Thursday, October 31, 2019
Quantitative methodology Assignment Example | Topics and Well Written Essays - 4750 words
Quantitative methodology - Assignment Example Quantitative research methods try to measure variables by assigning scores to them in order to ensure that they can be scaled easily. The root of quantitative research lies in the positivist research paradigm that believes everything happens due to causal relationship between variables by virtue of some fixed law. It is useful to use quantitative research particularly when researchers are trying to test hypothesis. It is quite useful to use quantitative research under certain circumstances. For instance, according to Frankfort-Nachmias & Nachmias (1992 cited in Johnson, 2001) quantitative research is particularly important when the research problem is very specific and the researcher wants to measure the outcome numerically. The quantitative research is important because it helps the researcher to set the dependent and the independent variables of the research and is able to show the exact nature and direction of relationship between the variables. In short it allows the researcher to explain the causal relationship between the variables. Balsley (1970) had pointed out that quantitative research is particularly useful as the researcher is able to establish internal and external validity of the data due to controlled observations, experiments and proper data cleaning techniques. Additionally, quantitative research is also able to eliminate subjectivity and bias from the research by eliminating human bias factor. There are two main methods of quantitative research designs namely experiential and non-experiential research. Experiential quantitative research focuses on natural science based approach and non-experiential quantitative research focus primarily on social sciences (Johnson, Onwuegbuzie & Turner, 2007). There are basically four main types of quantitative research namely descriptive, correlational, casual-comparative and true experimental. Descriptive quantitative research
Tuesday, October 29, 2019
Time Value of Money Essay Example for Free
Time Value of Money Essay The application of the time value of money theory is very useful in the case of making a decision about obtaining a loan or rejecting it. According to the theory of time value of money, the rule of thumb for making down payment is: if your bank account pays lower rate than the loan, than use your money in the bank account as down payment. This rule is based on the realization of the fact that the value of the money which has been placed on the deposit is going to decline with time, and the percent rate on the deposit which the bank offers is not going to ensure that the value of the personââ¬â¢s money is kept on the same level. At the same time, the person could benefit from making a down payment for a car or any other object because the value of the money would reduce with time and thus he would be paying less for the object which he bought as the result of the loan. Despite the fact that the statements of the time value of money theory are obvious, the author of the article ââ¬Å"Should You Pay Cash for a New Car?â⬠in Los Angeles Times seems to regard all of the issues connected with consumer loans in a different light. Most of the points which he makes in the article are either completely incorrect or need to be altered in order to correspond with the statements which theory of time value of money makes. First of all, the author marks that it is always much better for consumers to obtain loans at the bank instead of investing their own money which they have in deposits. He mentions that consumers did not have computers in order to calculate the benefits of obtaining loans. If they had, ââ¬Å"they might otherwise have seen the advantage in borrowing without taking anyones word for itâ⬠. However, as the rule of thumb states, it is profitable to make a down payment for the loan only in that case when the bank account pays a lower rate than the loan. The author does not take this rule into consideration and makes a statement that all of the consumers need to obtain loans, despite the differences between the rates of interest on deposits and loans. The point of view which he is trying to express is that no matter what, obtaining a loan will always be the best possible solution for the consumer. The author mentions the rule which Frank Sperling, vice president at Security Pacific National Bank gives in order to guide consumers in making a choice for or against consumer loans: if a consumer is able to obtain at least half of the interest rate on the investment in comparison with the interest rate on the loan, he is going to make a correct choice by obtaining a loan. This rule is quite similar to the rule of thumb which is being used in the theory of time value of money but it is too concrete of a case. It is impossible to make a conclusion about the interest rate on investment being exactly half of the interest rate on the loan for the deal to be beneficial for the consumer. The benefits of the consumer can be relatively larger if the gap is increased but the consumer can make a down payment for the item which he wants to buy whenever the rate on the loan excesses the yield on investment. The author also states that there can be differences between the rule applications for different types of loans but it is not true because the rule can be applied for any type of loan. It is based on the general objective principles on the theory of time value of money which are universal. Besides, the approach which the author describes does not work in any economic environment. The consumer needs first to realize in what environment the countryââ¬â¢s economy is functioning at this point. This can be either the environment of increasing interest rates or of decreasing interest rates. If the interest rates are going to decline in the future, the consumer will need to consider an option of refinancing the loan in the future. If the interest rates are increasing, the consumer might think of obtaining a loan with a lower interest rate now and investing his funds in securities which a higher interest rate in the following periods of time. He also needs to consider the possibilities of obtaining a fixed interest rate for the loan in order to ensure that his payments on the loan are not increasing and invest in floating-rate securities in order to benefit from the interest rate fluctuation in the future. Without the analysis of the economic environment, there is no possibility to make a conclusion about the best possible way of buying a car or any other item. The author also makes an incorrect statement that the major difference between making an investment and obtaining a loan is that the percent rate is calculated on a different basis. According to him, the percent rate on the loan is being compounded only annually and the rate of interest on the investment can be compounded monthly: ââ¬Å"Keppelâ⬠¦ calculated that 48 months of interest on a 14.2 percent loan of $8,239.05 would be $2,607.62, while the same principal invested at 8 percent, compounded monthly would earn interest of $3,095.06- a profit of $487.44â⬠. However, this rule is going to be true only in the case when both the loan and the investment have the mentioned characteristics. It is not the general case because interest rates on loans as well as on any other assets can be compounded in any number of ways. It is impossible to say that the investment is going to bring profits to Keppel only due to the different techniques of interest calculations because it is very far from the truth. The question is whether he will be able to obtain the loan and make the investment according to the terms which are favorable for him. The author of the article has expressed complete ignorance in the knowledge of the finance and particularly their theory of time value of money. In order to make a correct decision about the way of purchasing an item, consumers need to make sure they take all of the issues of this theory into consideration.
