Sunday, October 6, 2019

Samsung - Organization Behavior Essay Example | Topics and Well Written Essays - 2000 words

Samsung - Organization Behavior - Essay Example The three dimensions of management are summarized to be technical, conceptual and human.is important for the managers to evolve meaningful solutions and techniques for resolution of complex management problems, by employing innovative technological solutions that provide answers to problems people and organizations are having. For achieving management success, it is important to understand the extent of involvement of human resources needed for the deployment of these resources. COMPANY AND HENRI PRINCIPLES Samsung International has applied the principles of Henri Fayol, the father of management. The Samsung International has split the workforce into certain segments and has achieved better production and quality work input. The practice of division of work has provided the employer with an opportunity of maximizing employee efforts. It is applicable to all work including research and technical applications. There are limitations to specialization which are determined has been determ ined by the application. The company has stressed the importance and role of the authority, and therefore the authority has the rights to give orders and the power to exact obedience. Samsung International has made a clear distinction between a manager's official authority deriving from office and personal authority created through individual personality, intelligence, and experience. The company has introduced certain rules and regulations to ensure that there exist obedience and respect between the firm and its employees.

Saturday, October 5, 2019

Dell Computers - Supply and Demand Assignment Example | Topics and Well Written Essays - 250 words

Dell Computers - Supply and Demand - Assignment Example Consumers have an option of purchasing cheaper products because there are numerous suppliers in the market. Moreover, the monopoly force is low within the industry. Customer service affects demand especially within an industry that is experiencing stiff rivalries. This is because customers are likely to purchase from industries that offer satisfactory services. Consequently, elements such as online services and convenient procedures have the potential of affecting the demand of Dell’s products. Lastly, an improved economy leading to increased consumer income would increase the demand of Dell’s products (Mankiw, 2011). The main factors affecting the supply of Dell products include state of technology, political disturbance, the future price level, and the price of related products (Mankiw, 2011). Technological development is likely to reduce the cost of production as manufactures utilize economical and efficient procedures. This enhances production rates, which increases supplies. Furthermore, political disturbances affect supplies because they affect the product’s production and distribution. Political instabilities discourage the production and distribution of products causing a decrease in supplies (Frank & Bernanke, 2012). Future expectation of increase prices leads to shortages in supplies because distributors are likely to hold products. Lastly, changes in the prices of other related products may increase or decrease the supplies of Dell’s products depending on the relationship (Mankiw,

