Showing papers by "University of Oxford published in 1992"

Evolutionary games and spatial chaos

Abstract: MUCH attention has been given to the Prisoners' Dilemma as a metaphor for the problems surrounding the evolution of coopera-tive behaviour1–6. This work has dealt with the relative merits of various strategies (such as tit-for-tat) when players who recognize each other meet repeatedly, and more recently with ensembles of strategies and with the effects of occasional errors. Here we neglect all strategical niceties or memories of past encounters, considering only two simple kinds of players: those who always cooperate and those who always defect. We explore the consequences of placing these players in a two-dimensional spatial array: in each round, every individual 'plays the game' with the immediate neighbours; after this, each site is occupied either by its original owner or by one of the neighbours, depending on who scores the highest total in that round; and so to the next round of the game. This simple, and purely deterministic, spatial version of the Prisoners' Dilemma, with no memories among players and no strategical elaboration, can generate chaotically changing spatial patterns, in which cooperators and defectors both persist indefinitely (in fluctuating proportions about predictable long-term averages). If the starting configurations are sufficiently symmetrical, these ever-changing sequences of spatial patterns—dynamic fractals—can be extraordinarily beautiful, and have interesting mathematical properties. There are potential implications for the dynamics of a wide variety of spatially extended systems in physics and biology.

The Z notation: a reference manual

Abstract: Tutorial introduction background the Z language the mathematical tool-kit sequential systems syntax summary.

Rapid Solution of Problems by Quantum Computation

Abstract: A class of problems is described which can be solved more efficiently by quantum computation than by any classical or stochastic method. The quantum computation solves the problem with certainty in exponentially less time than any classical deterministic computation.

Procedures for the Analysis of Comparative Data Using Phylogenetically Independent Contrasts

Abstract: We discuss and clarify several aspects of applying Felsenstein's (1985, Am. Nat. 125: 1n15) procedures to test for correlated evolution of continuous traits. This is one of several available comparative methods that maps data for phenotypic traits onto an existing phylogenetic tree (derived from independent information). Application of Felsenstein's method does not require an entirely dichotomous topology. It also does not require an assumption of gradual, clocklike character evolution, as might be modeled by Brownian motion. Almost any available information can be used to estimate branch lengths (e.g., genetic distances, divergence times estimated from the fossil record or from molecular clocks, numbers of character changes from a cladistic analysis). However, the adequacy for statistical purposes of any proposed branch lengths must be verified empirically for each phytogeny and for each character. We suggest a simple way of doing this, based on graphical analysis of plots of standardized independent contrasts versus their standard deviations (i.e., the square roots of the sums of their branch lengths). In some cases, the branch lengths and/or the values of traits being studied will require transformation. An example involving the scaling of mammalian home range area is presented. Once adequately standardized, sets of independent contrasts can be analyzed using either linear or nonlinear (multiple) regression. In all cases, however, regressions (or correlations) must be computed through the origin. We also discuss ways of correcting for body size effects and how this relates to making graphical representations of relationships of standardized independent contrasts. We close with a consideration of the types of traits that can be analyzed with independent contrasts procedures and conclude that any (continuous) trait that is inherited from ancestors is appropriate for analysis, regardless of the mechanism of inheritance (e.g., genetic or cultural).

Measurement in Neurological Rehabilitation

Abstract: Part 1 Background to the choice and use of measures: pathology, impairment, disability, handicap - a useful model measurement and assessment - what and why? classification of impairment, disability and handicap choosing a measure. Part 2 Measurement at different levels: measures of pathology motor and sensory impairments cognitive and emotional impairments personal physical disability global disability measures, extended ADL and social interaction handicap and quality of life. Part 3 Measurement in practice: measurement in some specific diseases measurement in some specific circumstances. Part 4 Measures for use in neurological disability: measures of cognitive impairment and disability measures of motor impairment measures of "focal" disability activities of daily living (ADL) and extended ADL tests global measures of disability measures of handicap and quality of life measures of emotion and social interaction multiple sclerosis stroke scales head injury Parkinson's disease and other movement disorders miscellaneous measures.

