Showing papers by "University of Oxford published in 1999"
TL;DR: The 95% limits of agreement, estimated by mean difference 1.96 standard deviation of the differences, provide an interval within which 95% of differences between measurements by the two methods are expected to lie.
Abstract: Agreement between two methods of clinical measurement can be quantified using the differences between observations made using the two methods on the same subjects. The 95% limits of agreement, estimated by mean difference +/- 1.96 standard deviation of the differences, provide an interval within which 95% of differences between measurements by the two methods are expected to lie. We describe how graphical methods can be used to investigate the assumptions of the method and we also give confidence intervals. We extend the basic approach to data where there is a relationship between difference and magnitude, both with a simple logarithmic transformation approach and a new, more general, regression approach. We discuss the importance of the repeatability of each method separately and compare an estimate of this to the limits of agreement. We extend the limits of agreement approach to data with repeated measurements, proposing new estimates for equal numbers of replicates by each method on each subject, for unequal numbers of replicates, and for replicated data collected in pairs, where the underlying value of the quantity being measured is changing. Finally, we describe a nonparametric approach to comparing methods.
7,976 citations
TL;DR: The authors investigated the causes of civil war, using a new data set of wars during 1960-99 and found that economic viability appears to be the predominant systematic explanation of rebellion, while atypically severe grievances such as high inequality, a lack of political rights, or ethnic and religious divisions in society.
Abstract: This study investigates the causes of civil war, using a new data set of wars during 1960-99. Rebellion may be explained by atypically severe grievances, such as high inequality, a lack of political rights, or ethnic and religious divisions in society. Alternatively, it might be explained by atypical opportunities for building a rebel organization. Opportunity may be determined by access to finance, such as the scope for extortion of natural resources, and for donations from a Diaspora population. Opportunity may also depend upon factors such as geography: mountains and forests may be needed to incubate rebellion. These explanations are tested and find that opportunity provides considerably more explanatory power than grievance. Economic viability appears to be the predominant systematic explanation of rebellion. The results are robust to correction for outliers, alternative variable definition, and variations in estimation method
3,808 citations
21 Sep 1999
TL;DR: A survey of the theory and methods of photogrammetric bundle adjustment can be found in this article, with a focus on general robust cost functions rather than restricting attention to traditional nonlinear least squares.
Abstract: This paper is a survey of the theory and methods of photogrammetric bundle adjustment, aimed at potential implementors in the computer vision community. Bundle adjustment is the problem of refining a visual reconstruction to produce jointly optimal structure and viewing parameter estimates. Topics covered include: the choice of cost function and robustness; numerical optimization including sparse Newton methods, linearly convergent approximations, updating and recursive methods; gauge (datum) invariance; and quality control. The theory is developed for general robust cost functions rather than restricting attention to traditional nonlinear least squares.
3,521 citations
TL;DR: A number of 5-HT receptor ligands are currently utilised, or are in clinical development, to reduce the symptoms of CNS dysfunction and the functional responses attributed to each receptor in the brain are reviewed.
3,074 citations
TL;DR: The program ESPript allows the rapid visualization, via PostScript output, of sequences aligned with popular programs such as CLUSTAL-W or GCG PILEUP, and can read secondary structure files to produce a synthesis of both sequence and structural information.
Abstract: MOTIVATION: The program ESPript (Easy Sequencing in PostScript) allows the rapid visualization, via PostScript output, of sequences aligned with popular programs such as CLUSTAL-W or GCG PILEUP It can read secondary structure files (such as that created by the program DSSP) to produce a synthesis of both sequence and structural information RESULTS: ESPript can be run via a command file or a friendly html-based user interface The program calculates an homology score by columns of residues and can sort this calculation by groups of sequences It offers a palette of markers to highlight important regions in the alignment ESPript can also paste information on residue conservation into coordinate files, for subsequent visualization with a graphics program AVAILABILITY: ESPript can be accessed on its Web site at http://wwwipbsfr/ESPript Sources and helpfiles can be downloaded via anonymous ftp from ftpipbsfr A tar file is held in the directory pub/ESPriptMOTIVATION: The program ESPript (Easy Sequencing in PostScript) allows the rapid visualization, via PostScript output, of sequences aligned with popular programs such as CLUSTAL-W or GCG PILEUP It can read secondary structure files (such as that created by the program DSSP) to produce a synthesis of both sequence and structural information RESULTS: ESPript can be run via a command file or a friendly html-based user interface The program calculates an homology score by columns of residues and can sort this calculation by groups of sequences It offers a palette of markers to highlight important regions in the alignment ESPript can also paste information on residue conservation into coordinate files, for subsequent visualization with a graphics program AVAILABILITY: ESPript can be accessed on its Web site at http://wwwipbsfr/ESPript Sources and helpfiles can be downloaded via anonymous ftp from ftpipbsfr A tar file is held in the directory pub/ESPript
2,843 citations
TL;DR: The authors surveys the recent empirical literature on economic growth, starting with a discussion of stylized facts, data problems, and statistical methods and concludes that efficiency has grown at different rates across countries, casting doubt on neoclassical models in which technology is a public good.
