Genetic mapping Research Paper Example | Topics and Well Written Essays - 1250 words

Genetic mapping - Research Paper Example The dawn of modern genetics began with the unveiling of Mendel’s rules and Mendel’s paper in 1900. The term gene was first used in 1909; the first experiment on genetic mapping was published in 1910; and the first genetic map was materialized in 1913 (Kevles & Hood, 1992, p. 38). Thomas Hunt Morgan was the first person to elucidate the techniques of genetic mapping with his discovery of the X chromosome--the decisive sex gene, in 1910 (Kevles & Hood, 1992, pp. 43-44). In 1911, Morgan’s student, Alfred Sturtevant, mapped the location of the gene mutations that were studied by his esteemed professor (â€Å"Overview of the Human,† 2010). The initial blueprint of the human genome was broadcasted on February 2001 in the journal Nature; which showed the progression of the genome’s 3 billion base pairs. The completed gene arrangement was published in April 2003 (â€Å"Overview of the Human,† 2010). Future employment of the project in the field of mo lecular medicine includes: refined disease diagnosis; early identification of predisposition and disease process; objective drug design; gene therapy; and custom drugs (â€Å"Potential Benefits,† 2009). ... genes to develop alternative energy source, to create pollutant-detectors present in the environment, to prevent carbon emission that worsens global warming; for risk assessment; for information on the origin of species; for fast absolution of crime; and for agricultural purposes (â€Å"Potential Benefits,† 2009). On the down side, gene mapping can create an air of animosity, injustice, and abuse on the part of the gene-owner (Narcisse, 1998); it can induce a feeling of apprehension and disappointment; and it will implicate not only the tested individual, but the family as well. Apart from the aforementioned disadvantages, gene mapping is also contravened by many issues; among which are issues on information confidentiality, psychological effects, reproductive and clinical issues, conceptual and philosophical implications, health and environmental issues, commercialization of products, and other uncertainties, such as the causative agent for complex conditions (e.g. heart dise ase) (â€Å"Ethical, Legal, and Social Issues,† 2008). Information acquired through gene mapping, is presumptive and not prognostic (Rajeski, n.d., para. 3). It aids in the identification of gene mutation, insertion, and deletion that may or may not result in a disease. According to Claes et al. (2004), awareness of innate gene mutations can empower, as well as impose adverse emotional effects and feelings of distress. Knowledge of what could be can greatly alter the way an individual perceives the future and live one’s life. Some of the principles foreseen to be offended by the human genome project are autonomy, nonmaleficence, beneficence, justice, veracity, and fidelity (Daniels, 2004, p. 168). Easy access to the human genome database can violate a person’s right to autonomy. Confidentiality

Negotiating a Disciplinary Procedure Essay Example | Topics and Well Written Essays - 1250 words

Negotiating a Disciplinary Procedure - Essay Example According to the paper, alleged inadequacies of performance, which include proficiency and competence as set out in the Unfair Dismissal Act 1977 and conduct are grounds for punitive action, meaning that the disciplinary procedure may be initiated and that a sanction may follow if the case against the employee is found to have substance. It should be noted that minor instances are normally dealt with informally for a â€Å"ticking-off â€Å"incident for an isolated incident of lateness for example and this is because they will not require numerous procedures in coming to a decision. There is an obligation under section 14 of the Unfair Dismissal Act 1977 that within 13 weeks of starting employment in any organization, the employees must be given the procedure and rules used for disciplining or dismissing them from the workplace. Such procedures may be contained within a collective agreement, which is normally after a negotiation between the employer and employee or be established b y custom and practice. Other than this, there is no formal guidance on what the procedure should contain: the Act is silent, and currently there is no code of practice on the subject, although there is an area where the Labor Relations Commissions may take action. The guidance that is not provided for comes from decisions of the Employment Appeals Tribunal, which stipulates the rules of engagement. Conveying a clear punitive policy is important to define workplace expectations and the methods the employer will use in correcting behavior that is not in line with the organizational standards. This ensures that all employees are aware and adhere to the code of conduct in the organization failure to which they face sanctions or the disciplinary actions that the misconduct accrues.

