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Future Research Directions in Chronic Obstructive Pulmonary Disease. Published in college essay checklist, Am J Respir Crit Care Med Vol 165. pp 838 -844, 2002 Internet address: www.atsjournals.org. THOMAS L. CROXTON, GAIL G. Writing Uk? WEINMANN, ROBERT M. SENIOR, and JOHN R. HOIDAL. Division of Lung Diseases, National Heart, Lung, and college essay Blood Institute, Bethesda, Maryland; Division of Pulmonary and covering for employment Critical Care Medicine, Department of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri; and Department of Medicine, University of Utah Medical Center, Salt Lake City, Utah. Between 3 and 7 million Americans are currently diagnosed with chronic obstructive pulmonary disease (COPD), and the true prevalence is probably greater than 16 million (1). Many of these individuals suffer years of essay checklist progressive discomfort and disability. With the appointed place of duty essay number of deaths per year attributed to this disease at approximately 100,000 and increasing, COPD is now the fourth leading cause of death in this country (2) and is expected to be third by college checklist, the year 2020. Covering Letter? Cigarette smoking is essay checklist firmly established as the covering major cause of COPD, but approximately one-quarter of Americans continue to smoke, despite aggressive smoking prevention and cessation efforts.
Better means are clearly needed for the prevention and treatment of COPD, and more scientific research is needed to editing checklist, enable improvements in compare essay useful words, its clinical management. Unfortunately, research progress in college editing, this field has been slow. Most basic scientific research over the past 35 years has focused on appointed place essay, the pathogenetic roles of cigarette smoke, inflammation, and college essay editing checklist protease/antiprotease balance, based on the association of COPD with cigarette smoking and the early discovery that a subgroup of patients with emphysema is genetically deficient in an inhibitor of a neutrophil protease (3). Although the world war 2 essays cigarette-inflammation-protease theory captures key features of COPD epidemiology and pathology, this approach has not yet led to a reduction in COPD prevalence or morbidity, to the development of any therapy proven to modify the disease process itself, or to an adequate understanding of how risk factors other than cigarette smoking may contribute to COPD pathogenesis. However, there are encouraging indications for future COPD research. Data that support several novel concepts have been presented, there have been unanticipated discoveries, and college essay editing new experimental approaches and techniques that are aptly suited to COPD research have been developed. Furthermore, elucidation of cellular pathways that are critically involved in COPD pathogenesis may lead rapidly to clinical trials of potential therapeutics, given the improving capabilities of the pharmaceutical industry for development of mechanism-specific drugs.
Because of the enormous public health burden imposed by COPD and topic the urgent need for research progress in this area, the essay checklist National Heart, Lung, and Blood Institute (NHLBI, Bethesda, MD) convened a Working Group to discuss potential directions for future investigations. This group was charged with evaluating the current state of knowledge, identifying critical gaps in our knowledge, and understanding, recognizing the most promising opportunities, and essay topic developing specific recommendations to be used by college editing checklist, the NHLBI in planning its promotion of future COPD research. This article is a summary of that Working Group meeting. Of Duty Essay? Specific recommendations for college editing, future research directions in essays, COPD follow a discussion of several intriguing clinical and epidemiological characteristics of COPD that must be accounted for in a more complete theory of disease pathogenesis and a review of research advances that may foreshadow important new areas of investigation. COPD is college editing a collection of conditions, including emphysema and chronic obstructive bronchitis, which are characterized by persistent airflow limitation that is not substantially reversed by bronchodilators.
COPD is most commonly seen in green essay, long-term smokers and is usually associated with progressive decline in pulmonary function, more rapid than that associated with normal aging. A variety of injurious stimuli, including cigarette smoke, pancreatic elastase, bacterial lipopolysaccharides, cadmium, chloramine-T, oxidants, silica, and severe starvation, can induce changes in animal lungs that model aspects of human COPD (4). College Essay Editing Checklist? Because many seemingly unrelated pathways can cause emphysema or bronchitis, the relevance of any one model to human disease is uncertain. Conversely, no single theory of COPD is yet capable of encompassing the known correlates of the human disease. Hence, it is instructive to consider certain features of COPD that may not be consistent with a simple cigarette neutrophil protease theory. Airway inflammation and parenchymal inflammation are consistent findings in COPD, and the airways of smokers with airflow limitation contain greater numbers of inflammatory cells than do the airways of compare useful words smokers with normal FEV1 (5). College Essay? Nonetheless, several observations suggest that the connection between COPD and airways inflammation is world war 2 technology essays complex.
First, inflammation is observed in the lungs of smokers who do not meet clinical criteria for diagnosis of COPD. Second, inflammation persists long after smoking cessation (6). Third, there is overlap in essay, the profiles of inflammatory cells and mediators expressed in COPD and in place, asthma (7). Fourth, inhaled corticosteroids do not prevent the progressive loss of lung function in subjects with COPD (8). Fifth, the increased numbers of infiltrating macrophages, neutrophils, and lymphocytes in the lungs of individuals with COPD are less than those observed in other inflammatory lung conditions that are not associated with the development of COPD. Furthermore, the essay checklist geographical distribution of inflammatory cells is not always concordant with the sites of lung tissue destruction. In many patients, the expression of COPD is help writing dissertation dominated by essay checklist, signs and symptoms of chronic bronchitis with a common complaint of writing dissertation productive cough. The relationships between mucous hyper-secretion and pathogenetic mechanisms of emphysema and airways obstruction are poorly understood. Although early epidemiological studies of occupational cohorts failed to essay editing, associate mucous hypersecretion with rapid progression of help dissertation uk COPD, some more recent population-based studies have reported an association of chronic mucous hypersecretion with accelerated decline in FEV1 (9). The question of college editing whether mucous metaplasia and place of duty mucous hypersecretion cause annoying but innocuous symptoms or are instead etiologically related to long-term worsening of COPD remains unanswered.
Acute Exacerbations and Bacterial Infections. The slow progression of COPD is typically punctuated by acute exacerbations characterized by essay editing, increased dyspnea, cough, and writing uk mucous production often with a change in mucus color. Airway infections are involved in at least some cases but the cause of most exacerbations is not known. The possible role of pathogens or of the college acute exacerbations themselves in progression of COPD remains uncertain. One suggestion is that cigarette smoking predisposes to bacterial colonization and that bacterial products then contribute to inflammation, activation of proteases, and compare and contrast essay alteration in subsequent host responses to inhaled toxicants (10). Despite striking differences between COPD and asthma, several facts demand continued consideration of the relationship between these diseases. First, some patients with COPD show considerable, albeit partial, reversal of airflow limitation with bronchodilators. Second, methacholine reactivity, a hallmark characteristic of asthma, is strongly associated with accelerated decline in FEV1 in editing checklist, individuals with COPD (11). Third, inflammatory cells and cytokines typical of allergic disease are increased in the airways of patients with COPD and are associated with more severe disease (7, 12). Fourth, transgenic mice overexpressing mediators associated with asthma and allergic disease have shown characteristics of COPD such as airway neutrophilia and covering letter emphysema (13, 14). These observations suggest that certain pathogenetic processes may be common to asthma and COPD.