Sunday, October 27, 2019
Exosome as Nanoscale Vesicles | Pancreatic Cancer Research
Exosome as Nanoscale Vesicles | Pancreatic Cancer Research Abstract Exosome are nanoscale vesicles that are released from cancer cells, playing an important role in the microenvironment of cancerous tumour cells.6,8 The exosomal vesicles (EV) contribute to the progression and growth of the tumour, and can be targeted using gold nanoparticles (GNP).1,6,7 The exosomes are isolated from the blood plasma, and with their stability in bodily fluids, they can be targeted and inhibited using GNP.Ã The GNP will inhibit the cancer cell, and will stop tumour growth and production.Ã Using proteomic and quantitative methods, the exosome EphA2, showed the highest detection of specificity and sensitivity in pancreatic cancer patients.1,2,4,8 Further tests confirmed that EphA2-EV has potential in early detection for pancreatic cancer, due to the levels specificity and sensitivity being higher in comparison to pancreatitis patients and the control patients.1 Keywords: Biomarkers, Exosome, Pancreatic cancer, Nanoparticle, Proteomics, Vesicles, Plasma, Antibody Introduction Pancreatic cancer, is vastly terminal, with a survival rate of less than 5%.Ã Pancreatic ductal adenocarcinoma (PDAC), is the most common form of exocrine pancreatic cancer, accounting for around 95% of pancreatic cancer cases.10 PDAC is a silent cancer, and with the lack of testing, the need for novel biomarkers to aid in early detection is imperative.Ã With no valid early detection methods, and no symptoms of early stage PDAC, the cancer will progress rapidly throughout the body before it is detected.Ã There is need to find a biomarker, aiding in the early detection PDAC, so that a treatment can be provided to stop the cancer from progressing.Ã The current tumour biomarker, CA19-9, is not reliable in early detection due to falsely elevated results of diseases other than PDAC.10 Recent studies suggest that exosomes, a nanovesicle, has a high potential as the future biomarker of PDAC, due to the stability and detection sensitivity in human blood plasma.1,2,4,8 Malicious exosomes, are veiled by cancer cells, screening the importance in tumour maturation and progression.7 Studies show how to optimize a method, to isolate exosomes from the blood plasma, to further assist in biomarker discovery.Ã In regards to analysing exosomes as a potential biomarker, exosomes need to purified and isolated with differential centrifugation paired with ultracentrifugation (UC).Ã Another technique used, is affinity purification of the exosomal membrane antigens using density gradient (DG) centrifugation, separating the vesicles based on their density.8 A practise needs to be conducted, to purify exosomes, from only a small volume of blood plasma. With studies being conducted on the stability in fluids of circulating exosomes, it can be confirmed that these nanovesicles have the ability of targeting to uptake to hinder or delay tumour development.Ã With the size of the exosomes ranging from 40 100 nm, they are distinguished for tumour microenvironment.Ã Exosomes, a potential biomarker, for the early detection of PDAC, are also being studied as potential nanocarriers to target cancer cells and delaying tumour growth.1,7,8 The most common nanocarrier being studied is the gold nanoparticle (GNP), due to its imaging, diagnostics, and therapy abilities.Ã The GNP can be easily synthesized via the citrate reduction, which is why is has potential in medical theranostics.7 Extracellular vesicles (EV), are secreted into extracellular space, they are involved in tumour initiation, progression as well as metastasis.Ã EVs can be used as non-invasive biomarkers, but the current studied methods are time consuming in regards to EV isolation.1,7,8 The EV membrane markers which are part of the tetraspanin family, are CD9, CD63, and CD81, respectively, and an assay demonstrates similar features.6 A nanoparticle EV assay, will be captured by an EV-specific antibody with the dual binding of EV, using 2 nanoparticle probes.Ã The 2 nanoparticle probes, will produce a plasmon, promoting an increase in sensitivity and specificity for the discovery of an exosomal biomarker.Ã Ephrin type A receptor 2 (EphA2), has recently been identified as a biomarker, of the tumour derived pancreatic cell line, and enriched on EV.1Ã EphA2, shows overexpression, increases in vitro invasiveness and anoikis resistance in pancreatic cancer cell lines.1 A recent study has been conducted with healthy control patients, pancreatitis patients as well as pancreatic cancer patients, with the use of nanoplasmon-enhanced scattering (nPES) assay a fast, sensitive, and specific method in biomarker detection. Convention Tumour Markers in Pancreatic Cancer Carcinoembryonic Antigen CEA CEA, is a glycoprotein, that is measured in a common blood test used for testing patients with cancer, including pancreatic cancer.Ã This will measure the amount of the CEA protein that is in the blood of a patient who may have cancer, and the CEA levels can be used to determine whether treatment is working or if the cancer is spreading.Ã A CEA level of 5 ng/mL, is considered a normal level of this protein, but there are several conditions that can alter the levels of the CEA in your blood, which is why this is not a valid biomarker in the detection of pancreatic cancer.5 CEA testing can be useful in regards to recurrent colon cancer as well seeing if treatment is successful.Ã Levels of CEA can be elevated due to smoking, as well as in other diseases such as Crohns disease.Ã Due to the unreliability of CEA levels in cancer, this blood test confirms that CEA is not a consistent biomarker for the early detection of pancreatic cancer. CEA is expected to be paired with other biomarkers, for early detection reasons.Ã When paired with CA19-9, there is an increase in detection for sensitivity and specificity, showing an improvement in diseases including pancreatitis as well as pancreatic pseudocyst.