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Showing papers by "Utrecht University published in 1995"


Journal ArticleDOI
TL;DR: The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.
Abstract: The NMRPipe system is a UNIX software environment of processing, graphics, and analysis tools designed to meet current routine and research-oriented multidimensional processing requirements, and to anticipate and accommodate future demands and developments. The system is based on UNIX pipes, which allow programs running simultaneously to exchange streams of data under user control. In an NMRPipe processing scheme, a stream of spectral data flows through a pipeline of processing programs, each of which performs one component of the overall scheme, such as Fourier transformation or linear prediction. Complete multidimensional processing schemes are constructed as simple UNIX shell scripts. The processing modules themselves maintain and exploit accurate records of data sizes, detection modes, and calibration information in all dimensions, so that schemes can be constructed without the need to explicitly define or anticipate data sizes or storage details of real and imaginary channels during processing. The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.

13,804 citations


Journal ArticleDOI
17 Aug 1995-Nature
TL;DR: A role for PKB in PI(3)K-mediated signal transduction is suggested and a constructed Gag–PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity.
Abstract: A serine/threonine kinase, named protein kinase B (PKB) for its sequence homology to both protein kinase A and C, has previously been isolated. PKB, which is identical to the kinase Rac, was later found to be the cellular homologue of the transforming v-Akt. Here we show that PKB is activated by stimuli such as insulin, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Activation of PKB was inhibited by the phosphatidylinositol-3-OH kinase (PI(3)K) inhibitor wortmannin and by coexpression of a dominant-negative mutant of PI(3)K. PDGF receptor mutants that lack detectable associated PI(3)K activity also fail to induce PKB activation, PKB kinase activity is correlated with phosphorylation of PKB on serine. Finally, we show that a constructed Gag-PKB fusion protein, homologous to the v-akt oncogene, displays significantly increased ligand-independent kinase activity. Furthermore, this activity is sufficient to activate the p70 S6-kinase (p70S6K). These results suggest a role for PKB in PI(3)K-mediated signal transduction.

2,137 citations


Journal ArticleDOI
TL;DR: Current issues are laid out and the areas of consensus and controversy surrounding the evolution of plasticity and the reaction norm (the set of phenotypes produced by a genotype over a range of environments) are summarized.
Abstract: Phenotypic plasticity is an environmentally based change in the phenotype. Understanding the evolution of adaptive phenotypic plasticity has been hampered by dissenting opinions on the merits of different methods of description, on the underlying genetic mechanisms, and on the way that plasticity is affected by natural selection in a heterogeneous environment. During much of this debate, the authors of this article have held opposing views. Here, we attempt to lay out current issues and summarize the areas of consensus and controversy surrounding the evolution of plasticity and the reaction norm (the set of phenotypes produced by a genotype over a range of environments).

1,361 citations


Journal ArticleDOI
TL;DR: Morbidity and mortality differences persisted in almost all subgroup analyses, and D2 dissection should not be used as standard treatment for western patients.

984 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a conceptual model which explains benthic foraminiferal microhabitat preferences in terms of differences in the downward organic flux in the sediment.

957 citations


Journal ArticleDOI
TL;DR: In this paper, a fast and direct method, based on infrared spectroscopy, for quantitative determination of starch short-range structure has been developed, which can quantify the IR data in terms of shortrange order (SIR) over a range of 10−50% water.

897 citations


Journal ArticleDOI
02 Nov 1995-Nature
TL;DR: It is demonstrated that positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation, offering an alternative to the general opinion that meristems are the source of patterning information.
Abstract: Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity. In contrast to animal systems, there has been no direct evidence for inductive signalling in plants until now. Here we present evidence for such signalling using laser ablation of cells in the root meristem of Arabidopsis thaliana. Although these cells show rigid clonal relationships, we now demonstrate that it is positional control that is most important in the determination of cell fate. Positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation. This offers an alternative to the general opinion that meristems are the source of patterning information.

