The Role of Media in National and International Development Essay

The Role of Media in National and International Development - Essay Example This essay stresses that the role of media in national and international development is best described in relation to the community development theories. The community development theories give a guideline on the practicability of the community development plan. They also analyse various aspects of development such as the forms and processes it takes. Some of the most common community development theories include the diffusion theory, the decentralisation theory, group development theory, group behaviour theory and the growth pole theory among others. This paper makes a conclusion that the contribution of the media to the national and international development cannot be underestimated. An active and unbiased media is needed so as to maintain democracy, good leadership and equality in a country. It helps educate, inform, sensitise and mobilise the public among other functions. By carrying out the above functions, the media facilitates growth and development. National development is achieved through the positive change in the social, political and economic sectors of a country. On the other hand, international development is achieved thorough the creation of a developed world community. The dissemination of information portraying a positive image of the whole world has been the key factor in community development. The theory of community development helps in determining and understanding the role of media in development. The theories have been conceptualised to guide the implementers of policies focused to national and international development.

Music World Culture Assignment Example | Topics and Well Written Essays - 1250 words

Music World Culture - Assignment Example On discovering the legends and history behind the nation’s cultural heritage, it is possible to know how these iconic symbols got associated with its culture and society. The discussion here commences with the historical, sociological, and geographical information of Scotland regarding its people, culture, and society; and particularly focuses on the music world culture that includes cultural information about the country’s unique music, dance, and instruments of the Scottish people. The geographical location of Scotland lies approximately in the northern end of United Kingdoms mainland, encompassing about 7.5 million hectares of land. The country is surrounded by the Atlantic Ocean in the west, with the North Sea in the east and the North Channel and Irish Sea in the south-west. In addition to the mainland, the country is made up of around 790 small islands, including the Hebrides and the Northern Isles. Scotland’s population is estimated to be more than 5 million, as per the census 2011, with a population of 62 percent identified as being purely Scottish, 18 percent as Scottish and British, 8 percent as British only, and 4 percent as other national identities. (â€Å"Analysis: National Identity†). The diverse national identities in Scotland have contributed to the culturally divergent heritage of the land. Scotland has a complex yet engrossing history that can be stretched back to some thousands of years, from the Kingdom of Alba to the modern Scotland of today. The emergence of Scotland can be dated back to the Prehistoric period, when the Kingdom of Alba emerged after the primitive immigrants’ colonization of the land. After the invasion of British colonialism and the subsequent agreement Treaty of Edinburgh-Northampton in 1328, Scotland was recognized as an independent sovereign state and got merged with Great Britain in the seventeenth-century. Scotland

Treating Cystic Fibrosis with Gene Therapy

Treating Cystic Fibrosis with Gene Therapy In this dissertation we shall consider the field of gene therapy in specific relation to cystic fibrosis.   We examine the different delivery vector mechanisms that have already been explored and concentrate primarily on the adeno-associated vectors. We examine the current state of research and consider the advantages and drawbacks of the various methods considered. We conclude with a discussion and analysis of our findings and   make anumber of assumptions relating to the future direction of the researchin the field.   The rate of progress in the field of gene therapy has been enormous. We must remind ourselves that the first clinical gene transfer experiment took place in 1989 when a patient with malignant melanoma received genetically modified auto logous T cells. (Rosenberg SA et al1990) Gene therapy encompasses two major areas. The in vivo field, where genes are incorporated into the target cells of the living body and the ex-vivo field where the target cells themselves are genetically modified outside the body and then re-implanted. Medical science has been using the basic techniques of gene transfer for a long time. The technique has been exploited when viral genes are introduced to human cells when a viral vaccine is administered. The key technologies that allowed the transition from vaccination to gene therapy were the evolution of methods that allowed the genes to be isolated and replicated (cloned) and manipulated (engineered) prior to transfer into human cells (Freeman SM et al 1996) The key principle in this process is the efficient transfer of the manipulated therapeutic genes into the nuclei of target cells usually be means of various vectors. This dissertation will be considering the utilisation of these vectors in some detail. In broad terms, the new or modified genetic material is able to produce new proteins which can restore deficient or abnormal functions of genetically diseased tissues, to generate tissues that have entirely new properties or to create transplantable tissues for the controlled release of therapeutic proteins. (Russell SJ  1997) In terms of viral vectors, prior to 1996 science was dependent on the use of modified retroviral vectors (eg.MMLV) to effect gene transfer into the chromosomes of a target cell and the adenovirus vectors when such integration was not needed. Neither vector was particularly successful as the intact nuclear membrane (in then on-dividing state) was a major barrier for chromosomal gene integration. (Sikorski R et al 1998). A breakthrough came with the realisation that lentiviruses (e.g. HIV) have the same ability to transfer genetic coding into the cellular genome but could do this in the non-dividing or dormant phase cells. (Amado R G et al 1999) In vitro, lentiviruses have been shown to change the target cell’s expression of proteins for up to six months. importantly, they can be used for terminally differentiated cells such as respiratory epithelium. The only cells that the lentivirus cannot penetrate the nucleus are those in the quiescent (G0) state as this blocks the reverse transcription stages of protein synthesis. (Amado R G et al1999) Cystic fibrosis Cystic fibrosis is the most commonly lethal inherited recessive