Ã Despite the improved results for pancreatic diseases, CEA is still not valid for the detection of pancreatic cancer, even when it is paired with another marker such as CA19-9.5 Carbohydrate Antigen CA19-9 Carbohydrate antigen (CA19-9) was discovered in 1981, and is considered a sialyl lewis a (sLea).9 CA19-9 is found on the surface cancer cell, expressed as a glycolipid and an O linked glycoprotein, and is related to the Lewis blood group antigens.3Ã Patients with Le (alpha beta +) or Le (alpha + beta -) blood group, express levels of CA19-9 in their blood, whereas approximately 5 10% of patients with Le (alpha beta -) blood group do not express CA19-9, limiting the use as a valid biomarker.9 Due to the low, and uncertain sensitivity of CA19-9, it is a poor interpreter of PDAC, therefore it is not a valued biomarker. CA19-9 is unable to differentiate between benign, precursor lesions and malignant conditions in PDAC patients, and it gives elevated results in many other gastrointestinal cancers.3Ã This blood test can show elevated CA19-9 levels in patients with other non-cancer diseases including pancreatitis and cirrhosis.3,9 The CA19-9 blood test can be beneficial in regards to knowing if a pancreatic tumour is secreting it, and to judge the efficiency of treatment, and look for pancreatic cancer recurrence.Ã A healthy patient will have a CA19-9 level of 0 37 U/mL, therefore with increasing levels of CA19-9, this could indicate tumour growth.3 For more accurate results, a PDAC marker needs to be discovered and paired with CA19-9, to increase the sensitivity and specificity in early detection.Ã With CA19-9 as the only marker, studies show it was only elevated in 50 75% of patients having PDAC, confirming that is not consistent as a biomarker and should not be used in diagnostic testing.3,9 Expressing elevated levels in other diseases such as benign jaundice, pancreatitis, and ovarian cancer, confirms the lack of consistency using the CA19-9 marker and that it cannot be used as an accurate indication of early pancreatic cancer detection.3 Emerging Biomarkers With the absence of reliability using the current PDAC biomarker, C19-9, it is a necessity to discover a biomarker with improved sensitivity as well specificity for the early detection of PDAC.Ã Recent studies suggest, that exosomes can be detected in body fluid such as blood, and they have potential as disease biomarkers.Ã Exosomes, found in blood plasma, need to be collected from healthy patients to obtain individual and pooled samples.Ã The collected blood plasma, will need to be separated, by centrifugation, to isolate the exosomes for further proteomic and quantitative studies.8 Isolation Methods Isolation of exosomes using the UC method, involves normal human plasma, and diluting it with PBS.Ã The sample will be differentially centrifuged, to eradicate cell debris, which is followed by UC.Ã The subsequent pellet, is washed in PBS, and filtered, and the filtrate was ultracentrifuged.Ã The resulting exosomal pellet, used for the study, will be resuspended in PBS.8 Using the EI isolation method, the plasma, is diluted in PBS and centrifuged.Ã The supernant is filtered, and the filtrate will be incubated using a blocking agent.Ã A microcolumn was placed in magnetic separators, where the column was rinsed with rinsing solution.Ã Beads were bound to the exosome, and were applied to the magnetic column.Ã The column will be washed with rinsing solution, and the immune captured exosomes were recovered by removing them from the column and placing them in a collection tube.Ã The exosome bound microbeads are washed to elute the exosomes, and centrifuged to obtain the exosomal pellet.Ã The exosomal pellet will be resuspended in PBS.8 Lastly, isolation using DG method, involved the exosomal pellet that was obtained from UC as well as normal blood plasma that was layered on iodixanol solution and centrifuged.Ã To the top of the tube, there were 12 fractions, with increasing densities.Ã The fractions are diluted with PBS and centrifuged, the resulting pellet was washed with PBS, centrifuged and resuspended in PBS.8 Western Blot and Microscopic Analyses The western blot method, shows the enrichment of the exosomal marker proteins.Ã Gel electrophoresis is used to separate and identify the different proteins.Ã The thickness of the band, indicates the amount of the protein that is present.Ã There is a labelled antibody, that is bound to the protein of interest.Ã AFM is used, to get a 3D image of the exosomal vesicle. Recent studies confirma that the exosomal markers CD9 and CD63 are enriched in exosomes purified using UC and EI methods.8 The study indicates that the UC method, had four exosomal markers whereas the EI method had only two exosomal markers, CD9 and CD63.Ã Transmission electron microscopy (TEM) and atomic force microscopy (AFM), were used on the isolated exomes, from the three exosomal isolation techniques.Ã In the DG sample, the TEM reported homogeneous vesicle, with diameter ranging from 40 100 nm, confirming the characteristics of exosomes.Ã The AFM produced a 3D image of the exosome, and after further analysis it was revealed that the exosomes had round membranous vesicle characteristics. LC-MS/MS Liquid chromatography mass spectrometry (LC-MS/MS), is a quantitative method used for the identification of proteins at the peptide level.Ã The first quadrupole is for the selection of the precursor and the second quadrupole is highly specific for detection.Ã In comparison to gas chromatography mass spectrometry (GC-MS), LC-MS/MS is not limited to volatile substances, it is better for the detection of molecules.Ã LC-MS/MS can produce many quantitative results, and has a high specificity and sensitivity. The study was carried out, using an LTQ Orbitrap Velos with a nanoelectrospray interface coupled to an Ultimate 3000 RSLC nanosystem and the LTQ Orbitrap Velos mass spectrometer operates using a nano -ESI spray.Ã The LC-MS/MS spectra are searched against the human protein database using MASCOT.