A basic question regarding pulmonary function in COPD remains unanswered: Why is college editing a simple measure of airflow limitation such a useful index of severity and green delhi essay prognosis across the full range of disease manifestations? Although it is well established that individuals with low FEV1 are more likely to college essay, show rapid decline in drexel admissions essay topic, pulmonary function and are more likely to die from COPD (15, 16), the connection between specific disease mechanisms and impairment in pulmonary function remains unclear. In fact, neither CT quantification of emphysema nor pathological measures of airway structural abnormalities correlated well with FEV1 (17). The meaning of pulmonary function deficits in COPD is further obscured by the fact that FEV1 (% predicted) is college editing checklist significantly associated with lung cancer mortality and cardiovascular mortality, as well as COPD mortality (16). Finally, although FEV1 is an essential measure in COPD research, its usefulness is limited by its inability to reveal regional variations in disease within the compare and contrast essay useful lungs or to essay editing checklist, distinguish between a wide range of pathophysiological processes, including smooth muscle hypertrophy, fibrosis, mucous metaplasia, inflammation, and loss of bronchiolar tethering with alveolar destruction. Variation in Susceptibility to COPD and Disease Progression. Cigarette smoking is by far the most important causative factor for COPD; and in population studies the amount of help uk smoking correlates with loss of lung function. Nonetheless, only a minority of smokers, widely quoted as 15%, ever develop symptomatic COPD (18). College Essay Editing? Several genetic and environmental associations have been identified, but the greatest portion of individual variation in susceptibility cannot be attributed to known factors. Understanding why only world technology certain smokers develop COPD is important not only for understanding the true mechanisms of college editing checklist disease development, but also because such knowledge might allow targeting of intensive smoking interventions to drexel admissions essay, individuals at highest risk and essay editing might enhance the effectiveness of those interventions.
Even among those with COPD, the rate of decline in FEV1 can vary from apparently normal values to greater than 150 ml/year, despite similar smoking histories and writing dissertation uk levels of initial FEV1 (19). Such striking variation in college essay editing, the rate of green delhi decline in FEV1 among individuals suggests that as yet unknown intrinsic or environmental factors may be important determinants of disease course. These factors may or may not be the same as those determining susceptibility to disease. There is also remarkable unexplained variation in the manifestations of COPD with regard to the severity of bronchitic symptoms, the extent of emphysema, and the distribution of emphysematous changes in the lung (centrilobular vs. panlobular patterns). Other Lung Diseases Associated with Cigarette Smoking. Several interstitial lung disorders may be relevant to COPD pathogenesis because they typically occur in college, current or former smokers: idiopathic pulmonary fibrosis (including both usual interstitial pneumonitis and desquamative interstitial pneumonitis), respiratory bronchiolitis-associated interstitial lung disease, and pulmonary histiocytosis X (20). Although all of these conditions involve some form of lung inflammation, each presents a distinctive pattern of pathological findings, reversibility, responsiveness to corticosteroids, and prognosis. A more complete understanding of cigarette smoke effects in the lungs should explain these varied diseases as well as COPD. NEW RESULTS, CONCEPTS, AND OPPORTUNITIES IN COPD RESEARCH. COPD researchers have presented a number of unexpected results, novel ideas, and promising approaches for drexel essay, further research. This section briefly describes some innovative concepts identified by editing, the Working Group that may prove important in COPD pathogenesis and essay useful some more recent methodological advances that will likely be of value to college checklist, research in this field.
Diversity of Protease Functions. In addition to degradation of elastic fibers and other components of the extracellular matrix, it is now appreciated that proteases have many other pathophysiological actions that may be relevant to help uk, COPD pathogenesis (21). Proteases act to facilitate antigen presentation, inactivate host-defensive surfactant protein A, stimulate serous and mucous secretions, liberate chemotaxins from the extracellular matrix, inhibit removal of apoptotic cells, induce and inactivate interleukin 8, and activate tumor necrosis factor and interleukin 1 beta. College Essay Editing? Rational therapeutic agents may possibly be developed by clarification of which alpha protease actions are of importance in world war 2 technology, COPD, identification of which of the many proteases elaborated by inflammatory and college lung septal (endothelial, epithelial, smooth muscle, and fibroblast) cells perform those actions, and design of small molecules with an appropriate spectrum of protease inhibitory activity. Cigarette smoking imposes severe oxidative stress on the lungs both directly, via reactive species in the smoke, and indirectly through activation of inflammatory cells. Oxidative stress may contribute to COPD through many biological actions, including cellular injury, oxidation and world war 2 technology nitration of essay proteins, changes in place of duty essay, gene expression, stimulation of mucous secretion, inactivation of antiproteases, expression of proinflammatory mediators, remodeling of blood vessels, and college essay editing checklist enhancement of apoptosis (22). Markers of oxidative stress (e.g., hydrogen peroxide, 8-isoprostane, and lipid peroxides) are elevated in green, the breath or serum of subjects with COPD, and epidemiological studies have demonstrated negative associations of dietary antioxidant intake with pulmonary function and with obstructive airway disease (23). A plausible risk factor for college editing, the development of COPD is the presence of latent viral infection in the lung.
In a study of surgical specimens, a segment of the adenoviral genome was found in greater copy numbers in tissues from patients with airflow limitation than in tissues from control subjects. In a guinea pig model, latent adenoviral infection potentiated the inflammatory effects of cigarette smoke, and transfection of cells in vitro with adenoviral DNA was shown to activate nuclear factor B and potentiate corticosteroid-resistant production of interleukin 8 (24, 25). Chronic bronchitis is associated with hyperplasia of both epithelial goblet cells and submucosal glands in war 2 technology, the airways. Mucous hypersecretion may also be induced by essay editing, inflammation in the absence of substantial gland enlargement (26). Progress is being made in identifying the cellular pathways by which diverse stimuli, including reactive oxygen species, increase epithelial mucin secretion. The protein tyrosine kinase c-Src and the mitogenactivated protein kinase Erk 1/2 appear to be important in transducing signals initiated by components of cigarette smoke (27). Less is known about the regulation of submucosal glands, despite the fact that these are the source for most of the mucus in and contrast, the airways (28). Emphysematous human lungs showed increased numbers of college editing apoptotic alveolar endothelial and epithelial cells in comparison with control lungs (29). Although the cause and significance of this finding remain uncertain, there are several possible links between programmed cell death and mechanisms of COPD pathogenesis. World War 2 Essays? First, excess protease activity could cause cellular apoptosis through loss of cell matrix attachments.
Second, the apoptotic rate regulates the lifetimes of various inflammatory cells; and cigarette smoke extracts induced apoptosis of alveolar macrophages in vitro (30). Third, neutrophil elastase can inactivate a phosphatidylserine receptor involved in cellular uptake and removal of apoptotic cells (31), possibly enhancing inflammation through diminished release of transforming growth factor beta or through the release of inflammatory mediators from essay editing checklist neutrophils that are not properly removed. Role of Blood Vessels. Treatment of rats with a blocker of the vascular endothelial growth factor (VEGF) type 2 receptor caused emphysema that was associated with endothelial cell apoptosis and with markers of oxidant stress but was not accompanied by inflammation (32). The relevance of this process to COPD is supported by observations that oxidant stress decreases VEGF levels and drexel that expression of both VEGF and its receptor are decreased in emphysema (29). Emphysema might result from failure of a lung cellular and molecular maintenance program due to a vicious cycle of college essay checklist oxidant stress and protease activation. Essay? Little is known regarding chronic regulation of alveolar septal endothelial cells, but studies of college editing larger pulmonary vessels indicate that endothelial injury can lead to increased elastase activity and degradation of compare extracellular matrix (33).
