Showing papers by "Stockholm University published in 1998"

A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences

Abstract: A novel method to model and predict the location and orientation of alpha helices in membrane- spanning proteins is presented. It is based on a hidden Markov model (HMM) with an architecture that corresponds closely to the biological system. The model is cyclic with 7 types of states for helix core, helix caps on either side, loop on the cytoplasmic side, two loops for the non-cytoplasmic side, and a globular domain state in the middle of each loop. The two loop paths on the non-cytoplasmic side are used to model short and long loops separately, which corresponds biologically to the two known different membrane insertions mechanisms. The close mapping between the biological and computational states allows us to infer which parts of the model architecture are important to capture the information that encodes the membrane topology, and to gain a better understanding of the mechanisms and constraints involved. Models were estimated both by maximum likelihood and a discriminative method, and a method for reassignment of the membrane helix boundaries were developed. In a cross validated test on single sequences, our transmembrane HMM, TMHMM, correctly predicts the entire topology for 77% of the sequences in a standard dataset of 83 proteins with known topology. The same accuracy was achieved on a larger dataset of 160 proteins. These results compare favourably with existing methods.

Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms

Abstract: We have carried out detailed statistical analyses of integral membrane proteins of the helix-bundle class from eubacterial, archaean, and eukaryotic organisms for which genome-wide sequence data are available. Twenty to 30% of all ORFs are predicted to encode membrane proteins, with the larger genomes containing a higher fraction than the smaller ones. Although there is a general tendency that proteins with a smaller number of transmembrane segments are more prevalent than those with many, uni-cellular organisms appear to prefer proteins with 6 and 12 transmembrane segments, whereas Caenorhabditis elegans and Homo sapiens have a slight preference for proteins with seven transmembrane segments. In all organisms, there is a tendency that membrane proteins either have many transmembrane segments with short connecting loops or few transmembrane segments with large extra-membraneous domains. Membrane proteins from all organisms studied, except possibly the archaeon Methanococcus jannaschii, follow the so-called "positive-inside" rule; i.e., they tend to have a higher frequency of positively charged residues in cytoplasmic than in extra-cytoplasmic segments.

Customer loyalty and complex services: The impact of corporate image on quality, customer satisfaction and loyalty for customers with varying degrees of service expertise

Abstract: Based on theory from consumer behavior and cognitive psychology, the purpose of this paper is to discuss and test corporate image and customer satisfaction as two routes to customer loyalty. Based on data from 600 individual customers categorized as having high or low service expertise of three companies within the package tour industry, a conceptual model is proposed and tested empirically using structural equation modeling. The data used in the study are included in The Norwegian Customer Satisfaction Barometer. The paper concludes by claiming that for complex services, corporate image and customer satisfaction are not two separate routes to customer loyalty. Corporate image impacts customer loyalty directly whereas customer satisfaction does not. This finding was consistent with high and low service expertise. These results challenge the disconfirmation paradigm which predicts customer satisfaction as the primary route to customer loyalty. From a managerial perspective, information regarding the relative strength of the two routes is vital with regard to resource allocation in order to improve customer loyalty.

Plasticity in Life-History Traits

Abstract: We describe the impact of recent life-history plasticity theory on insect studies, particularly on the interface between genetics and plasticity. We focus on the three-dimensional relationship between three key life-history traits: adult size (or mass), development time and growth rate, and the connections to life cycle regulation, host plant choice, and sexual selection in seasonal environments. The review covers fitness consequences of variation in size, development time and growth rate, and effects of sex, photoperiod, temperature, diet, and perceived mortality risk on these traits. We give special attention to evidence for adaptive plasticity in growth rates because of the important effects of such plasticity on the expected relationships between development time and adult size and, hence, on the use of life-history, fitness, and optimality approaches in ecology, as well as in genetics.

