Operation Managerment Essay Example | Topics and Well Written Essays - 500 words

Operation Managerment - Essay Example Customer analyze employer in detail and hope that they build up excellent organizers at the entire levels, constantly engender confidence by open, sincere and apparent behavior, genuinely engross workers in decision-making and offer continuous advice, allow for collective exchanges in the place of occupation as long as intentions are conveyed, provide resourceful HR methods, willing to accept sundry and varying conditions and confer first choice to figure out and congregate customer needs (Cho and Park, 2003). I might prefer to be employed in Marketing Research field as it offers broad range of information used to classify and describe marketing issues; engender, treat, and appraise marketing events; supervise marketing performance; and advance understanding of marketing trends and methods. Due to the assimilation and alignment of the methods the organizations now meet their user needs splendidly.

Applications of Genomics in Cancer

Applications of Genomics in Cancer IN WHICH AREA OF HEALTH CARE CAN GENOMICS MAKE THE BIGGEST IMPACT, AND WHAT SCIENTIFIC ADVANCES ARE NEEDED TO MAKE THIS HAPPEN? Hozaifa S. Hassan Cancer management is one of the hottest areas in modern healthcare, especially with its increasing burden in both developing and developed countries. Genomics has changed the landscape of cancer management. This review highlights the current knowledge and concepts concerning how genomics with the advent of new technologies has revolutionised cancer management. Although we still have a long way to go till achieving full cure of cancer, the rapid development of cancer research carries fruitful promises for the near future. Keywords: Cancer, genomics, microRNA, immunotherapy The International Agency for Research on Cancer (IARC) has recently declared that global cancer burden rises to 14.1 million new cancer cases and 8.2 million cancer-related deaths occurred in  2012, compared with 12.7 million and 7.6 million,  respectively, in 2008, with prediction of a substantive increase to 19.3 million new cancer cases per year by  2025. Prevalence estimates for 2012, show that there  were 32.6 million people alive over the age of 15 years had a cancer diagnosed in the past five years. 1 This sets off the alarm bells, we have to develop more effective tools to face this current situation. Genome sequencing and the oncogenic landscape: Cancer is driven by various genomic alterations. The emergence of the draft human genome sequence in 2000 empowered the study of cancer genomes in many ways. With the arrival of the next generation sequencing (NGS) the tumour biology research has further revolutionized.2 With comprehensive sequencing of many cancer samples, huge number of mutated genes were discovered, so it is crucial to classify these genes into those whose mutations confer with selective gross advantage for the cancer ( driver genes mutations) and those which occur though the course  of tumourigenesis and do not have great impact on the selective gross advantage (passenger mutations). There are about 140 driver genes identified till now. A typical tumour contains two to eight of these driver gene mutations. Driver genes can be classified into 12 signalling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance (Fig. 1). Therefore, targeting the driver genes or their products could have a great impact on tumour growth. Besides, the administration of unnecessary, costly, and potentially toxic treatment will be  avoided.2 Fig ure 1. Cancer cell signaling pathways and the cellular processes they regulate. (Vogelstein et al ., 2013) Genomics and targeted therapy Targeted therapy towards the products of mutated driver genes has revolutionized the modern cancer therapy. This is best exemplified by imatinib which targets the Abelson (ABL) kinas in chronic myeloid leukaemia (CML). ABL kinase is a chimeric oncogenic fusion protein resulted from a reciprocal translocation of break point cluster (BCR) on chromosome 22 and ABL on chromosome 9. Food and drug administration (FDA) approved imatinib as first-line treatment for CML in 2001 for its magnificent response with  89% overall rate of 5-uear survival for patients treated. 