inthe caucasian population. It affects about 1 per 2,500 livebirths. Thetreatment of cystic fibrosis has improved enormously in the last fiftyyears with the life expectancy increasing from an average 10 years to30-40 years now. The prime cause of death in affected individuals is the repeatedcycle of infection, inflammation and fibrosis of the respiratory tractwhich eventually culminates in respiratory failure and death. The disease itself is caused   by mutations in the single gene forthe cystic fibrosis transmembrane conductance regulator (CFTR) whichproduces a protein found in sweat and pancreatic ducts, gut,seminiferous tubules, lungs and many other tissues. The mutationsresult in an abnormal protein which, when expressed in the lungs,produces thick viscous and dehydrated secretions. This does not allow for the efficient expulsion of bacterial pathogensfrom the lungs and a number of highly resistant forms of bacteria arecommonly found in cystic fibrosis (viz pseudomonas aeruginosa)(Porteous DJ et al 1997). An individual must receive a defective copy of the cystic fibrosisgene from each parent in order to develop the clinical picture ofcystic fibrosis. Following normal genetic principles, if two carriersconceive a child, there is a 25% chance that it will have cysticfibrosis, a 50% chance that it will be a carrier and a 25% chance thatit will have two normal cystic fibrosis genes. Viral and non viral vectors Viruses have an ability to enter a host cell and combine their owngenetic material with that of the host cell. This is the basicrationale behind the science of gene transfer therapy.   As we shalldiscuss in some detail in this dissertation, there are a number ofpotential viral vectors that have been explored, evaluated andexploited in the search for an efficient and safe form of therapy.Viruses are not the only vector that can be utilised . Simply placingDNA in the nasal mucosa will produce some incorporation into theepithelial cells (Knowles MR et al 1998). This â€Å"absorption† can bedemonstrably enhanced further by the combination of the DNA withvarious plasmid or lipid complexes(Zabner et al 1997) The advantages of lipid or plasmid assisted transfer mechanisms arethat they do not appear to generate the immunological responses thatare seen with the viral vectors. They can also be used to facilitatethe transport of much larger pieces of DNA which would otherwise belimited by the packaging consideration incumbent on the viral vectors.(Felgner P 1997). The use of retroviral vectors is far from straightforward. The heavilypublicised case in April 2000 brought some of the problems to theattention of the media. A retroviral manipulation of   a case of X-SCID(X linked severe combined immunodeficiency) was treated by gene therapywith an apparent degree of success (BBC 2002). This particular diseaseprocess is caused by a mutation on the gene which codes for the C chainof the cytokine receptors which is situated on the X chromosome andvital for the functional development of T Killer lymphocytes which aretherefore completely absent in the condition A multinational team used a retroviral vector to insert a functionalcopy of the gene into bone marrow stem cells which were thenre-transfused back into the patient. (Cavazzana-Calvo M et al 2000).This particular case resulted in a return to normal levels of T cellsin a comparatively short period of time. This was hailed in both thepopular media and the peer reviewed journals as a major success and itcan indeed be considered a landmark as it pioneered the successful useof an ex-vivo procedure that avoided direct in vivo transfer of thevector. The reason for specifically highlighting this particular case isthat following the initial optimism of the clinical team, two of thefirst ten patients with this condition who were treated in the same waysubsequently developed a leukaemia-like illness. Genetic analysis ofthe malignant cells suggested that the retroviral vector used in thetransfer had also activated an oncogene LIM-only2 (LMO2) which is knownto be associated with some forms of leukaemia. The clinicians reviewingthe situation felt that, although it was not the only cause of themalignancy it was one of the events that triggered it. Similar concernshave been raised in respect of other clinical trials. (Lehrman S 1999) The prime reason for presenting these events is to demonstrate thefact that there is both a theoretical and practical risk of insertionalmutagenesis. Reduction of the risk requires greater specificity of thetargeting of the genetic deficit   perhaps by directing the expressionof the therapeutic genes to various specific tissues utilising bothtransductional and transcriptional targeting. Relph K et al 2004), In terms of specific considerations of the arguments in favour of theuse of retroviral   vectors, one can cite the fact that they have ahighly efficient mechanism of gene transfer together with lowimmunogenicity. It is a well researched and well studied system and isknown to selectively infect actively dividing cells. The conversearguments reflect their disadvantages including their ability todisturb or activate oncogenes, the fact that they are difficulty tospecifically target and it is difficult to obtain high titres in theclinical situation (after Olsen, J. C. 1998). In broad terms, the principles behind the use of retroviral vectorsare that they must be modified in order not to be able to transmit anyovertly pathological coding. This involves the deletion of viral helpergenes such as gag, pol and env   to render the replication processinvalid. This is done by utilisation of a producer or packaging cellline. (Nichols, E. K 1998). An example of a commonly utilised and extensively researched vector isthe MoMuLV. It is an engineered vector which can store 8 kb of RNAwithout compromising packaging efficiency. It is a hybrid cell lineeasily grown in mouse fibroblast cells There is a subdivision of the retroviral vectors known as thelentivirus, which is the only retroviral vector capable of integratinginto the chromosomes of non-dividing cells. This has been effectivelydemonstrated in vitro (Naldini L et al 1996).    The biggest problem with the lentivirus vectors is that theyappeared to only produce very low titres. Some recent researchsuggested that a modification to a amphotropic envelope protien wascapable of allowing higher titre levels. (Rolls M et al 1999) At about the same time that the scientific press was learning aboutthe problems with retroviral transfer (see above) other investigatorswere working with adeno-associated viruses (AAVs). A similar processwas invoked using adeno-associated viruses to correct a genetic defectinvolving coagulation factor IX. The adeno-associated viruses were usedas they were considered to be amongst the safest candidates for genetransfer. They do not naturally cause disease processes in humans andhave only rarely been found to incorporate in a random fashion into thehuman genome. Although it is noted that adenoviruses do cause oncogeneactivation in rodents although it has not been found in humans(Blacklow NR 1988).   