Ã Equal amounts of protein from the three exosomal samples were separated, reduced, alkylated and digested with trypsin.Ã The DG sample had the highest number of protein identifications, followed by the UC isolation method.Ã Therefore, the western blotting, microscopy and MS results confirm that the DG isolation method is the most effective, in regards to isolating exosomes from blood plasma.8 Targeting with Gold Nanoparticles Malicious Exosomes The exosomes are formed from endosomal pathways, after they are fused from multivesicular bodies (MVBs) with plasma membrane.Ã The formation of malicious exosomes, also starts in the endosomal pathway.Ã The early exosome is formed from the migration from the cell periphery to the nucleus, by the formation of intraluminal vesicles (ILV).Ã The process interceded by exosomal complexes required for transport (ESCRT) and other proteins.Ã Late exosomes/ MVB, migrate to the periphery and fuse with the membrane, releasing the ILV, which are called exosomes.Ã The proteins, Rab GTPases, mediate the endosome migration.7 The malicious exosomes, are released from cancer cells found in the tumour microenvironment.Ã Exosomes play a role in variation and shaping of that tumour microenvironment.1,2,4,6,8 Malicious exosomes have potential as biomarkers, due to their stability in biological fluids including blood plasma.Ã There have been increased levels of circulating exosomes seen in several cancers including pancreatic cancer.1,6,7,8 Nanovesicles can be used to carry therapeutics, and have potential to limit cancer progression.1,7 The method consists of inhibiting the malicious exosomes biogenesis. Gold Nanoparticles The GNPs can be easily synthesised, as well they consist of a variety of shapes and sizes.Ã These nanoparticles exhibit intense light absorption and scattering, and they are deemed to be highly stable.1,7Ã They have potential in targeting, therapeutics as well as diagnostic capabilities. Regarding rapid tumour growth, a compressed lymphatic vessel will collapse causing lymph drainage, which will then allow for the nanosized molecule to be taken at the tumour site.7 This process will allow for passive targeting with nanosized molecules.Ã The cellular interest will be dependent upon the size and shape of the GNP.1,7 The tumour cells will overexpress their cell number receptors, which can be used for potential biomarkers.1,2,4,6,7,8 These cell surface receptors, will aid in the direction of the GNP to the tumour cells. Gold Nanoparticle Targeting The GNP will target malicious exosomes, by undertaking the malicious exosomes biogenesis with GNP specific targeting moieties as well as silencing moieties.7Ã Using antibodies to aim at the exosome for capture and selective retention.Ã Lateral flow immunoassay, will aid in exosome detection with CD9 and CD81 as antibodies, and CD63 with GNP.1,7 Therefore, GNP are being studied as a potential candidate for cancer therapy as well as for malicious exosome targeting.Ã The use of nanotheranostics to help quantify and inhibit the malicious exosomes. Sample Collection and Processing This recent study, developed a method for the purification of exosomes in blood plasma, as well as finding the EV concentrations in the plasma samples.Ã A three-probe EV capture was used, with a capture antibody that recognizes an EV membrane protein (anti-CD81), with antibody conjugated AuS and AuR to serve as two EV probes.Ã This EV capture was designed to form a plasmon, with the different GNP binding on an EV to improve sensitivity and specificity of EV detection.1Ã The study examined 59 pancreatic cancer patients, 48 pancreatitis patients, and 48 control patients, to see if early pancreatic cancer stage could be distinguished from pancreatitis patients and the control patients.1 Method The EV isolation consisted of cells grown in culture media, and washed with PBS.Ã The culture supernatants were collected and centrifuged to pellet cells, and centrifuged again to remove cell debris.Ã Concentrated with centrifugal filtering units, and centrifuged, the precipitates were collected and resuspended in PBS and centrifuged.Ã The resulting precipitates were collected and dissolved in PBS.Ã The ELISA assay, consisted of ninety-six well plates, which were incubated with antibody CD81.Ã The ELISA assay was analysed for absorbance, and the standard curve plotted the light absorbance versus the log10 EV standard concentration in pg/uL.1 The peptides were separated using Ultimate 3000 nano-LC, with an enrichment column as well as an analytical column.Ã The peptide fractions were analysed with Velos Dual-Pressure Linear Ion Trap mass spectrometer, and one MS scan, was followed by eight MS/MS scans. The nPES platform was constructed by filling sample wells with plasma sample or cell culture EV samples, followed by incubation and being washed three times with PBST and three times with PBS.Ã The sample wells were then filled with AuS and AuR PBST solution, and were incubated and washed three times each with PBST and PBS, respectively.Ã The sample wells were fitted with a cover slip and dark-field microscopy (DFM) was used for imaging.Ã The DFM images, that had image areas with brightness equal to 225 were selected, and the ratio of the image area to the whole image gave area ratios that were indicative to the nPES EV signal.1 A standard concentration curve was generated with a linear regression of nPES area ratio with log10 concentrations.1 SEM images analysed the images of GNP binding to EV, from EVs that were purified from human plasma.Ã The purified EVs were hybridized with anti-CD63-AuS and anti-CD9-AuR.Ã The SEM fields were analysed to calculate the total EVs, as well as the number of GNP-bound EVs per um2 of each assay. Proteomics and the Early Detection of PC An nPES was previously designed, for EV detection using GNP, that can scatter light at different wavelengths indicative to their shape and size.Ã Using both gold nanospheres (AuS) as well as gold nanorods (AuR), a plasmon is formed, increasing the scattering intensity.