Animal cell cycles and their control

Abstract: THE ONSET OF M PHASE IN ANIMAL CELLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . 444 Maturation-Promoting Factor and Growth-Associated Kinase 444 p34cdc2: the Catalytic Subunit of MPF .. . . ... . . . . . . . . . . . . . . . . . . . . . .. . . . ... . . . . . . . . . . . . . . . . . . . 445 Cyclin B: the Second Essential Component of MPF. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 Regulation of p34cdc2 Activity by Phosphorylation . . . . ...... . ..... . . . . . . . . . . . . .. . . . . . . . .. . . 447 Substrates of p34cdc2 and their Significance for M Phase Events . . . . . . . . . . . . . . . . . . . . . . . 450 Dependence of Mitosis on Completion of DNA Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 Meiotic Maturation and Cytostatic Factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455 Cell Cycle Roles for Phosphoprotein Phosphatases . . . . . . . . . . . . . .. . . . . . . . . . . . 456 CONTROL OF THE ANIMAL CELL CYCLE IN G I . . .... . . . . . . .. . . . ....... . . . . . . . . . . . .. . . 457 Growth Factor Requirements for Commitment of Fibroblasts to S Phase Entry 458 Protein Synthesis Requirements for Commitment of Fibroblasts to S Phase Entry. . . . . . . . . . . . . . ......... . . . . .. . . . . . . . . . . . . 460 The Search for an S Phase-Promoting Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 Growth Control and Cell Cycle Control . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 PROSPECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464

On undamped heat waves in an elastic solid

Abstract: This paper is concerned with thermoelastic material behavior whose constitutive response functions possess thermal features that are more general than in the usual classical thermoelasticity. After a general development of the constitutive equations in the context of both nonlinear and linear theories, attention is focused on the latter. In particular, the one-dimensional version of the equation for the determination of temperature in the linearized theory provides an easy comparative basis of its predictive capability: In one special case where the Fourier conductivity is dominant, the temperature equation reduces to the classical Fourier law of heat conduction, which does not permit the possibility of undamped thermal waves; however,'in another special case in which the effect of conductivity is negligible, the equation has undamped thermal wave solutions without energy dissipation.

Tit for tat in heterogeneous populations

Abstract: THE 'iterated prisoner's dilemma' is now the orthodox paradigm for the evolution of cooperation among selfish individuals. This viewpoint is strongly supported by Axelrod's computer tournaments, where 'tit for tat' (TFT) finished first1. This has stimulated interest in the role of reciprocity in biological societies1–8. Most theoretical investigations, however, assumed homogeneous populations (the setting for evolutionary stable strategies9,10) and programs immune to errors. Here we try to come closer to the biological situation by following a program6 that takes stochasticities into account and investigates representative samples. We find that a small fraction of TFT players is essential for the emergence of reciprocation in a heterogeneous population, but only paves the way for a more generous strategy. TFT is the pivot, rather than the aim, of an evolution towards cooperation.

Geometric invariance in computer vision

Abstract: Part 1 Foundations: algebraic invariants - invariant theory and enumerative combinatorics of young tableaux, Shreeram S. Abhyankar, geometric interpretation of joint conic invariants, Joseph L. Mundy, et al, an experimental evaluation of projective invariants, Christopher Coelho, et al the projection of two non-coplanar conics, Stephen J. Maybank the non-existence of general-case view-invariants, J. Brian Burns, et al invariants of non-algebraic curves - noise resistant invariants of curves, Isaac Weiss, semi-differential invariants, Luc J. Van Gool, et al, projective invariants for curves in two and three dimensions, Michael H. Brill, et al, numerical evaluation of differential and semi-differential invariants, Christopher Brown, recognizing general curved objects efficiently, Andrew Zisserman, et al fitting affine invariant conics to curves, Deepak Kapur and Joseph L. Mundy, projectively invariant decomposition of planar shapes, Stefan Carlsson invariants from multiple views - invariant linear methods in photogrammetry and model-matching, Eamon B. Barrett, et al semi-differential invariants for nonplanar curves, Luc J. Van Gool, et al disambiguating stereo matches with spatio-temporal surfaces, Olivier Faugeras and Theo Papadopoulo. Part 2 Applications: transformation invariant indexing, Haim J. Wolfson and Yehezkel Lamdan affine invariants for model-based recognition, John E. Hopcroft, et al object recognition based on moment (or algebraic) invariants, Gabriel Taubin and David B. Cooper fast recognition using algebraic invariants, Charles A. Rothwell, et al toward 3D curved object recognition from image contours, Jean Ponce and David J. Kriegman relative positioning with uncalibrated cameras, Roger Mohr, et al. Appendix: projective geometry for machine vision, Joseph L. Mundy and Andrew Zisserman.

Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin.

Abstract: Introduction of Ca2+ indicators (photoproteins, fluorescent dyes) that can be trapped in the cytosolic compartment of living cells has yielded major advances in our knowledge of Ca2+ homeostasis. Ca2+ however regulates functions not only in the cytosol but also within various organelles where indicators have not yet been specifically targeted. Here we present a novel procedure by which the free Ca2+ concentration of mitochondria, [Ca2+]m, can be monitored continuously at rest and during stimulation. The complementary DNA for the Ca2+ sensitive photoprotein aequorin was fused in frame with that encoding a mitochondrial presequence. The hybrid cDNA was transfected into bovine endothelial cells and stable clones were obtained expressing variable amounts of mitochondrially targeted apoaequorin. The functional photoprotein could be reconstituted in intact cells by incubation with purified coelenterazine and [Ca2+]m could thus be monitored in situ. This allowed the unprecedented direct demonstration that agonist-stimulated elevations of cytosolic free Ca2+, [Ca2+]i, (measured in parallel with Fura-2) evoke rapid and transient increases of [Ca2+]m, which can be prevented by pretreatment with a mitochondrial uncoupler. The possibility of targeting aequorin to cellular organelles not only offers a new and powerful method for studying aspects of Ca2+ homeostasis that up to now could not be directly approached, but might also be used in the future as a tool to report in situ a variety of apparently unrelated phenomena of wide biological interest.

Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures

Abstract: The differentiation of adipocytic and osteogenic cells has been investigated in cultures of adult rat marrow stromal cells. Adipocytic differentiation was assessed using morphological criteria, changes in expression of procollagen mRNAs, consistent with a switch from the synthesis of predominantly fibrillar (types I and III) to basement membrane (type IV) collagen, and the induction of expression of aP2, a specific marker for differentiation of adipocytes. Osteogenic differentiation was assessed on the basis of changes in the abundance of the mRNAs for the bone/liver/kidney isozyme of alkaline phosphatase and the induction of mRNAs for bone sialoprotein and osteocalcin. In the presence of foetal calf serum and dexamethasone (10(-8) M) there was always differentiation of both adipocytic and osteogenic cells. When the steroid was present throughout primary and secondary culture the differentiation of osteogenic cells predominated. Conversely, when dexamethasone was present in secondary culture only, the differentiation of adipocytes predominated. When marrow stromal cells were cultured in the presence of dexamethasone in primary culture and dexamethasone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; 10(-8) M) in secondary culture, the differentiation of adipocytes was inhibited whereas the differentiation of osteogenic cells was enhanced, as assessed by an increase in expression of osteocalcin mRNA. The results, therefore, demonstrate an inverse relationship between the differentiation of adipocytic and osteogenic cells in this culture system and are consistent with the possibility that the regulation of adipogenesis and osteogenesis can occur at the level of a common precursor in vivo.

Metabolic control analysis: a survey of its theoretical and experimental development.