535 citations


Journal ArticleDOI
TL;DR: The introduction of fructans in this non-fructan-producing species mediates enhanced resistance to drought stress and the total nonstructural carbohydrate content was higher in the transgenic plants.
Abstract: Fructans are polyfructose molecules produced by approximately 15% of the flowering plant species. It is possible that, in addition to being a storage carbohydrate, fructans have other physiological roles. Owing to their solubility they may help plants survive periods of osmotic stress induced by drought or cold. To investigate the possible functional significance of fructans, use was made of transgenic tobacco (Nicotiana tabacum) plants that accumulate bacterial fructans and hence possess an extra sink for carbohydrate. Biomass production was analyzed during drought stress with the use of lines differing only in the presence of fructans. Fructan-producing tobacco plants performed significantly better under polyethylene-glycol-mediated drought stress than wild-type tobacco. The growth rate of the transgenic plants was significantly higher (+55%), as were fresh weight (+33%) and dry weight (+59%) yields. The difference in weight was observed in all organs and was particularly pronounced in roots. Under unstressed control conditions the presence of fructans had no significant effect on growth rate and yield. Under all conditions the total nonstructural carbohydrate content was higher in the transgenic plants. We conclude that the introduction of fructans in this non-fructan-producing species mediates enhanced resistance to drought stress.

527 citations


Journal ArticleDOI
Rien Aerts1
TL;DR: It appears that the plant traits that are associated with low nutrient loss rates lead to low maximum-dry-matter production and to low rates of litter decomposition, which suggests a positive feedback between the evergreen habit and low nutrient availability.
Abstract: Recent research shows that the dominance of evergreen species in nutrient-poor environments can be explained by their low nutrient loss rates. From this work It appears that the plant traits that are associated with low nutrient loss rates lead to low maximum-dry-matter production and to low rates of litter decomposition. This suggests a positive feedback between the evergreen habit and low nutrient availability. The growth characteristics of evergreens lead to a low responsiveness to environmental changes. As a result, global warming may lead to changes in the distribution of evergreens.

518 citations


Journal ArticleDOI
Han de Vries1
TL;DR: In this paper, a randomization test is developed for assessing the significance of linearity or non-linearity in a set of observed dominance relationships, in particular if this set contains unknown or tied relationships.

515 citations


Journal ArticleDOI
TL;DR: A repeated measures study of job insecurity conducted during drastic organisational change in one of Australia's large public transport organisations is described in this article, where the authors found that in a redundant group (n...
Abstract: This paper reports on a repeated measures study of job insecurity conducted during drastic organisational change in one of Australia's large public transport organisations. In a redundant group (n ...

Journal ArticleDOI
TL;DR: A discrete dynamic model for defining contours in 2-D images is developed and the final shape of the model is a reproducible approximation of the desired contour.
Abstract: A discrete dynamic model for defining contours in 2-D images is developed. The structure of this model is a set of connected vertices. With a minimum of interaction, an initial contour model can be defined, which is then automatically modified by an energy minimizing process. The internal energy of the model depends on local contour curvature, while the external energy is derived from image features. Solutions are presented to avoid undesirable deformation effects, like shrinking and vertex clustering, which are common in existing active contour models. The deformation process stops when a local minimum of the energy function is reached. The final shape of the model is a reproducible approximation of the desired contour. Results of applying the method to computer-generated images, as well as clinical images, are presented. >

Book
01 Jan 1995
TL;DR: In this article, a broad introduction to epistemic logic is provided, based on courses taught at universities and summer schools, with many exercises and their solutions, and the authors consider applications in the areas of common knowledge, distributed knowledge, explicit and implicit belief.
Abstract: From the Publisher: Epistemic logic has grown from its philosophical beginnings to find diverse applications in computer science as a means of reasoning about the knowledge and belief of agents. This book, based on courses taught at universities and summer schools, provides a broad introduction to the subject; many exercises are included as well as their solutions. After presenting the necessary apparatus from mathematics and logic, the authors consider applications in the areas of common knowledge, distributed knowledge, explicit and implicit belief.