Friday, October 4, 2019

Analyzing Psychological Disorders Essay Example for Free

Analyzing Psychological Disorders Essay A psychiatric or psychological disorder is a disorder of psychological function severe enough to warrant treatment by a psychiatrist or clinical psychologist. Schizophrenia, emotional disorders, Anxiety and Tourette’s syndrome are all classified as psychiatric disorders. The distinguishing line between neuropsychological disorders and psychiatric disorders is quite thin. Though the two types of disorders are a result of a dysfunctional brain, the malfunctions which create psychiatric disorders remain undefined. Psychiatric disorders are often linked to environmental factors as well as dysfunction of the brain. As psychological research advances, treatments and a better understanding of psychiatric disorders comes to bear. The term schizophrenia means a psychic break or â€Å"splitting of psychic function†. (Pinel, 2007). The NIH National Library of Medicine web site defines schizophrenia as having five different categories: catatonic, disorganized, paranoid, residual, and undifferentiated. (NIH National Library of Medicine, 2008). Each category of the disorder has a specific set of symptoms that is mostly unique to that category of the disorder, but schizophrenia in general creates a delusional picture of reality which disrupts the person’s behavior, logic and emotions. A good example of schizophrenia and the related dissociative disorders are the movie Sybil or the more recent film A Beautiful Mind, and another fine example is the television show United States of Tara. Both movies and the Showtime network’s series depict the lives of a person suffering with schizophrenia or dissociative disorders. Neuroleptics and antipsychotic drugs are known to alleviate symptoms associated with schizophrenia. Clozapine is a type of neuroleptic that does not produce side effects like those associated with Parkinsons disease. The medication is known to cause blood disorders. Neuroleptic medication is used to block the dopamine receptors though it takes time for the drug to lessen schizophrenic symptoms. Though neuroleptics help schizophrenics, only certain patients do benefit from the relief these drugs can offer. Schizophrenic patients suffering from hallucinations and incoherence react to the medication; however; schizophrenics suffering from cognitive defects are not affected. The NIH National Library of Medicine web site mentioned atypical antipsychotics have proven to treat symptoms for schizophrenia  with few side effects and is the best option for those suffering with schizophrenia. (NIH National Library of Medicine, 2008). A surgeon in the 1950’s and early 1960’s used a drug called chlorpromazine on patients to alleviate swelling prior to surgery. The doctor noticed that the medicine acted as a calming agent and recommended chlorpromazine to relax hard to control psychotic patients. Chlorpromazine did not assuage the symptoms of psychosis, but the medicine showed potential for easing some symptoms in schizophrenic patients. During the research process the side effects of chlorpromazine which are symptoms of Parkinsons disease were evident. Researchers concluded that people suffering from Parkinsons disease die from a minute level of dopamine. Schizophrenics display a high-level of dopamine. Therefore Parkinsons and Schizophrenia seem to be on the opposite end of the spectrum. A breakthrough emerged in the dopamine theory with Carlsson and Lindqvist. The duo studied the Chlorpromazine in relation to schizophrenia and revised the dopamine theory of schizophrenia. Chlorpromazine was found to block dopamine receptors instead of the original theory of reducing dopamine levels. Therefore, the duo concluded through research that schizophrenia was  not due to high-levels of dopamine, but with over activity at the dopamine receptors. (Pinel, 2007). Emotional disorders are another form of a psychiatric disorder. Emotional disorders include: bipolar disorder, depression, and mania. Depression is classified as a state of unbearable sadness. At some point in a persons life one will encounter a period of depression due to a tragedy such as loss of a loved one, poor health, or a series of bad luck. However, most people will break through the grip of depression and return to a normal life. Those with depression have a hard time seeing anything in a positive light. Depression ruins relationships at work and in the home; the disease also takes over the person making it difficult to engage in a normal day-to-day routine. Mania is the opposite of depression and is linked to high energy and impulse. A person suffering from mania appears to be full of energy or â€Å"hopped up† on energy drinks like Red-Bull and caffeine; they are filled with such enthusiasm, have boundless energy and talk fast. Though it sounds like an exceptional  thing to be constantly in a good spirits there is a negative side to the disorder. Impulsiveness is a part of mania and many suffers act on impulse not thinking before they do anything. The end result is unfinished projects, bills that cannot be paid, and relationships ruined. A person who suffers from manic episodes and depression episodes is diagnosed with bipolar disorder. There are two theories created to explain the causes of emotional disorders. According to Pinel (2007), The monoamine theory of depression holds that depression is associated with under-activity at serotonergic and noradrenergic synapses. It is based on the fact that monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin-reuptake inhibitors, and selective norepinephrinereuptake inhibitors are all agonists  of serotonin, norepinephrine, or both. The second theory is Diathesis-Stress model. The second theory focuses on genetic predispositions of a person as well as environmental factors that influence the disorder. This means that people who have stress early on will overreact to stressful situations later in life in turn causing depression. (Pinel, 2007). There are four types of medicine used to treat emotional disorders. Iproniazid is a Monoamine Oxidase Inhibitor (MAOI) initially used to treat tuberculosis but failed. On the contrary the patients did not have as many depressive thoughts about the illness. Iproniazid has severe effects when combined with tyramine rich foods. Imipamine is a tricyclic antidepressant which has proven to be more effective than MAOI’s. The next medication is Lithium which was shown to alleviate symptoms of mania. The discovery was made when a researcher tested guinea pigs and the results proved to calm them. Lithium is used as a mood stabilizer in bi-polar patients since it blocks the patient from transitioning between extreme highs and lows. The fourth medicine used more commonly in recent years is selective serotonin-reuptake inhibitors (SSRIs). The most common of the SSRI’s are Prozac, Zoloft and Paxil. The SSRI’s are reported to have few side effects and are able to treat multiple disorders. (Pinel, 2007). Anxiety is chronic fear that persists in the absence of any direct threat. (Pinel, 2007). Anxiety is accompanied by rapid heartbeat, heavy or difficulty breathing and high blood pressure. There are five  types of anxiety disorders including: general anxiety, phobias, obsessive compulsiveness, panic, and post traumatic stress disorder. Theories involving anxiety disorders presume the amygdala has a role in anxiety disorders. The brain’s involvement in anxiety is cloudy at best since each patient tested shows different results. (Pinel, 2007). Benzodiazepines and serotonin agonists are the most effective medications used to combat anxiety. Valium and Librium are two of the most commonly prescribed medications, though they tend to make the patient drowsy. The medicine is  also known to be highly addictive and is recommended only for short-term usage. Buspirone is a serotonin agonist which relaxes the body and causes sleepiness. (Pinel, 2007). Tourette’s syndrome is known for involuntary movements or sounds known as tics. The Cedars-Sinai web site notes that the tics can vary from body movements and vocal tics. The tics can be a little as involuntary eye blinking or more noticeable yelling of obscene words or phrases. Little is known as to the cause of Tourette’s, however there is speculation that the limbic cortex, association cortex and thalamus are connected to the disorder. (Pinel, 2007). With the cause still a mystery there is no cure for Tourette’s, but though counseling, relaxation therapy and hypnosis healthcare professionals can help treat the disorder. (Cedars-Sinai. 2008). Psychiatric disorders vary in many ways. Schizophrenia affects the brain and causes hallucinations, emotional disorders affect a persons mood in extreme ways, and anxiety causes fear and health issues, while Tourette’s causes tics ranging from subtle to severe. Over time psychological advances in research and treatment have been made allowing professionals in the field to effectively treat each disorder. References CEDARS-SINAI. (2008). Tourettes syndrome. Retrieved June 10, 2009, from http://www.csmc.edu/5540.html NIH National Library of Medicine. (2008). Medical Encyclopedia: Schizophrenia. Retrieved June 9, 2009, from http://www.nlm.nih.gov/medlineplus/ency/article/000928.htm Pinel, J. P. J. (2007). Basics of Biopsychology. Boston, MA. Allyn and Bacon.