An attractive therapeutic goal would be reversal of emphysema by essay, increasing the number of compare alveoli. One model for this process is the septation of alveoli that occurs during late fetal and postnatal development. Although it has generally been assumed that adult lungs lack a capability for alveolar plasticity, the emphysema caused by lung instillation of elastase in adult rats was reversed by treatment with all- trans retinoic acid (34). A feasibility study of retinoic acid is college essay checklist underway in subjects with COPD. There has been encouraging progress in the identification of technology chemical markers of college essay checklist COPD.
Subjects with stable COPD were shown to covering for employment, have elevated markers of oxidant stress in exhaled air (35), of editing inflammation in help writing uk, serum and sputum (36, 37), and of elastin degradation in editing checklist, urine (38). These results suggest that multifaceted characterization of appointed place COPD patients may be possible by college essay checklist, noninvasive means. Pulmonary function is influenced by help writing uk, heredity (39, 40). There is also familial aggregation of COPD, indicating probable heritability of risk factors for the disease (41). Essay? Precisely how genetic factors contribute to the risks of development and progression of COPD remains unknown, but there has been progress toward identification of covering letter for employment relevant genes. Case control studies suggested associations between COPD and polymorphisms of the alpha1-antitrypsin, tumor necrosis factor alpha, and surfactant protein B genes (19, 42, 43).
A genome-wide screen of families having a proband with severe, early-onset COPD identified interesting regions on several chromosomes that may yield linkages with phenotypes of airflow obstruction and chronic bronchitis (44). Only modest progress has been made in characterizing the lung inflammation associated with COPD, particularly in comparison with the extensive profiling that has been performed in college editing checklist, individuals with asthma. There are increased numbers of CD8 + T cells in the airways and covering letter lung parenchyma of smoking subjects with COPD, and there is a negative correlation between FEV1 (% predicted) and college CD8+ T cell number (45). The large airways of smokers with severe COPD show increased numbers of neutrophils, macrophages, and delhi essay natural killer lymphocytes in comparison with smokers without clinically defined COPD; and essay editing each of these cell types is negatively associated with FEV1 (5). Neutrophils tend to localize with the airway epithelium, but nodules of B lymphocytes are found in the submucosa and adventitia (46). Substantial progress in immunological research should provide a basis for detailed characterization of the place essay inflammatory process in COPD.
Airspace enlargement has been seen in numerous genetic mouse models, including both inbred strains (e.g., tight skin, pallid, and blotchy mice) and mice designed with constitutive overexpression of particular genes (e.g., collagenase or platelet-derived growth factor B). More recently, mouse models with inducible, lung-specific expression of particular cytokines have been shown to manifest lung abnormalities that are clearly not attributable to college checklist, aberrant development of the lung. Overexpression of interleukin 11 in adult mice produced peribronchiolar lymphoid nodules similar to those observed in human COPD but did not cause emphysema (47). Overexpression in adult mice of useful either interferon, a major product of CD8+ lymphocytes, or interleukin 13, a mediator associated with CD4+ T cells and asthma, produced emphysema-like changes (14, 48). These models showed distinguishable profiles of increased protease expression and only interleukin 13 caused mucous metaplasia. Finally, a gene-targeting approach (loss of checklist function) has proven useful for testing the contributions of various matrix metalloproteinases in the development of cigarette smoke-induced emphysema in the mouse (4).
Developments in three techniques for covering for employment, lung imaging may allow more sensitive detection and better quantification of lung injury in smokers and patients with COPD. High-resolution computed tomography (CT) now provides images of essay editing airways as small as 2 mm and indices of parenchymal density that correlate well with diffusing capacity (49). Help? Magnetic resonance imaging (MRI) of tracer gases in essay checklist, the lungs can demonstrate ventilation in real time (50) and may provide a measure of drexel alveolar size (51). Positron emission tomography (PET) can potentially be used to quantify inflammatory cell activity in the lungs (52). These methods may prove to be of great value for characterization of the lung in COPD with respect to localization of disease (e.g., pattern of emphysema by college editing, CT), physiological sequelae (e.g., air trapping by MRI), and in vivo biochemical and cellular analyses (by PET).
Molecular Characterization of Diseased Tissues and Cells. The identification of most human genes paves the way for characterization of diseased tissues at an unprecedented level of molecular detail. The expression levels of a multitude of genes in drexel admissions topic, a tissue can be assayed with microarrays of gene-specific probes, whereas reverse transcription in histological sections can be used to show the distribution of expression of a particular gene at high spatial resolution. Development of antibody-based microarrays may allow characterization of the expression of essay editing multiple genes at the protein level. Of particular interest to COPD research, given the multiplicity of cell types in compare, the lung, are methods such as laser capture microdissection for college essay editing, isolation of RNA from single cells (53) and covering techniques for college editing, reverse transcription and cDNA amplification in situ . Coupled with sensitive assays, these developing methods may allow gene expression profiling at the single-cell level (54). Immunoblot analysis of compare useful words a protein from a single cell may also be possible by amplification of a double-stranded DNA label on the secondary antibody (55). Classes of pharmaceuticals of editing potential usefulness in appointed place of duty, COPD that are either available now or are anticipated in essay, the near future include long-acting M3-selective muscarinic antagonists, leukotriene B4 inhibitors, 5-lipoxygenase inhibitors, phosphodiesterase 4 inhibitors, thromboxane antagonists, endothelin antagonists, adenosine A2a agonists, antioxidants, nuclear factor kappa B inhibitors, adhesion molecule antagonists, p38 mitogen-activated protein kinase inhibitors, interleukin 8 antagonists, tumor necrosis factor antagonists, neutrophil elastase inhibitors, matrix metalloproteinase inhibitors, tachykinin antagonists, mucolytics, antiapoptotic compounds, and enhancers of mucociliary clearance. Even when proof of principle is established, the ability of any of these agents to alter outcomes in COPD remains speculative because the critical pathogenetic pathways for this disease have not yet been determined. An important limiting factor in world war 2, development of drug treatments for COPD is the lack of efficient and economical means to identify which drugs are most likely to be of value and to test their clinical efficacy.
RECOMMENDATIONS FOR FUTURE RESEARCH. There was consensus among members of the Working Group that the following objectives are important to COPD research and college checklist are feasible within approximately five years. Letter For Employment? It was noted that the accomplishment of these goals will require a substantial increase in essay editing, COPD research activity, with training and recruitment of green essay additional researchers and essay enhanced cooperation between universities and essay the pharmaceutical industry. In many cases, the need has long been recognized, but the opportunity to accomplish the research has come about as a result of the development of essay editing new experimental tools and green delhi essay techniques. Description of the Disease Process. Characterization of human lung tissues by advanced molecular, biochemical, microbiological, and histopathological methods. Research progress in COPD is hampered by a lack of fundamental knowledge regarding the college editing pathology of this disease, particularly with regard to dissertation uk, small airways.
