Showing papers by "Uppsala University published in 2003"

MrBayes 3: Bayesian phylogenetic inference under mixed models

Abstract: Summary: MrBayes 3 performs Bayesian phylogenetic analysis combining information from different data partitions or subsets evolving under different stochastic evolutionary models. This allows the user to analyze heterogeneous data sets consisting of different data types—e.g. morphological, nucleotide, and protein— and to explore a wide variety of structured models mixing partition-unique and shared parameters. The program employs MPI to parallelize Metropolis coupling on Macintosh or UNIX clusters.

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

Abstract: Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

The Ecology of Individuals: Incidence and Implications of Individual Specialization

Abstract: Most empirical and theoretical studies of resource use and population dynamics treat conspecific individuals as ecologically equivalent. This simplification is only justified if interindividual niche variation is rare, weak, or has a trivial effect on ecological processes. This article reviews the incidence, degree, causes, and implications of individual-level niche variation to challenge these simplifications. Evidence for individual specialization is available for 93 species dis- tributed across a broad range of taxonomic groups. Although few studies have quantified the degree to which individuals are specialized relative to their population, between-individual variation can some- times comprise the majority of the population's niche width. The degree of individual specialization varies widely among species and among populations, reflecting a diverse array of physiological, be- havioral, and ecological mechanisms that can generate intrapopu- lation variation. Finally, individual specialization has potentially im- portant ecological, evolutionary, and conservation implications. Theory suggests that niche variation facilitates frequency-dependent interactions that can profoundly affect the population's stability, the amount of intraspecific competition, fitness-function shapes, and the population's capacity to diversify and speciate rapidly. Our collection of case studies suggests that individual specialization is a widespread but underappreciated phenomenon that poses many important but unanswered questions.

Glacial Refugia: Hotspots But Not Melting Pots of Genetic Diversity

Abstract: Glacial refuge areas are expected to harbor a large fraction of the intraspecific biodiversity of the temperate biota. To test this hypothesis, we studied chloroplast DNA variation in 22 widespread European trees and shrubs sampled in the same forests. Most species had genetically divergent populations in Mediterranean regions, especially those with low seed dispersal abilities. However, the genetically most diverse populations were not located in the south but at intermediate latitudes, a likely consequence of the admixture of divergent lineages colonizing the continent from separate refugia.

Ferromagnetism above room temperature in bulk and transparent thin films of Mn-doped ZnO

Abstract: The search for ferromagnetism above room temperature in dilute magnetic semiconductors has been intense in recent years. We report the first observations of ferromagnetism above room temperature for dilute ( 700 °C) methods were used, samples were found to exhibit clustering and were not ferromagnetic at room temperature. This capability to fabricate ferromagnetic Mn-doped ZnO semiconductors promises new spintronic devices as well as magneto-optic components.

Communication of emotions in vocal expression and music performance: different channels, same code?

Abstract: Many authors have speculated about a close relationship between vocal expression of emotions and musical expression of emotions. but evidence bearing on this relationship has unfortunately been lacking. This review of 104 studies of vocal expression and 41 studies of music performance reveals similarities between the 2 channels concerning (a) the accuracy with which discrete emotions were communicated to listeners and (b) the emotion-specific patterns of acoustic cues used to communicate each emotion. The patterns are generally consistent with K. R. Scherer's (1986) theoretical predictions. The results can explain why music is perceived as expressive of emotion, and they are consistent with an evolutionary perspective on vocal expression of emotions. Discussion focuses on theoretical accounts and directions for future research.

The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial.

Abstract: BackgroundThe prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago, but are less clear in those with mildly to moderately elevated blood pressure.ObjectiveTo assess whether candesartan-based antihypertensive treatment in el

The role of phenotypic plasticity in driving genetic evolution.