Thursday, October 3, 2019

Oncolytic Virus Therapy for Cancer

Oncolytic Virus Therapy for Cancer Abstract Interest of oncolytic virotherapy is mounting from over the past few decades for treating many kinds of malignancies. Despite oncolytic viruses attain many successes in cancer therapeutic era; they all have still challenges in their developments. The interaction between virulence factors of viruses, hosts immune defense system, microenvironments and tumour factors are the hazardous influences in their achievements of novelties. Currently, with the thanks of modern recombinant biotechnology, most of the oncolytic viruses are increasing their tumour selectivity and specificity. On the other hand, they reduce their efficacies on physiologically functioning cells. Furthermore, combinational therapies with traditional anti-cancer treatment regimes have also promising and relevance outcomes. In 2004, Chinese food and drug administration (FDA) approved first oncolytic virus in treatment of head and neck tumours. However, they have some still unsolved obstacles in proper cancer therapy. In m y paper, the current issues and future prospects of the oncolytic viruses are highlighted how to use as therapeutic weapons. Keywords: Oncolytic viruses; Oncolytic virotherapy; Cancer gene therapies; recombinant 1. Introduction Cancer is one of the leading causes of death globally comprising 13% of all deaths (7.6 million deaths) in 2008. Although well established conventional therapies including surgery, radiotherapy and chemotherapy are existed, we still need new therapies and strategic plans. Local therapies such as surgery and radiotherapy have been limited in disseminated tumours. Likewise, chemotherapy has some intolerable adverse effects and sometimes, pre-existing chemo-sensitive tumours are resistance to chemotherapy after prolonged used. Thus, we really need certain promising therapies to handle these problems. Recent years, oncolytic virotherapy is uprising and promising for the various types of cancers. Ideology of virotherapy treating the malignancy has been introduced since early 20th century. However, since early oncolytic viruses were targeted not only tumour cells but also the normal cells, interest in the virotherapy was declined. Therefore, many trials related with such therapy were termi nated during the following decades. Late 1990s, interest of virotherapy was re-active with the advance of modern biotechnology. Today, concern of the virotherapy is high and it has the potential promises as a reasonable cancer treatment by itself or conjunction with other conventional therapies such as surgery, radio and/ or chemotherapy (synergic effect). Advance technology allows the development of oncolytic viruses which only effective on dividing cancer cells but not attack the normal dividing cells. There are generally two types of oncolytic viruses namely non-engineered (naturally occouring) and engineered agents. Both types may destroy the malignant cells without harming the normal cells. Generally, oncolytic viruses only infect and preferentially replicate within the cancer cells followed by lyses these cells. In recent years, many therapeutic virus candidates are emerging and testing their oncolytic prosperities with preclinical and clinical trials. Among them, adenovirus H101 was the first virus approved by C hinese food and drug administration (FDA) in 2004 as the adjuvant oncolytic virotherapy combined with pre-existing conventional chemo- and radiotherapy in the head and neck cancers. 2. Type of oncolytic viruses Oncolytic viruses are principally divided into 4 types according to their mechanisms of action. There are intrinsically tumour selective viruses, virulent gene deleted viruses, promoter inserted viruses and pseudotyped viruses. Genetic modified oncolytic viruses are manipulated whether insertion of the transgenes or deletion of the virulence genes. Naturally occouring tumour selective viruses are the viruses that are not genetically modified, direct targeting on the malignant cells. For instance, New castle disease virus, Vesicular stomatitis virus, Poliovirus and Reovirus are intrinsically tumour selective. However, affectivity is less due to depend on the natural strength of their lytic properties. Virulent gene deleted oncolytic viruses are more popular because their selectivity on target tumours are more specific without infectivity to normal ones. For example, herpes simplex virus, adenovirus, measles virus and vaccinia virus can be modified by deletion of their virulence protein coding genes. In addition, inserting of foreign genetic elements such as promoter region boost tumor specificity and selectivity of oncolytic viruses. Thus, tumour cells allow the replication of these viruses because only tumour cells can activate the promoter region of them. For example, prostate specific antigen (PSA) promoter inserted adenovirus CG7870 applies in prostate cancer and promising results were came out. Pesudotyped oncolytic viruses are modified with ligands which target tumour selective cell surface receptors. Therefore, they solely have their infectivity on malignant cells. (E.g. adenovirus delta 24RGD). Moreover, these viruses may reduce toxicity and dose requirement. 3. Characteristic features of standard oncolytic virus Since viruses can infect not only the malignant cells but also the functioning cells, oncolytic virotherapy is the critical therapy. Hence, safety and efficacy of the virotherapy are considerable issue and still challenging for further improvement. Potential oncolytic viruses are needed to confirm or compare whether they have real ideal characters of oncolytic virus or not. Standard characters of the oncolytic virus stated that (1) they only replicate within tumour with high multiplication rate, not on normal cells (2) less or no infectivity and virulence than their wild types (3) genetically stable so that mutations and recombination with other viruses are minimized for manufacturing and safety issues. DNA virus is more stable than RNA virus (4) can inactivated anytime with antiviral drugs or other mechanisms (5) considerable mass production (commercially available) can be possible with good manufacturing practices. Therefore, for development of virotherapy, all oncolytic viruses sh ould be fulfilled above criteria. Adenovirus and Herpes simplex virus (HSV) have high selectivity and specificity on tumour cells with massive replication rate of 1000 folds in 1st cycle. Besides, they are considerably stable whereas terminate anytime with their respective antiviral therapy (e.g. adenovirus is self-limiting and HSV is treated by acyclovir). 