Journal ArticleDOI
TL;DR: Six mutations causing alterations in the radial organisation of the primary root of Arabidopsis thaliana are analysed andEmbryonic phenotypes resulting from wooden leg, gollum, pinocchio, scarecrow, shortroot and fass mutations are described.
Abstract: The primary root of Arabidopsis thaliana has a remarkably uniform cellular organisation. The fixed radial pattern of cell types in the mature root arises from proliferative divisions within the root meristem. The root meristem, in turn, is laid down during embryogenesis. We have analysed six mutations causing alterations in the radial organisation of the root. Embryonic phenotypes resulting from wooden leg, gollum, pinocchio, scarecrow, shortroot and fass mutations are described. While mutations in the fass gene affect morphogenesis of all cells, the five other mutations cause alterations in specific layers. Wooden leg and gollum mutations interfere with the proper organisation of the vascular tissue. Shortroot, scarecrow and pinocchio affect the endodermis and cortex. The layer- specific phenotypes caused by all five mutations are also apparent in the hypocotyl. All these phenotypes originate from defects in the radial organisation of the embryonic axis. Secondary roots, which are formed post-embryonically, also display layer-specific phenotypes.

Journal ArticleDOI
TL;DR: In this paper, a systematic study was performed to evaluate the quality and reliability of the quantitative relationship between the soil sorption coefficients and the n-octanol/water partition coefficients (log KOC vs. log KOW).

Journal ArticleDOI
17 Nov 1995-Science
TL;DR: The rotor, the frequency of rotation of the rotor, and the wave speed prechit and R. Desrosiers, AIDS Pes.
Abstract: 18. R. C. Desrosiers, AIDS Pes. Horn. Retrovlr. 10, 331 fibrillation (6). Fuirthermi-ore, the width of 8. R. M. Ruprecht et al., J. AIDS 3, 591 (1990); P. M. (1994). thcse frcurc pcr a erltdt Ruprecht et al., Proc. Nat!. Acad. Sci. U.S.A. 87, 19. D. D. Ho and Y. Cao. N. Engl. 3. Med. 332. 1647reule spcrca beeatdo 5558 (1990); R. C. Horn, P. W. Finberg, S. Mullaney, (1995). the frequency of rotation of the rotor, thei H. M. Ruprecht, 3. Virol. 65, 220 (1991);R. M. RU20. F. Kirchhoff, H. W. Kostler, R. C. Desrosiers. 3. Virol. speed of its motion, and the wave speed prechit and R. Bronson, DNA Ce//Pie!O. 13, 59 (1994). 68. 2031 (1994). throuui h oplrpeninnicod 9 R. M. Huprecht et al.. unpublished data. 21.~Wethank L. Geronimo tor preparing this maniuscript. \"I~teDppe hnmeo cod 10. M. L. Marthas et a!., 3. Virol. 64, 3694 (1990). Supported in part by NIH grants 2RD1 A132330-05 MItL to the following relationship: 11 3. 5. Dibbs et a)., AIDS Res. Hum. Retrovir. 10, 607 and 2BD1 A135533 02, DAMD grant 1 7 94-J-4431 (1994). to H.M.R., and bytheCentertorAIDS Research core 1/1+ O, ./)<~5t 12, M. L. Marthas et a)., 3. Virol. 69, 4198 (1995). grant (P3

Journal ArticleDOI
TL;DR: Although pneumococcal conjugate vaccines are close to being licensed, a more profound knowledge of the virulence factors responsible for the morbidity and mortality caused by Streptococcus pneumoniae is necessary.

Journal ArticleDOI
14 Sep 1995-Nature
TL;DR: It is concluded that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum, with a > 1,000-fold higher risk of developing sunlight-induced skin cancer.
Abstract: Xeroderma pigmentosum patients with a defect in the nucleotide-excision repair gene XPA are characterized by, for example, a > 1,000-fold higher risk of developing sunlight-induced skin cancer. Nucleotide-excision repair (NER) is involved in the removal of a wide spectrum of DNA lesions. The XPA protein functions in a pre-incision step, the recognition of DNA damage. To permit the functional analysis of the XPA gene in vivo, we have generated XPA-deficient mice by gene targeting in embryonic stem cells. The XPA-/-mice appear normal, at least until the age of 13 months. XPA-/-mice are highly susceptible to ultraviolet (UV)-B-induced skin and eye tumours and to 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumours. We conclude that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum.