Cell penetration by transportan

Abstract: Transportan is a 27 amino acid-long peptide containing 12 functional amino acids from the amino terminus of the neuropeptide galanin and mastoparan in the carboxyl terminus, connected via a lysine Transportan is a cell-penetrating peptide as judged by indirect immunofluorescence using Ne13-biotinyl-transportan The internalization of biotinyl-transportan is energy independent and takes place efficiently at 37°, 4°, and 0°C Cellular uptake of transportan is probably not mediated by endocytosis, since it cannot be blocked by treating the cells with phenylarsine oxide or hyperosmolar sucrose solution and is nonsaturable The kinetics of internalization was studied with the aid of the 125I-labeled peptide At 37°C, the maximal intracellular concentration is reached in about 20 min The internalized transportan is protected from trypsin The cell-penetrating ability of transportan is not restricted by cell type, but seems to be a general feature of this peptide In Bowes' melanoma cells, transportan first lo

Overtraining and recovery. A conceptual model.

Abstract: Fiercer competition between athletes and a wider knowledge of optimal training regimens dramatically influence current training methods. A single training bout per day was previously considered sufficient, whereas today athletes regularly train twice a day or more. Consequently, the number of athletes who are overtraining and have insufficient rest is increasing. Positive overtraining can be regarded as a natural process when the end result is adaptation and improved performance: the supercompensation principle--which includes the breakdown process (training) followed by the recovery process (rest)--is well known in sports. However, negative overtraining, causing maladaptation and other negative consequences such as staleness, can occur. Physiological, psychological, biochemical and immunological symptoms must be considered, both independently and together, to fully understand the 'staleness' syndrome. However, psychological testing may reveal early-warning signs more readily than the various physiological or immunological markers. The time frame of training and recovery is also important since the consequences of negative overtraining comprise an overtraining-response continuum from short to long term effects. An athlete failing to recover within 72 hours has presumably negatively overtrained and is in an overreached state. For an elite athlete to refrain from training for > 72 hours is extremely undesirable, highlighting the importance of a carefully monitored recovery process. There are many methods used to measure the training process but few with which to match the recovery process against it. One such framework for this is referred to as the total quality recovery (TQR) process. By using a TQR scale, structured around the scale developed for ratings of perceived exertion (RPE), the recovery process can be monitored and matched against the breakdown (training) process (TQR versus RPE). The TQR scale emphasises both the athlete's perception of recovery and the importance of active measures to improve the recovery process. Furthermore, directing attention to psychophysiological cues serves the same purpose as in RPE, i.e. increasing self-awareness. This article reviews and conceptualises the whole overtraining process. In doing so, it (i) aims to differentiate between the types of stress affecting an athlete's performance: (ii) identifies factors influencing an athlete's ability to adapt to physical training: (iii) structures the recovery process. The TQR method to facilitate monitoring of the recovery process is then suggested and a conceptual model that incorporates all of the important parameters for performance gain (adaptation) and loss (maladaptation).

Interactions of Persistent Environmental Organohalogens With the Thyroid Hormone System: Mechanisms and Possible Consequences for Animal and Human Health:

Abstract: Several classes of environmental contaminants have been claimed or suggested to possess endocrine-disrupting potency, which may result in reproductive problems and developmental disorders. In this paper the focus is on the multiple and interactive mechanisms of interference of persistent polyhalogenated aromatic hydrocarbons (PHAHs) and their metabolites with the thyroid hormone system. Evidence suggests that pure congeners or mixtures of PHAHs directly interfere with the thyroid gland; with thyroid hormone metabolizing enzymes, such as uridine-diphosphate-glucuronyl transferases (UGTs), iodothyronine deiodinases (IDs), and sulfotransferases (SULTs) in liver and brain; and with the plasma transport system of thyroid hormones in experimental animals and their offspring. Changes in thyroid hormone levels in conjunction with high PHAH exposure was also observed in captive as well as free ranging wildlife species and in humans. Maternal exposure to PHAHs during pregnancy resulted in a considerable fetal transfer of hydroxylated PHAHs, which are known to compete with thyroxine (T4) for plasma transthyretin (TTR) binding sites, and thus may be transported to the fetus with those carrier proteins that normally mediate the delivery of T4 to the fetus. Concomitant changes in thyroid hormone concentrations in plasma and in brain tissue were observed in fetal and neonatal stages of development, when sufficient thyroid hormone levels are essential for normal brain development. Alterations in structural and functional neurochemical parameters, such as glial fibrillary acidic protein (GFAP), synaptophysin, calcineurin, and serotonergic neurotransmitters, were observed in the same offspring up to postnatal day 90. In addition, some changes in locomotor and cognitive indices of behavior were observed in rat offspring, following in utero and lactational exposure to PHAHs. Alterations in thyroid hormone levels and subtle changes in neurobehavioral performance were also observed in human infants exposed in utero and through lactation to relatively high levels of PHAHs. Overall these studies indicate that persistent PHAHs can disrupt the thyroid hormone system at a multitude of interaction sites, which may have a profound impact on normal brain development in experimental animals, wildlife species, and human infants.

Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo.

Abstract: Peptide nucleic acids (PNAs) form stable and tight complexes with complementary DNA and/or RNA and would be promising antisense reagents if their cellular delivery could be improved. We show that a 21-mer PNA, complementary to the human galanin receptor type 1 mRNA, coupled to the cellular transporter peptides, transportan or pAntennapedia(43–58), is efficiently taken up into Bowes cells where they block the expression of galanin receptors. In rat, the intrathecal administration of the peptide-PNA construct results in a decrease in galanin binding in the dorsal horn. The decrease in binding results in the inability of galanin to inhibit the C fibers stimulation-induced facilitation of the rat flexor reflex, demonstrating that peptide-PNA constructs act in vivo to suppress expression of functional galanin receptors.

A peptidoglycan recognition protein in innate immunity conserved from insects to humans

Abstract: Innate nonself recognition must rely on common structures of invading microbes. In a differential display screen for up-regulated immune genes in the moth Trichoplusia ni we have found mechanisms for recognition of bacterial cell wall fragments. One bacteria-induced gene encodes a protein that, after expression in the baculovirus system, was shown to be a peptidoglycan recognition protein (PGRP). It binds strongly to Gram-positive bacteria. We have also cloned the corresponding cDNA from mouse and human and shown this gene to be expressed in a variety of organs, notably organs of the immune system—i.e., bone marrow and spleen. In addition, purified recombinant murine PGRP was shown to possess peptidoglycan affinity. From our results and the sequence homology, we conclude that PGRP is a ubiquitous protein involved in innate immunity, conserved from insects to humans.

Calculations of near-edge x-ray-absorption spectra of gas-phase and chemisorbed molecules by means of density-functional and transition-potential theory

Abstract: We explore the utility of density-functional theory ~DFT! in conjunction with the transition-potential ~TP! method to simulate x-ray-absorption spectra Calculations on a set of small carbon-containing molecules and chemisorbed species show that this provides a viable option for obtaining excitation energies and oscillator strengths close to the experimental accuracy of core-valence transitions Systematic variations in energy positions and intensities of the different spectra in the test series have been investigated, and comparison is made with respect to the static exchange-, self-consistent-field, and explicit electron-correlation methods The choice between standard exchange-correlation functionals is shown to be of little consequence for the valence resonant, here p*, parts of the x-ray-absorption spectra, while the long-range behavior of presently available functionals is found not to be completely satisfactory for Rydberg-like transitions Implementing a basis set augmentation technique, one finds that DFT methods still account well for most of the salient features in the near-edge x-ray-absorption spectra, save for the multielectron transitions in the near continuum, and for some loss of Rydberg structure For clusters modeling surface adsorbates, the DFT transition potential method reproduces well the spectral compression and intensity reduction for the valence level absorption compared to the free phase, provided fairly large clusters are taken into account While for near-edge x-ray-absorption fine-structure ~NEXAFS! spectra of free molecules the DFT-TP and Hartree-Fock/static exchange methods have complementary advantages, the DFT-TP method is clearly to be preferred when using clusters to simulate NEXAFS spectra of surface adsorbates @S0163-1829~98!00136-2#

Nature's Subsidies to Shrimp and Salmon Farming

Abstract: Although many fisheries stocks have declined precipitously throughout the world, fish farming--and especially shrimp and salmon farming--has boomed. The increasingly large scale of these enterprises is now having unforeseen ecological consequences on ocean resources through habitat destruction, effluent discharge, exotic species introductions, and heightened fish catch for feed use. Ending unsustainable production practices will require reorienting regulatory policies and fiscal incentives in shrimp- and salmon-producing counties, and enhancing restrictions on environmentally unsound practices.