4. Tumour selective mechanism With the knowledge of the malignant cells molecular biology, oncolytic virotherapy can be created to attack the tumour cells selectively. Cancer cells undergo changes ranging from subtle point mutation to chromosomal instability. Inherent tumour selective viruses specifically attack the tumour cells by targeting the specific tumour promoting pathway of the malignant cells such as activated Ras and AKT pathway, defective interferon (IFN) pathway etc. RNA-activated protein kinase (PKR) pathway is a natural process that inhibits viral protein synthesis. Physiologically, interferon (IFN) secreted from infected cells phosphorylates the PKR which subsequent phosphorylates eIF-2ÃŽ ±. Then, phosphorylated eIF-2ÃŽ ± interfere the oncolytic viral protein synthesis that require for their virulence. In contrast, Ras mutation and defective IFN in malignant cells disturbs the PKR pathway and favours the oncolytic virus activity. For instance, herpes simplex virus (HSV) containing neurovirulence gene ÃŽ ³34.5 that binds with intracellular phosphatase and dephosphorylates eIF-2ÃŽ ± allowing replication of HSV in both normal and tumour cells. However, deletion of this gene permits to replicate only in Ras mutated or interferon (IFN) defective cells. Controversially, recent finding suggested that ÃŽ ³34.5 deleted HSV can also replicate in PKR functional malignant cells. It is seen to be defects in PI-3 kinase pathway which favours translation of ÃŽ ³34.5 mutant HSV. Moreover, genetically modified adenovirus (dl331), VAI mutant strain, prefers to replicate only in tumour cells with Ras activation. Similarly, dl331 is also effective in Epstein-Barr virus (EBV) associated tumours such as nasopharyngeal malignancy because Epstein-Barr virus expresses viral associated RNAs (VA RNAs) that defect PKR pathway. Many cancer cells over-express receptors for virus in high level. Thus, exploiting this mechanism, many oncolytic viruses are selectively homed in their specific malignant cells. For example, over-expression of intracellular adhesion molecule 1 (ICAM-1) and decay acceleration factor (DAF) in tumour favours to infect Coxsackie virus A21. Besides, Newcastle disease virus (NDV) binds sialic acid receptors. Alpha virus similarly uses heparin sulphate or ICAM-1 as its receptors. Both of them are highly express in tumor population. Therefore, these viruses are highly concentrated in tumour cells. 5. Immunogenicity of virotherapy Likewise as many other viruses, oncolytic viruses also stimulate and activate the body defense mechanisms including innate as well as adopted immunity. These viruses produce the viral proteins required for their replication within tumour cells. These proteins also stimulate the MHC class I gene to present it on the cellular surface of tumour cells as well as on the normal cells. MHC class I antigen was recognized by cytotoxic T cells (CTLs) or CD8+ cells which may destroy any cells representing MHC I antigens. Therefore, nature immunity allows eliminating both tumour and normal non-dividing cells. So, oncolytic viruses may also destroy normal cells apart from abnormal ones. An immune mechanism on the oncolytic viruses is one of the major constraints for developing modern virotherapy. However, to date, genetically modified viruses can only replicate and lyses p53 mutant cells. They cannot inactivate p53 gene of the normal host cells. p53 is functional and prevent replication of these viruses in the normal host cells. So, they are allowed their functions only in mutant tumour cells. 6. Conversion of oncogenic to oncolytic Many oncogenic viruses are potential to use as oncolytic therapy nowadays after genetically manipulation. Generally, 15-20% of the carcinogenesis is contributed by various kinds of oncogenic viruses such as herpes papilloma virus (HPV), Epstein-Barr virus etc. Reversely, these viruses can be changed to treat the malignancies by exploiting their lytic effects on the dividing cells. One of the classical examples is herpes simplex virus type 2 which is ongoing trials in many tumour cell lines by deleting its oncogenic genes coding thymidilase kinase or ribonucleotide reductase. Therefore, even tumourogenic agents can be used as oncolytic therapy by engineering their oncogenic gene components. 7. Novel oncolytic viruses 7.1. Adenovirus Adenovirus is interested in treatment of brain tumour especially in glioma multiforme. This tumour is never metastasized and contributed as single lesion. Moreover, it is almost resistance to systemic therapy because of blood-brain barrier and lack of cell mediated antigen drainage. However, fortunately, oncolytic viruses can replicate and spread within the tumour population since blood brain barrier create immune privileged site. In glioma cells, tumour suppressor gene (Rb) is inactivated and lack of expression. Taking this advantage, genetically modified adenoviruses are constructed by deletion of eight amino acids in Rb binding region of E1A protein. Therefore, they are unable to replicate in the normal cells because viruses cannot inactivate Rb gene of the functioning cells. But they can easily divide within the malignant cells owing to the lack of Rb protein. Additionally, adenoviruses induce autophagy in infected cells (malignant cells) through down-regulation of AKT/TOR pathwa y. Many genetically engineered adenoviruses are still on trials including in vitro and in vivo tests. ONYX-015 (dl1520) is a simple adenovirus lack of E1B 55K protein which do not replicate in the normal cells. So, they only express their functions in