Penalties and Offences in Tax Essay Example for Free

Penalties and Offences in Tax Essay In understanding the context of penalties and offences in Self-Assessment System, we first need to understand the overall meaning of Self-Assessment System. Self-Assessment System is based on the concept Pay, Self Assess and File. Whereby, Pay stands for monthly salary deductions are made for the individuals who are having an employment income or also for the individuals who are having business income through installments. The Self assess stands whereby the taxpayers are responsible in computing their own taxes. And the file stands for the Income Tax Revenue Form (ITRF) where it will be submitted to the Inland Revenue Board Malaysia together with the payment for the balance of the income tax payable where it is to meet any shortfall in the monthly payments or maybe a claim for a repayment, in case if there is an overpayment. Self-Assessment System (SAS) is being practiced in some developed countries such as United States, United Kingdom, Australia, Japan and The Organization for Economic Co-operation and Development (OECD) Countries as a group. There are some other developing countries also practicing Self-Assessment System such as Cambodia, Sri Lanka and also Malaysia. As we realize that the central motivations of the Self-Assessment System is being introduced is to increase the efficiency of tax collection for the tax authority. But yet there are some broad groups whereby they offences against the Act, filling inaccurate returns and providing incorrect information, fraud and willful evasion. This leads to the introduction of penalty and offences provision under Income Tax Act. There are few penalties for each offence under Income Tax Act. All the provision of penalties does helps to ensure the proper compliance by the taxpayers with the tax laws. But how does it ensure the proper compliance. First of all, all the taxpayers are responsible in submitting their income tax for every year assessment. In a way, by submitting their income tax for every year, influence directly where it helps the country to increase its revenue. Income tax is a major source of revenue to a country which it is required to pay for schools buildings and maintenance of schools and hospitals, rural development and other multifarious services which directly and indirectly benefits the publics. Therefore, a development of a country is depends on the residents. If a taxpayer fail to furnish return or give notice of chargeability will be liable under Section 112 (1) of the Income Tax Act which explains that any person who fail to furnish the return without any reasonable excuse, be guilty of an offence and shall be liable to a fine of not less than RM 200 and not more than RM 2,000 or to imprisonment for a term which not exceeding six months or to both. As this offence will slow down the countries tax administration cycle. The provision for penalties and offences ensures the taxpayer to avoid submitting the incorrect return. In Section 113(1) under Income Tax Act explains that any person who makes an incorrect return by omitting, understating any income or gives any incorrect information where in relation to any matter affects his own chargeability to tax or any other person. As stated in the law, the taxpayers who have submitted an incorrect return will be liable to a fine of not less than RM 1,000 and not more than RM 10,000 and also shall pay a special penalty of double the amount of tax that has been undercharged in the consequence of the incorrect return or for incorrect information and no imprisonment. Those penalties will be a courage for the taxpayers for not to submit an incorrect return or incorrect information. This is because those penalties are an extra burden for the taxpayers. Providing an incorrect return and incorrect information will also burden the IRB, for them to come with a report for the year. Therefore as a resident of Malaysia, we should avoid ourselves from submitting an incorrect return and incorrect information to the IRB. Thus, we also have to play a part in developing our country. The higher is the penalty rate the greater the discouragement for potential tax evasion. There was a few studies has been carried out, and they summarized that penalty rates impact upon tax compliance behavior. When the taxpayers are aware of the offences that they are committing when evading tax and the consequences of being a non-compliant taxpayers, therefore they might reduce their tendency to evade tax. As stated in Section 114 (1) Malaysian Income Tax Act, which explains that any person who willfully and with intent to evade or assist any other person to evade tax, will be liable to a fine of not less than RM 1,000 and not more than RM 20,000 or to imprisonment for a term which is not exceeding 3 years or to both, and also shall pay a special penalty of treble the amount of tax uncharged. This section in the act, seems to be a big burden for those who willful the evasion. The awareness of the penalties for the offences, will help the taxpayers to not against the laws and always ensures the proper compliances. In conclusion, the provision for penalties and offences under the Malaysian Income Tax Act 1965 help to ensures proper compliance by taxpayers with tax laws. Imposing the penalties is the most effective way to ensure the proper compliance. The taxpayers must be co-operative, well-mannered, fair, and honest with high integrity. They should also provide all reasonable facilities and assistance to enable the audit office to carry out his duties as it has outlined in Public Ruling No. 7/2000.

