showed that FOXA1 is essential for estrogen signaling in mammary cells and is required for the direct interaction of ER to chromatin sites, and depletion of FOXA1 abolishes ESR1-binding capacity and transcriptional activity [1, 31]. In this study, results showed GATA3 could bind to 5’-upstream of FOXA1 only in MCF-7 and T47-D cells, which was in agreement with the previous study . In addition, our results also showed GATA3 in MCF-7 and T47-D cells could bind to 5’-upstream and intron region of FOXA1 and ESR1, and GATA3 in A549 and SK-N-SH cells only bind to 3’-intron region. Thus, GATA3 could enhance ESR1 transcription activity by acting on upstream of FOXA1 in mammary cells. AKR1C1 encodes human aldo-keto reductase-1, an enzyme that catalyzes the metabolic reduction and either activate or inactivate severalxenobiotics . Over-expression of AKR1C1 has been reported in A549 cells [32-34]. However, compared with non-stem cells of A549 cells, higher expression levels of AKR1C1 in stem cells of A549 cells . In this study, pathway enrichment analysis and GO enrichment analysis revealed that AKR1C1 was enriched in process related with xenobiotics metabolism. Thus, AKR1C1 might be positively correlated with cancer stem cell properties through xenobiotics metabolism and promote cell differentiation. In addition, we also detected binding signal of AKR1C1 with GATA3 with three apparent peaks in A549 cells. Therefore, we suggest that presence of AKR1C1 might be enhance regulatory effect of GATA3 on A549 cells. Certainly, it is indispensible for further research to verify the relationship between AKR1C1 and GATA3 in A549 cells. LGALS1 protein belongs to galactoside-binding protein family that could influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells . Researchers have reported expression and secretion of LGALS1 in human and mouse neuroblastoma cells, and LGALS1 could induce T cell apoptosis and inhibit dendritic cell maturation . Furthermore, LGALS1 has been receiving considerable attention, since it plays an important role in cell proliferation, cell apoptosis and cell migration [37-42]. In this study, our results showed that GATA3 could bind to LGALS1 in SK-N-SH with three apparent peaks in SK-N-SH cells. Thus, in neuroblastoma cells, GATA3 might exhibit regulatory effect, which might be associated with LGALS1. Of course, further experimental studies are needed to verify the association between GATA3 and LGALS1. Motif analysis revealed that the motifs achieved among the four cells were in good agreement with known GATA3 motif. In addition, significant enrichment of “GAT” motif was identified in the four motif, with slight difference in flanking sequence around “GAT” motif. Reasons might be that GATA3 may bind to different regions in the four tumor cells. In addition, significant enrichment of “GAT” motif indicated that “GAT” might play an important role in identification and combination of GATA3 and DNA. In conclusion, we compared and analyzed the GATA3 ChIP-Seq data in the four tumor cells (A549,T47-D, MCF7 and SK-N-SH). The results include many genes and pathways which are correlated with regulatory effect of GATA3 on tumor directly or indirectly. We suggest ER1, FOXA1, AKR1C1, and LGALS might play an important role in regulatory action of GATA3 on tumor cells. However, due to large amount of specific GATA3 target genes in the four tumor cells, we could not find the specific regulatory mechanism in the four tumor cells. In addition, the specific regulation of GATA3 in the four tumor cells need to be demonstrated in combination with experimental data. Analysis of GATA3 ChIP-seq in the Four Cells
“How schools can help lower rates of teen dropout/violence?”.
“How schools can help lower rates of teen dropout/violence?”.. I’m working on a Writing exercise and need support.
nterpret information through close and critical reading.
Demonstrate effective use of the writing process.
Employ effective academic tone, style, mechanics, and citation method.
Integrate relevant source material effectively and ethically.
Support a position appropriate to the rhetorical situation.
You will submit a five- to seven-page (1,250 to 1,800 word) well-structured essay that is formatted in proper APA style. This final draft assignment must integrate prior feedback and show effective improvement from the prior rough draft assignment. Your essay is expected to be the product of a complete and thorough writing process.
The argument presented in your essay must be sound, valid, and based upon evidence from at least eight credible sources—at least five of which must be scholarly. (Review the Scholarly, Peer Reviewed, and Other Credible Sources (Links to an external site.) table for more information about appropriate sources). Information and evidence must be integrated properly, cited accurately, and used with integrity. The essay must be appropriate for an academic audience.
“How schools can help lower rates of teen dropout/violence?”.
Compare and contrast the accounts of the state of the nature provided by Hobbes, Locke, and Rousseau. – VERY HARD GRADER
Compare and contrast the accounts of the state of the nature provided by Hobbes, Locke, and Rousseau. – VERY HARD GRADER.
VERY HARD GRADER- please do not reply if you are not an EXCELLENT writer. I need nothing less than an “A” PLS 372 –Modern Political PhilosophyFinal Paper Assignment: Answer the following questions in a single essay. Essays should be 5-7 pages and should answer each of the questions in a single coherent paper. Be sure to cite where appropriate. If you have any questions regarding the assignment, please email me. It is due Thursday, June 27th at midnight. The final paper is worth 40% percent of your final grade. It will be graded on a 100-point scale.Prompt: Compare and contrast the accounts of the state of the nature provided by Hobbes, Locke, and Rousseau. In doing so, be sure to address the following questions: How do the above thinkers describe human nature? What is our condition in the state of nature? What are our relations with other people? Why do we leave the state of nature?Formatting: Your essay should be written in Times New Roman and be in 12 -point font. It should have 1-inch margins on each side and be double- spaced. In the top left corner of the first page only, write your name and nothing else (no need to include date, semester, etc.).Citations: I do not require a specific style of citation, but you are required to cite the sources and be consistent in your style of citation. There is no strict rule as to number of citations, but a good rule of thumb is that you should average three citations per page. Avoid excessive quoting of the text, but do recognize that a citation may be needed even if you are not directly quoting. Avoid secondary materials. Secondary materials vary in quality, will likely only confuse you further, and generally will not help you write a better paper. Stick with the primary sources.General tip: Instead of looking at outside sources, work closely with the primary texts. The best papers will present the arguments in their own terms and provide original examples to explain the material. The best papers will also explain how each of the ideas are related and connected to one another. Thinking through the primary texts on your own, and in your own words, will be rewarded. Relying upon the language of others is obvious, lazy, shows less understanding, and may also be guilty of plagiarism. A paper that is written in your own words, and displays a personal and close interaction with the primary text, even if it makes minor slip-ups, will earn a higher grade than a paper that uses meaningless academic jargon that you do not understand, but is more “accurate.”Please be grammatically correct, and follow directions. This professor is a VERY HARD grader, and I cannot afford a grade lower than an “A.”Links MANDATORY- provided belowRousseau, Second Discourse (Pages 100-181)- you can find this by going to google and typing in “The first and second discourses Rousseau pdf” it is the first link listed Aristotle, Politics: Book I http://classics.mit.edu/Aristotle/politics.1.one.h…
Compare and contrast the accounts of the state of the nature provided by Hobbes, Locke, and Rousseau. – VERY HARD GRADER
Essay Writing at Online Custom Essay
Review This Service