p53 mutant cells. In other word, their function does not work in p53 competent cells. Onyx-015 is a first oncolytic virus that has been approved by china FDA to treat the head and neck cancers especially refractory nasopharyngeal cancer combining with standard cisplatin based chemotherapy. Onyx-015 should be given intratumoural or peritumoural injection because of their side effects (e.g. flu-like syndrome). In addition, it showed 50% response rate observed in phase I and II clinical trials of pancreatic cancer. Recent studies found that Onyx-015 replication is not solely dependent on p53 function. Onyx-015 can replicate within some p53 competent cells whereas sometimes, cannot replicate even in mutant p53 cells. It may think to be reliable on E1B 55K independent nuclear late mRNA export of the tumour cells but not in functionally norma l cells. Besides, other co-founding effects should be considered. For example, increasing the temperature (fever, hyperthermia or drugs) promotes replication of E1B deficient adenovirus in the malignant cells rather than normal ones. dl250 mutant strain is engineered by deletion of E1B 19K which is homologue of Bcl-2 and also inhibits pro-apoptotic protein Bax. Functionally, Bcl-2 is the anti-apoptosis protein. Hence, deletion of E1B 19K leads to permit cell death in Bcl-2 over-expressed tumour cells. It may also reduce expression of anti-apoptosis proteins and various growth factors. This type of virus is more potent in anti-tumour activity than dl1520. Delta 24 (dl922-947) adenoviruses are genetically modifying agents which are deleted the gene related with virulence factors and upregulate the transcription elements sensitive to the transcription factors of tumour cells. E.g. Delta-24 is modified by deleting of 24 nucleotides (pRb binding region) in E1A gene so that it is unable to inactivate Rb gene in the normal cells. So, it can only effective in the malignant cells. Now, many studies promise that it has potent anti-tumor effect in glioma. E1A mutants are more superior in oncolysis than E1B strains in vivo and vitro. Besides, Delta-24 RGD is more efficient in treating the low CAR (coxsackie-adenovirus receptor) expression malignant cells such as glioma and bronchogenic carcinoma cells. 7.2. Herpes Simplex virus First herpes simplex virus (dlsptk) as an oncolytic agent is developed in 1991 that is deleted in thymine kinase (TK) genes required for nucleic acid metabolism. Lacking of this gene, Herpes Simplex virus (HSV) lose its ability of replication in the normal cells. Hence, HSV only prefer to infect the tumour cells. HSV is a primarily potential treatment in several paediatric cancers including brain tumours. So far, ÃŽ ³34.5 deleted HSV are tracking on the clinical trials. These all vectors directly target to the tumour cells by deletion of neurovirulant gene ÃŽ ³34.5 (30kb) which is not essential for replication of the malignant cells. G47Δ HSV virus is derived from G207 parent virus. They are constructed by deletion of both copies of ÃŽ ³34.5 gene (1kb) and deletion of 312bp in ICP47 gene increasing oncolyitc efficacy. Also, they promote MHC class I expression in the tumour cells enhancing the immunogenicity of these cells. G207 variant was completed phase I study in glioblastoma multiforme resulting with no serious side-effects. Similarly, HSV 1716 is a genetically engineered variant by manipulating HSV1 stain 17 and deleting both copies of neurovirulent gene, ÃŽ ³34.5. Pilot study has already completed in Metastatic melanoma. NV 1020 (R7020) stain is the chimeric recombinant of HSV 1 and 2 with deleting one copy of ÃŽ ³34.5 gene, UL24 and 56 genes. Originally, it is developed as HSV vaccination. However, recently, it is still ongoing phase II trial on hepatic metastases of colorectal cancer by direct infusion into the hepatic artery. OncoVEXTM is recombinant vector with deletion of ÃŽ ³34.5 gene as well as ICP47. Deletion of ÃŽ ³34.5 reduces intrinsic neuro-pathogenecity of HSV whereas ICP47 deletion restores MHC class I presentation. Additionally, insertion of GM-CSF gene stimulates immune response of the host to the tumour cells. Releasing of GM-CSF promotes recruitment of dendritic cells for tumour specific response. It promotes tumour specific antigen (TSA) expression as well. Thus, OncoVEXTM affects not only on local tumour but on metastases or distant tumours. Currently, OncoVEXTM improved loco-regional control of head and neck cancers combining with chemo-radiotherapy. Intralesional injection of OncoVEX GM-CSF is ongoing phase I trials on cutaneous metastases and melanomas although it has dose related limitation such as injection site inflammation. Another advantage is that it is able to carry large transgenes up to 150kb. It is the main advantage of these viruses using for oncolytic agent although they ma y produce neurotoxity at high doses, difficult cloning and reactivate latent herpes infection which are hidden in the nervous systems (Ganglions). 7.3. Newcastle disease virus Newcastle disease virus (NDV) is paramyxovirus containing single stranded RNA which causes Newcastle disease in avian (birds). Earliest NDV (73-T strain) has been started to use as a clinical trial oncolytic virus for cervical cancer in 1965. Based on their oncolytic properties, NDV is divided into lytic and non-lytic stains. Lytic strains direct lyses the targeted cells. Currently, 2 lytic strains of NDV are ongoing trials which are NDV-HUJ and PV701. Both are naturally occouring live attenuated viruses. As NDV-HUJ strain is a neurotropic virus, it applies in glioblastoma multiforme (GBM). Likewise, NDV-PV701 strain has effect on many types of tumours. Results of their trials have potential promising. One of the advantages of NDV is that it selectively replicates in the tumour cells, not on normal ones. When NDV has also studied in breast cancer patients neoadjuvant with chemotherapy, outcome was desirable with minimal adverse effects including fever, flu-like syndrome, hypotension etc. Occourance and severity of side effects is reduced in subsequent therapy due to development of NDV antibodies in patients serum. On the other hand, non-lytic strains disturb the malignant cell metabolisms leading to allow regression of the tumours. Common non-lytic strains include Ulster stain. NDV damages the malignant cells by either direct lysis of the cells, induction of cytokine production (Interferon, Tumour necrotic factor) or enhance apoptosis including both intrinsic and extrinsic pathways. 