The trial had a very positive outcome. (Kay MA et al 2000), but thetrial author (in later research work) published a study which suggestedthat, in study mice, the vector used in the trials actually integrateditself into gene containing regions of DNA more frequently that it didinto non-coding regions (Kay MA et al 2003). The findings were reportedas the fact that new genetic material was randomly distributed amongstall of the chromosomes particularly at sites of gene activity. On thisbasis, there appears to be at least a theoretical basis for thepossibility of similar cellular defects such as occurred in the X-SCIDpatients. Adenoviruses are comparatively simple structures. They arecategorised as double stranded DNA viruses. They have icosahedralcapsids with twelve vertices and seven surface proteins. The virionitself is spherical and non-enveloped and in the region of 70-90 nm insize. Their natural history is that they are spread easily in the naturalstate by the faeco-oral route and also by respiratory inhalation whichclearly has great implications for the treatment of cystic fibrosis. A theoretical analysis would immediately suggest that the adenovirus should be a suitable candidate for gene therapy as they can codefor specific proteins and they do not produce infection pathogenicviral offspring.    The early trials into this particular area were reviewed by Griesenbach(Griesenbach U et al 2002) who pointed out that the cystic fibrosisgene was first cloned in 1989 and in the subsequent   years, 18different trials were carried out, all with rather low degrees ofsuccess. They collectively trialed three different vectors, namelyadenoviruses, adeno-associated viruses 2 and cationic liposomes, andalmost universally found that each vector had a very low rate ofclinically significant gene transfer and none was sufficient to achieveclinical benefit    Plasmid Complexes At its most basic level, a plasmid is a small accessory collection ofDNA which is found in the cytoplasm outside of the nucleus. They arecapable of independent replication and can be manipulated with rathermore ease than nuclear DNA. Early investigations into the field of gene transfer explored thepossibility of plasmid vectors   and demonstrated the feasibility of themethod to effect CFTR gene transfer in vitro (Alton EW 1993). Otherteams had demonstrated the fact that, in clinical use theplasmid-liposome is both nontoxic and non-immunogenic (Hyde,SC et al1993).   This appeared to raise the possibility that many of theimmunological problems encountered by teams working with viral mediatedgene transfer mechanisms might be circumvented. In vivo work (Yoshimura,K et al. 1992) had demonstrated that genescould be transferred into the cytoplasm by this method and Stribling, R(et al 1992) demonstrated that, once there, they would then replicatenormally. Alton experimented with a CFTR-plasmid preparation in miceand demonstrated that it was capable of correcting the chloride levelsin cystic fibrosis mice back to normal levels (Alton EW 1993) Although the initial results were encouraging, clinical trials weredisappointing as the plasmid complex could not easily penetrate thethick mucous residues in the diseased lungs of patients with cysticfibrosis. (Erickson,R 1993) The plasmids typically have a positively charged head-group which isable to bind to the DNA strand and a hydrophobic tail group whichfacilitates the transfer of the complex across the cellular membranes.Initial studies suggest that   between 100-1000 times more DNA isrequired to effect successful gene transfer when this method iscompared to viral vectors. (Santis,G et al 1994). One alternative adaptation has been reported by Stern M (et al 2003)who points out that one of the solution of delivery is to ensure thatthe respiratory epithelium is exposed to the DNA over a long period.Their solution was to encapsulate the CFTR-plasmid in a slow releasebiocompatible polymer. Clinical trials are underway but not yetreported. The adeno-associated vectors appear to have (at least on atheoretical basis) a number of advantages over the vectors that we havealready discussed. They are based on a virus vector that is alreadynon-pathogenic (Berns, KI et al 1995) and has a mechanism that allowsit to be a long-term persistent entity in human cells (Blacklow, NR etal 1989). The adeno-associated vectors are particularly useful indealing with disease process that involve single gene mutations. This,therefore   makes it particularly suitable for single gene disorderssuch as cystic fibrosis and alpha 1 antitrypsin deficiency. (Flotte, TRet al 1998). In addition, some workers have also developed vectors which are capableof   producing either inducible or constitutive expression of thecytokine, interlukin-10   (IL-10) which is an importantanti-inflammatory protein which, on a theoretical basis, could beuseful not only in cystic fibrosis   but in other disease process whichhave chronic inflammation as their prime manifestation (viz Type Idiabetes mellitus or inflammatory bowel disease) (Egan, M et al 1992).These manifestations have been studied and have now reached the stageof early clinical trials (Wagner J et al 2002). With specific reference to the implications of cystic fibrosis, wecan point to trials which have resulted in the expression of cysticfibrosis transmembrane conductance regulator (CFTR) from rAAV(recombinant adeno-associated vectors) in cell cultures (Flotte, TR etal 1993), in animal models (primates) (Afione, SA et al 1996), andagain in early phase I clinical trials (Wagner, J et al 1998) The rAAV-IL-10 model has been studied in bronchial cell culturesfrom cystic fibrosis patients, to determine the functional consequencesof CFTR complementation. This has not yet been demonstrated in vivowith humans but in both mice (Song, S et al 1998), and monkeys (Conrad,CK et al 1996) The overall results of these (and other) studies have shown that   itis possible to achieve long term gene transfer and functionalexpression of the replaced gene (some studies for as long as 18 months)without any overt pathological findings. The histological findings are something of a surprise however, as,at least in both primate and mouse studies, the vector-introduced DNAin this form does not appear to be assimilated into the geneticmaterial of the chromosome, but persists in log strings or concatemersthat are episomal, which is in complete contrast to what happens whenthe naturally occurring agent infects the cell. There is some evidenceto suggest that host cell intrinsic factors such as DNA-dependentprotein kinase play some role in this process (Song, S 2001). The significance of this finding could be that the exclusion of thefunctional, newly introduced DNA from the rest of the nuclear gene poolmay be less likely to produce effects that could be either potentiallydisruptive to the host cell and less likely to activate oncogenes.Phase I trials have demonstrated significant rises of CFTR levels inboth sinus and lung tissue with no evidence of vector-related toxicity.