Abstract: As the details of the chemical transformations in metabolism have become increasingly clear, and the enzymes catalysing many of the reactions have been characterized, it is understandable that biochemists should want to explain at the molecular level the metabolic homeostasis observed at the physiological level. How are the rates of synthesis and degradation of metabolites kept in close balance over a very wide range of external conditions without catastrophic rises or falls in the metabolite concentrations? The discoveries of feedback inhibition, co-operativity and covalent modification in enzymes, and of mechanisms for the control of enzyme synthesis and degradation, have disclosed a repertoire of molecular effects that potentially alter the fluxes in metabolic pathways. With such a range of effects to choose from, it is not surprising that disputes arise over explanations for the changes in flux through particular pathways under given circumstances. Since the explanations are usually verbal and qualitative, discrimination between different explanations, or assessment of their adequacy, is difficult. More recently, several groups have attempted theoretical analysis of the potential of these different molecular mechanisms to contribute to the control of metabolic flux. Since these theories can be given a mathematical formulation, they can be used in combination with appropriate experimental measurements to provide quantitative explanations and, potentially, predictions. The theories have often been controversial. Matters at issue have included the extent to which it is feasible to perform experiments to obtain the necessary data, the adequacy of the theories for making useful predictions, and the degree to which the quantitative measures of the theories do actually capture the relevant aspects of regulation and control. To some extent, this is a matter of semantics; a mathematical theory is more explicit about its underlying assumptions and the meaning of its statements, but regulation and control are two terms that have been used without strict adherence to any agreed definition in many different contexts (as noted in [1]). It is therefore inevitable that some will find that the use of these terms in the context of a mathematical theory places a narrower construction on them than they would like. These theories all include a form of sensitivity analysis; that is, the magnitude of the effect of some small change in a parameter (such as an enzyme activity) on a metabolic system property (such as the flux or the concentration of a metabolite) is mathematically related to the properties of the components of the system. Sensitivity analysis is widely used for analogous problems in other fields, including economics, ecology [2], engineering [3] and chemical kinetics [4-6]. Its application in biochemistry was pioneered by Higgins [7], but three variants subsequently arose: Metabolic Control Analysis, Biochemical Systems Theory and Crabtree and Newsholme's 'flux-oriented' theory (the term used in [8]). It is not possible to give a succinct account of the differences between the approaches, which is a controversial area [9-18] even though the underlying mathematics is equivalent to a considerable extent. One area of difference is the choice of the type of parameter that is changed for the determination of sensitivities. In Metabolic Control Analysis, enzyme concentration (or activity) is usually chosen; the response to an external modifier of a metabolic pathway is derived from the resulting sensitivities. In Biochemical Systems Theory [19-25], the primary parameters for the sensitivities are the 'rate constants' for synthesis and degradation of metabolite pools. Savageau has given many reasons for this choice of parameter; Cornish-Bowden has articulated some of the problems with it [15]. Although using these 'rate constants' simplifies the analysis procedures within Biochemical Systems Theory, there is not a one-to-one relationship between them and the enzymes of the system, which can create a slight complication in determining the sensitivity to variation of an enzyme activity. Savageau's theory is part of an integrated system for stability analysis and simulation, in addition to sensitivity analysis. Crabtree and Newsholme's theory [8,10,26-30] is intermediate between the two others, and the primary sensitivities are to an external modifier (a hypothetical one if necessary), but its mathematical development is less rigorous. In this review, I shall concentrate on Metabolic Control Analysis. This is because, apart from considerations of space, approximately two-thirds of the literature citations of theories of metabolic regulation in the past 5 years have been to Metabolic Control Analysis. This may relate to perceived ease of use, which has been compared using the different approaches on the same set of experimental results [31]. In the following review, I will not give a complete derivation and description of the basic concepts of Metabolic Control Analysis; clear accounts can be found in previous articles and reviews [9,32-39]. Instead I will try to indicate areas of disagreement, the scope of the basic theory and where it has been modified or extended, and recent approaches to experimental applications.

The Book of Memory: A Study of Memory in Medieval Culture

Abstract: Introduction 1. Models for the memory 2. Descriptions of the neuropsychology of memory 3. Elementary memory design 4. The arts of memory 5. Memory and the ethics of reading 6. Memory and authority 7. Memory and the book Afterword Appendixes List of abbreviations Bibliography.

Suppressing the formation of dwarf galaxies via photoionization

Abstract: In hierarchical clustering theories, some sort of feedback mechanism is required to prevent most of the baryonic material collapsing into subgalactic objects at high redshifts. It is argued that a photoionizing background of the magnitude suggested by applying the Gunn-Peterson constraint to high-redshift quasars, would strongly suppress the cooling of a hydrogen-helium plasma and so inhibit the formation of dwarf galaxies. The effectiveness of this mechanism depends on the spectrum of the photoionizing radiation and so galaxy formation could depend on the proximity of protogalactic perturbations to unusual sources of hard photons such as luminous quasars

The folding of hen lysozyme involves partially structured intermediates and multiple pathways.

Abstract: The folding of hen lysozyme involves partially structured intermediates and multiple pathways

Quality of life measures in health care. I: Applications and issues in assessment.

Abstract: Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.

Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels.