Transparency and Credibility: Monetary Policy with Unobservable Goals

Abstract: We de…ne and study transparency, credibility, and reputation in a model where the central bank’s characteristics are unobservable to the private sector and inferred from the policy outcome. A low-credibility bank optimally conducts a more expansionary policy than a high-credibility bank, in the sense that it induces higher in‡ation, but a less expansionary policy in the sense that it induces lower in‡ation and employment than expected. Increased transparency makes the bank’s reputation and credibility more sensitive to its actions. This moderates the bank’s policy, and induces the bank to follow a policy closer to the socially optimal one. Full transparency of the central bank’s intentions is generally socially bene…cial, but frequently not in the interest of the bank. Somewhat paradoxically, direct observability of idiosyncratic central bank goals removes the moderating in‡uence on the bank and leads to the worst equilibrium. JEL Classi…cation: E52, E58

Language switches in L3 production : Implications for a polyglot speaking model

Abstract: In general, discussion of cross-linguistic influence has focussed almost exclusively on the role of L1 in L2 production, both in the form of cross-linguistic influence on the learner's interlanguage and in the form of language switches to the L1 during L2 production. As yet, there has been little work done on the influence of a learner's other previously learned L2s in the acquisition of a new language (L3). The few studies that have been been carried out on the role of L2 in L3 production however show that L2 does play an important role in L3 acquisition. This paper presents the results of ongoing research on non-adapted language switches, using data from a two-year longitudinal case study of an adult learner of L3 Swedish with L1 English and L2 German. Our study is based on 844 non-adapted language switches. We identified four main types of switch, three of which had pragmatic purpose, namely: (i) EDIT (marking self-repair, beginning of turntake etc.), (ii) META (used for asides, to comment on L3 performance or ask for help) and (iii) INSERT (use of non-L3 items to overcome lexical problems in L3), and the last of which we refer to as Without Identified Pragmatic Purpose (WIPP switch; cf. 'non-intentional switches', Poulisse and Bongaerts 1994). We found that while L1 English prevailed in EDIT, META and INSERT functions, almost only L2 German occurred in WIPP switches. Most of these WIPP switches were function words. We also noticed that a number of the English utterances used in INSERT function appeared to show German influence, although this was not the case when English was used in META function. Our results show that in this case study of L3 acquisition, L1 and L2 play different roles. We suggest that L2 German, which was shown to be the non-L3 language predominantly used to supply material for lexical construction attempts in the L3 (Williams and Hammarberg 1994), is activated in parallel to the L3 interlanguage, underlying L3 production and even L1 producti

Polybrominated diphenyl ethers and hexabromocyclododecane in sediment and fish from a Swedish River

Abstract: Fish and sediments from several places along the Swedish River Viskan, sampled in 1995, were analyzed for polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD). The samples were collected up- and downstream from several possible point sources (textile industries) for these compounds. Tetrabromodiphenyl ethers (TeBDEs), pentabromodiphenyl ethers (PeBDEs), and decabromodiphenyl ether (DeBDE [BDE209]) were found in sediment. Tetrabromodiphenyl ethers and PeBDEs were also found in fish. Hexabromocyclododecane was identified in sediment and fish. Large fish to sediment ratios for TeBDE, PeBDEs, and HBCD indicate that these are highly bioavailable, whereas BDE209 seems not to be as bioavailable. The lowest PBDE and HBCD levels were found upstream of the industries and concentrations generally increased progressively further downstream as more industries were passed. This is in agreement with earlier investigations of PBDEs in fish from the same river. Many brominated compounds are photolabile, which can complicate their analysis. Under the conditions used in this investigation it was observed that BDE209 in a solvent that was subject to the clean-up procedure partly decomposed to compounds with shorter retention times, whereas BDE209 seemed to be stable in the sample extracts. Another matrix effect could be observed in the increased sensitivity obtained for some of the investigated compounds in fish and sediment extracts as compared to standard solutions. This effect may obscure analytical results obtained with electron capture mass spectrometric detections.