Abstract: Why do growth rates differ? This paper surveys the recent empirical literature on economic growth, starting with a discussion of stylized facts, data problems, and statistical methods. Six research questions are emphasized, drawing on growth and convergence research. In answering these questions, the paper argues that efficiency has grown at different rates across countries, casting doubt on neoclassical models in which technology is a public good. The latter half of the paper rounds up a variety of findings before providing answers to all six questions, including a short summary of how differences in growth rates arise.
2,396 citations
TL;DR: It is found that 39 different behaviour patterns, including tool usage, grooming and courtship behaviours, are customary or habitual in some communities but are absent in others where ecological explanations have been discounted.
Abstract: As an increasing number of field studies of chimpanzees (Pan troglodytes) have achieved long-term status across Africa, differences in the behavioural repertoires described have become apparent that suggest there is significant cultural variation1,2,3,4,5,6,7. Here we present a systematic synthesis of this information from the seven most long-term studies, which together have accumulated 151 years of chimpanzee observation. This comprehensive analysis reveals patterns of variation that are far more extensive than have previously been documented for any animal species except humans8,9,10,11. We find that 39 different behaviour patterns, including tool usage, grooming and courtship behaviours, are customary or habitual in some communities but are absent in others where ecological explanations have been discounted. Among mammalian and avian species, cultural variation has previously been identified only for single behaviour patterns, such as the local dialects of song-birds12,13. The extensive, multiple variations now documented for chimpanzees are thus without parallel. Moreover, the combined repertoire of these behaviour patterns in each chimpanzee community is itself highly distinctive, a phenomenon characteristic of human cultures14 but previously unrecognised in non-human species.
1,964 citations
TL;DR: This paper is a contribution from the Oxford Centre for Molecular Sciences, which is funded by the BBSRC, EPSRC and MRC.
1,938 citations
TL;DR: It is argued that preeclampsia arises when a universal maternal intravascular inflammatory response to pregnancy decompensates in particular cases, which may occur because either the stimulus or the maternal response is too strong.
1,519 citations
TL;DR: While some subjectivity is required for rating certain criteria, the findings demonstrate that the instrument can be applied by experienced users and providers of health information to discriminate between publications of high and low quality.
Abstract: OBJECTIVE: To develop a short instrument, called DISCERN, which will enable patients and information providers to judge the quality of written information about treatment choices. DISCERN will also facilitate the production of new, high quality, evidence-based consumer health information. DESIGN: An expert panel, representing a range of expertise in consumer health information, generated criteria from a random sample of information for three medical conditions with varying degrees of evidence: myocardial infarction, endometriosis, and chronic fatigue syndrome. A graft instrument, based on this analysis, was tested by the panel on a random sample of new material for the same three conditions. The panel re-drafted the instrument to take account of the results of the test. The DISCERN instrument was finally tested by a national sample of 15 information providers and 13 self help group members on a random sample of leaflets from 19 major national self help organisations. Participants also completed an 8 item questionnaire concerning the face and content validity of the instrument. RESULTS: Chance corrected agreement (weighted kappa) for the overall quality rating was kappa = 0.53 (95% CI kappa = 0.48 to kappa = 0.59) among the expert panel, kappa = 0.40 (95% CI kappa = 0.36 to kappa = 0.43) among information providers, and kappa = 0.23 (95% CI kappa = 0.19 to kappa = 0.27) among self help group members. Higher agreement levels were associated with experience of using the instrument and with professional knowledge of consumer health information. Levels of agreement varied across individual items on the instrument, reflecting the need for subjectivity in rating certain criteria. The trends in levels of agreement were similar among all groups. The final instrument consisted of 15 questions plus an overall quality rating. Responses to the questionnaire after the final testing revealed the instrument to have good face and content validity and to be generally applicable. CONCLUSIONS: DISCERN is a reliable and valid instrument for judging the quality of written consumer health information. While some subjectivity is required for rating certain criteria, the findings demonstrate that the instrument can be applied by experienced users and providers of health information to discriminate between publications of high and low quality. The instrument will also be of benefit to patients, though its use will be improved by training.