72-T stain induces cytokine release while Ulster stain over-expresses the TRAIL receptors on tumour cells surface which may lead to apoptosis. 7.4. Mump virus and Simian virus Mump virus is the first paramyxovirus trying to treat in variety of human malignant cells. Vaccine strain 79 (S79) has potential promising oncolytic virus because S79 can only be infected to the cancer cells but not in normal ones. Studying in nude mice, mump virus demonstrated its tumour inhibition effect significantly. Simian virus is also a rubulavirus and among them, strain 5 can be genetically engineered as an oncolytic virus. This modified strain is able to attack several different cancer cell types significantly. 7.5. Vesicular stomatitis virus Vesicular stomatitis virus (VSV) is only rhabdovirus potentially using in cancer therapy. VSV is a single stranded RNA virus considering for oncolytic therapy. Developing of the recombinant VSV virus in 1995, the role of VSV is amounting in virotherapy. In recent studies, genetically modified replication competent VSV prolonged survival of hapatocellular carcinoma, breast cancer and malignant melanoma. Oncolytic properties of VSV is more effective in type I interferon (IFN) resistance malignant cells. Tumour cells are defect in interferon (IFN) signaling pathways but activated in Ras -ERK pathway. However, VSV can also impact on the normal cells especially in high doses. Thus, early (prophylactic) interferon therapy is required concomitant with VSV virotherapy because interferon appears to prevent the viral replication within the normal cells. Using the advantage of replication within the interferon defect cells, recombinant VSV deltaM51 which is defective in M (matrix) protein (poin t mutation) was constructed. Matrix protein is the regulator protein that increases replication and transcription of the virus but blocks the host cells anti-viral mechanism. Studies showed that VSV deltaM51 strain has beneficial role in glioma cells xenografted nude mice. Furthermore, VSV shutdown the blood supply to the tumour leading to deprivation of oxygen and nutrients which may require for tumour growth. 7.6. Measles Measles as oncolytic therapy is more interesting since there was significant regression of Hodgkins lymphoma after infecting with measles virus. Resent study suggested that recombinant measles virus (Edmonston B strain) showed significant inhibition on xenograft SCID mice with human lymphoma cells. Next, Edmonston B stain specifically attracts CD 46 cell surface receptors that are highly expressed in human mesothelioma cells. Thus, this strain has highly attractive role in treatment of mesothelioma. In addition, engineered measles virus with interferon (IFN) ÃŽ ² gene inhibits tumour angiogenesis rather than parental strain. Despite most of the people previously encountered with measles infection or vaccination in their early life which may cause therapeutic failure, the evidence highlighted that replication of measles virus was taken place even in the immune individuals. It seems to be immunosuppression due to cancer itself or concurrent use of other anti-cancer therapies such as ra diotherapy, and (or) chemotherapy. 7.7. Poxvirus Vaccinia virus (VV) is the most potential candidate poxvirus utilized as virotherapy recently. This virus is genetically engineered by deletion of thymidine kinase genes like herpes simplex virus (HSV). For instance, JX-594 strain which is transfected with GM-CSF gene, displayed oncolytic activity in animal models. However, it may rarely affective in the normal cells. Most Vaccinia viruses kill the targeted malignant cells by apoptosis as well as traditional mechanisms. Myxoma virus, another poxvirus, is significantly effective on human glioma cancer cell lines. In addition, rapamycin (immunosuppressant) reinforced its oncolytic efficacy when using combination. 7.8. Togaviruses Togaviruses (Sindbis and Semliki Forest Virus) also show their potential roles in the oncolytic therapy. Sindbis virus (SIN) is an RNA virus that naturally infects human by mosquito bites. This virus binds with its receptors of 65kD (Laminin receptors) which are highly express on the tumor cells (tumour homing property). To take the advantage, Sindbis virus promotes considerably regression of the several tumor cell lines in vitro testing and xenograft SCID mice. In human study, it has promising effect on cervical and ovarian malignancies with minimal or no remarkable adverse effect on normal cells. Next, Semliki Forest Virus (SFV) may inoculate repeatedly without prominent immune response. Togaviruses favour as the oncolytic virotherapy agents due to their high replication rate, broad spectrum of host ranges, increase transgene expression and stable in blood stream. Apart from these viruses, Venezuelan equine encephalitis virus (VEE) is also a replication competent virus which is int eresting in certain circumstance of oncolytic therapy. 7.9. Retrovirus Gamma retrovirus (moloney murine leukemia virus (MoMLV)) may have effect on the tumour cells not in the non-dividing cells. So, it may safe as oncolysis. For instance, when U87 glioma xenografted nude mice were administrated with MoMLV, significant oncolytic result has been reported. These viruses are less effect on normal cells due to lack of nuclear transport of viral genome. Certainly, they cannot replicate well within non-dividing cells. In addition, modified MoMLV viruses expressing HSV thymidine kinase (TK) have synergistic effect on glioblastoma cells combining with ganciclovir (anti-viral agent for HSV). Another retrovirus such as fomy virus has also intrinsic oncolytic property. It is researched recently on glioma implanted nude mice. However, the result is still controversial.