Abstract: Models of population divergence and speciation are often based on the assumption that differences between populations are due to genetic factors, and that phenotypic change is due to natural selection. It is equally plausible that some of the differences among populations are due to phenotypic plasticity. We use the metaphor of the adaptive landscape to review the role of phenotypic plasticity in driving genetic evolution. Moderate levels of phenotypic plasticity are optimal in permitting population survival in a new environment and in bringing populations into the realm of attraction of an adaptive peak. High levels of plasticity may increase the probability of population persistence but reduce the likelihood of genetic change, because the plastic response itself places the population close to a peak. Moderate levels of plasticity arise whenever multiple traits, some of which are plastic and others not, form a composite trait involved in the adaptive response. For example, altered behaviours may drive selection on morphology and physiology. Because there is likely to be a considerable element of chance in which behaviours become established, behavioural change followed by morphological and physiological evolution may be a potent force in driving evolution in novel directions. We assess the role of phenotypic plasticity in stimulating evolution by considering two examples from birds: (i) the evolution of red and yellow plumage coloration due to carotenoid consumption; and (ii) the evolution of foraging behaviours on islands. Phenotypic plasticity is widespread in nature and may speed up, slow down, or have little effect on evolutionary change. Moderate levels of plasticity may often facilitate genetic evolution but careful analyses of individual cases are needed to ascertain whether plasticity has been essential or merely incidental to population differentiation.

Mosquitoes and their Control

Abstract: General Aspects.- Systematics.- Biology of Mosquitoes.- Medical Importance of Mosquitoes.- Mosquito Research Techniques.- Morphology of Mosquitoes.- Identification Keys Morphology Ecology and Distribution of European Species.- Key to Female Mosquitoes.- Key to Male Mosquitoes.- Key to Mosquito Fourth Instar Larvae.- Subfamily Anophelinae.- Subfamily Culicinae.- Identification Keys, Morphology, Ecology and Distribution of Important Vector and Nuisance Species - Worldwide.- Africa.- Asia.- Australia.- Central and South America.- North America.- Control of Mosquitoes.- Biological Control.- Environmental Management of Mosquitoes.- Chemical Control.- Physical Control.- Genetic Control of Mosquitoes.- Personal Protection.- Implementation and Integration of Mosquito Control Measures.

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

Abstract: Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

On robust Capon beamforming and diagonal loading

Abstract: The Capon (1969) beamformer has better resolution and much better interference rejection capability than the standard (data-independent) beamformer, provided that the array steering vector corresponding to the signal of interest (SOI) is accurately known. However, whenever the knowledge of the SOI steering vector is imprecise (as is often the case in practice), the performance of the Capon beamformer may become worse than that of the standard beamformer. Diagonal loading (including its extended versions) has been a popular approach to improve the robustness of the Capon beamformer. We show that a natural extension of the Capon beamformer to the case of uncertain steering vectors also belongs to the class of diagonal loading approaches, but the amount of diagonal loading can be precisely calculated based on the uncertainty set of the steering vector. The proposed robust Capon beamformer can be efficiently computed at a comparable cost with that of the standard Capon beamformer. Its excellent performance for SOI power estimation is demonstrated via a number of numerical examples.

Ethnic Enclaves and the Economic Success of Immigrants—Evidence from a Natural Experiment

Abstract: Recent immigrants tend to locate in ethnic ”enclaves” within metropolitan areas. The economic consequence of living in such enclaves is still an unresolved issue. We use an immigrant policy initiative in Sweden, when government authorities distributed refugee immigrants across locales in a way that may be considered exogenous. This policy initiative provides a unique natural experiment, which allows us to estimate the causal effect on labor market outcomes of living in enclaves. We find substantive evidence of sorting across locations. When sorting is taken into account, living in enclaves improves labor market outcomes; for instance, the earnings gain associated with a standard deviation increase in ethnic concentration is in the order of four to five percent.

A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig

Abstract: Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation.

Timed Automata: Semantics, Algorithms and Tools

Abstract: This chapter is to provide a tutorial and pointers to results and related work on timed automata with a focus on semantical and algorithmic aspects of verification tools. We present the concrete and abstract semantics of timed automata (based on transition rules, regions and zones), decision problems, and algorithms for verification. A detailed description on DBM (Difference Bound Matrices) is included, which is the central data structure behind several verification tools for timed systems. As an example, we give a brief introduction to the tool Uppaal.

Architecture of succinate dehydrogenase and reactive oxygen species generation.