(Wagner, JA et al 1999)   The adeno-associated vectors are constructed from proviraladeno-associated vectors plasmids, which have the Rep and Cap proteinsdeleted and substituting the appropriate gene (CFTR or equivalent)between the rAAV2 inverted terminal repeats together with other signalsequences such as promoter and polyadenylation sequences (Flotte, TR etal 1994) The packaging processes allows for about 5 kb of rAAV genomes to becarried   in the vectors which are prepared using a cotransfectiontechnique utilising human embryonic kidney cells (HEK-293) where thevector plasmid is cotransfected into the cells with helper agents(plasmid pDG) being used to encode the rAAV2-rep and -cap genestogether with the adenovirus helper functions (Grimm, D et al 1998).These are incubated for between 48 and 72 hrs. The cells are then lysedand the resultant agents are then separated by ultracentrifugationagainst a density gradient and affinity chromatography (Zolotukhin, Set al 1999).   The vectors are thereby amenable to being separated by both theirphysical characteristics and also their biological characteristics(infectious units). They are carefully screened to ensure the absenceof any possible contamination from non-modified (replication competentAAVs) prior to clinical usage. (Muzyczka N 1994) The comparatively small â€Å"payload† of the adeno-associated vectorsis proving to be a significant problem. The vector itself is small whencompared to the comparatively large size of the CFTR gene. (Flotte TRet al 1993) It does not leave any room to manoeuvre to manipulate thevector-specific sequences in the way that we have described with theretroviral and adenoviral groups. (Flotte TR et al 2001). A number of authors have characterised the problem with theobservation that the rAAV is typically about 20 nm across which allowspackaging of about 4.7 kb (kilobases) of transferable modified gene(exogenous DNA). (Dong JY et al 1996), If   it is combined with otherenhancers such as the promoter, the polyadenylation signal, thisclearly reduces the capacity for the DNA component. (Duan D et al2000). The Yan paper (Yan Z et al 2000) has outlined a novelexploitation of the unique ability of the rAAV genomes to link togetherin strings which appears to have the ability to bypass this particularlimitation.( Flotte TR 2000). The mechanism itself is the capacity of two distinct rAAV genomes thathappen to simultaneously infect the same target cell to undergo anintermolecular recombination insider the transduced nucleus of thetarget cell. This was a chance finding which arose from work involvingrAAV-derived episomes (Kearns WG et al 1996) in primate airways. It wasfound that some of these episomes were configured as circular head totail concatemers (Duan D et al 1999). This could have been either froma â€Å"rolling circle† replication from a single vector or alternatively,from an intermolecular recombination of material from multiple cellularpenetrations which combined within the palindromic inverted terminalrepeat sequences that are an intrinsic part of the AAV genomestructure. The authors were of the opinion that it was likely to be thelatter eventuality (Duan D et al 1998) It was a logical progression to try to exploit this phenomenon andthereby bypass the limitations imposed by the relatively smallpackaging capacity of rAAV. The adeno-associated vectors capsid onlyhas a capacity of about 5 kb. If we consider that the 145 nucleotidestretch of the AAV-ITR (inverted terminal repeat) sequence has to be inplace at both ends of the single-strand DNA for the vector DNA to beboth replicated and packaged, this only leaves in the region of 4.7 kbof genetically active material in each rAAV particle. As we have cited earlier in relation to the Dong paper (Dong JY et al1996) the CFTR gene accounts for about 4.5 kb which leaves very littlespace for other enhancing material. Because of this, the actual CFTRvector that has been used in the clinical trials to date uses only theminimal promoter activity of the AAVs-ITR itself to actually activateand drive the CFTR expression (Flotte TR et al. 1993). To look at this potentially important development in a little moredetail we can consider Duan’s original paper (et al 2000) and theauthors describe what they call a â€Å"superenhancer†. They describe acombination of a potent simian virus (SV40) and CMV immediate earlyenhancer elements as being packaged in one rAAV vector and a luciferasegene assisted by a small minima;l promoter in another rAAV vector. Invitro experiments suggested that either the SV40 or the intrinsicpromoter activity of the AAV-ITR was sufficient for this purpose. Theintermolecular recombination described above, was found to occur inboth vitro and in vivo experiments and was found to be sufficient tohave a greater than additive effect. Initial results from these varying methods are encouraging insofaras they are producing results of transgene expression which are 100-600times greater than with the unenhanced vector alone. (Yan, Z et al2000) Although not directly referable to our considerations of cysticfibrosis, we should note that Yan’s group and other workers have doneexperimental work which has culminated in the long term expression offunctional levels of erythropoetin with this two vector method in micein vivo. (Naffakh N et al 1995), This basic principle has been further enhanced by Sun (Sun L et al2000) with an ingenious manipulation of the system. They triedinserting the promoter and the first half of the coding sequence in onerAAV vector, immediately followed by a splice donor and then theupstream half of an intron. In the other rAAV vector was the downstreamhalf of the intron, the splice acceptor, the second half of the geneand the polyadenylation signal. To quote the author verbatim: This strategy is efficient enough to mediate high-level expressionand the intermolecular junctions are apparently stable enough tomediate expression for several months in vivo. Although this is clearly an ingenious augmentation of the sameprinciple , we should note that there are both advantages anddisadvantages to both pathways. The strategy that adopts the superenhancer takes its strengths fromthe fact that the recombination mechanisms optimise theposition-independent and orientation-independent functions of theenhancers.   