3 It is crucial to accurately match patients with the most appropriate drugs. Otherwise, some anti- cancer drugs would be clinically useless because the personal and financial costs would far outweigh the benefits. For example, targeted epidermal growth factor receptor (EGFR) inhibitors achieve a response rate of 71% in patients with non-small cell lung cancer whose tumour harbour an activating EGFR mutation compared with 1% for those  without a mutation.3 There are many targeted drugs that are already used or will enter the clinic soon (Table 1).3 Genetic networks and pathways: one hit is not enough Genomics has shed the light on genetic networking and pathways, where tumourigenesis results from multiple mutations in different genetic networks driving one or more pathways that eventually lead to the acquisition of the growth advantage. This could explain why some targeted drugs are thwarted by resistance. Moreover, this could provide novel combinations for therapeutic  intervention.4 For example, most of melanomas are driven by mitogen-activated protein kinase (MAPK) pathway which is composed of Ras-Raf-MEK-ERK switches. Melanoma patients who have B-RAF V600E variant greatly respond to the B-RAF inhibitors (vemurafenib and dabrafenib). Vemurafenib was approved by FDA in 2011 for  increasing the survival in melanoma patients. 4 Unfortunately, this response is short-lived and  regulation of two other agonists of MAPK- signalling, C-RAF and MAP3K8/COT, could bypass the requirement for B-RAF by re-activating the pathway downstream of the drug target. In a similar vein, Nazarian et al. (2010) have shown that another member in the same pathway called MEK – a downstream kinase to B-RAF- is also mutated in resistant cases. Therefore, adding MEK inhibitors to vemurafenib, could effectively  eliminate most of resistant cells.4 Recently, Villanueva et al. (2013) have shown that the response rate to MEK inhibitor (trametinib) is decreasing. Resistance to MEK and BRAF inhibitors was conferred to MEK2-Q60P mutation and BRAF-V600E amplification, respectively, resulting in sustained MAPK activation in the resistant cells. Interestingly, concurrent use of both dabrafenib and trametinib from the start, not after developing resistance, could significantly improve the efficacy and decrease resistance to therapy. Moreover, a triple combination of dabrafenib, trametinib, and the PI3K/mTOR inhibitor GSK2126458 led to sustained tumour growth  inhibition.5 This paves the way for novel combinations of drugs targeting multiple nodal points in cancer- driving pathways. As a result, cancer therapy will be more efficacious with less resistance. Oncogenic signatures: completing the atlas Many cancer genome projects unleashed in the past decade have identified essentially complete sets of protein-coding genes, coupled with the discovery of novel microRNAs. Moreover, deeper coverage of many cancer genomes has identified a wealth of somatic mutations, including copy- number changes (deletions and amplifications of DNA), rearrangements, point mutations and small insertions in many tumour types. However, the real challenge is to classify these enormous data sets and translate them into functional and actionable  alterations.6 Recently, computational algorithms and functional genomics together with the sequencing of complete genomes of human cancers provide comprehensive catalogues of somatic mutations that fuel different types of cancers. Moreover, these catalogues predict possible targets for therapy in a  resistance emerged towardsB-RAF inhibitors. Johannessen et al. (2010) have shown that up-selected cancer. *PARP denotes poly (adenosine diphosphate–ribose) polymerase. (McDermott et al., 2011) For example, The Cancer Genome Atlas (TCGA) provides molecular tumour maps in unprecedented detail. 3,299 TCGA tumours from 12 cancer types are classified according to their genetic and epigenetic alterations, and then they are gathered into pathways that affect oncogenesis with correlation between these functional alteration and available targeted therapy (Fig. 2). The globally coordinated International Cancer Genome Consortium (ICGC), of which TCGA is a member, will add thousands more samples and additional tumour types which together with computational algorisms will lead to better  understanding of cancer.6 In the future, we would have a genomic atlas for different types of cancers guiding us through our quest for finding a cure for cancer. MicroRNA and cancer: tiny but powerful MicroRNAs (miRNAs) are small noncoding RNAs which enhance the cleavage or translational