Wednesday, October 2, 2019

The Crow Review :: essays research papers

The Crow Reviewed   Ã‚  Ã‚  Ã‚  Ã‚  Throughout the history of movies, movie companies have tried to do it bigger better and more exciting. They bring in bigger stars, better special effects and more convincing stories, which causes the masses to flock to the theatres in eager anticipation of each movie. The audience usually gets what the audience wants—more violence and more action the world over. â€Å"The Crow† has elements of different types of movie genres the horror, adventure, film noir and the western. In this movie there is no difference as is about to be shown in the following paper. They mix the genres together quite well in this movie to make it a true hybrid genre. From the mean streets, the use of shadows and surprise like the horror movie, to the adventure of the over all story. They also mix in a bit of western with the black cowboy that is in the comic, but doesn’t even appear in the movie itself. Now this paper shows how the movie appeals to the different genres using characters, settings, lighting and other effects to make the movie more interesting.   Ã‚  Ã‚  Ã‚  Ã‚  In â€Å"The Crow,† it starts out with a legend of the crow showing the horror aspect of the movie. It says that â€Å"when a person dies, a crow carries there soul to the land of the dead and sometimes a soul dies with such anguish that the soul cant rest, and sometimes, just sometimes the crow can bring that spirit back to put the wrong things right.† Which was in the case of Eric Draven, is what happened. Him and his fiancà © (Shelly) both are killed while fighting tenant eviction eviction in there building. Eric Draven being the way that he was before he was killed, a rock singer and guitarist, truly makes him the unlikely hero of this story. The way that he paints his face in a mimes face with a smile is quite different then was in the comic, he was suppose to paint his face like the face of tragedy. Instead they do it like a mime, and this is quite ironic as to what he is supposed to stand for. This creates a sense of dramatic horror to an eff ect throughout the movie. The street gang that killed him for the tenant eviction made him quite the man made demon, having only one thing that was on his mind, the revenge of his and Shelly’s death to put his soul to rest.

Supersize Me :: Film Movie Films Movies Supersize Me

Supersize Me Some of the people interviewed for this film suggest that Americans can always refuse to eat fast food, but is it really that easy? No, because there are many factors involved when an individual or family decides to eat fast food for any particular meal of the day. Several factors in this decision include but are not limited to: Firstly most people pack their day with activities continuously so there is not much time left in the day to cook. Secondly children play a large role in whether a mother will stop at McDonalds.   Ã‚  Ã‚  Ã‚  Ã‚  In a society where the thought of idle hands as the devils workshop, more people are joining more gym clubs, children are participating in more extra-curricular activities like sports, dance, and the like. More people are going back to extend their education, and subsequently forced to attend classes in the evening. Couple this with parents who work at night or families who have teen-age children who are independent and these factors equal families who spend more time in restaurants than they do in their own kitchen. When families get home late in the evening then dinner often become a snack. This is not to say that every family in America follows this routine, but Caucasians in particular are most likely to become victim to this trend. Caucasians in particular encourage their children to participate in anything. Families who have two parents working have an opportunity to maybe enjoy a home cooked meal a couple nights a week.   Ã‚  Ã‚  Ã‚  Ã‚  McDonald’s marketing plan is a clever ploy direct at the children of this planet. If not for children and their addiction to clowns, and maybe time factors, mothers would have no reason to stop at fast food restaurants. A great deal of McDonald’s have a play land where the parents can come to appease their child and end up sitting for a two or three hours. Many women meet and make it a social activity. This is how the beginning of eating unhealthy begins. As a result of this, people grow and become cozy with the idea of McDonalds.