1,510 citations
TL;DR: LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.
Abstract: The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and em- bryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.
TL;DR: In this article, the authors presented a method to construct an LNNME-ARTICLE-1999-004, which is used in PhysRevLett.82.944.
Abstract: Reference LNNME-ARTICLE-1999-004doi:10.1103/PhysRevLett.82.944View record in Web of Science Record created on 2007-04-23, modified on 2016-08-08
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TL;DR: In this article, a survey of available economectric evidence accumulated over the past 35 years is presented to help organize and summarize the findings of econometric studies based on time series and cross-section data from various levels of aggregation (laboratory, firm, industry, country).
Abstract: Is public R&D spending complementary and thus "additional" to private R&D spending, or does it substitute for and tend to "crowd out" private R&D? Conflicting answers are given to this question. We survey the body of available economectric evidence accumulated over the past 35 years. A framework for analysis of the problem i is developed to help organize and summarize the findings of econometric studies based on time series and cross-section data from various levels of aggregation (laboratory, firm, industry, country). The findings overall are ambivalent and the existing literature as as a whole is subject to the criticim that the nature of the "experiment(s)" that the investigators envisage is not adequately specified. We conclude by offering suggestions for improving future empirical research on this issue.
TL;DR: In this article, chemical, elemental and isotopic parameters for the assessment of collagen quality are discussed, and it is concluded that there is no unequivocal way to detect natural levels of contamination with the discussed parameters, although their use can identify many cases.
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TL;DR: In this article, Collier and Dollar derive a poverty-efficient allocation of aid and compare it with actual aid allocations, and find that aid is targeted disproportionately to countries with severe poverty and adequate policies -the type of countries where 74 percent of the world's poor live.
Abstract: In the efficient allocation of aid, aid is targeted disproportionately to countries with severe poverty and adequate policies. For a given level of poverty, aid tapers in with policy reform. In the actual allocation of aid, aid tapers out with reform. Aid now lifts about 30 million people a year out of absolute poverty. With a poverty-efficient allocation, the same amount of aid would lift about 80 million people out of poverty. Collier and Dollar derive a poverty-efficient allocation of aid and compare it with actual aid allocations. They build the poverty-efficient allocation in two stages. First they use new World Bank ratings of 20 different aspects of national policy to establish the current relationship between aid, policies, and growth. Onto that, they add a mapping from growth to poverty reduction, which reflects the level and distribution of income. They compare the effects of using headcount and poverty-gap measures of poverty. They find the actual allocation of aid to be radically different from the poverty-efficient allocation. In the efficient allocation, for a given level of poverty, aid tapers in with policy reform. In the actual allocation, aid tapers out with reform. In the efficient allocation, aid is targeted disproportionately to countries with severe poverty and adequate policies - the type of country where 74 percent of the world's poor live. In the actual allocation, such countries receive a much smaller share of aid (56 percent) than their share of the world's poor. With the present allocation, aid is effective in sustainably lifting about 30 million people a year out of absolute poverty. With a poverty-efficient allocation, this would increase to about 80 million people. Even with political constraints introduced to keep allocations for India and China constant, poverty reduction would increase to about 60 million. Reallocating aid is politically difficult, but it may be considerably less difficult than quadrupling aid budgets, which is what the authors estimate would be necessary to achieve the same impact on poverty reduction with existing aid allocations. This paper - a joint product of the Office of the Director, and Macroeconomics and Growth, Development Research Group - is part of a larger effort in the group to examine aid effectiveness.
TL;DR: It is shown that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification.
Abstract: We examine the issue of population stratification in association-mapping studies. In case-control studies of association, population subdivision or recent admixture of populations can lead to spurious associations between a phenotype and unlinked candidate loci. Using a model of sampling from a structured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification. We suggest guidelines as to the number of unlinked marker loci to use.
TL;DR: The sequence of the euchromatic part of human chromosome 22 is reported, which consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
Abstract: Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
TL;DR: Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation to find sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself.
Abstract: The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.
TL;DR: The results indicate that formation of amyloid occurs when the native fold of a protein is destabilized under conditions in which noncovalent interactions, and in particular hydrogen bonding, within the polypeptide chain remain favorable.
