Showing papers by "University of York published in 2004"

Coot: model-building tools for molecular graphics.

Abstract: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics. The map-fitting tools are available as a stand-alone package, distributed as `Coot'.

The metacommunity concept: a framework for multi-scale community ecology

Abstract: The metacommunity concept is an important way to think about linkages between different spatial scales in ecology. Here we review current understanding about this concept. We first investigate issues related to its definition as a set of local communities that are linked by dispersal of multiple potentially interacting species. We then identify four paradigms for metacommunities: the patch-dynamic view, the species-sorting view, the mass effects view and the neutral view, that each emphasizes different processes of potential importance in metacommunities. These have somewhat distinct intellectual histories and we discuss elements related to their potential future synthesis. We then use this framework to discuss why the concept is useful in modifying existing ecological thinking and illustrate this with a number of both theoretical and empirical examples. As ecologists strive to understand increasingly complex mechanisms and strive to work across multiple scales of spatio-temporal organization, concepts like the metacommunity can provide important insights that frequently contrast with those that would be obtained with more conventional approaches based on local communities alone.

The Emotional Brain: The Mysterious Underpinnings of Emotional Life

Abstract: What happens in our brains to make us feel fear, love, hate, anger, joy? do we control our emotions, or do they control us? Do animals have emotions? How can traumatic experiences in early childhood influence adult behavior, even though we have no conscious memory of them? In The Emotional Brain, Joseph LeDoux investigates the origins of human emotions and explains that many exist as part of complex neural systems that evolved to enable us to survive. Unlike conscious feelings, emotions originate in the brain at a much deeper level, says LeDoux, a leading authority in the field of neural science and one of the principal researchers profiled in Daniel Goleman's Emotional Intelligence. In this provocative book, LeDoux explores the underlying brain mechanisms responsible for our emotions, mechanisms that are only now being revealed. The Emotional Brain presents some fascinating findings about our familiar yet little understood emotions. For example, our brains can detect danger before we even experience the feeling of being afraid. The brain also begins to initiate physical responses (heart palpitations, sweaty palms, muscle tension) before we become aware of an associated feeling of fear. Conscious feelings, says LeDoux, are somewhat irrelevant to the way the emotional brain works. He points out that emotional responses are hard-wired into the brain's circuitry, but the things that make us emotional are learned through experience. And this may be the key to understanding, even changing, our emotional makeup. Many common psychiatric problems - such as phobias or posttraumatic stress disorder - involve malfunctions in the way emotion systems learn and remember. Understanding how thesemechanisms normally work will have important consequences for how we view ourselves and how we treat emotional disorders.

A Survey of Outlier Detection Methodologies

Abstract: Outlier detection has been used for centuries to detect and, where appropriate, remove anomalous observations from data. Outliers arise due to mechanical faults, changes in system behaviour, fraudulent behaviour, human error, instrument error or simply through natural deviations in populations. Their detection can identify system faults and fraud before they escalate with potentially catastrophic consequences. It can identify errors and remove their contaminating effect on the data set and as such to purify the data for processing. The original outlier detection methods were arbitrary but now, principled and systematic techniques are used, drawn from the full gamut of Computer Science and Statistics. In this paper, we introduce a survey of contemporary techniques for outlier detection. We identify their respective motivations and distinguish their advantages and disadvantages in a comparative review.

Specific reading disability (dyslexia): what have we learned in the past four decades?

Abstract: We summarize some of the most important findings from research evaluating the hypothesized causes of specific reading disability (dyslexia) over the past four decades. After outlining components of reading ability, we discuss manifest causes of reading difficulties, in terms of deficiencies in component reading skills that might lead to such difficulties. The evidence suggests that inadequate facility in word identification due, in most cases, to more basic deficits in alphabetic coding is the basic cause of difficulties in learning to read. We next discuss hypothesized deficiencies in readingrelated cognitive abilities as underlying causes of deficiencies in component reading skills. The evidence in these areas suggests that, in most cases, phonological skills deficiencies associated with phonological coding deficits are the probable causes of the disorder rather than visual, semantic, or syntactic deficits, although reading difficulties in some children may be associated with general language deficits. Hypothesized deficits in general learning abilities (e.g., attention, association learning, cross-modal transfer etc.) and low-level sensory deficits have weak validity as causal factors in specific reading disability. These inferences are, by and large, supported by research evaluating the biological foundations of dyslexia. Finally, evidence is presented in support of the idea that many poor readers are impaired because of inadequate instruction or other experiential factors. This does not mean that biological factors are not relevant, because the brain and environment interact to produce the neural networks that support reading acquisition. We conclude with a discussion of the clinical implications of the research findings, focusing on the need for enhanced instruction.