Ã With the plasmon, antibodies against CD9, CD81, and CD63 can capture and detect EV in a sample.1,7Ã AuS and AuR are detectable using dark field microscopy (DFM), and will form the complexes AuS-EV-AuR, AuS-EV and AuR-EV.Ã These complexes can be analysed using scanning electronic microscopy (SEM), examining the binding and distribution.Ã Following the pure preparation of EV samples, EV plasma was added to give the EV plasma standard.Ã The anti CD81 was incubated with the standard and two antibodies conjugated GNPs, AuS-Anti-CD63 and AuR-Anti-CD9, which exhibited ratios >0.35%.Ã A comparison was done with nPES and enzyme linked immunosorbent assay (ELISA), of the sensitivity and linearity of thei r EV values.Ã The nPES assays showed to be highly sensitive, requiring less plasma as well has exhibiting more advantages over ELISA in regards to measuring EV concentrations.1 Since CA19-9 is the only accepted pancreatic cancer marker that is not valid, pancreatic cancer derived EV marker is a more feasible biomarker due to the multiple factors that the pancreatic cancer cells express.Ã The nPES assay will quantitate tumour derived EV from blood samples, and one of the two EV specific GNP were replaced with one specific for the membrane protein.Ã LC-MS/MS proteomics, bioinformatics is used to identify trans-membrane proteins on EV PC (PANC-1 and MIAPaCa-2) and PDAC (BxPC-3).1 There were 128 membrane proteins identified, and 26 were expressed on EV.Ã The EphA2 showed the highest expression and is associated with cancer progression, metastasis, and prognosis.Ã The EphA2, was also not expressed by EV in HPNE. EphA2 was chosen as the potential marker, and CD81 and CD9 were chosen for EV capture.Ã The nPES was modified, using one capture antibody (anti-CD81) and two antibody-conjugated GNP probes (anti-EphA2-AuS and anti-CD9-AuR).1 The plasma EphA2-EV levels were higher in pancreatic cancer patients, in comparison to pancreatitis patients and the normal control (NC).Ã With the strong association between the circulating EphA2-EV and early stage pancreatic cancer, there is potential for EphA2-EV to be used as an early detection marker.1Ã The CA19-9 levels were increased in the pancreatic cancer patients in comparison to the pancreatitis patients and the NC, but the levels were not increased in the early stages of PC.Ã The receiver operating characteristic (ROC) curves, showed that the plasma EphA2-EV levels are promising in the classification of pancreatic cancer stages. The current EV analysis methods are tedious and lengthy for the isolation procedures, as will having volume requirements.Ã The nPES platform that has been studied, assimilates EV capture and detection with the use of the plasmon coupling effect, to have an increase in both detection sensitivity and specificity in small volume samples and fast sensitive biomarker quantification.Ã This EV nPES platform, can be generalizable for any disease state that has a specific EV marker.1Ã Ã The nPES EphA2-EV blood assay shows substantial value regarding pancreatic cancer screening tests, due to being a rapid, accurate and non-invasive blood test for the early diagnosis of pancreatic cancer. Conclusions This review article explains the need to find a valid biomarker in the early detection of pancreatic cancer, as well as discussing how exosomes have potential to be that marker in the early detection process.1,2,4,6,7,8Ã The existing biomarkers for pancreatic cancer, are not valid markers in the early detection due to the lack of sensitivity and specificity that they exhibit when differentiating between benign and malignant stages.Ã The use of exosomes for the early detection of pancreatic cancer, shows potential as a biomarker, with the use of nPES platform.1 The platform allows for EV capture using plasmon coupling, which increases in detection sensitivity and specificity, which allows for the discovery of an ultrasensitive biomarker.Ã The nPES EphA2-EV assay could differentiate between pancreatic cancer patients (stage I and II) and pancreatitis and NC patients.1 The role of EphA2-EV, could help to improve early detection rates as well as improving patient outcome, and th is blood test is inexpensive, accurate and non-invasive.Ã This review involved proteomic and quantitative methods, to find a novel biomarker for the early detection of pancreatic cancer, and non-invasive nPES EphA2-EV analysis can aid in improving early pancreatic cancer detection and treatment. References Liang, K.; Liu, F.; Fan, J.; Sun, D.; Liu, C.; Lyon, C. J.; Bernard, D. W.; Li, Y.; Yokoi, K.; Katz, M. H.; Koay, E. J.; Zhao, Z.; Hu, Y. Nature Biomedical Engineering 2017, 1 (0021). Duxbury, M. S.; Ito, H.; Zinner, M. J.; Ashley, S. W.; Whang, E. E. Biochemical and Biophysical Research Communications 2004, 320 (4), 1096-1102. Jazieh, K. A.; Foote, M. B.; Diaz, L. A. Seminars in Radiation Oncology 2014, 24 (2), 67-76. Ansuini, H.; Meola, A.; Gunes, Z.; Paradisi, V.; Pezzanera, M.; Acali, S.; Santini, C.; Luzzago, A.; Mori, F.; Lazzaro, D.; Ciliberto, G.; Nicosia, A.; Monica, N. L.; Vitelli, A. Journal of Oncology 2009, 2009, 1-10. Ballehaninna, U. K.; Chamberlain, R. S. Tumor Biology 2013, 34 (6), 3279-3292. Melo, S. A.; Luecke, L. B.; Kahlert, C.; Fernandez, A. F.; Gammon, S. T.; Kaye, J.; Lebleu, V. S.; Mittendorf, E. A.; Weitz, J.; Rahbari, N.; Reissfelder, C.; Pilarsky, C.; Fraga, M. F.; Piwnica-Worms, D.; Kalluri, R. Nature 2015, 523 (7559), 177-182. Roma-Rodrigues, C.; Raposo, L.; Cabral, R.; Paradinha, F.; Baptista, P.; Fernandes, A. International Journal of Molecular Sciences 2017, 18 (1), 162. Kalra, H.; Adda, C. G.; Liem, M.; Ang, C.