Abstract: We have been able to convert a small alpha/beta protein, acylphosphatase, from its soluble and native form into insoluble amyloid fibrils of the type observed in a range of pathological conditions. This was achieved by allowing slow growth in a solution containing moderate concentrations of trifluoroethanol. When analyzed with electron microscopy, the protein aggregate present in the sample after long incubation times consisted of extended, unbranched filaments of 30-50 A in width that assemble subsequently into higher order structures. This fibrillar material possesses extensive beta-sheet structure as revealed by far-UV CD and IR spectroscopy. Furthermore, the fibrils exhibit Congo red birefringence, increased fluorescence with thioflavine T and cause a red-shift of the Congo red absorption spectrum. All of these characteristics are typical of amyloid fibrils. The results indicate that formation of amyloid occurs when the native fold of a protein is destabilized under conditions in which noncovalent interactions, and in particular hydrogen bonding, within the polypeptide chain remain favorable. We suggest that amyloid formation is not restricted to a small number of protein sequences but is a property common to many, if not all, natural polypeptide chains under appropriate conditions.
01 Jan 1999
TL;DR: In this paper, a model of the economic effects of civil war and the post-war period is developed, where the adjustment of the capital stock through capital flight is used to distinguish war-vulnerable and war-safe activities.
Abstract: A model of the economic effects of civil war and the post-war period is developed. A key feature is the adjustment of the capital stock through capital flight. Post-war this flight can either be reversed or continue, depending partly upon how far the capital stock has adjusted to the war. The model is tested on data for all civil wars since 1960. After long civil wars the economy recovers rapidly, whereas after short wars it continues to decline. We then consider the effect on the composition of economic activity, distinguishing between war-vulnerable and war-safe activities. Evidence for Uganda shows such compositional effects to be substantial.
TL;DR: This paper found that bilinguals named numerals in either their first or second language unpredictably, and that the language switching cost was consistently larger when switching to the dominant language from the weaker one.
TL;DR: In this paper, the effects of climate variability and temperature extremes on wheat yields in the context of extreme event effects on crop processes for climatic impacts studies are discussed. But, the authors focus on the effect of temperature on rates of growth and development.
TL;DR: Evidence is found for significant coupling between local and global features of the conformational ensembles adopted in such states and the effective dimensions of the polypeptide chain are found to depend significantly on the level of persistence of regions of secondary structure or features within a conformational ensemble.
Abstract: Pulse field gradient NMR methods have been used to determine the effective hydrodynamic radii of a range of native and nonnative protein conformations. From these experimental data, empirical relationships between the measured hydrodynamic radius (Rh) and the number of residues in the polypeptide chain (N) have been established; for native folded proteins Rh = 4.75N 0.29A and for highly denatured states Rh = 2.21N 0.57A. Predictions from these equations agree well with experimental data from dynamic light scattering and small-angle X-ray or neutron scattering studies reported in the literature for proteins ranging in size from 58 to 760 amino acid residues. The predicted values of the hydrodynamic radii provide a framework that can be used to analyze the conformational properties of a range of nonnative states of proteins. Several examples are given here to illustrate this approach including data for partially structured molten globule states and for proteins that are unfolded but biologically active unde...
TL;DR: In this article, different types of anthropometric measurement error are reviewed, ways of estimating measurement error is critically evaluated, guidelines for acceptable error presented, and ways in which measures of error can be used to improve the interpretation of anthropometrical nutritional status discussed.
Abstract: Anthropometry involves the external measurement of morphological traits of human beings. It has a widespread and important place in nutritional assessment, and while the literature on anthropometric measurement and its interpretation is enormous, the extent to which measurement error can influence both measurement and interpretation of nutritional status is little considered. In this article, different types of anthropometric measurement error are reviewed, ways of estimating measurement error are critically evaluated, guidelines for acceptable error presented, and ways in which measures of error can be used to improve the interpretation of anthropometric nutritional status discussed. Possible errors are of two sorts; those that are associated with: (1) repeated measures giving the same value (unreliability, imprecision, undependability); and (2) measurements departing from true values (inaccuracy, bias). Imprecision is due largely to observer error, as is the most commonly used measure of anthropometric measurements error. This can be estimated by carrying out repeated anthropometric measures on the same subjects and calculating one or more of the following: technical error of measurement (TEM); percentage TEM, coefficient of reliability (R), and intraclass correlation coefficient. The first three of these measures are mathematically interrelated. Targets for training in anthropometry are at present far from perfect, and further work is needed in developing appropriate protocols for nutritional anthropometry training. Acceptable levels of measurement error are difficult to ascertain because TEM is age dependent, and the value is also related to the anthropometric characteristics of the group or population under investigation R>0.95 should be sought where possible, and reference values of maximum acceptable TEM at set levels of R using published data from the combined National Health and Nutrition Examination Surveys I and II (Frisancho, 1990) are given. There is a clear hierarchy in the precision of different nutritional anthropometric measures, with weight and height being most precise. Waist and hip circumference show strong between-observer differences, and should, where possible, be carried out by one observer. Skinfolds can be associated with such large measurement error that interpretation is problematic. Ways are described in which measurement error can be used to assess the probability that differences in anthropometric measures across time within individuals are due to factors other than imprecision. Anthropometry is an important tool for nutritional assessment, and the techniques reported here should allow increased precision of measurement, and improved interpretation of anthropometric data.