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.   The GNP will inhibit the cancer cell, and will stop tumour growth and production.   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%.   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.   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.   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.   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.   In regards to analysing exosomes as a potential biomarker, exosomes need to purified and isolated with differential centrifugation paired with ultracentrifugation (UC).   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.   With the size of the exosomes ranging from 40 100 nm, they are distinguished for tumour microenvironment.   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.   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.   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.   The 2 nanoparticle probes, will produce a plasmon, promoting an increase in sensitivity and specificity for the discovery of an exosomal biomarker.   Ephrin type A receptor 2 (EphA2), has recently been identified as a biomarker, of the tumour derived pancreatic cell line, and enriched on EV.1   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.   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.   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.   Levels of CEA can be elevated due to smoking, as well as in other diseases such as Crohns disease.   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.   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.   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.3   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.3   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.   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.   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.   Recent studies suggest, that exosomes can be detected in body fluid such as blood, and they have potential as disease biomarkers.   Exosomes, found in blood plasma, need to be collected from healthy patients to obtain individual and pooled samples.   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.   The sample will be differentially centrifuged, to eradicate cell debris, which is followed by UC.   The subsequent pellet, is washed in PBS, and filtered, and the filtrate was ultracentrifuged.   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.   The supernant is filtered, and the filtrate will be incubated using a blocking agent.   A microcolumn was placed in magnetic separators, where the column was rinsed with rinsing solution.   Beads were bound to the exosome, and were applied to the magnetic column.   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.   The exosome bound microbeads are washed to elute the exosomes, and centrifuged to obtain the exosomal pellet.   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.   To the top of the tube, there were 12 fractions, with increasing densities.   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.   Gel electrophoresis is used to separate and identify the different proteins.   The thickness of the band, indicates the amount of the protein that is present.   There is a labelled antibody, that is bound to the protein of interest.   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.   Transmission electron microscopy (TEM) and atomic force microscopy (AFM), were used on the isolated exomes, from the three exosomal isolation techniques.   In the DG sample, the TEM reported homogeneous vesicle, with diameter ranging from 40 100 nm, confirming the characteristics of exosomes.   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.   The first quadrupole is for the selection of the precursor and the second quadrupole is highly specific for detection.   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.   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.   The LC-MS/MS spectra are searched against the human protein database using MASCOT.   Equal amounts of protein from the three exosomal samples were separated, reduced, alkylated and digested with trypsin.   The DG sample had the highest number of protein identifications, followed by the UC isolation method.   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.   The formation of malicious exosomes, also starts in the endosomal pathway.   The early exosome is formed from the migration from the cell periphery to the nucleus, by the formation of intraluminal vesicles (ILV).   The process interceded by exosomal complexes required for transport (ESCRT) and other proteins.   Late exosomes/ MVB, migrate to the periphery and fuse with the membrane, releasing the ILV, which are called exosomes.   The proteins, Rab GTPases, mediate the endosome migration.7 The malicious exosomes, are released from cancer cells found in the tumour microenvironment.   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.   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.   These nanoparticles exhibit intense light absorption and scattering, and they are deemed to be highly stable.1,7   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.   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.7   Using antibodies to aim at the exosome for capture and selective retention.   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.   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.   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.   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.1   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.   The culture supernatants were collected and centrifuged to pellet cells, and centrifuged again to remove cell debris.   Concentrated with centrifugal filtering units, and centrifuged, the precipitates were collected and resuspended in PBS and centrifuged.   The resulting precipitates were collected and dissolved in PBS.   The ELISA assay, consisted of ninety-six well plates, which were incubated with antibody CD81.   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.   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.   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.   The sample wells were fitted with a cover slip and dark-field microscopy (DFM) was used for imaging.   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.   The purified EVs were hybridized with anti-CD63-AuS and anti-CD9-AuR.   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.   Using both gold nanospheres (AuS) as well as gold nanorods (AuR), a plasmon is formed, increasing the scattering intensity.   With the plasmon, antibodies against CD9, CD81, and CD63 can capture and detect EV in a sample.1,7   AuS and AuR are detectable using dark field microscopy (DFM), and will form the complexes AuS-EV-AuR, AuS-EV and AuR-EV.   These complexes can be analysed using scanning electronic microscopy (SEM), examining the binding and distribution.   Following the pure preparation of EV samples, EV plasma was added to give the EV plasma standard.   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%.   A comparison was done with nPES and enzyme linked immunosorbent assay (ELISA), of the sensitivity and linearity of thei r EV values.   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.   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.   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.   The EphA2 showed the highest expression and is associated with cancer progression, metastasis, and prognosis.   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.   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).   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.1   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.   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.   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.   This EV nPES platform, can be generalizable for any disease state that has a specific EV marker.1  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.1,2,4,6,7,8   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.   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.   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.   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).