Consideration of the options would suggest that there arefour potential recombination outcomes from the process described.Either of the two vectors could be on the 5’ end of the heterodimericmolecule and clearly either molecule could be in either orientation. With the superenhancer option, all four of these possibleintermolecular recombination outcomes should be functional fortransgene expression whereas if compared to the split intron strategy,by using the same reasoning, it is clear that only one out of the fourcould work. On the other side of the argument, the superenhancer option has thedisadvantage that the actual coding sequence of the gene to betransferred must still fall within the packaging capacity of the vectoritself whereas the split intron allows for a greater functionalexpansion of the packaging capacity. (after Flotte TR et al 2000)   In either event it can be seen that these ingenious modificationseffectively eliminate the main size limitation of the rAAV deliverysystem. Although initial pre-clinical work is encouraging it appearsthat there is still some potential for a degree of immune responseparticularly if the host organism has not experienced the newlyproduced protein before. A number of studies have been done on animal (vertebrate andprimate) with only minimal success. Different administration methodshave been studied including direct administration into the lung (WagnerJ et al 1999), IM injection (Song, S et al 2001 B) and hepatic portalvein infusion (Song, S et al 2001 A)       Human clinical trials have taken place with these vectors (Flotte T etal 1996)(Wagner J et al 1998) (Virella-Lowell, I et al 2000). Thestudies were done on adult male and female patients (18-47 yrs) whowere pseudomonas free and had recently been hospitalised for IVantibiotic infusions The disappointing results were probably a reflection of the factthat the CFTR defect is also interconnected in some way with   aproinflammatory phenotype which appears to be triggered by the abnormalprotein via an unfolded protein response. The authors were able to showevidence that the rAAV-CFTR mechanism was able to   correct the proteinproduction defect, they found it clinically difficult to transduce asufficient number of cells in the airway to reverse the inflammatoryresponse. It is proposed to run further experimental work which combines the  CFTR expression with an anti inflammatory   gene such as the IL-10.There is some in vitro work to suggest that this may be a possibleworkable approach (Teramoto, S et al 1998). Other work on ways ofenhancing the phenotypic expression of the modified genotype hassuggested that the use of various promoters and the rAAV-CMV/beta-actinhybrid promoter (CB-AAT) was found to be tone of the most efficient, atleast when it was compared to the other tested options such as the CMV,E1, U1a and U1b promoter constructs (Teramoto, S et al 1998) Overall, the initial results appear to be encouraging. A singleinjection of an rAAV-CB-AAT vector in animal studies has resulted inhigh level, stable transgene expression which has persisted over thelife span of the experimental animals and that there was no detectableinflammatory response in the animals who had received this form oftreatment (Flotte TR 2002) Flotte (et al 2002) reports that four human clinical trials at bothPhase I and Phase II level are currently underway examining the effectsof the rAAV-CFTR vector. They had an entry cohort of seven patientswith the vector being applied to the nasal lining, the maxillary sinusand the bronchus. The authors report no adverse effects being found andthat they have observed transgene expression at doses of 6 x 108 drp inthe sinus or 1 x 1013 drp in the lung. There are no reported interimfindings from the Phase II trials as yet.    There is clearly a potential for clinical benefit on the basis of theresults found to date if one can extrapolate from in vitro and animalexperiments. The authors comment that, in contrast to the adenovirusvectors there is a marked lack of inflammatory toxicity with the rAAVvectors. Despite these positive comments, we should not, however, overlook thepotential limitations of this particular delivery system. These havebeen identified by various authors as:    The inhibitory effect of preexisting airway inflammation on rAAV transduction in the lungs (Virella-Lowell, I et al 2000) A relative paucity of receptors on the apical surface of airway epithelial cells (Summerford, C et al 1998), The relatively weak nature of the minimal promoters used in the first-generation rAAV-CFTR vectors(Flotte, TR et al 1993), The potential for adverse long-term effects from rAAV vector DNA persistence. (Wu, P et al 2000) The Flotte group are currently investigating this problem by examiningthe hypothesis that the barriers in the airways of the cystic fibrosissufferer are primarily   due to the neutrophil-derived -defensins (HNP1and HNP2) and are actually reversible by the mechanism of AAT proteindelivery (Virella-Lowell, I 2000) Wu and his co-workers have been looking at ways of manipulating thegenetic make up of the rAAV2 capsid and thereby trying to enhance thetargeting ability so that the vector specifically targets the serpinenzyme complex receptor on IB3–1 cells – which is virtually specificfor the Cystic fibrosis bronchial cells Zabner, J (et al 2000), have considered alternative rAAV serotypesin the hope of finding one that will bind more specifically to thebronchial cells Other peripheral adjuncts have also been explored includingpromoters to enhance the effects of complementation and superenhancerswhich have been shown to improve the ability of the rAAV toconcatermerise with the help of smaller amounts of promoter agents  (Duan, D et al 2000). Perhaps it is appropriate to conclude this section on considerationof adeno-associated vectors with a critical analysis of a very recentmulticentre, double-blind, placebo-controlled trial (Moss RB et al2004) This was a well constructed, fully statistically significant anddouble blinded trial which considered   both the safety and thetolerability of repeated doses of adeno-associated serotype 2 vectorrepeatedly given by aerosol inhalation. The vector contained â€Å"cysticfibrosis transmembrane conductance regulator (CFTR) complementary DNA(cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding thecomplete human CFTR cDNA.† The entry cohort was comparatively small with 42 patients, of whom20 received the active agent. A number of indices of airway functionwere measured. Of particular interest to our considerations in thisdissertation was the fact that   vector shedding was found in alltreated subjects up to 90 days after inoculation. And that all subjectswho received the active agent exhibited at least a fourfold increase inthe serum AAV2 neutralising antibody levels. Of the 20 treated patients, six subsequently underwent bronchoscopy.Of those six, gene transfer but not gene expression was demonstrated inall of them. On this basis, it would appear that the actual transfermechanism is effective, but there are other factors present whichappear to interfere with the subsequent expression of the gene in termsof protein production. The study did not comment on the possiblereasons for this. The authors were able to conclude that the delivery system workedwell with no evidence of adverse effects and that treated patientsdemonstrated an â€Å"encouraging trend in improvement in pulmonary functionin patients with CF and mild lung disease.† Lipid 67 We have discussed the various shortcomings of the virus-associatedvectors and this has prompted researchers to explore and consider otheroptimising options for facilitating gene transfer. Zabner (J et al1997) considered the use of cationic lipids in this process and foundone   GL-67:DOPE (colloquially known as lipid 67) which appeared to beparticularly helpful in the process. Cationic lipids appear to show a degree of promise as possible vectorsfor CFTR cDNA transfer into respiratory epithelial cells