Oxygen Production in Nature: A Light-Driven Metalloradical Enzyme Process

Abstract: Dioxygen is thermodynamically hot but kinetically cool, which makes it an ideal reagent for maximizing biological free energy production and for carrying out difficult chemical transformations in enzyme active sites.1 The widespread use of dioxygen in biological catalysis has led to an enzyme classification scheme s monooxygenases, dioxygenases, oxidases s that is based on the specifics of the chemistry in which O2 participates. Examples of the remarkable utility of dioxygen in biology abound and include its use in maximizing ATP production in aerobic respiration, in C-H bond activation in the P450 enzymes and methane monoxygenases, and in the degradation of important biomaterials such as lignin. Although nature has devised a multitude of mechanisms by which to activate dioxygen for useful chemistry, only one system, Photosystem II (PSII) in plants and algae, has evolved that has the capacity to lift water out of its thermodynamic well to generate dioxygen. This singular development provided photosynthetic organisms with an abundant and ubiquitous substrate for growth and diversification. The molecular mechanism by which PSII is able to strip hydrogen atoms from water and release O2 as waste is coming into view. In this article, we review the physical structure and energetics of PSII. We then discuss and analyze a metalloradical enzyme mechanism for the water-oxidation process it catalyzes.

Modelling the response of glaciers to climate warming

Abstract: Dynamic ice-flow models for 12 glaciers and ice caps have been forced with various climate change scenarios The volume of this sample spans three orders of magnitude Six climate scenarios were considered: from 1990 onwards linear warming rates of 001, 002 and 004 K a-1, with and without concurrent changes in precipitation The models, calibrated against the historic record of glacier length where possible, were integrated until 2100 The differences in individual glacier responses are very large No straightforward relationship between glacier size and fractional change of ice volume emerges for any given climate scenario The hypsometry of individual glaciers and ice caps plays an important role in their response, thus making it difficult to generalize results For a warming rate of 004 K a-1, without increase in precipitation, results indicate that few glaciers would survive until 2100 On the other hand, if the warming rate were to be limited to 001 K a-1 with an increase in precipitation of 10% per degree warming, we predict that overall loss would be restricted to 10 to 20% of the 1990 volume

Resilience in natural and socioeconomic systems

Abstract: We, as a society, find ourselves confronted with a spectrum of potentially catastrophic and irreversible environmental problems, for which conventional approaches will not suffice in providing solutions. These problems are characterized, above all, by their unpredictability. This means that surprise is to be expected, and that sudden qualitative shifts in dynamics present serious problems for management. In general, it is difficult to detect strong signals of change early enough to motivate effective solutions, or even to develop scientific consensus on a time scale rapid enough to allow effective solution. Furthermore, such signals, even when detected, are likely to be displaced in space or sector from the source, so that the motivation for action is small. Conventional market mechanisms thus will be inadequate to address these challenges.

Productivity, quality and relationship marketing in service operations

Abstract: The purpose of this article is to draw the reader’s attention to service productivity and its connection to service quality and eventually to profits. In service operations the customer plays an active role in influencing productivity and quality. Furthermore, contemporary companies are networks, not delimited hierarchies, and the productivity and quality issues affect all members of a network, not just the provider and the customer. This is clear from the new developments in relationship marketing and imaginary (virtual) organizations. In order to assess the financial outcome, the concept of return on relationships is introduced based on the notions of intellectual capital and the balanced scorecard. The article ends with challenging questions as well as recommendations for practising managers.