Changes with COPD in the structure, cellular composition, inflammatory status, and chemical milieu of the lung are poorly defined, as are the relationships of these changes to clinical manifestations of the disease. There is a need for systematic comparison of lung structural, inflammatory, and essay checklist biochemical characteristics with clinical history, status, and course. Characterization of lung tissues can now be performed with exquisite detail, using advanced methods of immunology, viral and microbial detection, molecular histopathology, microarray profiling of gene expression, and proteomic analysis. An appropriate source of tissues for such studies may be surgical specimens from individuals with suspected lung cancer, a population that is at substantial risk for COPD. An appropriate mechanism might be a cooperative research program that combines the efforts of academic and industrial researchers in characterization of letter a large number of subjects and in the establishment of a repository for essay editing, DNA, tissues, other biological specimens, and green delhi essay clinical data. Biomarkers and intermediate end points. One limitation in COPD research is the lack of readily measurable markers that correlate with disease severity or outcome. Long-term monitoring of declines in FEV1 has been used to identify risk factors and gauge the essay editing efficacy of putative therapies, but that approach is covering slow and expensive. Biomarkers of COPD would be of value for investigations of the college editing natural history and epidemiology of COPD, for phenotyping in genetic studies, and for war 2, clarifying the relationships of animal models to college, human disease.
Validated surrogate markers of essay COPD might also serve as intermediate end points for college essay checklist, evaluations of efficacy and appropriate dosage of drexel potential therapeutic agents in college essay editing checklist, relatively short-term studies. Of Duty Essay? Markers involving noninvasive methods would be of college checklist particular value. A wide range of possible approaches exists, including ( 1 ) chemicals in breath, sputum, blood, or urine that reflect lung inflammation or injury; ( 2 ) improved noninvasive mechanical tests of lung function; ( 3 ) proteomic and help writing dissertation gene expression profiling; and essay checklist ( 4 ) lung imaging by CT, MRI, or PET. Longitudinal and cross-sectional studies of compare and contrast essay well characterized smokers with and without COPD are needed to evaluate the correlation of a broad array of putative markers with COPD susceptibility, severity, exacerbation, and progression. Inflammation. Despite the failure of inhaled corticosteroids to slow the decline of essay editing checklist FEV1 in delhi essay, COPD (8), other anti-inflammatory agents might be highly effective.
Studies are needed to editing, better characterize the inflammation of COPD, to define what is appointed of duty appropriate immune function in the lung, and to discover pharmacological means for ensuring beneficial, rather than injurious, contributions of lung inflammatory cells. Three lines of investigation may be involved. First, extensive characterization of the inflammatory status of essay editing smokers with and without COPD is place of duty needed to college essay editing, define the subtypes of inflammatory cells present, the movement and fate of immune cells recruited to the lung, and the particular cytokines involved. Second, genetic factors governing immune responsiveness should be identified and tested as possible determinants of susceptibility to lung injury. Third, in delhi essay, vitro systems and animal models should be utilized to investigate the effects of tobacco smoke components on inflammatory cells and to study inflammatory cell trafficking and mechanisms of sustained inflammation.
Genetic risk factors. A knowledge of genetic determinants of COPD could lead to recognition of biochemical pathways that contribute to the disease and allow targeting of public health interventions to individuals at college essay greatest risk. A program for identification of genes related to COPD should consider several issues: First, simultaneous characterization of multiple phenotypes will be necessary because different genes may be related to different aspects of the disease (e.g., susceptibility, severity, propensity to exacerbation, rate of progression, and chronic bronchitis vs. Admissions Essay Topic? emphysema). Second, family-based studies involving genome-wide screening by linkage analysis of affected sibling pairs or extended pedigrees should be used because there is a high probability that unsuspected genes are involved. Families in isolated populations, rather than outbred populations like the general U.S. population, may be studied more efficiently. Third, animal models are an essential component of a human genetics program because they can be used to identify candidate genes and to study the pathophysiological ramifications of a defined genotype.
Fourth, case-control association studies of particular candidate genes will eventually be needed to test the relevance of results obtained in particular families to the disease in the general population. Selection criteria for college essay editing, candidate genes should include probable biological relevance to known pathophysiology, evidence of involvement with disease in animal models, and data from human studies for gene linkage with COPD. Fifth, although not ideal for genetic studies, clinical trials involving large numbers of well-characterized subjects with COPD should obtain and archive DNA samples whenever possible to allow for later analysis of candidate genes. Causes and consequences of exacerbations. Although disease exacerbations are a major concern of world technology both patients with COPD and their physicians, an understanding of the origins and development of college essay editing these episodes is lacking. There is a need for research directed toward identifying the bases of COPD exacerbations and clarifying the pathophysiological processes that contribute to worsening of symptoms.
Of particular interest are the roles of infectious agents, other environmental insults, and immune responsiveness in exacerbations and the relationships between exacerbations and the underlying disease process. Mucous metaplasia and excess mucous secretion. Mucous production is troublesome to many patients with COPD, yet little is known regarding the mechanisms of mucous hypersecretion, the benefits and risks associated with increased mucous production, or the means whereby mucin secretion, mucus composition, and appointed of duty essay mucociliary clearance might be therapeutically regulated. Research is college essay editing checklist needed to expand our understanding of the drexel admissions essay topic molecular and cellular mechanisms of mucous metaplasia and excess mucous production. Studies of the submucosal glands of college essay small airways are especially needed because these glands are probably of most importance in COPD and have attracted relatively little research interest. Animal models. The development of new animal models of COPD is important for hypothesis testing regarding pathogenetic mechanisms of COPD. Topics of special interest include the biochemical basis of lung growth, damage, and repair; the necessity and sufficiency of specific inflammatory and mucous pathways for the development of small airways disease; and the reversibility of lung damage.
Efforts should be made to correlate pulmonary physiological abnormalities, radiographic images, proteomic profiles, and small airway pathology in covering letter, these animal models. Lung development and alveolar regeneration. Stimulation of alveolar regeneration is an exciting possibility for disease-modifying therapy of COPD. Fundamental advances in this area are likely to college essay, derive from compare and contrast words animal studies of editing alveolar development in appointed of duty, the late fetal and postnatal periods. Such research might include gene expression and proteomic analyses of the developing lung, studies of the regulation of expression of relevant genes, studies of the coordination of editing checklist vascularization and lung development and repair, use of transgenic mice to evaluate the essay topic role of specific growth factors in the lung, and investigations of the mechanisms whereby toxins (e.g., in utero nicotine) impair lung growth. In addition, studies of alveolar regeneration in adults of essay checklist multiple species are needed to deter-mine the technology capacity of mature lungs for alveolar regrowth and the conditions under which alveolar regeneration can occur. Clinical studies.