The Transcontinental Railroad Essay -- Transportation, Railroad Compa

The Transcontinental railroad could be defined as the most monumental change in America in the 19th century. The railroad played a significant role in westward expansion and on the growth and development of the American economy (Gillon p.653). However, the construction of the transcontinental railroad may not have occurred if not for the generous support of the federal government. The federal government provided land grants and financial subsidies to railroad companies to ensure the construction. The transcontinental railroad contributed to the formation of industry and the market economy in America and forever altered the American lifestyle. The Pacific Railroad bill of 1862 launched the transcontinental railroad construction project. The Pacific Railroad bill granted 6,400 acres of public lands and government loans ranging from $16,000 to $48,000 per mile of track completed to the Union Pacific Railroad and Central Pacific Railroad companies. (Pacific Railroad Bill) Following the Pacific Railroad bill a series of federal and state acts between 1862 and 1871 granted more than 130 million acres of public land and supplied additional monetary loans of approximately $150 million dollars to the expansion of the railroads. (Gillon p.652) There is no refuting that the railroad companies transformed business operations and encouraged industrial expansion. The raw materials required for construction of the transcontinental railroad directly resulted in the expansion of the steel, lumber and stone industries. (Gillon p.652) The railroad stimulated growth in manufacturing and agriculture providing an efficient manner to ship raw materials and products throughout the country. Which in turn, increased consumerism and introduced t... ...ich developed new corporations. (Gillon p.652) Many in the railroad industry and these newly developed corporations were accused of price fixing, providing illegal kick- backs and challenging government regulations. (Gillon p.652-657) Thus, one could argue that the railroad industry and the titans it produced had a monopolistic approach to business that actually challenged the free market system. In the end, the transcontinental railroad changed the American landscape both physically and culturally. It formed the foundation for the industrial economy, it produced new business practices and management style of large workforces. It helped established government regulations, taxation and support of public transportation. Above all it drastically changed the American lifestyle, changed where people lived, how they shopped, how they ate, and how they worked.

Theories addressing learning styles Essay -- essays papers

Theories addressing learning styles There are several different learning styles and theories about approaching them. Some students learn better through one or more of the learning styles than another. As Rita Dunn of St. John’s University says, â€Å"A students best â€Å"modality† for learning may be visual, auditory, or tactile, according to the speakers†(Walton,1991). An auditory learner may learn better through hearing material spoken. A visual learner learns better by reading instructions to himself. And finally, a tactile learner will usually learn most effectively when they are able to use models or things that they can touch or manipulate. Technology supports these three learning styles; auditory, visual and tactile. Animated graphics of computer software support the needs of visual learners. Not just in a regular classroom can children benefit through visual aids, but also in a music classroom. Amy Casey, a former elementary teacher in the Kansas City school district said, â€Å"My exper iences in my own classroom have proven that integrating technology into the music curriculum entices students to actively engage in learning† (2005). Setting up music centers in a classroom allows students to learn to use technology in various ways. Children are able to learn how to read music or learn the piano keys with the use of a computer. Students who excel through auditory learning may use technology so regularly they do not realize how beneficial it is to them. Auditory learners may prefer to listen to a book on tape or sing a song about numbers or multiplication facts. These are all ways to reach out to the auditory learner in a classroom. Technology in the classroom also enhances the skills of tactile learners with the use of a keyboard o... ... from the World Wide Web:http://search.epnet.com Serim, Ferdi. Building Virtual Communties for Professional Development. www.ed.gove/technology/futures/serim.html Schank, Roger. Futureperspective- A vision of Education for the 21st Century. www.thejournal.com/magazine/vault/A2598.cfm www.aten.scps.kl2fl.us www.nces.ed.gov/quicktables/details.asp?key1069 Fine, L. (January, 2002). Writing takes a digital turn for special-needs students. Education Weekly. Retrieved April 22, 2005 from the World Wide Web: https://www.edweek.org/ew/articles/2001/01/30/20wordte ch.h21.html?querystring=assistive%20technology Walton, S. (November, 1991). Experts urge teachers to adapt to students’ learning styles. Education Weekly. Retrieved April 22, 2005 from the World Wide Web: http://www.edweek.org/ewarticles/1991/11/23/20wordtechh21.html