Carbohydrate-binding modules: fine-tuning polysaccharide recognition

Abstract: The enzymic degradation of insoluble polysaccharides is one of the most important reactions on earth. Despite this, glycoside hydrolases attack such polysaccharides relatively inefficiently as their target glycosidic bonds are often inaccessible to the active site of the appropriate enzymes. In order to overcome these problems, many of the glycoside hydrolases that utilize insoluble substrates are modular, comprising catalytic modules appended to one or more non-catalytic CBMs (carbohydrate-binding modules). CBMs promote the association of the enzyme with the substrate. In view of the central role that CBMs play in the enzymic hydrolysis of plant structural and storage polysaccharides, the ligand specificity displayed by these protein modules and the mechanism by which they recognize their target carbohydrates have received considerable attention since their discovery almost 20 years ago. In the last few years, CBM research has harnessed structural, functional and bioinformatic approaches to elucidate the molecular determinants that drive CBM–carbohydrate recognition. The present review summarizes the impact structural biology has had on our understanding of the mechanisms by which CBMs bind to their target ligands.

The plastic plant: root responses to heterogeneous supplies of nutrients

Abstract: Contents I. Introduction 000 II. Morphological responses 000 III. Root demography 000 IV. Physiological plasticity 000 V. Root plasticity in patches in competition and symbiosis with microorganisms 000 VI. Influence of patch attributes 000 VII. Control of root proliferation 000 VIII. Conclusions 000 Acknowledgements 000 References 000 Summary When roots encounter a nutrient-rich zone or patch they often proliferate within it. Roots experiencing nutrient-rich patches can also enhance their physiological ion-uptake capacities compared with roots of the same plant outside the patch zone. These plastic responses by the root system have been proposed as the major mechanism by which plants cope with the naturally occurring heterogeneous supplies of nutrients in soil. Various attempts to predict how contrasting species will respond to patches have been made based on specific root length (SRL), root demography and biomass allocation within the patch zone. No one criterion has proved definitive. Actually demonstrating that root proliferation is beneficial to the plant, especially in terms of nitrogen capture from patches, has also proved troublesome. Yet by growing plants under more realistic conditions, such as in interspecific plant competition, and with a complex organic patch, a direct benefit can be demonstrated. Thus, as highlighted in this review, the environmental context in which the root response is expressed is as important as the magnitude of the response itself.

Alien plants in checklists and floras: towards better communication between taxonomists and ecologists

Abstract: The number of studies dealing with plant invasions is increasing rapidly, but the accumulating body of knowledge has unfortunately also spawned increasing confusion about terminology. Invasions are a global phenomenon and comparison of geographically distant regions and their introduced biota is a crucially important methodological approach for elucidation of the determinants of invasiveness and invasibility. Comparative studies of alien floras provide substantial new insights to our understanding of general patterns of plant invasions. Such studies, using information in previously published floras and checklists, are fundamentally dependent on the quality of the assessment of particular species with respect to their taxonomic identity, time of immigration and invasion status. Three crucial decisions should be made when defining the status of a plant species in a given region: (1) whether the taxon is native or alien to that region (origin status); (2) what is its position in the invasion process, i.e., when was it introduced (residence status); and (3) what is the degree of its naturalization and possible invasion (invasion status). Standard floras differ hugely in their treatment of non-native species and those with appropriate categorization of alien species according to their status are rather rare. The present paper suggests definitions of terms associated with plant invasions and places these into the context of floras. Recommendations are outlined on how to deal with the issue of plant invasions in standard floras with the aim of contributing to a better understanding between taxonomists and ecologists and allowing more detailed comparative analyses of alien floras of various regions of the world.

REFMAC5 dictionary: organization of prior chemical knowledge and guidelines for its use.