Although not extensively discussed, Working Group participants recommended controlled studies to validate or revise current clinical practices. Potential areas for such research include, but are not limited to, indications for long-term oxygen therapy, management of sleep disturbance in college editing, COPD, alleviation of nocturnal hypoxemia, prevention and treatment of exacerbations, and better tools for disease monitoring. Acknowledgment : Participants: Chair John R. World Technology? Hoidal, M.D. (Salt Lake City, UT); Session Chairs David M. Center, M.D. (Boston, MA), Donald J. Massaro, M.D. (Washington, DC), Robert M. Senior, M.D. (St. Louis, MO), Steven D. Shapiro, M.D. (St. Louis, MO), and Edwin K. Silverman, M.D. (Boston, MA); and Carol B. Basbaum, Ph.D. (San Francisco, CA), Linda B. Essay? Clerch, Ph.D. (Washington, DC), Thomas L. Croxton, Ph.D., M.D. (Bethesda, MD), Francis M. Help Writing Dissertation Uk? Cuss, M.D. (Kenilworth, NJ), James Eberwine, Ph.D. (Philadelphia, PA), Dorothy B. College Editing Checklist? Gail, Ph.D. Words? (Bethesda, MD), Jack A. Elias, M.D. (New Haven, CT), Michael D. Goldman, M.D., Sc.D. College Essay Editing Checklist? (Los Angeles, CA), Douglas Hay, Ph.D. (King of Prussia, PA), Peter M. Henson, Ph.D. Of Duty Essay? (Denver, CO), Jonathan Jaffe, M.D. (Kenilworth, NJ), James P. Kiley, Ph.D. College Checklist? (Bethesda, MD), Talmadge E. King, M.D. (San Francisco, CA), Barbara Knorr, M.D. (Rahway, NJ), Claude Lenfant, M.D. (Bethesda, MD), Gloria D. Massaro, M.D. (Washington, DC), George T. O'Connor, M.D. (Boston, MA), Marlene Rabinovitch, M.D. (Toronto, Canada), Sri Ram, Ph.D. Useful? (Bethesda, MD), Garth Rapaport, M.B.Bch., MRCP, FFPM (Greenford, Middlesex, UK), Anuradha Ray, Ph.D. (New Haven, CT), Stephen I. Rennard, M.D. (Omaha, NE), James R. Snapper, M.D. (Research Triangle Park, NC), Rubin M. Tuder, M.D. (Baltimore, MD), Norbert F. Essay Editing? Voelkel, M.D. Help Writing Dissertation Uk? (Denver, CO), Gail G. Weinmann, M.D. (Bethesda, MD), Scott T. Essay? Weiss, M.D., M.S. (Boston, MA), Robert A. Wise, M.D. (Baltimore, MD), Theodore J. Witek, Jr., Dr.P.H. (Ridgefield, CT). 1. Stang P, Lydick E, Silberman C, Kempel A, Keating ET.
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41. Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'Donnell WJ, Reilly JJ, Ginns S, Mentzer S, et al. Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. College Essay Editing? Am J Respir Crit Care Med 1998;157:1770 -1778. 42. Keatings VM, Cave SJ, Henry MJ, Morgan K, O'Connor CM, FitzGerald MX, Kalsheker N. A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to covering, a poor prognosis in COPD. Chest 2000;118:971 -975. 43. Guo X, Lin H-M, Lin Z, Montano M, Sansores R, Wang G, DiAngelo S, Pardo A, Selman M, Floros J. Polymorphisms of surfactant protein gene A, B, D, and of SP-B-linked microsatellite markers in college, COPD of a Mexican population.
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Nakano Y, Muro S, Sakai H, Hirai T, Chin K, Tsukino M, Nishimura K, Itoh H, Pare PD, Hogg JC, Mishima M. Green Essay? Computed tomographic measurements of airway dimensions and editing checklist emphysema in world war 2 technology essays, smokers: correlation with lung function. Am J Respir Crit Care Med 2000;162:1102 -1108. 50. de Lange EE, Mugler JP III, Brookeman JR, Knight-Scott J, Truwit JD, Teates CD, Daniel TM, Bogorad PL, Cates GD. Lung air spaces: MR imaging evaluation with hyperpolarized 3 He gas. Radiology 1999;210:851. 51. Chen XJ, Hedlund LW, Moller HE, Chawla MS, Maronpot RR, Johnson GA.
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( Received in original form August 8, 2001; accepted in final form November 26, 2001 ) Sponsored by the Division of Lung Diseases, National Heart, Lung, and Blood Institute on March 5-6, 2001 in Bethesda, Maryland.
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5 Steps to college essay editing checklist Submitting a Writing Sample That Will Blow Hiring Managers Away. Your resume is down to one page. Your cover letter is memorable, yet professional, and world war 2 technology explains why you’re a great fit for the position. But, you’re not done yet. You scroll down to the supplemental requirements and college essay editing checklist see that you’re supposed to drexel submit a writing sample.
Now what? Should you submit a research paper you wrote as an undergrad, a persuasive email, a personal blog post, a speech that’s kind of college essay editing boring (but that you gave at a prestigious event), or maybe a newsletter you co-wrote? Too often, you’re told that writing samples are simply there to demonstrate your writing ability. Certainly, that’s part of it. And if you start with the process of elimination, this discounts anything with typos, or run-ons, or that’s boring (bye-bye speech). But the trick is what you do next: Conceptualize your application as a complete picture, with your writing sample as a supporting element. Here’s how it works. Drexel Admissions! You know that the essay checklist objective statement is wasted space on your resume (because obviously your objective is to land the for employment job). However, you should come up with a tagline for yourself . Who are you as an essay applicant? Are you a leader? Are you over-the-moon creative?
What do you want the covering interviewer to remember about you? Get really clear about the impression you want to make—maybe even jot down a few words. College Essay Editing! Let’s say you decide you want your tagline to essay words be “brilliant, thoughtful client services professional with a passion for college editing checklist, politics and compare and contrast essay useful words tech startups.” Just so we’re clear, this is for your eyes only, so feel free to think as big—and be as ballsy—as you’d like. Step 2: See What Needs Reinforcement. Essay Editing Checklist! Now that you know what you want to demonstrate, re-read your slogan, resume, and cover letter one right after the other. Do your desired attributes shine through?
For example, maybe you don’t think it’s clear how thoughtful you are (because, “considered all clients’ feelings” would make for technology, kind of a strange resume bullet). Look at your writing samples: A paper on presidential succession—no matter how mind-blowingly well written—isn’t going to evidence how you work with people. So, in this case you’d want to choose a persuasive memo, or perhaps part of essay editing checklist grant that you’ve written; something that shows you think through how programs influence people. Or, perhaps it’s a technical position and you want to underscore your research skills. Take a pass on the witty blog post, and choose the well-researched paper. You can say that you’re a quick and talented study in dissertation, your cover letter, but your writing sample is an opportunity to show (rather than only college tell). Step 3: Consider the Classic Advice. Now that you’ve targeted in on how your writing sample will present you as a candidate, it’s time to revisit the classic advice. First, never send a writing sample with a typo.
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It looks like this: Please see below for a press release I wrote in June 2016 to promote the college editing checklist launch of a new product. I chose this as my writing sample because I believe it demonstrates my ability to concisely and effectively generate interest around new ideas. Photo of covering for employment woman typing courtesy of Marcy Milks#46; Sara McCord is a freelance writer and editing checklist editor, who most frequently covers the career beat. For nearly three years, she was an editor at war 2, The Muse, and she's regularly contributed career advice to Mashable. Her advice has been published across the web ( Forbes , Newsweek , Fast Company , TIME , Inc. , Business Insider , CNBC and more). Sara has experience managing programs; recruiting, interviewing, and referring job applicants; building strategic partnerships; advising executive directors; and supporting a national network of volunteers. Learn more and send her a note through her website, or follow her on Twitter @sarajmccord. Hmmm, seems you#39;ve already signed up for this class.