-S.; Mechler, A.; Simpson, R. J.; Hulett, M. D.; Mathivanan, S. Proteomics 2013, 13 (22), 3354-3364. Ballehaninna, U. K.; Chamberlain, R. S. Indian Journal of Surgical Oncology 2011, 2 (2), 88-100. Pancreatic Cancer https://www.cancer.org/cancer/pancreatic-cancer.html (accessed Mar 20, 2017). Eldorado by Edgar Allan Poe | Analysis Eldorado by Edgar Allan Poe | Analysis In the poem Eldorado, poet Edgar Allan Poe delivers a fundamental message that can be understood if carefully evaluated. Poe gives the account of a knight in search of a land called Eldorado, which holds riches and fortune. After much futile searching, the knights enthusiastic quest for treasure ends in death. The foremost theme of this poem is the desire for wealth and treasure. This theme is an influence from Poes life and the relevant Gold Rush of 1849 (Coad 60). The literary devices, symbols, relevancy, and personal experiences offer a deeper meaning to the poem than what lies on the surface. Poes skillful use of these elements helps to stress the ignorant desire humans have for wealth and fortune. The poem delivers a reflective moral issue many readers can, in some way or another, relate to. Poe uses the word shadow in each of the four stanzas of the poem, each stanza consisting of six lines. The third line in each stanza is where the use of the word shadow is introduced. Though the word occurs multiple times, it has a different meaning each time. The first shadow represents a literal shadow, a casting shadow of the sun. It could also be interpreted as happiness and sadness. The second shadow represents the shadow that has overcome the knights heart after much unsuccessful searching. The third shadow represents a live figure, possibly his or maybe an angel. And the fourth shadow figuratively refers to Valley of the Shadow (21). The fact the knight has grown old and weak, and must cross Over the Mountains Of the Moon, Down the Valley of the Shadow is seen as a symbol of the knights death, relating to the Biblical valley of death (19-21). Through Poes use of the word shadow and the period in which the poem was written, readers can understand Poes message. Poe uses the shadow in each stanza to convey his message. As the meaning of the shadow changes, so do readers emotional state. As he begins the first stanza, readers see a happy, gaily, bedighted knight who is enthusiastic about going on his search for gold. This start gives readers a sense of happiness and jolt of energy. His shadow could also be a foreshadowing of future events. However, Poe begins the second stanza with the word But. This contradictory word signals a shift between the first and second stanza and also a shift in emotion. The knight has become old, disheartened, and dismayed as the shadow is used in context to signal the emotional state of the knight. This signal causes readers to suddenly have a change in emotion; readers become sympathetic towards the knight. Poe continues to elaborate on the disappointment of the knight in stanza three. The knight encounters a live or possibly imaginative figure and asks the shadow where is Eldorado, reflecting on his hopeless jo urney in which he wasted his life. This figure could possibly be an angel providing guidance, an angel of death, or even himself. As the shadow replies to the question in stanza 4, readers are left with the idea that he has come to the end of his life and has died. With the closing of the poem, the audience can relate to the pain the knight feels. In all, the repetitive shadow becomes engraved in the readers mind, helping to sway the emotions. The life of the knight also provides a moral for people to learn. Poes moral in Eldorado is not to seek for riches on earth. The only true riches are the riches one receives after death. The knight in the poem seeks for physical riches for many years without any hope, leaving him disheartened and at the end of his life. When asked where Eldorado could be, the knight was told Down the Valley of the Shadow (21). This insinuation emphasizes the main point that true riches are found in Heaven, not earth, and any riches sought on earth leads to despair and death. As suggested by The Meaning of Poes Eldorado by the John Hopkins University Press, it can be argued Poe portrayed himself as the knight (Coad 60). Poe published his poem in 1849, the same year as his death. Like the knight, Poe had sought after an accomplished life, which he failed to do during his life. He was also unstable in the last years of his life. However, the knight most probably was a reference to the many prospectors of the California Gold Rush, which took place during the time the poem was written. The poem may have been Poes warning to the many prospectors that would experience the same hardships of the knight. Poes repetition of shadow and Eldorado and use of other symbols play an important part in his poem. It helps to further stress his main point. Other such devices Poe uses to communicate to his audience is through auditory and imagery senses. Poe uses aabccb rhyme scheme in the first three stanzas and xxabba rhyme scheme in the fourth stanza of his poem . Poes creatively written stressed and unstressed poem is one way Poe remarkably appeals to the readers auditory and imagery senses. The use of this rhyme scheme creates a thumpity, thump sound when read aloud, bringing the clattering of the horses trot to life. The symbols and rhyme scheme helps to immerse the reader into the scene of the poem and drives them to continue reading until the end. Eldorado is a poem by Edgar Allan Poe that has a stressed message to readers. It tells the story of a knight who traveled for a period of his life searching for a city of gold, Eldorado. It provides a message to all readers that true riches and happiness are only acquired through Heaven after death. If one attempts to search for wealth, in hopes happiness will follow, that person will come to the end of their life saddened and in despair. Poes use of symbols, rhyme scheme, and repetition brings life to his poem, which keeps the readers entertained and helps to convey his message. The poem brings light to the life of everyone and anyone searching for happiness and wealth on earth. Thus, Eldorado is Over the Mountains Of the Moon, Down the Valley of the Shadow, Ride, boldly ride . . . If you seek for Eldorado! (19-24).