Causes of the French Revolution Essay -- History France French Revolut

Causes of the French Revolution The French Revolution was essentially a class war between the emerging Bourgeoisie against the Privileged class, this meant they saw the Privileged class as the only hurdle between themselves and equality within French society. Many of the ideas they pursued stemmed from the enlightenment and they believed that in order to gain their full economic, social and political potential and gain equality, the Bourgeoisie had to eradicate the privileges that were halting their rise in society. To do this they had to seize power for themselves and gaining power within the government and making badly needed changes, such as, improving the tax system, creating a fair system of production where profits went to the producer, improving the whole fiscal system of the government, improving the geographical divisions of France and the problems they caused, plus many more. The revolution was a fight for equality and recognition by the Bourgeoisie, it was not a revolt against poverty, for many of the French people had been living in poverty for centuries and had learnt to live with it . France had prospered in the Eighteenth century. France had had no major famines or plagues, its population had increased, there had been no wars on its soil, industry such as textiles was doing well and offshore trading had increased enormously. It was the Bourgeoisie that had enabled this abundance of wealth and they were emerging as the economic power inside France. But their new found power was being smothered by the privileged class. The privileged class of nobility and clergy, who owned the bulk of the land, were using their ancient rights to plunder most of the profits that were made by the lower classes. This meant that the; Ã ¬Prosperity came only to those who held fairly large estates, who exercised feudal rights, or who could manipulate farm rents.Ã ®1 The only people who fell under these categories were the Nobles of the robe and the clergy. So in order to get the prosperity equally divided in society and thus profit themselves, the bourgeoisie had to get rid of the privileged classes ancient rights. To do this they had to revolt against the government, that supported the privileged classes and which was reluctant to make the necessary reforms. It is seen here that it was the Bourgeoisie were struggling against the Privileged class ... ...hed to them, because their privileges were taking large percentages of profits, adding on-costs to goods, causing massive inflation and reducing the wages of the middle class. In order to do this though they had get the reforms they wanted by having a role in government and take some of the power from the king, because he supported the Aristocracy. At no point in the build up to the revolution did poverty become an issue, the Bourgeoisie were looking after their own interests and trying to create a equal society in which they would become the most powerful and richest. Word Count:- 2,148 words Citation 1. Johnson, D. (1970) The French Revolution, Wayland, London. 2. Townson, D. (1990) France in Revolution, Hodder and Stoughton, London. 3. Townson, D. (1990) France in Revolution, Hodder and Stoughton, London. Bibliography 1. Microsoft Encarta, USA, Funk and Wagnall's, 1994 2. Ergang, R. Europe From the Renaissance to Waterloo Third Edition, USA, Heath and Company, 1967 3. Townson, D. France in Revolution, London, Hodder and Stoghton, 1990 4. Fisher, H. A History of Europe Volume 2, G Modern European History - French Revolution Essay - Jonah Haines - 1293

30 Days Challenge

Day 01 – A picture of yourself with ten facts – Day 01 – A picture of yourself with ten facts *I love God. *I have a Labrador Retriever named Buddy. *My full name is Sharmaine Anne Mediavilla Baloyo. *I'm currently 18 years old. *I love to swim but I'm too afraid to take my life vest during snorkeling. *I have a secret passion in dancing. *My greatest dream is that someday I'll be able to visit Greece. *Taking up Dentistry. *My favorite food is Lasagna. *I sometimes hate my mom but I love her so much.Day 02 – A picture of you and the person you have been closest with the longest – Day 02 – A picture of you and the person you have been closest with the longest. Her name is Imee. We've been bestfriends since Grade2. She's so smart, soft spoken, and I love her to the max. She knows a lot about me. Way back then she's my secret keeper and chismis buddy. Day 03 – A picture of the cast from your favorite show – Day 03 – A pictu re of the cast from your favorite show She plays as Blaire Waldorf in Gossip Girl, but she's known as Leighton Meester. She's my idol.Aside from being so good in acting she also has the talent in singing. =) Day 04 – A picture of your night – Day 04 – A picture of your night A picture with my friends from Ilo-ilo. This was taken after my debut party at chalet. Day 05 – A picture of your favorite memory – Day 05 – A picture of your favorite memory Dec. 12 2009, the very first time I've introduced him to all of my girlfriends. =) wala lang batabata pada sa akon kag cute!!! =) highschool.  ¦ Day 06 – A picture of a person you'd love to trade places with for a day – Day 06 – A picture of a person you'd love to trade places with for a day kay, her name is Esti Ginzburg. The girl whom Chace Crawford my love is currently dating. 🙠 She's very pretty and so hot!!! =))) Day 07 – A picture of your most treasured it em – Day 07 – A picture of your most treasured item hahaha wala lang amo ni ang phone ko nga bag o sbg latest model na sya sang nokia. pati ah, happy lng ko kay sng naguba ang phone ko nakita ko ni sa salakyan ni daddy. MY SAVIOR!  ¦ hahahah Day 08 – A picture that makes you laugh – Day 08 – A picture that makes you laugh Wala lang natawa lang gid ko ya! ))) hahaha! Day 09 – A picture of the person who has gotten you through the most – Day 09 – A picture of the person who has gotten you through the most He's my cousin, he knows everything about me. He's always there for me through thick and thin, love you nong! Day 10 – A picture of the person you do the most screwed up things with – Day 10 – A picture of the person you do the most screwed up things with Her name is Marianne Geena Zaldivar Urbiztondo. vital statistics, 24-36-24. hahhaha! pati joke. she's my bestestfriend ever. indi ko na maalala kung anon g kabalastugan ang mga nagawa natin dahil ang dami dami kaya!!! =) hahahhaa! Day 11 – A picture of something you hate – Day 11 – A picture of something you hate okay, I know most of you like cats. but me, HELL NO! I really cant forget sang time na i thought may gahibi nga baby sagwa gin check ko gulpi lang nag lumpat nagkaradusmo ko sang dalagan. Kag basta daw ka layo gid ya buot ko sa kuring. HAHAHAHAHA ;:) Day 12 – A picture of something you love – Day 12 – A picture of something you love I love dogs, especially if they're still a puppy.Cutie patootie na super cuddly pa. Makakita ko puppy sa dalan or wherever ga stop gid ko na ya, gaka stun ko kay ka mga cute cute bi. =))))  ¦  ¦  ¦ Day 13 – A picture of your favorite band or artist Day 14 – A picture of someone you could never imagine your life without Day 15 – A picture of something you want to do before you die Day 16 – A picture of someone who inspires you Day 17 – A picture of something that has made a huge impact on your life recently Day 18 – A picture of your biggest insecurity Day 19 – A picture and a letterDay 20 – A picture of somewhere you'd love to travel Day 21 – A picture of something you wish you could forget Day 22 – A picture of something you wish you were better at Day 23 – A picture of your favorite book Day 24 – A picture of something you wish you could change Day 25 – A picture of your day Day 26 – A picture of something that means a lot to you Day 27 – A picture of yourself and a family member Day 28 – A picture of something you're afraid of Day 29 – A picture that can always make you smile Day 30 – A picture of someone you miss

Explain and evaluate claims made by linguistic relativists regarding the relationship between language, thought and culture Essay

The relationship between language, culture and thought has been a controversial discussion over decades. Many linguists and thinkers have argued that language lead to large differences in culture and thoughts. Some argue that language controls people’s view and thought of the world, where language embodies worldview, and some argue the otherwise. Language, culture and thought may always refer as together, but any one of them implies the other two. In this essay, I am going to focus on linguistic relativism and I will evaluate claims made by linguistic relativists. Linguistic relativism is a weaker interpretation of linguistic determinism. It is â€Å"a window through which to view the cognitive process, not as an absolute. It’s set forth to be used in looking at a phenomenon differently than one usually would. † (Badhesha, 2001) Linguistic categorize and usage influence thought and certain kinds of non-linguistic behavior. Linguistic relativity hypothesis has always been a controversial and serious topic. In late-eighteenth and early nineteenth century, Boas claimed that there’s no intrinsic relationship between culture and language. (Boas, 1911) Acquainted with Boas, Edward Sapir was impressed with Boas’ statement. Later, he proposed a theory which becomes the most famous attempt in demonstrating relationship between language, culture and thoughts, â€Å"Sapir-Whorf Hypothesis† (Whorfian Hypothesis). The Sapir-Whorf Hypothesis can be broken into two simple concepts: Linguistic Determinism and Linguistic Relativism. Linguistic determinism holds a stronger view. It refers to â€Å"the concept that what is said has only some effect on how concepts are recognized by the mind†, â€Å"A strict view that what is said is directly responsible for what is seen by the mind. † (Badhesha, 2002) This stronger point is supported by Sapir. Sapir: â€Å"language and culture are not intrinsically associated† but â€Å"language and our thought-grooves are inextricably interwoven, [and] are, in a sense, one and the same† (1921: 228, 232) Sapir believes that language and culture are not explicitly related but language, culture and thoughts are interwoven that cannot be unwoven each other. Sapir also expressed his view that language affects how we perceive the world, â€Å"Even comparatively simple acts of perception are very much more at the mercy of the social patterns called words than we might suppose. †¦ We see and hear and otherwise experience very largely as we do because the language habits of our community predispose certain choices of interpretation. † (1929, p. 210) Sapir here explained that language determines our thoughts and culture, it affects our views of the world and culture is a product of language. Sapir’s student, Benjamin Lee Whorf supported and made his theory stronger. Whorf’s claims are both to the extreme, strongest but to the weaker and more cautious at the same time. The extreme perspective is linguistic determinism, where the weaker is linguistic relativism. In fact, linguistic relativism is widely spread through Whorf’s work. Whorf: â€Å"The background linguistic system of each language is not merely a reproducing instrument for voicing ideas but rather is itself the shaper of ideas. † (1940, â€Å"Science and Linguistics,† Technology Review 42: 229-31, 247-8) In this quote, Whorf proposed the stronger form where language determines thought, language shapes our ideas. â€Å"The world is presented in a kaleidoscopic flux of impressions which have to be organized largely by the linguistic systems in our minds. † (Whorf, 1940a:231) This is a weaker form where Whorf argue that the world is somehow under the influence of our linguistic systems. Both in stronger and weaker form, Sapir-Whorf Hypothesis argue that our thoughts, ideas, behavior and culture are under the influence of language. This hypothesis is supported with evidence. Perception of colors is one of the obvious evidence that support language influences our thoughts. Different languages has their way to encode and categorize colors, in English, there are sixteen basic colors and common two color terms â€Å"dark† and â€Å"light†. However, Russian has different words to distinguish light blue (boluboy) and dark blue (siniy). When Russian and English speakers are put to a test to discriminate the two blue colors, Russian is found to be better at it. As Russian perceive the two blue colors as different colors unlike English speakers who categorize it as blue generally. In both English and Chinese, when giving directions verbally, we tend to use â€Å"left† and â€Å"right† instead of E/W/S/N, this is also true in many other languages. However, Kuuk Thaayorra (aboriginal language spoken in Queensland, Australia), they use E/W/S/N to represent â€Å"left† and â€Å"right†, e. g. when they refer to right hand, they may say east hand. Their perception of the world differs from us due to the use of direction terms. To them, the world needs to include precise orientations. This is an example of perception of space which display language affects our perceptions and thoughts. Grammatical feature is another proof of language affects our culture. Whorf asserts that â€Å"users of markedly different grammars are pointed by their grammar towards different types of observations†¦ and hence are not equivalent as observers but must arrive at somewhat different views of the world† (Whorf 1940b:61) Whorf suggested that speakers of different languages will think about the world differently. Hopi language (aboriginal