Abstract: One of the most important aspects of macromolecular structure refinement is the use of prior chemical knowledge. Bond lengths, bond angles and other chemical properties are used in restrained refinement as subsidiary conditions. This contribution describes the organization and some aspects of the use of the flexible and human/machine-readable dictionary of prior chemical knowledge used by the maximum-likelihood macromolecular-refinement program REFMAC5. The dictionary stores information about monomers which represent the constitutive building blocks of biological macromolecules (amino acids, nucleic acids and saccharides) and about numerous organic/inorganic compounds commonly found in macromolecular crystallography. It also describes the modifications the building blocks undergo as a result of chemical reactions and the links required for polymer formation. More than 2000 monomer entries, 100 modification entries and 200 link entries are currently available. Algorithms and tools for updating and adding new entries to the dictionary have also been developed and are presented here. In many cases, the REFMAC5 dictionary allows entirely automatic generation of restraints within REFMAC5 refinement runs.

Developmental dyslexia and specific language impairment: same or different?

Abstract: Developmental dyslexia and specific language impairment (SLI) were for many years treated as distinct disorders but are now often regarded as different manifestations of the same underlying problem, differing only in severity or developmental stage. The merging of these categories has been motivated by the reconceptualization of dyslexia as a language disorder in which phonological processing is deficient. The authors argue that this focus underestimates the independent influence of semantic and syntactic deficits, which are widespread in SLI and which affect reading comprehension and impair attainment of fluent reading in adolescence. The authors suggest that 2 dimensions of impairment are needed to conceptualize the relationship between these disorders and to capture phenotypic features that are important for identifying neurobiologically and etiologically coherent subgroups.

Plant and mycorrhizal regulation of rhizodeposition

Abstract: The loss of carbon from roots (rhizodeposition) and the consequent proliferation of microorganisms in the surrounding soil, coupled with the physical presence of a root and processes associated with nutrient uptake, gives rise to a unique zone of soil called the rhizosphere. In this review, we bring together evidence to show that roots can directly regulate most aspects of rhizosphere C flow either by regulating the exudation process itself or by directly regulating the recapture of exudates from soil. Root exudates have been hypothesized to be involved in the enhanced mobilization and acquisition of many nutrients from soil or the external detoxification of metals. With few exceptions, there is little mechanistic evidence from soil-based systems to support these propositions. We conclude that much more integrated work in realistic systems is required to quantify the functional significance of these processes in the field. We need to further unravel the complexities of the rhizosphere in order to fully engage with key scientific ideas such as the development of sustainable agricultural systems and the response of ecosystems to climate change. Contents I. Introduction 460 II. What is rhizodeposition? 460 III. Regulation of rhizodeposition 460 IV. How large is the root exudation C flux? 463 V. How responsive is the root exudation C flux? 463 VI. How responsive is the microbial community to root exudation? 464 VII. The role of root exudates in nutrient acquisition 464 VIII. Mycorrhizal fungi and rhizodeposition 471 IX. Future thoughts 474 Acknowledgements 474 References 474.

Phonemes, rimes, vocabulary, and grammatical skills as foundations of early reading development: evidence from a longitudinal study.

Abstract: The authors present the results of a 2-year longitudinal study of 90 British children beginning at school entry when they were 4 years 9 months old (range = 4 years 2 months to 5 years 2 months). The relationships among early phonological skills, letter knowledge, grammatical skills, and vocabulary knowledge were investigated as predictors of word recognition and reading comprehension. Word recognition skills were consistently predicted by earlier measures of letter knowledge and phoneme sensitivity (but not by vocabulary knowledge, rhyme skills, or grammatical skills). In contrast, reading comprehension was predicted by prior word recognition skills, vocabulary knowledge, and grammatical skills. The results are related to current theories about the role of phonological, grammatical, and vocabulary skills in the development of early reading skills.

Water Manganese Exposure and Children's Intellectual Function in Araihazar, Bangladesh

Abstract: Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child’s home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose–response manner, such that children with water As levels > 50 μg/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 μg/L. The association was generally stronger for well-water As than for urinary As.

Overcoming barriers to health service access: influencing the demand side.

Abstract: Evidence suggests that demand-side barriers may be as important as supply factors in deterring patients from obtaining treatment. Yet relatively little attention is given, either by policy makers or researchers, to ways of minimizing their effect. These barriers are likely to be more important for the poor and other vulnerable groups, where the costs of access, lack of information and cultural barriers impede them from benefiting from public spending. Demand barriers present in low- and middle-income countries and evidence on the effectiveness of interventions to overcome these obstacles are reviewed. Demand barriers are also shown to be important in richer countries, particularly among vulnerable groups. This suggests that while barriers are plentiful, there is a dearth of evidence on ways to reduce them. Where evidence does exist, the data and methodology for evaluating effectiveness and cost-effectiveness is insufficient. An increased focus on obtaining robust evidence on effective interventions could yield high returns. The likely nature of the interventions means that pragmatic policy routes that go beyond the traditional boundaries of the public health sector are required for implementing the findings.