Friday, October 25, 2019
Frankenstein Notes :: essays papers
Frankenstein Notes Observations: 1. We commonly refer to the enormous monster as ââ¬Å"Frankensteinâ⬠, when in fact he was never given a name. 2. Many references are made throughout the story to other famous literary works, such as Miltonââ¬â¢s, Paradise Lost and Coleridgeââ¬â¢s, The Rime of the Ancient Mariner. 3. Victor is a seeker of knowledge; he seeks answers to what occurs in nature and the physical world. 4. Upon his arrival at the University, Victor puts all his time and energy into his studies; he even disregards his health and family. 5. Many gothic elements of the grotesque are found throughout this book. 6. The environment of the book is described as dark and eerie. 7. After the creation of his monster, Victor suffers a so-called ââ¬Å"living tortureâ⬠for the consequences of his actions. 8. The weather plays a big role in setting the overall tone of the book. 9. The idea that man is born good, but it is society and other pressures that create an evil in man is relevant and part of the romantic theme depicted in the story. 10. The central concern of the novel is the basic need for companionship. Humans seek other individuals for their mate, in which they can share a life-long relationship together. Vocabulary: 1. capacious: able to contain or hold much; roomy; spacious. 2. paroxysm: a sudden outburst as of laughter, rage, or sneezing; fit; spasm. 3. chamois: a small goat antelope of the mountains of Europe. 4. galvanism: electricity produced by a chemical reaction. 5. chimera: an impossible or foolish fancy. 6. dogmatism: dogmatic assertion of opinion, usually without reference to evidence. 7. lassitude: state or feeling of being tired and listless; weariness; languor. 8. mien: a way of carrying and conducting oneself; manner. 9. ignominy: loss of oneââ¬â¢s reputation; shame and dishonor; infamy. 10. aiguilles: a peak of rock shaped like a needle. 11. hovel: a small shed for sheltering animals or storing supplies. 12. offalââ¬â¢s: refuse; garbage. 13. viands: food of various kinds; especially choice dishes. 14. vestige: a trace, mark, or sign of something that once existed but has disappeared. 1. Robert Walton is the narrator of the novel. The time period in which the story is told is in the 1800ââ¬â¢s. 2. The characters of the story are Victor Frankenstein, the ââ¬Å"monsterâ⬠, Robert Walton, Alphonse, Caroline, Ernest, and William Frankenstein, Elizabeth Lavenza, Justine Mortiz, Henry Clerval, M. Krempe, M. Waldman, M. De Lacy, Felix De Lacy, Agatha De Lacy, Safie, Mr. Kirwin, and Margaret Saville. 3. The setting takes place in Europe. 4. The general themes of the novel are use of knowledge for good and evil purposes, the use of new technology in modern life, the treatment of the poor and uneducated, and the powers of nature and the human physiology.
Thursday, October 24, 2019
All we need is love
All we need is love Love is a very deep feeling that goes with us in our life. Without love there is no true life and no meaning of life. From the moment we are born we are surrounded with love of our parents and other relatives and we love them back. First we love our mother ââ¬â the first person we see in our life. You may say that in our babyhood it is an unconscious feeling, it is an instinct, but nevertheless it is true innocent love and affection. As we start sense the world we start feel love to father and other close people.We take and give this love s self-evident and can't even imagine our life without these people. Growing older we experience first love to somebody in kindergarten or at school. It is always pretty to kick at the little children attracted to each other. And it is a wonderful moment to realize that you are in love for the first time. In childhood and also in our adult life we also love our pets ââ¬â cats, dogs, goldfish, tortoises etc. Our pets can a lways make us kind and happy. Have never understood people who don't love animals, and I am sure that every child should have a puppy or a kitten.Besides, care of domestic animals helps to bring up a conscious, responsible, attentive person. In our mature love we may love some persons, and we are very lucky if there is somebody who loves us back. Sure there can't always be mutual love, and we can't make somebody to love us as we do. But when we feel it, the world seems wonderful. Without a doubt love makes us stronger, happier, and more motivated. We get desire to become better for the person we are in love with, and to make good deeds. Love inspires everybody. Many poets, writers, artists, composers devoted heir works to beloved persons.If there was no love in our life there will be no outstanding works of art known all over the world. Sure it is a hard job to love someone, in spite of his/her imperfections, and the marriage build on love is the strongest. A person who does not lov e cannot be happy. He is usually grumpy, nervous, and strict. He cannot understand those who are experience this feeling. Feel sorry to such people because love is the most beautiful thing that can happen. I wish everyone to feel it, and I hope you and your close people love each other, and this love Will last forever.
Wednesday, October 23, 2019
Media: Celebrities
Coming from a Latin word celeber, the word celebrity means a person widely recognised by the public and the media, person who through his command in the public creates media attention and is widely covered. One of prerequisite of a person being celebrity is fame, but that has to be associated with the media attention. Mass communication play a vital role in making someone celebrity as the person can be famous and well known but if the media is not piqued by that person, then the person cannot reach the celebrity level.People become celebrities in accordance to their professions, what they do to the public; this can be politicians or Chief Executive Officer (CEO) of certain large organisations such as Bill Gates, who stepped out of it few months ago, but still a celebrity. Celebrities to be in that status with the help of media are being known across the world, meaning can be famous not only in their countries but even outside their countries, and this category caters especially to th e politicians and actors and actresses.Religious leaders example Bishop Desmond Tutu for his involvement in freedom fight in South Africa and cultural leaders such as Dalai Lama of China for his outstanding performance in fighting for the rights of Tibet people; these people can be famous not only in their countries but not abroad due to their extensive coverage in the media. Excellence in sports also can make people famous not only in their countries but even worldwide such as Serena and Venus Williams are known globally due to their excellent performance in Tennis sport.Apart from sports, some people become celebrated due to their nature of their professions especially the highly paid ones which make them in contact with the media in most of their work schedules. These include people in the media presenters who are highly paid and well respected due to their exceptional work to the public, interior decorators, movie producers and sports coaches to mention a few who have caught the media attention and have been covered in mass entertainment.Some people become celebrities due to their family backgrounds, especially if some member of family were and are celebrities. This is found mostly in families engaged in music and movies industries like Jacksons, Winans and Osbournes while for politician families we can say Bushes, Clinton and Kennedys in United States of America (USA).Nevertheless, in accordance with the definition of celebrity that is something that has to be commanded by a person both in public and through the media, most of people must asking themselves how these people have earned the celebrity title. Due to this some scholars did start studying this celebrity phenomenon, by looking at the celebrity characteristics, psychology and even the interaction with the members of public, which makes people sometimes get too carried away with the celebrity worship. In America the number of people worshipping celebrities keeps on going up which has even affected people psychologically. Famously the syndrome now is known as celebrity-worship syndrome (CWS), the term invented by media but psychologists call it Celebrity Worship Scale (WCS).This situation has made people to look closely to the whole issue of celebrity, its attachment with the society and how people are reacting to it. Why people acting they way they do to the point of stalking celebrities. In survey conducted in USA, more people are affected by CWS which has led to people seek psychological help as Kate Douglas portrayed in her article when you wish upon a star, ââ¬Å"Psychologists are starting to suspect that worshipping celebrities is the top of a slippery slope that leads to depression, anxiety and psychosis.