Journal ArticleDOI
TL;DR: In the present review, the toxicity of narcotic chemicals to aquatic organisms is discussed, the possible mechanisms underlying narcosis are reviewed, and a comparison is made between membrane burdens that are lethal in vivo and membranes burdens that cause an effect in in vitro systems.
Abstract: The well-known correlation between the hydrophobicity of narcotic chemicals and the exposure concentration needed to produce an effect indicates that a lipid phase in the aquatic organism is the most likely target. The molar concentration in aquatic organisms at death is found to be approximately constant for different narcotic chemicals, varying from 2 to 8 mmol/kg organism. Because the proportion of lipid is known, the lethalin vivo membrane burden can be calculated to be 40 to 160 mmol/kg lipid.The exact mechanism underlying narcosis is still unknown. However, disturbance by narcotic chemicals in model membrane systems has been investigated, attention having been paid to disturbance of phospholipids and proteins, and of the interaction between the two groups. Model membrane burdens of different chemicals have been shown to be approximately constant for a particular effect. Different effects are found at different membrane concentrations.In the present review, the toxicity of narcotic chemicals ...

Book ChapterDOI
01 Jan 1995
TL;DR: In this article, a simple specification language based on CRL (Common Representation Language) and therefore called μCRL (micro CRL) is proposed, which contains only basic constructs with an easy semantics.
Abstract: A simple specification language based on CRL (Common Representation Language)and therefore called μCRL (micro CRL) is proposed. It has been developed to study processes with data. So the language contains only basic constructs with an easy semantics. To obtain executability, effective μCRL has been defined. In effective μCRL equivalence between closed data-terms is decidable and the operational behaviour is finitely branching and computable. This makes effective μCRL a good platform for tooling activities.

Journal ArticleDOI
TL;DR: It is concluded that trafficking through early and late endosomes, but not to lysosome, continued upon inactivation of the vacuolar proton pump.
Abstract: Endocytosed proteins are sorted in early endosomes to be recycled to the plasma membrane or transported further into the degradative pathway. We studied the role of endosomes acidification on the endocytic trafficking of the transferrin receptor (TfR) as a representative for the recycling pathway, the cation-dependent mannose 6-phosphate receptor (MPR) as a prototype for transport to late endosomes, and fluid-phase endocytosed HRP as a marker for transport to lysosomes. Toward this purpose, bafilomycin A1 (Baf), a specific inhibitor of the vacuolar proton pump, was used to inhibit acidification of the vacuolar system. Microspectrofluorometric measurement of the pH of fluorescein-rhodamine-conjugated transferrin (Tf)-containing endocytic compartments in living cells revealed elevated endosomal pH values (pH > 7.0) within 2 min after addition of Baf. Although recycling of endocytosed Tf to the plasma membrane continued in the presence of Baf, recycled Tf did not dissociate from its receptor, indicating failure of Fe3+ release due to a neutral endosomal pH. In the presence of Baf, the rates of internalization and recycling of Tf were reduced by a factor of 1.40 +/- 0.08 and 1.57 +/- 0.25, respectively. Consequently, little if any in TfR expression at the cell surface was measured during Baf treatment. Sorting between endocytosed TfR and MPR was analyzed by the HRP-catalyzed 3,3'-diaminobenzidine cross-linking technique, using transferrin conjugated to HRP to label the endocytic pathway of the TfR. In the absence of Baf, endocytosed surface 125I-labeled MPR was sorted from the TfR pathway starting at 10 min after uptake, reaching a plateau of 40% after 45 min. In the presence of Baf, sorting was initiated after 20 min of uptake, reaching approximately 40% after 60 min. Transport of fluid-phase endocytosed HRP to late endosomes and lysosomes was measured using cell fractionation and immunogold electron microscopy. Baf did not interfere with transport of HRP to MPR-labeled late endosomes, but nearly completely abrogated transport to cathepsin D-labeled lysosomes. From these results, we conclude that trafficking through early and late endosomes, but not to lysosomes, continued upon inactivation of the vacuolar proton pump.

Book ChapterDOI
01 Jan 1995
TL;DR: In this article, a direct proof using the theory of modular forms of a beautiful fact explained in the preceding paper by Robbert Dijkgraaf was given, and the proof was used to give a proof for the existence of quasi-modular forms on the full modular group.
Abstract: In this note we give a direct proof using the theory of modular forms of a beautiful fact explained in the preceding paper by Robbert Dijkgraaf [1, Theorem 2 and Corollary]. Let \( {\tilde M_*}({\Gamma _1}) \) denote the graded ring of quasi-modular forms on the full modular group Γ= PSL(2, ℤ). This is the ring generated by G2, G4, G6, and graded by assigning to each G k the weight where \( {G_k} = - \frac{{{B_k}}}{{2k}} + \sum\limits_{n = 1}^\infty {\left( {{{\sum\limits_{d|n} d }^{k - 1}}} \right)} {q^n}\left( {k \geqslant 2,{B_k} = kth Bernoulli number} \right) \) are the classical Eisenstein series, all of which except G 2 are modular.