CD133, a novel marker for human prostatic epithelial stem cells

Abstract: Stem cells are clonogenic cells with self-renewal and differentiation properties, which may represent a major target for genetic damage leading to prostate cancer and benign prostatic hyperplasia. Stem cells remain poorly characterised because of the absence of specific molecular markers that permit us to distinguish them from their progeny, the transit amplifying cells, which have a more restricted proliferative potential. Human CD133 antigen, also known as AC133, was recently identified as a haematopoietic stem cell marker. Here we show that a small population (approximately 1%) of human prostate basal cells express the cell surface marker CD133 and are restricted to the alpha(2)beta(1)(hi) population, previously shown to be a marker of stem cells in prostate epithelia. alpha(2)beta(1)(hi)/CD133(+) cells exhibit two important attributes of epithelial stem cells: they possess a high in vitro proliferative potential and can reconstitute prostatic-like acini in immunocompromised male nude mice.

Sources of Variation and Bias in Studies of Diagnostic Accuracy: a Systematic Review

Abstract: Diagnostic tests are of crucial importance in health care. They are performed to reduce uncertainty concerning whether a patient has a condition of interest. A thorough evaluation of diagnostic tests is necessary to ensure that only accurate tests are used in practice. Diagnostic accuracy studies are a vital step in this evaluation process. Diagnostic accuracy studies aim to investigate how well the results from a test being evaluated (index test) agree with the results of the reference standard. The reference standard is considered the best available method to establish the presence or absence of a condition (target condition). In a classic diagnostic accuracy study, a consecutive series of patients who are suspected of having the target condition undergo the index test; then, all patients are verified by the same reference standard. The index test and reference standard are then read by persons blinded to the results of each, and various measures of agreement are calculated (for example, sensitivity, specificity, likelihood ratios, and diagnostic odds ratios).

The logrank test.

Abstract: We often wish to compare the survival experience of two (or more) groups of individuals. For example, the table shows survival times of 51 adult patients with recurrent malignant gliomas1 tabulated by type of tumour and indicating whether the patient had died or was still alive at analysis—that is, their survival time was censored.2 As the figure shows, the survival curves differ, but is this sufficient to conclude that in the population patients with anaplastic astrocytoma have worse survival than patients with glioblastoma? View this table: Weeks to death or censoring in 51 adults with recurrent gliomas1 (A=astrocytoma, G=glioblastoma) Fig 1 Survival curves for women with glioma by diagnosis We could compute survival curves3 for each group and compare the proportions surviving at any specific time. The weakness of this approach is that it does not provide a comparison of the total survival experience of the two groups, but rather gives a comparison at some arbitrary time point(s). In the figure the difference in survival is greater at some times than others and eventually becomes …

Corporate cash holdings: An empirical investigation of UK companies

Abstract: This paper investigates the empirical determinants of corporate cash holdings for a sample of UK firms. We focus on the importance of managerial ownership among other corporate governance characteristics including board structure and ultimate controllers of companies. We present evidence of a significant non-monotonic relation between managerial ownership and cash holdings. In addition, we observe that the way in which managerial ownership exerts influence on cash holdings does not change with board composition and, in general, the presence of ultimate controllers. The results reveal that firms' growth opportunities, cash flows, liquid assets, leverage and bank debt are important in determining cash holdings. Our analysis also suggests that firm heterogeneity and endogeneity are crucial in analysing the cash structure of firms.

Emotion perception from dynamic and static body expressions in point-light and full-light displays.