repression of specific mRNA with recognition site(s) in the 3’-untranslated region (3’UTR). They are involved in multiple biological activities as well as disease progression including cancer. Depending on the functions of their targets, they could act as either tumour suppressors or oncogenes. Dysregulation of miRNAs has been widely observed in different stages of cancer either by structural genetic alterations, epigenetic changes or abnormal biogenesis.7 Recently, miRNA-based anticancer therapies have been exploited, either alone or in combination with current targeted therapies. MicroRNA approaches could concurrently target multiple effectors of pathways involved in cell differentiation proliferation and survival (Fig. 3). 7 For example, O’Day et al. (2010) have shown that miR-24 inhibits proliferation through direct targeting of c-Myc, E2F1 and a number of related molecules. Interestingly, Ma et al. (2010) have shown the crucial role of miR-10b in breast cancer metastasis. This group has also exploited a possible therapeutic application, reporting that systemic treatment of tumour-bearing mice with miR-10b antagomirs suppresses breast cancer metastasis. This opens the door for the use of oligonucleotides or virus-based constructs to either block the expression of an oncogenic Figure 2. Map of functional and actionable alterations across 12 tumor types. Tumor types abbreviated as: BLCA, Bladder urothelial carcinoma; BRCA, Breast invasive carcinoma; COADREAD, Colon and rectum adenocarcinoma; GBM, Glioblastoma multiform; HNSC, Head and neck squamous cell carcinoma; KIRC, Kidney renal clear-cell carcinoma; LAML, Acute myeloid leukemia; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; OV, Ovarian serous cystadenocarcinoma; UCEC, Uterine corpus endometrioid carcinoma; MSS, Microsatellite stable; MSI, microsatellite instability; Ultra, ultramutators; Low CNA, endometrioid; RTK, receptor tyrosine kinase; DSB, double-strand break.  (Ciriello et al., 2013)  miRNA or to reintroduce a tumour suppressor miRNA lost in cancer.7 Cancer inunwtotherapy: awaken the giant For a cancer to develop and metastasise, it must first escape the immune surveillance. Cancer uses a Houdini mechanism to hide its antigens and deceive the immune system. Hanks et al. (2013) have shown that loss of tumour-expressed type III transforming growth factor receptor (TGF R3), enhance TGF-signalling within loco-regional dendritic cells (DCs) and up-regulated both the immune-regulatory enzyme indoleamine 2, 3- dioxygenase (IDO) in plasmacytoid DCs and the CCL22 chemokine in myeloid DCs. These alterations mediate T regulatory cells infiltration  and the suppression of antitumor immunity.8 Interestingly, the therapeutic benefit derived from the combination of an antigen-specific vaccine with a TGF- signalling inhibitor in murine HER2/NEU-expressing 4T1 tumours was primarily mediated by an enhanced antitumor T cell response. This opens the door for using novel TGF- signalling inhibitor in enhancing the  immune therapy.8 Another recent approach in this field is releasing the brakes of the immune system by using checkpoint blocking antibodies. For example, antibodies directed against cytotoxic T ­ lymphocyte antigen 4 (CTLA-4) (e.g. Ipilimumab) and programmed death 1 receptor (PD-1) (e.g. Nivoluma) have demonstrated significant recent promise in the treatment of an expanding list of malignancies. Ipilimumab was approved by FDA in 2011 for significantly improving the survival of patients with metastatic melanoma. Further research will demonstrate much more checkpoints that can enhance immunotherapy either alone or  with combinations with other drugs.9 Interestingly, cancerous cells also have some tricks to escape the radar of the natural killer cells (NKs). For example, cancerous cells down ­ express their natural killer group 2, member D ­ ligands (NKG2D-Ls) required for activation of  NKG2D receptors on NKs. 10 Bedel et al. (2011) have shown a pivotal and novel role for signal transducer and activator of transcription 3 (STAT3) in modulating the expression ofMHC-I chain-related A (MICA) -one member ofNKG2D-L family- in cancer cells. Interestingly, neutralizing STAT3 with pharmacologic inhibitors or siRNA has led to an  increase in NK degranulation and IFNy Figure 3. MicroRNAs targeting the hallmarks of cancer. (Iorio et al., 2012) This sets the stage for developing novel effective immunotherapies in the future