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cixous essay By Verena Andermatt Conley* Hélène Cixous was born on June 5, 1937, in Oran, Algeria. Essay Editing. In the colonial environment where she grew up, Cixous was in the minority. Her father, a doctor of French-colonial but Jewish origin, died when she was still a little girl. This event marked all of help writing dissertation uk, her writing. College Editing Checklist. Her mother, Eve, now living in Paris, was of Austro-German origin, and German, rather than French, is Cixous's native tongue.
Cixous continues to insist that for her, German is a richer, more guttural language than the more abstract idiom of French. Members of her family were Sephardic Jews, and help writing uk she lived through the persecutions of World War II. Subsequently, Cixous never lost her desire to fight the encroachment of power in all of its forms upon the human body and college essay checklist the human mind. She felt the need to break out of the world in which she was born and look for appointed place other worlds or realities less marked by the horrors of the checklist, political events of her childhood. She found these worlds in fiction. Sensitive to power at institutional levels--familial, academic, political--she has striven to find out help where, historically, such repression occurs and how exclusions are articulated. In addition to reading myths and the German romantics, such as Heinrich von Kleist, Cixous began to study English literature, especially Shakespeare, whose passionate and diverse writings held much attraction.
Antony and Cleopatra and The Tempest , with their scenes of transformations between man and woman, father and daughter, marked her. Cixous went to study in France and began her career as an academic. In 1959, at the age of twenty-two, she passed the prestigious agrégation in English. She married and had two children, a daughter and a son, born in 1959 and 1962. In 1962 she became assistante at the Université de Bordeaux. In 1965 she and her husband were divorced and college checklist Cixous moved from Bordeaux to Paris.
She was maître assistante at the Sorbonne from 1965 to 1967 and was appointed maître de conférences at Nanterre in 1967. Also in delhi essay 1967 she published her first text, Le Prénom de Dieu (God's First Name). In 1968 she became docteur ès lettres . She was appointed chargé de mission to found the experimental Université de Paris VIII-Vincennes, now at Saint Denis, in the aftermath of the student riots of essay checklist, May 1968. An alternative to for employment, the traditional and, in the view of many, repressive French academic environment, Paris VIII was to college, be a center of learning where power structures and hierarchies would be kept to a minimum. The new university soon distinguished itself through the exceptionally high quality of its faculty. Since 1968 Cixous has been professor of English literature at Paris VIII. There, in 1974, she founded the Centre de Recherches en Etudes Féminines, which she is still chairing. In 1969, Cixous founded with Tzvetan Todorov and covering letter Gérard Genette the experimental review Poétique , which soon became a forum for new ways of reading texts on both sides of the Atlantic.
As a university professor, Cixous published her thesis, L'Exil de James Joyce ou 1' art du remplacement (1968; translated as The Exile of James Joyce , 1972). Also in 1969, Cixous published her novel Dedans (Inside, 1986), for which she was awarded the prestigious Prix Médicis. Since then she has published close to fifty novels and plays and some more theoretical essays like La Jeune Née (1975; translated as The Newly Born Woman , 1986), the best known of Cixous's texts to date in college the United States. Cixous continues to be the champion of freedom in her writings. The causes she espouses vary. From a need for personal liberation through a reading of psychoanalysis, she moves on to more collective struggles, the delhi, woman's cause, an interest in the Third World (expressed in her interest in editing Clarice Lispector and Nelson Mandela and in her plays on Cambodia or India), the German and Russian death camps (through Paul Celan, Ossip Mandelstam, Marina Tsvetayeva, Anna Akhmatova). Her involvement in these causes is green, paralleled by other textual and personal encounters: the philosophical texts of Jacques Derrida help her develop her own textual readings; her encounters with Antoinette Fouque, one of the most prominent figures in the women's movement in France, a psychoanalyst and checklist founder of the world war 2 essays, French publishing house Des Femmes, who, for political reasons, never wrote a work of her own; Ariane Mnouchkine, the editing checklist, director of the world war 2 essays, experimental Théâtre du Soleil with whom Cixous has been collaborating for the past decade. Cixous conceives of her life as a constant search for new ways of emancipating the self and others, along with an checklist, ongoing discovery of the mystery of life.
The themes of her work are therefore intricately linked to letter, her meditations and editing cannot simply be abstracted. What sets Cixous apart from many of admissions topic, her contemporaries is college essay editing, her insistence on, and celebration of, life rather than death. Cixous's work does not deal with themes in writing any standard sense of the term. Theme, for her always between quotation marks, deals with ways of inscribing life or death and with articulating the two. Her privileging of life is accompanied by college editing checklist a growing insistence on the fictional and the poetic. The poetic for her, though distinct from the fictional or from theater is not limited to verse. It deals with deliverance from social stigmas through a freeing of language, through invention of new ways of speaking and writing, as well as other ways of seeing, hearing, touching, and compare and contrast essay tasting. Checklist. It is always her relationship with the other, with otherness, that allows for an opening. A transformation of the dynamics of self and useful words other constitutes the political dimension underlying all of college checklist, her writing. That transformation follows a general shift, in her words, from the scene of the unconscious to that of history, or from the essay, autobiographical write yourself! to theater dealing with history. This shift in Cixous's work is similar to college essay editing checklist, that taking place on the French intellectual scene over the last twenty years or so.
Cixous's trajectory, a combination of a fight for life and a meditation on writing, leads her through various causes: the freeing of the self under the impact of psychoanalysis, the freeing of women, legal injustice in France around the letter, trial of the Jewish immigrant Pierre Goldman, the college essay editing, cause of the Third World, the exposure of torture in the death camps. As a young professor of English, Hélène Cixous published articles on English literature in world war 2 technology essays Tel Quel and wrote her thesis on James Joyce. Cixous never hid her ambivalence toward Joyce. On the one hand, she was interested in his techniques, his belief that transformations of linguistic structures would alter mental structures, and his awareness of ideological and college editing checklist political manipulations through language. On the other, she always marked her distance from drexel admissions essay topic, a writing caught up in guilt and the anguish of paradox. Though Joyce influenced her work through his insistence on the necessity to create new languages, on musicalizing literature and joining body and spirit, she criticized him for his creative paradox: for Joyce, one must lose in order to have. In other words, one must kill in college order to covering letter, live, and the movement to life starts with a killing of the other, with death and editing with guilt. This concept differs significantly from letter for employment, Cixous's recognition that even though loss and death are inevitable and indeed necessary for life, the emphasis must be on life. Cixous's first fictional texts, Dedans (1969), and especially her trilogy, Le Troisième Corps , Les Commencements , and Neutre (The Third Body, Beginnings, and Neuter), published from 1970 to 1972, mark a period of college checklist, great hope.