Should College Tuition Be Based on Major

Professor Johnson EC 111H 26 October 2012 The Problem with College Tuition Every year, students wishing to attend college are faced with the steep price that comes with their prospective education. For many, the belief that it will play dividends in the long run is enough reason to pay the high price. However, college majors have a wide variance of starting median salaries, which leads to the question of whether or not tuition should be based on your field of study.Students knowing they will be making less than another student after graduating should not be required to pay the same tuition. College tuition is too high. Since the demand for an education and the supply of schools are both high, cost should be low. What we see, however, are colleges taking advantages of what people see as necessary in todays society, a college degree, and raising the prices in awareness people will pay it no matter what. Keeping the same system we have today will not fix the amount people are paying.Bas ing tuition off majors can change what universities are charging for the better. However, there is the question on what majors you raise. Many argue that the higher paying jobs should receive the increase, while others say the degrees in demand should stay the same or lower, while the other not as important majors deserve the raise. While the concept of basing tuition off majors sounds simple enough, it brings about a number of problems. The first and perhaps biggest problem is that the majors with a higher tuition receive would more funding.This leads to better professors, more resources, and an overall better education. Engineering majors, for example, have the highest average starting salary according to TIME Magazine. If their tuition was increased because of the potential monetary benefit, than the university would have the obligation to focus more on that major than a social work major, who are paid the least on average. Not only could it impact the universities allocation of funds, it could also influence people’s decisions on why they are picking a certain major.In the state of Florida, for example, they are trying to change the state’s public universities change to base tuition off of your major. Their belief is to keep the costs down of the majors that are important to the state. If the state needs more social workers or engineers, then those costs would stay low, while other â€Å"unnecessary† majors tuition is increased. Also, there is again an emphasis in the programs the state needs, meaning the funds of the college are going to the degrees high in demand.If students only focus on what the state sees as important, it could cause a lack of students in other equally important majors. Some argue it is not fair to send a drama major deep into debt and leave an engineering major well of right out of school. However, if it will stimulate the economy and add more jobs, than you can argue putting an emphasis on higher demanded degree s is necessary. Since it is our own tax dollars that they are using at these public institutions, it is in our own interest to have students who will further our economy rather than be unemployed after graduation.On the other hand, The University of Nebraska-Lincoln charges on based on starting exit salary. They charge an extra fifty dollars per credit in their business and engineering programs. They believe that since the programs are more demanding, take more resources to complete, and lead to higher salary If you look at the highest paid majors, you see it dominated by engineering and business degrees. A petroleum engineering major makes on average $98,000 out of college, while an economics degree could earn you $48,500, but $94,000 in the long run.This is attractive to many students, who desire to be making high salaries. With the high salary comes hard work, and the hard work put in is worth more. Engineers, for example, require labs and experiments that cost large amounts of m oney. Doctors have to study in hospitals and take hand on classes that also consumes university budgets. On the other hand, English majors are focused more on their books, which are individually expensive, but don’t cost universities much money.Universities should be obliged to allocate funds into the degrees that benefit them the most. They should not have to put as much money into a degree that does not make them money, as colleges are a business. There is no clear-cut choice on which way this system will work most effectively. It is obvious that both systems have their pros and cons. While one system favors government interest, the other favors university interests. Either way, people will be affective both positively and negatively. The way the state of Florida is approaching this looks stronger.If students who are going to help out the economy are rewarded by lower tuition, they will be more inclined to do so. And the degrees will start to vary, because once the need for doctors is filled, a state could now realize there is a need for economists. Also, if students are aware of what degrees business are most looking for, than there will be a better chance of them being hired straight out of the completion of there degree. College tuition needs to change, and basing it on your major is a great way to start.