as well as increasing todays ones efficacy. Conclusion Genomics has revolutionary changed the landscape of cancer management. Whole genome sequencing of many cancer types combined with computational algorithms will add a wealth of information to our current knowledge. In the future, complete comprehensive genomic atlas will be available for most cancer types. Therefore, the mutations driving an individuals cancer could be exactly identified then precisely targeted by chemotherapeutics, immunotherapy, synthetic oligonucleotides or combinations of those. This will increase the efficacy of the therapy. Besides, the administration of unnecessary, costly, and potentially toxic treatment will be avoided. It will be true that cancer could be cured! References [1] Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. http://www.iarc.fr/en/mediacentre/pr/2013/pdfs/pr223_E.pdf. (12 December 2013) [2] Vogelstein, B et al. Cancer genome landscapes.  SCIENCE 2013; 339: 1546–1558 [3] McDermott, U, Downing, JR, Stratton, MR. Genomics and the continuum of cancer care. N Engl J Med 2011;  364:340-50 [4] Sandmann, T, Boutros, M. Screens, maps networks: from genome sequences to personalized medicine. Current Opinion in Genetics Development 2012; 22:36–44 [5] Villanueva, J et al. Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Reports 2013; 4: 1090–1099 [6] Ciriello, G et al. Emerging landscape of oncogenic signatures across human cancers. Nature Genetics 2013;  45:1127-1133 [7] Iorio, MV, Croce, CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. a comprehensive review. EMBO Mol Med 2012; 4:143–159 [8] Hanks,BA et al. Type III TGF-ÃŽ ² receptor downregulation generates an immunotolerant tumor microenvironment. The Journal of Clinical Investigation  2013; 123: 3925-3940 [9] Kyi, C, Postow, MA. Checkpoint blocking antibodies in cancer immunotherapy. FEBS Letters 2014; 588: 368–376 [10] Bedel, R et al. Novel role for STAT3 in transcriptional regulation of NK immune cell targeting receptor MICA on cancer cells. Cancer Res 2011; 71:1615-1626 (Word count: 2,124) Three lab choices 1. Cancer genome project(Prof. Mike Stratton ) 2. Gene expression genomics(Dr. Sarah Teichmann) 3. Epigenetic reprogramming(Prof. Wolf Reik) 8

How to Lift Heavy Objects :: essays research papers

How to Lift Heavy Objects It is important to understand how to lift objects correctly. The results of improper handling of materials may result in a painful hernia, a strained or pulled muscle, or a disk lesion. The following rules are to be observed when lifting heavy objects. 1. Do NOT lift an object if it is too heavy or too bulky for good balance. Get help or use mechanical aids such as a dolly or hand truck. 2. Keep the load as close to the centre of your body. The farther the load is from the small of your back, the greater the strain. That is the reason a heavy compact load is easier to lift than a bulky, lighter load - you just cannot get the bulky object close to you. The best way to handle a compact load is to squat down close to the load with one foot alongside it and the other foot behind it. With the feet comfortably spread, you will have better stability with the rear foot in the position for the upward thrust of the lift. 3. Pull the load toward you, then lift it gradually. Avoid quick and jerky motions. Push up on your legs while keeping your back straight. A straight back keeps the spine, back muscles, and other organs of the body in the correct alignment. Tucking in your chin helps to align the spine. No matter what size the load, get as close to it as you can; then get a good grip by using the full palm and extending your fingers and hands around the object. Remember that your fingers have very little power and need the strength of your entire hand. Keep your arms and elbows tucked into the side of your body to help keep the body weight centred. Avoid twisting your body during the lift or while moving the load; change directions by moving your feet. Twisting your body during a lift is one of the most common causes of back injury. 4. Be sure to have a clear vision over the load you are handling. 5. Do NOT change your grip while you are carrying the load. 6. Face the spot in which you intend to set the object down; bend your knees keeping your back as straight as possible and the weight of the object close to your body. 7. Always allow enough room for the load to prevent injury to your toes and fingers.