In the aftermath of May 1968, everything seemed possible. Writing under the sign of Marx and Freud or of political and essay libidinal economies, Cixous questions power structures and editing checklist advocates a freeing of self and -- or through -- writing. Written at a time when the euphoria of new discoveries outweighed theoretical divergences, these texts combine many incompatible theories. And Contrast. The freeing of the essay editing checklist, subject and drexel topic the undoing of repression go along with a reevaluation of what has been repressed: body, woman, writing. Dialogue among different voices, and, in the form of intertextual references, with other writings, replaces the monologue of authorial control to keep the text open.
In Le Troisième Corps , for example, the essay editing, voice of the lover echoes that of other fictional lovers, especially those of Kleist's Jeronimo and the count F. from Das Erdbeben in Chili (The Earthquake in Chile) and Die Marquise von O (The Marquise of O), respectively. Freud's rewriting of help, Wilhelm Jensen's Gradiva , a love story dealing with fetishism, entombment, entrapment, and editing checklist life and death in the archeological setting of Pompeii, examining passion in its relation to life and drexel essay death, also haunts Cixous's text. Cixous's political and ideological commitments made her take a stand in editing checklist the 1970s on a trial that polarized the French, that of Pierre Goldman, accused, without sufficient evidence, of murder. Cixous, like Foucault and appointed place essay others, wrote in his defense. Un K. Editing. incompréhensible: Pierre Goldman (An Incomprehensible Kase: Pierre Goldman, 1975), the letter K playing on echoes from Kafka's Der Prozess (The Trial) and covering for employment Vor dem Gesetz (Before the essay editing, Law), is a violent outcry against prejudice in the French legal system. Her stance against repression and social injustice, which she sees as one with the of duty, death drive, led Cixous to espouse the cause of women. In her theoretical Prénoms de personne (Nobody's Name, 1974), a collection of essay checklist, essays on Freud, Hoffmann, Kleist, Poe, and Joyce, she deals with the dissertation uk, association of the unified (phallic) subject, narcissism and death. She denounces in her readings of Poe and Joyce the attempt to college essay editing, put woman on the side of death. She shows how these writers' dialectical structures enclose women in a limited economy and an exchange dominated by help writing dissertation uk a desire for death. To this, she opposes a general economy, a term that Georges Bataille, the contemporary French writer and philosopher, popularized via his works on anthropology and psychoanalysis. Cixous proposes an economy of the college essay, gift, related to spending and loss.
Because for help dissertation Cixous and other contemporary theoreticians the subject exists only in a differential relationship with other subjects, the insistence is on modes of college editing, exchange. Exchange, thought of in terms of giving and receiving, plays a crucial role in the woman question. How does one give, how does one receive? What, in green essay such an exchange, is the relationship to essay editing, alterity and the other? How does exchange affect language and writing? Like many contemporary writers and thinkers, Cixous believes that there is no possible social change -- one with new ways of exchanging -- without linguistic change.
Emphasis on new ways of writing, exchanging and an affirmation of life function as the most important concerns of La Jeune Née (1975), by Cixous and Catherine Clément. The title La Jeune Née plays on Là-je-nais , there I am being born, and La Genet , a reference to the writer Jean Genet, whose poetic writings insist on the general equality of all human beings. In La Jeune Née , Cixous insists on the necessity of displacing the desire for recognition, always based on essay, sexual war, which ends, symbolically, with the succumbing of of duty essay, one of the college, partners. To this, she opposes a desire for alterity, by which, through a journeying toward the other, through a process of identification without fusion, the self goes as far as possible toward the other, lets herself be altered by the other, yet does not become the other. This desire keeps the other alive. To bring about change, Cixous urges women to break their silence, to write themselves. They must write their bodies, their desires, which heretofore have only been talked about by men. Freud's Dora is a central concern in La Jeune Née . Dora's no, which terminates prematurely and on her own volition her sessions with Freud, leaves the latter despondent and defensive. Dora's no stops momentarily the familial merry-go-round of lies and adultery. It also strips Freud of his authority. Yet, and this is clear, Dora's no represents only a strategic moment in a historical configuration, a moment which must be exceeded.
Dora is a major preoccupation in Portrait du soleil (Portrait of the Sun, 1974) and in green delhi essay a play, Portrait de Dora , performed at the Théâtre d'Orsay in 1975, published in 1976, and college checklist translated in 1977. It puts Freud on stage to show the analyst's own projections in world technology his treatment of Dora and his writings on her. Feminine pleasure, which has been denied to women and confiscated by men, is a preoccupation of such texts as La Missexualité, où jouis-je? (The Missexual, Where Am I Having Pleasure?), published in Poétique in 1976, and La Venue à l'écriture (Her Arrival in Writing, 1977; translated 1990), written in collaboration with Annie Leclerc and Madeleine Gagnon. In the latter, playing on la venue , she who has come, and college essay checklist l'avenue , the path, Cixous traces the origin of women's writing to the mother's voice and body. In Souffles (Breath, 1975) --the title evokes breath, inspiration, rhythm--Cixous proposes to analyze the origin of writing in terms of a mother/daughter relationship. Men have made women into covering letter for employment, hysterics; they have vitiated the relationships between women, especially between mother and daughter. Cixous insists on the origin of writing as song, as something that comes from the body. Souffles insists on the necessity of rewriting mythology, the Bible, and literary history from a feminine point of view.
Cixous's personal difficulties contributed to the 1977 text Angst , which deals with the breakdown of a love relationship. College Essay Editing Checklist. The pain and anguish are not expressed in existential, representational terms, but in a metaphoric exchange of letters. The text, as always one of transformation, led Cixous to another phase in her consideration of women's issues. For the next few years Cixous espoused the cause of women in a more militant language, and her work appeared almost exclusively under the imprint of the publishing house Des Femmes, where Cixous enjoyed a close association with Antoinette Fouque, founder of a controversial but influential political group within the women's movement called Politique et Psychanalyse (Psych et po). Technology. She explained her decision to espouse the woman's cause in more militant fashion in an interview (published in essay checklist Verena Andermatt Conley, Hélène Cixous: Writing the Feminine , 1984 and 1990) as reflecting her having attained an intellectual limit which, she felt, had to be surpassed. Consequently she developed a more marked interest in relationships among women, because, as she says, any liberation of women has to come from essay, women, though men are never completely absent in her writing. Cixous's work from this period intersects with both Derrida's essay on Kant, Economimesis, in Mimesis désarticulation (1975) and Jean-François Lyotard's Economie libidinale (1974). College Essay Editing. The attributes masculine and feminine will eventually be replaced by other descriptive terms which make no reference to sexual difference, she believes. For Employment. In this time of transition, Cixous clearly privileges women, capable, in her terms, of giving. She redefines the maternal.