Journal ArticleDOI
TL;DR: It is concluded, that the low density of the biomass of D. glomerata is the pivotal trait responsible for its faster growth at all nutrient levels and enables simultaneously a good nutrient acquisition capacity by the roots as well as a superior carbon acquisition by the leaves.
Abstract: Despite their difference in potential growth rate, the slow-growing Brachypodium pinnatum and the fast-growing Dactylis glomerata co-occur in many nutrient-poor calcareous grasslands. They are known to respond differently to increasing levels of N and P. An experiment was designed to measure which characteristics are affected by nutrient supply and contribute to the ecological performance of these species. Nutrient acquisition and root and shoot traits of these grasses were studied in a garden experiment with nine nutrient treatments in a factorial design of 3 N and 3 P levels each. D. glomerata was superior to B. pinnatum in nutrient acquisition and growth in all treatments. B. pinnatum was especially poor in P acquisition. Both species responded to increasing N supply and to a lesser extent to increasing P supply by decreasing their root length and increasing their leaf area per total plant weight. D. glomerata showed a higher plasticity. In most treatments, the root length ratio (RLR) and the leaf area ratio (LAR) were higher for D. glomerata. A factorization of these parameters into components expressing biomass allocation, form (root fineness or leaf thickness) and density (dry matter content) shows that the low density of the biomass of D. glomerata was the main cause for the higher RLR and LAR. The biomass allocation to the roots showed a considerable plasticity but did not differ between the species. B. pinnatum had the highest leaf weight ratio. Root fineness was highly plastic in D. glomerata, the difference with B. pinnatum being mainly due to the thick roots of D. glomerata at high nutrient supply. The leaf area/leaf fresh weight ratio did not show any plasticity and was slightly higher for B. pinnatum. It is concluded, that the low density of the biomass of D. glomerata is the pivotal trait responsible for its faster growth at all nutrient levels. It enables simultaneously a good nutrient acquisition capacity by the roots as well as a superior carbon acquisition by the leaves. The high biomass density of B. pinnatum will then result in a lower nutrient requirement due to a slower turnover, which in the long term is advantageous under nutrient-poor conditions.

Journal ArticleDOI
TL;DR: Benzodiazepines are a major, independent risk factor for falls leading to femur fractures, and the increased risk is probably explained by prescribing too-high doses to the elderly.
Abstract: Background: In the past decade, the use of benzodiazepines has been identified as a major independent risk factor for accidental falls. Objective: To study the role of dosing, timing, elimination half-life, and type of benzodiazepine in relation to the occurrence of accidental falls leading to hospitalization for femur fractures. Methods: A 1:3 age-, sex-, and pharmacy-matched case-control study was performed using data from a Dutch record linkage system (PHARMO) (N=300 000). Cases included 493 patients (55 years and older), newly admitted to the hospital for a femur fracture resulting from an accidental fall (between 1986 and 1992). Relative risk estimates were calculated using conditional logistic regression analyses to control for the potential confounding effects of concomitant drug use and presence of a wide range of underlying diseases. Results: Falls were significantly associated with current use of benzodiazepines (odds ratio, 1.6; 95% confidence interval, 1.2 to 2.1) and in particular with short half-life benzodiazepines (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0), sudden dose increases (odds ratio, 3.4; 95% confidence interval, 1.0 to 11.5),and concomitant use of several benzodiazepines (odds ratio, 2.5; 95% confidence interval, 1.3 to 4.9). A strong dose-response relationship ( P Conclusions: Benzodiazepines are a major, independent risk factor for falls leading to femur fractures, and the increased risk is probably explained by prescribing too-high doses to the elderly. (Arch Intern Med. 1995;155:1801-1807)

Journal ArticleDOI
TL;DR: In this article, a method is presented which enables prediction of the equilibrium conditions for the occurrence of braided and high sinuosity meandering rivers in unconfined alluvial floodplains, based on two, almost channel pattern independent, boundary conditions: median grain size of the river bed material, and a potential specific stream power parameter related to bankfull discharge or mean annual flood and valley gradient.