Why One Should Not Steal

Someone would say stealing is only right when you are poor, homeless, or to help your family. There are many times when people have said â€Å"we needed to steal even though we did not want to, because we had to survive. † In my opinion, no matter what the circumstances are, stealing anything, from anyone, is not morally right, is unjust, causes consequences, and most importantly, defies, breaks, and sometimes completely diminishes, trust. Although I did not intentionally steal from my parents, this essay will be about why stealing money from parents is wrong.First of all, stealing things is not morally or ethically, the right thing to do. At a young age, people learn that taking things from other people without their permission is not going to be accepted as good behaviour. It is important to know that if something isn’t yours, you do not have a right to it. I’m pretty sure even in the bible it says; â€Å"thou shall not steal. † If you know something is going to be frowned upon if done, or that you would be frowned upon, upon participating in something, you simply should not partake in that action.Another reason stealing should not be performed, is because it is unjust. Just like Antoine Lavoisier's Law of Conservation of Mass, to gain something physical from one person, means that person must have lost something. Stealing money from someone means that the amount you took is the amount they lost, and they have to make up for that loss somehow. This is not fair, because the person earned that money themselves, and should not have to work extra, to accommodate more than just them. The effort they are making for the money is not equal to the effort the thief is making, which is unjust.Thirdly, people should refrain from robbing others, is because what comes with crime or bad behavior, is consequences. Stealing is obviously against the law. If caught doing it, it could cause you to have that on your record and this could hinder you fro m getting a job, etc. Not to mention, in the end, it is your loss, because you would get fined, or have to pay off the value of what you had taken. On a less lawful note, your parents could find out, and this could bring about many repercussions, of their choice.If that doesn’t scare you, you are of another species. Lastly, and most importantly, stealing destroys almost all trust you had with the person you stole from. Robbing things can leave someone, such as my parents, to feel utterly betrayed. They think they have a good relationship with you, and then when you take something from them without their permission, it can make them re-evaluate the bond they have with you. Stealing makes people feel vulnerable and sad, like you used them, and don’t care about their feelings, values, beliefs or thoughts.This can seriously affect what they (and other people) think of you, and you never know, you may need them at some point and they won’t be there to help you. This is because they will remember what you did to them, and think twice before doing something nice to/for you. Clearly, it is not worth it to steal anything, from anyone because it will not affect you positively in the end. I have learned my lesson, and will never take money if I am not one hundred percent sure it is mine. My sincere apologies for my actions, and I will pay you back every penny of it.

Philosophy: The Ethics of Human Cloning

In order to make a fully justified decision on whether human cloning is ethical or not, one must be exposed to the background of the subject. To start, a clone is an exact replica of an organism, cell, or gene. The process itself is done asexually with the use of a cell from the original human. It is then placed inside a female capable of bearing a child and is then born as a clone. Along with this comes questions of whether or not it is right to clone a human being based on different facts and opinions of small groups or communities(Dudley 11). The technology of cloning is not quite developed enough for a doctor to be certain that an experiment will be successful. In Scotland, the first sheep was cloned and was named Dolly. It took over 250 tries before they were successful in creating the clone. When news of this reached America, immediately polls showed that ninety percent of Americans were against the idea of cloning humans. Those who support cloning research replied by saying the public based their opinions on fallacies of the news media and, therefore, could not comprehend the whole picture(Farnsworth). Those in favor of cloning might say it can push forward medical research. For example, with cloning technology it may be possible to learn how to replace old cells with new ones. This could lead to a longer life for each individual. Also, with enough research scientists could create clones to act as donors. Some scientists say that human cloning may eventually reverse heart attacks. This accomplishment would take place by injecting healthy heart cells into damaged heart tissue. In addition, cloning could help improve family life. For example, if a couple lost a hild they loved dearly and could not reproduce naturally, cloning that