The daughter is always in college tune with the mother. The woman gives because she nourishes the child. War 2 Essays. Because she is college essay editing, able to contain the child, the mother is both container and contained; her relationship to otherness is different from that of for employment, men, to whom things happen from the outside. In her works from the college essay checklist, late l970s and early 1980s, influenced by her reading of Heidegger on poetry and world technology essays language, Cixous asks and works through questions of essay editing checklist, knowledge, innocence, the law, life, and death in Préparatifs de noces au-dela de l'abîme (Wedding Preparations Beyond the writing, Abyss, 1978), Anankè (1979), Illa (1980), With ou l'art de l'innocence (With or the college checklist, Art of Innocence, 1981), and letter for employment Limonade tout était si infini (Lemonade All Was So Infinite, 1982). Her militancy has taken a different turn. Less concerned with flight, flow, and abundance, she now meditates on editing, the sublime and develops the uk, notion of the college essay editing checklist, infinitely small. In the 1970s Cixous also discovered the Brazilian author Clarice Lispector. Meditating on the relationship between life and writing, Lispector put emphasis on the flowing quality of the word and on the origin of--or, as Cixous says, the arrival in--language and world war 2 technology essays writing. In a sense, she had already put into practice what Cixous had been seeking. Cixous's article in Poétique , L'Approche de Clarice Lispector, appeared in college editing checklist 1979, the same year as the bilingual text Vivre l'orange/To Live the Orange , which insists on sweet nourishing juices and on the necessity of keeping the other alive.
In this work, the orange is closely related to uk, the child and birth, to life, as well as to that other paradisiacal fruit, the apple, read simultaneously in English and French as fruit and calling, as apple and appel . Orange, as noun and adjective, as fruit and college checklist color, functions as a locus of correspondences of sight, touch, smell, taste, affecting reading and dissertation writing. A break with Antoinette Fouque in college essay editing the early 1980s prompted Cixous to leave Des Femmes temporarily. Her relationship with the publishing house had been increasingly strained. Cixous claims that she resented the limits a certain militancy imposed on place of duty essay, her freedom. Another text, Le Livre de Promethea ( The Book of college essay checklist, Promethea or Promethea's Book , 1983; translated 1990), written after her encounter with Ariane Mnouchkine, the director of the experimental Théâtre du Soleil, marks a turn. The book is a celebration of their encounter and a feminine rewriting of the dissertation uk, Promethean myth, which, along with the myths of Orpheus and Ulysses, has figured prominently in literature. Le Livre de Promethea marks the culmination of a search for a positive passion, for a positive love and a language that touches lightly, intermittently, without seizing or appropriating, but infusing with life. The Promethean myth, from its epic dimensions of freeing the world and essay editing checklist mankind, is transposed to quotidian passion, to detail, to a market scene, to fruits and flowers. Cixous's encounter with Mnouchkine proved decisive. Mnouchkine was known for her innovative productions of Shakespeare, linking the Elizabethan stage with Far Eastern techniques.
The collaboration also marks in help writing dissertation uk Cixous's production a shift toward what she calls the scene of history. With Mnouchkine, Cixous traveled to Cambodia to study a group of people that had been disinherited by their neighbors. Cixous's and Mnouchkine's play L'histoire terrible mais inachevée de Norodom Sihanouk roi du Cambodge (The Terrible but Unfinished Story of Norodom Sihanouk, King of Cambodia), performed in 1984, is the college essay checklist, story of a people that had lived in happiness and who paid for their innocence with their lives. Always haunted by the notion of paradise, Cixous found in Cambodia the remnants of a people who had lived according to these ethics. Such an overtly political play is a continuation of Cixous's fight against all forms of bodily and spiritual repression. The play is infused with a contemporary reading of the concept of freedom which, for Cixous, is linked to poetry and writing. L'Indiade ou l'lnde de leurs rêves (The Indiad or India of Their Dreams), a play produced in 1986, deals with problems of colonialism, the liberation of India, and nonviolence.
Today, Cixous's major impact may be said to be on the stage, and a new play, Akhmatova (1990), about the Russian poetess Anna Akhmatova, who was caught in the Revolution, develops further in the direction of theater. A script written for a televised film directed by Mnouchkine, La Nuit miraculeuse (The Miraculous Night, 1989), about the heritage of covering, 1789, adds a new twist, that is, an opening to the world of cinema and television. Cixous's historical and political contributions, possibly under the influence of Ariane Mnouchkine, are now her most compelling. Yet, she herself is more at ease in, and derives more pleasure from, the writing of fiction. La Bataille d'Arcachon (The Battle of college essay editing, Arcachon, 1987) extends her experiments with new ways of writing about love, of linking absence and presence, self and other. She also produced Entre l'écriture (Between Writing, or Enter Writing, 1986), a collection of new and previously published meditations on writing and painting. She has also focused on the relationship between writing and history in her lyrical account Manne (Manna, 1988), a tribute to Ossip Mandelstam, the Jewish Russian poet who died under the Stalinist regime, and the poet and fighter against apartheid, Nelson Mandela. A recently published work, Jours de l'an (Days of the Year, 1990), returns to a meditation on green delhi, authorship, on the relation between author and writing, something dear to college essay, Cixous but that seems less pressing today than other more political issues raised in her plays. SURVEY OF CRITICISM. In French, Claudine Fisher's La Cosmogonie d'Hélène Cixous is a painstaking and possibly the writing dissertation uk, most complete explication to date of many of Cixous's writings. Another volume entirely devoted to Cixous consists of the proceedings of a conference organized in college essay her name at the Utrecht Summer School of green delhi, Critical Theory, entitled Hélène Cixous, chemins d'une écriture . Articles have appeared in many reviews, such as Critique and Poétique . Among the best is essay, Lucette Finas's Le Pourpre du neutre, reprinted in drexel essay her Le Bruit d'Iris . Christiane Makward, in Structures du silence ou délire: Marguerite Duras, Hélène Cixous, performs a Lacanian reading in an analysis of the two women writers.
It appears that it is in college editing checklist Great Britain and in the United States that Cixous's work has attracted the most critical attention, especially around issues of feminism. In Great Britain, the chapter in help writing dissertation uk Toril Moi's Sexual/Textual Politics entitled Cixous: An Imaginary Utopia tries to take Cixous to task for being essentialist and for not tying her writing to a precise political and social context. A recent article by Morag Sihach, Their 'Symbolic' exists, it holds power--we, the sowers of disorder, know it only too well, in Between Feminism and Psychoanalysis , rehabilitates Cixous. Though Sihach mainly concentrates on La Jeune Née , she extends her article to Cixous's more recent plays. Writing Differences , edited by Susan Sellers, consists of college checklist, articles by Cixous and her students. It illustrates how students can read in Cixous's way.
The proceedings of a British conference organized around Hélène Cixous in Liverpool in 1989 have been published under the green essay, title The Body and college editing checklist the Text: Hélène Cixous Reading and Teaching (1990). The volume includes many sympathetic articles on and around Cixous. In the United States, chapters have appeared in works such as Jane Gallop's The Daughter's Seduction ; Dina Sherzer's Postmodernist Feminist Fiction, in her Representation in Contemporary French Fiction ; and green Domna C. College Editing. Stanton's, Language and essay Revolution: The Franco-American Disconnection, in The Future of Difference . My own study, Hélène Cixous: Writing the Feminine , presents Cixous to American readers. For a more critical overview that historicizes Cixous without being antagonistic, see my introductions to Cixous's Reading with Clarice Lispector and Readings . * Excerpted from Sartori, Eva, and Dorothy Zimmerman, Editors. French Women Writers: A Bio-Bibliographical Source Book . New York: Greenwood Press, 1991, 66-73.
The bibliography has not been included.