Tuesday, October 1, 2019

Staying Informed: Old News

There was a time when news information was disseminated by a select few who had access to the relevant reports, files, and statistics.   When this was the case, the world gathered around a radio, shared a newspaper, or turned on the television—one that had fewer than ten channels).   This â€Å"news† was often like a leftover meal in terms of value: by the time it was released, the world had moved forward, and something new was hot. Progress was made, and television news programs began to delve deeper into stories; reporters suddenly began delivering â€Å"breaking† news reports, and the information was at least lukewarm when the public got its hands it.   It was the era of reporters like Paul Harvey who took what the world knew, dug more deeply, and presented â€Å"the rest of the story† (Radio Legend Paul Harvey Biography, 2003). Today, a cell phone can alert its owner of breaking news stories from around the world; reporters deliver broadcasts live from battlefields; and the internet has made it possible to receive information almost instantly.   Most consumers now get their news online, via one of hundreds of television channels, or through a variety of print media.   Unfortunately, the days of print media and even local reporting seem to be dying, and while their loss may not even create a ripple, what they have to offer the consumer is irreplaceable. It is true that the average printed report cannot provide the live-action, emotionally packed footage of a series of photographs or a streaming video, but words do matter, and while one’s brain struggles to capture the intricacies of backgrounds, sounds, and images that flash in front of the eyes in photographs and videos, the thought-process of the viewer is overwhelmed by the visual imagery. MSNBC online featured a written report and a series of videos and slide shows on October 16, 2006 that captured the story surrounding the earthquake in Hawaii the previous day. When compared, the headline video and headline print report reveal some very interesting trends in the ways in which the news is disseminated. The headlining video report â€Å"Powerful Earthquakes Shake Hawaii† is two and one-half minutes long and features a variety of images that show damage to a local woman’s home, the picture of a landslide caught by a photographer, various tourists being inconvenienced, file footage of volcanic eruption, the Hawaiian coastline, people buying gas, and shoppers at a grocery store. These pictures are accompanied by interview sound bites or voiced-over by reporter Howard Dashefsky, but the entire report is devoid of real information.   What might one expect as the aftermath of an earthquake on a populated island that is also a tourist attraction?   If I had guessed at the â€Å"aftermath,† I would have imagined almost everything I saw in Dashefsky’s report.   Although the images were fascinating and even engaging at times, I left the report with virtually no residual caring and no remnant thoughts: nothing of value had been added to my brain. The headline print report begins with â€Å"officials fanned out across Hawaii early Monday to inspect bridges and roads following the strongest earthquake to rattle the islands in more than two decades, a 6.6-magnitude quake that caused blackouts and landslides, but no immediate reports of fatalities† (Associated Press).   In the opening paragraph of the print report, I found out what happened; I felt sorrow and relief; and I was driven to consider the after-effects of the earthquake in ways not even broached by the video report.   It took me less than one minute to read the print report, but in that minute I learned about what had happened, where it had happened, that no tsunami was expected, what was being done, what would be done—the list is almost endless. Those who watch the video report will stand around water coolers discussing benign elements of the event.   The will recall the semi-ravaged home of one resident and the fight to get gas and groceries; moreover, they will congratulate themselves on not having wasted their own money on a spoiled Hawaiian vacation.   This is the kind of thinking that is being fostered in the United States: superficial, image-based, self-centered, and desensitized. Those who take (less) time to actually read about the earthquake will stand around the water cooler discussing factual details.   They will likely be amazed by the good fortune of such a historically large earthquake resulting in no fatalities; they will wonder if the roads and bridges where they live would be damaged after such an event; they may ponder how long the state of disaster will remain in effect; they will think about how happy they are not to be there on vacation, but it will most likely not be the first thing on which they comment.   This is the kind of thinker that is in danger of dying in the United States: one who craves facts and the chance to critique them while expanding his/her knowledge base. The ability to receive immediate information is a boon to the news consumer; however, the availability of instant images, facts, and reports must be combined with words that are as stimulating, powerful, and informative as the visual clues—or a numbing of the mind and the senses is bound to occur.   Reports that are piping hot can be delivered to the public as a combination of the best of what can be seen, what can be heard, and what can be read.   Like a dinner filled with the necessary food groups, communication needs to combine its sources and resources for the most palatable and healthiest results. References Associated Press, The.   (October 16, 2006).   Hawaii checks bridges, roads after quake: Landslides and power outages but no reports of deaths.   MSNBC.   Retrieved October 16, 2006, from http://www.msnbc.msn.com/id/15286294/. Dashefsky, H.   (October 16, 2006).   Powerful earthquakes shake Hawaii.   MSNBC Video.   Retrieved October 16, 2006, from http://video.msn.com. Radio Legend Paul Harvey Biography.   (2003).   Paul Harvey: The Voice of the New Millennium.   paulharvey.com: ABC Radio Networks.   Retrieved October 16, 2006, from http://www.paulharvey.com/bio.shtml.