TL;DR: The importance of water is not only a recent development in Spain, but also a long-standing phenomenon in the Iberian peninsula as discussed by the authors, where water politics, economics, culture, and engineering have infused and embodied the myriad tensions and conflicts that drove and still drive Spanish society.
Abstract: Spain is arguably the European country where the water crisis has become most acute in recent years. The political and ecological importance of water is not, however, only a recent development in Spain. Throughout this century, water politics, economics, culture, and engineering have infused and embodied the myriad tensions and conflicts that drove and still drive Spanish society. And although the significance of water on the Iberian peninsula has attracted considerable scholarly and other attention, the central role of water politics, water culture, and water engineering in shaping Spanish society on the one hand, and the contemporary water geography and ecology of Spain as the product of centuries of socioecological interaction on the other, have remained largely unexplored. The hybrid character of the water landscape, or “waterscape,” comes to the fore in Spain in a clear and unambiguous manner. The socionatural production of Spanish society can be illustrated by excavating the central role of water po...
TL;DR: A model of three-dimensional shear wave velocity variations in the mantle reveals a tilted low velocity anomaly extending from the core-mantle boundary region beneath the southeastern Atlantic Ocean into the upper mantle beneath eastern Africa, suggesting that Cenozoic flood basalt volcanism in the Afar region and active rifting beneath the East African Rift is linked to an extensive thermal anomaly at the CMB.
Abstract: A model of three-dimensional shear wave velocity variations in the mantle reveals a tilted low velocity anomaly extending from the core-mantle boundary (CMB) region beneath the southeastern Atlantic Ocean into the upper mantle beneath eastern Africa. This anomaly suggests that Cenozoic flood basalt volcanism in the Afar region and active rifting beneath the East African Rift is linked to an extensive thermal anomaly at the CMB more than 45 degrees away. In contrast, a low velocity anomaly beneath Iceland is confined to the upper mantle.
TL;DR: It is suggested that, with joint constraints and a global error compensation scheme, the effects of measurement errors on the reconstruction of the musculoskeletal system and subsequent mechanical analyses can be reduced globally.
01 Feb 1999
TL;DR: In this article, a method of monitoring the efficiency of particle filters is introduced which provides a simple quantitative assessment of sample impoverishment and the authors show how to construct improved particle filters that are both structurally efficient in terms of preventing the collapse of the particle system and computationally efficient in their implementation.
Abstract: The Kalman filter provides an effective solution to the linear Gaussian filtering problem. However where there is nonlinearity, either in the model specification or the observation process, other methods are required. Methods known generically as 'particle filters' are considered. These include the condensation algorithm and the Bayesian bootstrap or sampling importance resampling (SIR) filter. These filters represent the posterior distribution of the state variables by a system of particles which evolves and adapts recursively as new information becomes available. In practice, large numbers of particles may be required to provide adequate approximations and for certain applications, after a sequence of updates, the particle system will often collapse to a single point. A method of monitoring the efficiency of these filters is introduced which provides a simple quantitative assessment of sample impoverishment and the authors show how to construct improved particle filters that are both structurally efficient in terms of preventing the collapse of the particle system and computationally efficient in their implementation. This is illustrated with the classic bearings-only tracking problem.
TL;DR: The rescued influenza A virus is rescued by transfection of 12 plasmids into Vero cells by plasmid-based reverse genetics technique, which facilitates the generation of recombinant influenza viruses containing specific mutations in their genes.
Abstract: We have rescued influenza A virus by transfection of 12 plasmids into Vero cells. The eight individual negative-sense genomic viral RNAs were transcribed from plasmids containing human RNA polymerase I promoter and hepatitis delta virus ribozyme sequences. The three influenza virus polymerase proteins and the nucleoprotein were expressed from protein expression plasmids. This plasmid-based reverse genetics technique facilitates the generation of recombinant influenza viruses containing specific mutations in their genes.