child could be an alternative. In this way, the parents would have the chance to love the clone just as much as the original child. On the other hand, those against cloning would say that it is wrong for a doctor to harm a clone. If this were allowed, eventually we would compromise the individual. Clones would become second-class citizens. Cloning strips humanity from natural reproduction by leaving a clone with only one parent. In addition, there would be a decline in genetic diversity. In ther words, if some day we all have the same genetic makeup and lose the technology of cloning, we would have to resort back to natural reproduction. This would cause problems because it has the same effect as inbreeding. In the same way, clones would feel like they had lost their individuality. For example, their genetic makeup would be known. Also, there could be negative psychological effects that will impact the family and society. For instance, if a clone finds out that s/he has no biological father it may suppress the clone’s feeling of equality among other naturally born people. Also, there is a chance that the mother or the clone may become sterile. Among all of these there are too many risks for the bearing mothers and embryos. Eventually, it would turn into a routine to destroy human embryos in the process of cloning(†The Ethics of Cloning†). According to Latter-Day Saints, cloning does not respect the fact that humans have souls and it robs clones of their humanity. God intended the power to create humans to be practiced between a man and a woman in the boundaries of marriage. Do otherwise is taking the work of God into your own hands. This means that humans lack the authority to make ecisions about creating or destroying a life. In addition, humans do not have enough knowledge or power to control outcomes of certain events (Dudley 56). However, others believe religion has no place in the debate. They argue, interpreters of the Bible can not agree on what actions God would allow to be done with justified means. In addition, the Koran or the Bible have limits to their validity because they do not address specific issues that need to be answered(Dudley 66). After analyzing the situation, Aristotle would say that human cloning is unethical because bad means are used. For instance, it took scientists 277 tries to create the first cloned sheep. This means that there were hundreds of deformities before the successful specimen was created. In the same way, deformities of humans would be a result of experimentation, which would decrease the quality of life for those specific clones. And, even if we found a cure for a disease, let’s say cancer, it would be reaching a good end through bad means. On the other hand, Kant would say that human cloning is ethical in that the number of people who benefit from it outweighs the number of people who suffer from it. For example, cloning could be a way to help expand the length of human life, but it would cost the lives of clones who were failures in the experiment. In this way, Kant would agree that bettering all of humanity in exchange for a small group of less fortunate people is justified. Somewhat closer to agreeing with Aristotle than Kant, Sartre would say the act of cloning a human being is an act of free will. Therefore, if an individual decided to go forward in this act, they would be correct because each situation is unique. According to Sartre, owever, the individual is involved in this action is, in fact, responsible and would receive the consequences that come about in the particular act. Therefore, Sartre would come to a consensus that it is ethical to clone humans, but the consequences of doing so are upon those who are apart of the act. After taking into account many of the alternatives and situations of cloning, I would not support human cloning. The effects from all of the harms that are unknown outweigh all of the good that can come from the research of cloning. In addition, I agree with Aristotle that ou must not use bad means to reach a good end. Therefore, seeing that cloning human is both degrading to the clone and to humanity, I believe that cloning involves too much unknown information that we would need in order to even consider it. However, if scientists had enough information to be able to clone a human without a shadow of a doubt, then it might be more ethical to clone. But, the social glitch would still be present; clones would be seen as inferior to naturally reproduced humans. Therefore, I do not support the legalization of cloning or any practices thereof. My solution bends more towards the objective part of the spectrum. I think that if humans could be cloned without the risk of death or intentional killing of clones for organ transplants it would be more acceptable to practice it. But, the clone’s social status could not change as easily as the latter. Universally, therefore, cloning should be banned in order to preserve the natural functions which we were made to perform as human beings. A general rule for cloning humans is â€Å"do not clone unless there are no negative consequences as a result of performing the act. †