Journal ArticleDOI
TL;DR: In this paper, the interaction between large spheres in a dilute solution of mutually avoiding small spheres (of diameter σ ⪡ R and volume fraction φ), to third order in φ, is calculated.
Abstract: The entropic depletion force, in colloids, arises when large particles are placed in a solution of smaller ones, and sterically constrained to avoid them. We calculate the interaction between large spheres (of radius R) in a dilute solution of mutually avoiding small spheres (of diameter σ ⪡ R and volume fraction φ), to third order in φ. In addition to the well-known attractive force for 0 < h < σ, we find a repulsive barrier at larger separations, and beyond that a secondary minimum. Except for unusually large size ratios (perhaps abetted by relatively high density φ), these features of the interaction potential are too small, compared to kBT, for kinetic stabilization (arising from the barrier) or flocculation into the secondary minimum, to be widespread, although such effects are possible in principle. For feasible size ratios, the same features should have observable consequences for the radial distribution function of the large spheres. Such effects can be viewed as precursors, at low density, of liquidlike structuring (solvation forces) expected at higher φ. Our third order calculation gives satisfactory agreement with a recent computer simulation at moderate density and size ratio (2R/σ = 10; φ = π/15).

Journal ArticleDOI
TL;DR: Epidermal growth factor is a single polypeptide of 53 amino acid residues which is involved in the regulation of cell proliferation and its effects in the target cells by binding to the plasma membrane located EGF receptor.

Journal ArticleDOI
TL;DR: Peripheral blood leukocytes incubated with a semisynthetic phage antibody library and fluorochrome-labeled CD3 and CD20 antibodies were used to isolate human single-chain Fv antibodies specific for subsets of blood leucocytes by flow cytometry, showing hitherto-unknown staining patterns of B-lineage cells.
Abstract: Peripheral blood leukocytes incubated with a semisynthetic phage antibody library and fluorochrome-labeled CD3 and CD20 antibodies were used to isolate human single-chain Fv antibodies specific for subsets of blood leukocytes by flow cytometry. Isolated phage antibodies showed exclusive binding to the subpopulation used for selection or displayed additional binding to a restricted population of other cells in the mixture. At least two phage antibodies appeared to display hitherto-unknown staining patterns of B-lineage cells. This approach provides a subtractive procedure to rapidly obtain human antibodies against known and novel surface antigens in their native configuration, expressed on phenotypically defined subpopulations of cells. This approach does not depend on immunization procedures or the necessity to repeatedly construct phage antibody libraries.

Journal ArticleDOI
TL;DR: This review summarizes the mechanisms which lie at the root of translational control, and suggests that a better understanding of these mechanisms will eventually provide new drugs and antisense oligonucleotide technology, aimed at influencing the level of expression of single proteins.
Abstract: Translational regulation of mRNA is an important step in the control of gene expression. In a general way, the efficiency of the translational apparatus can be influenced either positively or negatively by changing the level or the activity of rate-limiting protein factors taking part in the process of translation. But translational control can also be very specific, affecting only a single mRNA or class of mRNA molecules. In most of these cases regulation takes place at the level of initiation of translation, which is often attributable to structural peculiarities of the mRNA in question, especially of the 5'-untranslated region or leader. This review summarizes the mechanisms which lie at the root of translational control. A better understanding of these mechanisms will eventually provide us with new drugs and antisense oligonucleotide technology, aimed at influencing the level of expression of single proteins. These developments are of interest to basic researchers and clinicians alike, because they may profoundly change the ways in which we treat, e.g. viral infections and malignancies in the future.

Journal ArticleDOI
TL;DR: Attention is devoted to the technical aspects of integration as well as to the use of GTS—based potential modelling in Dutch physical planning practice.
Abstract: This paper focuses on the integration of models, especially potential models, in a geographical information system (GIS). This exercise was prompted by the inability of common geographical information systems to deal adequately with the problem of accessibility. Attention is devoted to the technical aspects of integration as well as to the use of GTS—based potential modelling in Dutch physical planning practice.