â⬠(Douglas Kate, When you wish upon a star, 2003).The effect is not only to the celebrities themselves, but the public also get affected by the whole issue of celebrity. Most of people wishing to be stars so as to be treated like star especially due to the media coverage these people get. Studying celebrity academically can help the society understand both parts that means celebrities themselves and the public which is affected by the concept of celebrity.The effect is much grave especially to the adolescents who spend most of their time wishing to be star, having cuttings and pictures of stars in their rooms and things they possess. Yes teenagers can think about celebrities as it is bring sense of social attachment, but not that excessively which affect the way of thinking of these teenagers or even adult for that matter which sometimes experience difficulties when encountered with problems.The effect if not dealt with early leads to more effects such as disorder to the worshipers like stalking celebrities or disillusion stalker gets that celebrity is love with him/her. The situation apart from stalking stars and celebrities, some of fans are copying what these celebrities are doing even if are bad things. This condition has sparked a lot of academics into researching the issue of celebrity and looking deeply for its effects to the society.An example that can be used here is the case of John Warnock Hinckley, Jr. who stalked Judie Foster after watching the Taxi Driver movie. He was seeking Judieââ¬â¢s attention to the point of following her to another state, the situation led into Hinckley attempting to assassinate President Ronald Regan in 1981 so as to catch Judieââ¬â¢s attention. He was later charged but found not guilty on basis of insanity and admitted at Saint Elizabeth in Washington DC. With experience like this studying celebrity should be taken into account as to understand psychological effects that associate with celebrities.The effect does not end to the fans only, but celebrities too are affected by the whole idea of being celebrity. Celebrities sometimes are also affected with the way society take them, their image and sometimes they are supposed to do things which is not in their heart simply be cause they have to comply with public especially in maintaining good image. The good image does not necessarily be the star image but sometimes can be the image of the organisations they are representing. This notion tend to make celebrities pretend sometimes especially in front of members of media and photographers.In his book The Image (1961), historian Daniel Boorstin criticised the way American society was living where it was heading concerning public image. The image that keeps on being fabricated and staged by the influential people especially politicians, movie stars and other celebrities. ââ¬Å"Just as there were now counterfeit events, so, he said, there were also counterfeit people ââ¬â celebrities ââ¬â whose identities were being staged and scripted, to create illusions that often had no relationship to any underlying reality.â⬠(Boorstin Daniel, The Image, 1961). The tendency, which has forced some of celebrities to get depressed and frustrated, hence seeki ng medical help which has led to some psychologists researching into the matter.The good example here can be referred to an icon which has made history in Hollywood, Marilyn Monroe who died by overdose from drugs. Marilyn was under chronic depression which made be constant contact with psychologists but later she paid with her life. Though not most of celebrities in movie industry die by overdosing themselves, but most of them undergo depression, which later on lead into drug addictions.Not only movie superstars experience the other side of the coin, which is depression even politicians and other celebrities do. The good example being Abraham Lincoln (1809-1865), the President of America in 1800s has also underwent severe depression too which was claimed to be associated with a horse blow he got when he was 10 years of age, while it sometimes associated with the death of his first love and mother. The only therapy in those days was through churches in Christian moral treatment but L incoln managed to overcome his depression by engaging himself in politics which later on he become a well respected one.Despite the fact that movie icons get into addictions, not all celebrities are like that as there is difference between these two categories. Film star is the one that get his/her stardom due to the participation in movie industry but celebrities can be from any field apart from film industry. Taking examples of film stars the list is long from Tom Cruise, Will Smith, Judie Foster, Meg Ryan and Nicholas Cage to mention a few.In conclusion, it is worthy studying celebrity issues, as it is the only way of understanding the interactions between celebrities and their surroundings, the people they mingle with, how they maintain their personalities and images to the public. Many celebrities are being used to advertise products such as David Beckham, Roberto Carlos and others like Christina Aguilera in Pepsi advert. This advertising involves media and through that people tend to question the authenticity of the products displayed, hence lead to more research on them.Apart from advertisements, studies can be done to the people around celebrities, how are they interacting with them and what effects do they get, but all in all it is worthy a study.Reference:Boorstin Daniel, The Image: A Guide to Pseudo-Events in America, 1961Douglas Kate, When you wish upon a star, Newscientist, issue 2408, August 2003www.mindhacks.com/blog/2006/08/star_struck.html
Tuesday, October 22, 2019
Love Story Essays
Love Story Essays Love Story Essay Love Story Essay John and Mary was so love in each other, Mary never knew that John would change her life so much, since she got in love with him. They were like Romeo and Julie together. For every day that goes, their love gets bigger and bigger, they came so closer to each other. Every day and night, they spent their time together; there was not a single day when they were not together. They could not live without each other. John was so romantic to Mary, he spoils her with flowers and chocolates, he gave her the love that no one else was been able to give.They had been together for more than 3 years. John and Mary graduates at the same time, and then they bought together a very big house, they was happy together. Their love was so strong; there was nothing that could separate them. One day John and Mary invited their both parents on a dinner. That night every one of them was happy, they was having a good night all of them. They was dancing and singing all together. John and Maryââ¬â¢s parents w ere so happy for their children.They were always wishing for them to married one day. Suddenly John stood up, and and held a speech to Mary, he told how much he loved her. Suddenly he stood up and held a speech to Mary; he told how much he loved her. John knelt for Mary, and came up with the most beautiful diamante, and so he asked Mary if Mary wants to marry him. Mary says yes, and then they live a happily life. To ââ¬â delt eksamen. Lydside- BilledE- Ideudvikling- klipning-Casting .
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