Abstract: An algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure-based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root. The algorithm encoded in STAMP (STructural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases. In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij' provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij' values and thus provide a reproducible resource for studies of residue conservation within structural motifs.

Lifespan of human lymphocyte subsets defined by CD45 isoforms.

Abstract: THE lifespan of thymic-derived or T lymphocytes is of particular interest because of their central role in immunological memory. Is the recall of a vaccination or early infection, which may be demonstrated clinically up to 50 years after antigen exposure1, retained by a long-lived cell, or by its progeny? Using the observation that T lymphocyte expression of isoforms of CD45 corresponds with their ability to respond to recall antigens, we have investigated the lifespan of both CD45RO (the subset containing responders, or 'memory' cells) and CD45RA (the unresponsive, or 'naive' subset) lymphocytes in a group of patients after radiotherapy. Here we report rapid loss of unstable chromosomes from the CD45RO but not the CD45RA pool. Immunological memory therefore apparently resides in a population with a more rapid rate of division. Differing survival curves for the two subsets are best described by a model in which there is also reversion in vivo from the CD45RO to the CD45RA phenotype. Expression of CD45RO in T cells may therefore be reversible.

Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network.

Abstract: The CA3 network in the hippocampus may operate as an autoassociator, in which declarative memories, known to be dependent on hippocampal processing, could be stored, and subsequently retrieved, using modifiable synaptic efficacies in the CA3 recurrent collateral system. On the basis of this hypothesis, the authors explore the computational relevance of the extrinsic afferents to the CA3 network. A quantitative statistical analysis of the information that may be relayed by such afferent connections reveals the need for two distinct systems of input synapses. The synapses of the first system need to be strong (but not associatively modifiable) in order to force, during learning, the CA3 cells into a pattern of activity relatively independent of any inputs being received from the recurrent collaterals, and which thus reflects sizable amounts of new information. It is proposed that the mossy fiber system performs this function. A second system, with a large number of associatively modifiable synapses on each receiving cell, is needed in order to relay a signal specific enough to initiate the retrieval process. This may be identified, we propose, with the perforant path input to CA3.

Molecular analysis of the association of HLA-B53 and resistance to severe malaria.

Abstract: The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.

Impaired mesial frontal and putamen activation in Parkinson's disease: A positron emission tomography study

Abstract: Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.

Probe theory - the orbital motion approach

Abstract: A review is given of the orbital motion limited (O.M.L.) theory of cylindrical and spherical Langmuir probes. In many cases the O.M.L. theory is invalid and the second orbital motion theory presented here, that of Bohm, Burhop and Massey, shows that the concept of an absorption radius must be introduced. The extensive numerical extensions to this theory are briefly discussed. Recent experimental work is referred to in which measurements of ion currents to cylindrical probes showed better agreement with the ABR (radial-motion) theory than with the calculations of Laframboise. It is suggested that the mean free path must be greater than the probe radius by a large factor if the calculations of the Laframboise are to apply; the numerical value depends on the ratio of probe potential to ion temperature.

Sparse population coding of faces in the inferotemporal cortex.

Abstract: How does the brain represent objects in the world? A proportion of cells in the temporal cortex of monkeys responds specifically to objects, such as faces, but the type of coding used by these cells is not known. Population analysis of two sets of such cells showed that information is carried at the level of the population and that this information relates, in the anterior inferotemporal cortex, to the physical properties of face stimuli and, in the superior temporal polysensory area, to other aspects of the faces, such as their familiarity. There was often sufficient information in small populations of neurons to identify particular faces. These results suggest that representations of complex stimuli in the higher visual areas may take the form of a sparse population code.

Oligonucleotide hybridizations on glass supports: a novel linker for oligonucleotide synthesis and hybridization properties of oligonucleotides synthesised in situ.

Abstract: A novel linker for the synthesis of oligonucleotides on a glass support is described. Oligonucleotides synthesised on the support remain tethered to the support after ammonia treatment and are shown to take part in sequence specific hybridisation reactions. These hybridizations were carried out with oligonucleotides synthesised on 'ballotini' solid sphere glass beads and microscope slides. The linker has a hexaethylene glycol spacer, bound to the glass via a glycidoxypropyl silane, terminating in a primary hydroxyl group that serves as starting point for automated or manual oligonucleotide synthesis.