The Escherichia coli SRP and SecB targeting pathways converge at the translocon

Abstract: Two distinct protein targeting pathways can direct proteins to the Escherichia coli inner membrane. The Sec pathway involves the cytosolic chaperone SecB that binds to the mature region of pre-proteins. SecB targets the pre-protein to SecA that mediates pre-protein translocation through the SecYEG translocon. The SRP pathway is probably used primarily for the targeting and assembly of inner membrane proteins. It involves the signal recognition particle (SRP) that interacts with the hydrophobic targeting signal of nascent proteins. By using a protein cross-linking approach, we demonstrate here that the SRP pathway delivers nascent inner membrane proteins at the membrane. The SRP receptor FtsY, GTP and inner membranes are required for release of the nascent proteins from the SRP. Upon release of the SRP at the membrane, the targeted nascent proteins insert into a translocon that contains at least SecA, SecY and SecG. Hence, as appears to be the case for several other translocation systems, multiple targeting mechanisms deliver a variety of precursor proteins to a common membrane translocation complex of the E.coli inner membrane.

Person-context interaction theories

Abstract: A basic proposition for this chapter's presentation and discussion is that the individual is an active, purposeful part of an integrated, complex, and dynamic person-environment system. Our position is that, as a fundamental prerequisite for success, empirical research must start with a careful analysis of the phenomena relevant to the specific problem under study. With reference to this proposition, the main part of this chapter is devoted to an attempt to analyze the structures and processes involved in the operation of person-environment systems and the way in which the individual functions and develops within this general type of system. The main thesis emphasizes the close dependency of individual functioning and individual development on the social, cultural, and physical characteristics of the environment. At the end of the chapter, certain methodological and research strategy implications of the theoretical analysis will be presented.

Price competition and market concentration: An experimental study

Abstract: The classical price competition model (named after Bertrand), prescribes that in equilibrium prices are equal to marginal costs. Moreover, prices do not depend on the number of competitors. Since this outcome is not in line with real-life observations, it is known as the Bertrand Paradox". Many theoretical problems with the original model have been considered as an explanation of the paradox in the literature. In this paper we experimentally investigate a model which is immune to the theoretical critique of the original model. We find, nevertheless, that the outcome does depend on the number of competitors: the Bertrand solution does not predict well when the number of competitors is two, but after some opportunities for learning are provided it tends to predict well when the number of competitors is three or four. A bounded rationality explanation of this is suggested.

Benefits of multiple mates in the cricket gryllus bimaculatus.

Abstract: Despite the importance of polyandry for sexual selection, the reasons why females frequently mate with several males remain poorly understood. A number of genetic benefits have been proposed, based on the idea that by taking multiple mates, females increase the likelihood that their offspring will be sired by genetically more compatible or superior males. If certain males have intrinsically "good genes," any female mating with them will produce superior offspring. Alternatively, if some males have genetic elements that are incompatible with a particular female, then she may benefit from polyandry if the sperm of such males are less likely to fertilize her eggs. We examined these hypotheses in the field cricket Gryllus bimaculatus (Orthoptera: Gryllidae). By allocating females identical numbers of matings but different numbers of mates we investigated the influence of number of mates on female fecundity, and both short- and long-term offspring fitness. This revealed no effect of number of mates on number of eggs laid. However, hatching success of eggs increased with number of mates. This effect could not be attributed to nongenetic effects such as the possibility that polyandry reduces variance in the quantity or fertilizing ability of sperm females receive, because a control group receiving half the number of copulations showed no drop in hatching success. Offspring did not differ in survival, adult mass, size, or development time with treatment. When males were mated to several different females there were no repeatable differences between individual males in the hatching success of their mate's eggs. This suggests that improved hatching success of polyandrous females is not due to certain males having genes that improve egg viability regardless of their mate. Instead, our results support the hypothesis that certain males are genetically more compatible with certain females, and that this drives polyandry through differential fertilization success of sperm from more compatible males.

Trees tell of past climates: But are they speaking less clearly today?

Abstract: The annual growth of trees, as represented by a variety of ringwidth, densitometric, or chemical parameters, represents a combined record of different environmental forcings, one of which is climat...