Abstract: Research on emotion recognition has been dominated by studies of photographs of facial expressions. A full understanding of emotion perception and its neural substrate will require investigations that employ dynamic displays and means of expression other than the face. Our aims were: (i) to develop a set of dynamic and static whole-body expressions of basic emotions for systematic investigations of clinical populations, and for use in functional-imaging studies; (ii) to assess forced-choice emotion-classification performance with these stimuli relative to the results of previous studies; and (iii) to test the hypotheses that more exaggerated whole-body movements would produce (a) more accurate emotion classification and (b) higher ratings of emotional intensity. Ten actors portrayed 5 emotions (anger, disgust, fear, happiness, and sadness) at 3 levels of exaggeration, with their faces covered. Two identical sets of 150 emotion portrayals (full-light and point-light) were created from the same digital footage, along with corresponding static images of the 'peak' of each emotion portrayal. Recognition tasks confirmed previous findings that basic emotions are readily identifiable from body movements, even when static form information is minimised by use of point-light displays, and that full-light and even point-light displays can convey identifiable emotions, though rather less efficiently than dynamic displays. Recognition success differed for individual emotions, corroborating earlier results about the importance of distinguishing differences in movement characteristics for different emotional expressions. The patterns of misclassifications were in keeping with earlier findings on emotional clustering. Exaggeration of body movement (a) enhanced recognition accuracy, especially for the dynamic point-light displays, but notably not for sadness, and (b) produced higher emotional-intensity ratings, regardless of lighting condition, for movies but to a lesser extent for stills, indicating that intensity judgments of body gestures rely more on movement (or form-from-movement) than static form information.

Review of guidelines for good practice in decision-analytic modelling in health technology assessment

Abstract: BACKGROUND: Decision-analytic models represent an explicit way to synthesise evidence currently available on the outcomes and costs of alternative (mutually exclusive) healthcare interventions. Usually their objective is to obtain a clear understanding of the relationship between incremental cost and effect in order to assess relative cost-effectiveness and to determine which interventions should be adopted given existing information. Given that the use of decision-analytic modelling for health technology assessment has increased exponentially in recent years, there is a need to consider how good practice in the field has been defined. Since the 1980s, several published guidelines have been available for those developing and evaluating decision-analytic models for health technology assessment. However, given the speed at which economic evaluation methodology has progressed, it is timely to review, critically appraise and consolidate those existing guidelines on the use of decision-analytic modelling in health technology assessment, and to identify key issues where guidance is lacking. OBJECTIVES: To identify existing guidelines and develop a synthesised guideline plus accompanying checklist. In addition to provide guidance on key theoretical, methodological and practical issues and consider the implications of this research for what might be expected of future decision-analytic models.

Detection of Oxygen and Carbon in the Hydrodynamically Escaping Atmosphere of the Extrasolar Planet HD 209458b

Abstract: Four transits of the planet orbiting the star HD 209458 were observed with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope. The wavelength domain (1180-1710 A) includes H I as well as C I, C II, C IV, N V, O I, S I, Si II, Si III, and Si IV lines. During the transits, absorptions are detected in H I, O I, and C II (5% ± 2%, 13% ± 4.5%, and 7.5% ± 3.5%, respectively). No absorptions are detected for other lines. The 5% mean absorption over the whole H I Lyα line is consistent with the previous detection completed in 2003 at higher resolution (Vidal-Madjar et al.). The absorption depths in O I and C II show that oxygen and carbon are present in the extended upper atmosphere of HD 209458b (nicknamed "Osiris"). These species must be carried out up to the Roche lobe and beyond, most likely in a state of hydrodynamic escape.

Criticizing and reassuring oneself: An exploration of forms, styles and reasons in female students.

Abstract: Objectives. Self-critical people, compared with those who self-reassure, are at increased risk of psychopathology. However, there has been little work on the different forms and functions of these self-experiences. This study developed two selfreport scales to measure forms and functions of self-criticism and self-reassurance and explore their relationship to depression. Methods. A self-report scale measuring forms of self-criticism and self-reassuring, and a scale measuring possible functions of self-criticism, together with a measure of depression and another self-criticism scale (LOSC), were given to 246 female students. Results. Self-criticizing vs. self-reassuring separated into two components. Forms of self-criticizing separated into two components related to: being self-critical, dwelling on mistakes and sense of inadequacy; and a second component of wanting to hurt the self and feeling self-disgust/hate. The reasons/functions for self-criticism separated into two components. One was related to desires to try to self-improve (called self-improving/ correction), and the other to take revenge on, harm or hurt the self for failures (called self-harming/persecuting). Mediation analysis suggested that wanting to harm the self may be particularly pathogenic and is positively mediated by the effects of hating the self and negatively mediated by being able to self-reassure and focus on one’ s positives. Conclusions . Self-criticism is not a single process but has different forms, functions, and underpinning emotions. This indicates a need for more detailed research into the variations of self-criticism and the mechanisms for developing self-reassurance.