language spoken in Arizona) is early evidence to Whorfian Hypothesis on language and thought. In Hopi language system, they don’t have tenses such as –ed, -ing, -s in SAE [1], they have different perspective of time from SAE speakers. Also, in Hopi, the concept of time cannot be counted and talked like a physical quantity. Language also affects and reflects our culture and values. In Hong Kong, we refer to relatives in different terms, not only â€Å"aunt/uncle†, â€Å"cousins† unlike English. For example, we have different terms for cousins that are older and younger than us, e. g. â€Å"biu-gor† (older male cousin), â€Å"biu-mui† (younger female cousin). It reflects the hierarchy and projects the importance of respecting senior in Chinese family. We can see that Chinese family, including families in Hong Kong divides and identifies its members. For Chinese people, they perceive seniors as people to respect. Sapir-Whorf Hypothesis is the idea that the language that person speaks will affect their perception of the world and accordingly their behavior and culture. In stronger form, language determines the way we think and what we are capable to think of where as linguistic relativity; the weaker form indicates that our thoughts and culture are under the influence of language. Although there are more and more scientific and real life examples that support Sapir-Whorf Hypothesis, anthropologists and linguists still argues weather the hypothesis is too strong or not today. Many argue that instead of language determining our thoughts and culture, they are in fact inter-related and none of them should be dominating the other two. The Sapir-Whorf Hypothesis has received criticism over the years, and it summed up to be three main criticisms, the idea of causality, the methods and translations. While Whorf and Sapir claimed that language affects our perception of the world and the formation of our cultures. Both of them didn’t include the evolution of language, what made up our language, the cultural values that may have been included while setting language system. It is possible that cultural values that might have developed language helped the way we perceive the world. Humboldt (late 18th century) also questioned Sapir-Whorf’s hypothesis, â€Å"The spiritual traits and the structure of the language of a people are so intimately blended that, given either of the two, one should be able to derive the other from it†¦ language is their spirit, and their spirit is their language; it is difficult to imagine any two things more identical. † He also questioned the causality of such hypothesis. Whether if language is the spirit of thoughts and culture or the otherwise. He claims that it is uncertain which one should be derives and to be the spirit of the others. Another obvious criticism is the methods Whorf’s methods. Some believed that Whorf deliberately translated Hopi language in a certain way to support his own hypothesis, to emphasis another thinking system. Linguists, Steven Pinker accused Whorf’s method with strong attitude, â€Å"No one is really sure how Whorf came up with his outlandish claims, but his limited, badly analyzed sample of Hopi speech and his long-term leanings towards mysticism must have helped. † (Pinker, 1994) He also overthrown Whorf’s claim of Hopi people has different perception of time as â€Å"anthropologist Malotki (1983) has found that the Hopi do have a concept of time very similar to ours. † (Neil Parr-Davies, 2001) Translation is another criticism of Sapir-Whorf Hypothesis. Many critics raised the question, if our thoughts are really affected and determined by language, then presumably certain concepts would only be understandable to people that shared the same language. That suggested that if the hypothesis is entirely true, Whorf would have been failed to understand Hopi people’s concept, needless to say even to understand their first thought. Although criticisms are raised against Sapir-Whorf Hypothesis, there are more evidence and claims that support it even in modern days. In fact, psycholinguistic have been studying far beyond perception of color and Hopi language currently, it has been studying and discovering more evidence in modern days such as emotion perception, memory etc. Modern famous researchers like Lera Boroditsky, John A. Lucy believe in Sapir-Whorf Hypothesis, that language indeed influences thoughts, however in relatively narrow ways. I agree the Sapir-Whorf Hypothesis to a large extent. I believe language does influence our thoughts and perceptions of the world. Recently, I have been studying different accents in the world and discovered that it is evidence supporting the linguistic relativists. For example, if someone speaks English in BBC accents or Queen’s English, we would immediately refer them coming from higher social status in Britain. Indeed, our perception can be easily affected by the trivial elements in language as accents. Even nowadays, there are more and more evidence that prove linguistic relativists; we cannot deny the fact that language does somehow shape our daily thoughts and life. Language changes the way we see different culture, it can reflect a certain culture and background of people. Taking Soviet Ukraine as an example, as the prices and supply of product was centrally controlled, they were very cheap and hard to find, and instead of saying â€Å"What are they selling? † they ask, â€Å"Shcho dajut? †(What are they giving? ). Through the language, we can see the cultural values and background of a country, allowing us to understand and perceive different cultures. Nonetheless, I disagree to a small extent as I believe, on one hand, language may shape our thoughts and culture; on the other hand, our culture and thoughts also shape language. Language may act as a tool merely reflecting our thoughts and culture. Under patriarchy and stereotyping, many European countries referred male as a stronger, rational and more dynamic member of the society while female were emotional, silent and subtle one. Leading European languages like French, Spanish are some examples that reflect social stereotyping under patriarchal influence. In French, almost all sport and daylight activities are referred as male, â€Å"le soleil† (the sun) while almost all night time activities are referred as female, â€Å"la lune† (the moon). Sapir-Whorf Hypothesis is a powerful and leading linguistic theory that suggests the relationship between language, culture and thoughts. It can be interpreted as linguistic determinism and relativism; it remains arguable and controversial whether this hypothesis is too strong. Much evidence arises even until today supporting the hypothesis. It is inevitable that every hypothesis receives criticism, but I truly believe the reason why Whorfianism is still being studied today is because we can never deny the influence of language on our thoughts and culture. Language may not be the one the strongly defines our perception and values, but it does affects us in our everyday life.