Real Time Scheduling Theory: A Historical Perspective

Abstract: In this 25th year anniversary paper for the IEEE Real Time Systems Symposium, we review the key results in real-time scheduling theory and the historical events that led to the establishment of the current real-time computing infrastructure. We conclude this paper by looking at the challenges ahead of us.

Beyond phonological skills: broader language skills contribute to the development of reading

Abstract: This paper reports a study that followed the development of reading skills in 72 children from the age of 8.5 to 13 years. Each child was administered tests of reading, oral language, phonological skills and nonverbal ability at time 1 and their performance on tests of reading comprehension, word recognition, nonword decoding and exception word reading was assessed at time 2. In addition to phonological skills, three measures of non-phonological oral language tapping vocabulary knowledge and listening comprehension were unique concurrent predictors of both reading comprehension and word recognition at time 1. Importantly, all three measures of oral language skill also contributed unique variance to individual differences in reading comprehension, word recognition and exception word reading four and a half years later, even when the autoregressive effects of early reading skill were controlled. Moreover, the extent to which a child's word recognition departed from the level predicted from their decoding ability correlated with their oral language skills. These findings suggest that children's oral language proficiency, as well as their phonological skills, influences the course of reading development.

Explaining income-related inequalities in doctor utilisation in Europe.

Abstract: This paper presents new international comparative evidence on the factors driving inequalities in the use of GP and specialist services in 12 EU member states. The data are taken from the 1996 wave of the European Community Household Panel (ECHP). We examine two types of utilisation (the probability of a visit and the conditional number of positive visits) for two types of medical care: general practitioner and medical specialist visits using probit, truncated Negbin and generalised Negbin models. We find little or no evidence of income-related inequity in the probability of a GP visit in these countries. Conditional upon at least one visit, there is even evidence of a somewhat pro-poor distribution. By contrast, substantial pro-rich inequity emerges in virtually every country with respect to the probability of contacting a medical specialist. Despite their lower needs for such care, wealthier and higher educated individuals appear to be much more likely to see a specialist than the less well-off. This phenomenon is universal in Europe, but stronger in countries where either private insurance cover or private practice options are offered to purchase quicker and/or preferential access. Pro-rich inequity in subsequent visits adds to this access inequity but appears more related to regional disparities in utilisation than to other factors. Despite decades of universal and fairly comprehensive coverage in European countries, utilisation patterns suggest that rich and poor are not treated equally.

Developments in the CCP4 molecular-graphics project

Abstract: Progress towards structure determination that is both high-throughput and high-value is dependent on the development of integrated and automatic tools for electron-density map interpretation and for the analysis of the resulting atomic models. Advances in map-interpretation algorithms are extending the resolution regime in which fully automatic tools can work reliably, but at present human intervention is required to interpret poor regions of macromolecular electron density, particularly where crystallographic data is only available to modest resolution [for example, I/σ(I) < 2.0 for minimum resolution 2.5 A]. In such cases, a set of manual and semi-manual model-building molecular-graphics tools is needed. At the same time, converting the knowledge encapsulated in a molecular structure into understanding is dependent upon visualization tools, which must be able to communicate that understanding to others by means of both static and dynamic representations. CCP4mg is a program designed to meet these needs in a way that is closely integrated with the ongoing development of CCP4 as a program suite suitable for both low- and high-intervention computational structural biology. As well as providing a carefully designed user interface to advanced algorithms of model building and analysis, CCP4mg is intended to present a graphical toolkit to developers of novel algorithms in these fields.

Plant cell cultures for the production of recombinant proteins

Abstract: The use of whole plants for the synthesis of recombinant proteins has received a great deal of attention recently because of advantages in economy, scalability and safety compared with traditional microbial and mammalian production systems. However, production systems that use whole plants lack several of the intrinsic benefits of cultured cells, including the precise control over growth conditions, batch-to-batch product consistency, a high level of containment and the ability to produce recombinant proteins in compliance with good manufacturing practice. Plant cell cultures combine the merits of whole-plant systems with those of microbial and animal cell cultures, and already have an established track record for the production of valuable therapeutic secondary metabolites. Although no recombinant proteins have yet been produced commercially using plant cell cultures, there have been many proof-of-principle studies and several companies are investigating the commercial feasibility of such production systems.