Abstract: The structure of Escherichia coli succinate dehydrogenase (SQR), analogous to the mitochondrial respiratory complex II, has been determined, revealing the electron transport pathway from the electron donor, succinate, to the terminal electron acceptor, ubiquinone It was found that the SQR redox centers are arranged in a manner that aids the prevention of reactive oxygen species (ROS) formation at the flavin adenine dinucleotide This is likely to be the main reason SQR is expressed during aerobic respiration rather than the related enzyme fumarate reductase, which produces high levels of ROS Furthermore, symptoms of genetic disorders associated with mitochondrial SQR mutations may be a result of ROS formation resulting from impaired electron transport in the enzyme

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

Abstract: Background Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. Methods Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206–222)amide and [Tyr224]FGF-23(225–244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted f...

Space-Time Block Coding for Wireless Communications

Abstract: Space-time coding is a technique that promises greatly improved performance in wireless networks by using multiple antennas at the transmitter and receiver. Space-Time Block Coding for Wireless Communications is an introduction to the theory of this technology. The authors develop the topic using a unified framework and cover a variety of topics ranging from information theory to performance analysis and state-of-the-art space-time coding methods for both flat and frequency-selective fading multiple-antenna channels. The authors concentrate on key principles rather than specific practical applications, and present the material in a concise and accessible manner. Their treatment reviews the fundamental aspects of multiple-input, multiple output communication theory, and guides the reader through a number of topics at the forefront of current research and development. The book includes homework exercises and is aimed at graduate students and researchers working on wireless communications, as well as practitioners in the wireless industry.

Promoting Relationship Learning

Abstract: The authors develop a theory of how management can develop and promote the learning capabilities of targeted customer-supplier relationships. The theory suggests that a supplier and a customer can improve their joint learning activities by facilitating information exchange, developing common learning arenas, and updating their behavior accordingly. The authors suggest that learning within a customer-supplier relationship cannot be mandated by either organization, but rather learning depends on both parties’ willingness to cooperate in joint learning activities. Management can promote relationship learning by cultivating a collaborative culture, formulating specific objectives for joint learning activities, and developing relational trust. However, as relational trust develops, the effectiveness of learning is reduced as a result of “hidden costs” of trust. The authors use data from 315 dyads to test the theory empirically, and they find that the learning capability of a relationship has a strong,...

Key Principles for User-Centred Systems Design

Abstract: The concept of user-centred systems design (UCSD) has no agreed upon definition. Consequently, there is a great variety in the ways it is applied, which may lead to poor quality and poor usability in the resulting systems, as well as misconceptions about the effectiveness of UCSD. The purpose of this paper is to propose a definition of UCSD. We have identified 12 key principles for the adoption of a user-centred development process, principles that are based on existing theory, as well as research in and experiences from a large number of software development projects. The initial set of principles were applied and evaluated in a case study and modified accordingly. These principles can be used to communicate the nature of UCSD, evaluate a development process or develop systems development processes that support a user-centred approach. We also suggest activity lists and some tools for applying UCSD.

Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.

Abstract: the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease–related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease–related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n=118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease–related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). Conclusions The CONVINCE trial did not demonstrate equivalence of a COER verapamil–based antihypertensive regimen compared with a regimen beginning with a diuretic or -blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or -blocker treatment. JAMA. 2003;289:2073-2082 www.jama.com

A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2.

Abstract: Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP). TIMP3, which encodes a potent angiogenesis inhibitor, is mutated in Sorsby fundus dystrophy, a macular degenerative disease with submacular choroidal neovascularization. In this study we demonstrate the ability of TIMP3 to inhibit vascular endothelial factor (VEGF)-mediated angiogenesis and identify the potential mechanism by which this occurs: TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule.

On robust Capon beamforming and diagonal loading

Abstract: Whenever the knowledge of the array steering vector is imprecise (as is often the case in practice), the performance of the Capon beamformer may become worse than that of the standard beamformer. Diagonal loading (including its extended versions) has been a popular approach to improve the robustness of the Capon beamformer. In this paper we show that a natural extension of the Capon beamformer to the case of uncertain steering vectors also belongs to the class of diagonal loading approaches but the amount of diagonal loading can be precisely calculated based on the uncertainty set of the steering vector. The proposed robust Capon beamformer can be efficiently computed at a comparable cost with that of the standard Capon beamformer. Its excellent performance is demonstrated via a number of numerical examples.

Reliability of Bayesian posterior probabilities and bootstrap frequencies in phylogenetics.

Abstract: Many empirical studies have revealed considerable differences between nonparametric bootstrapping and Bayesian posterior probabilities in terms of the support values for branches, despite claimed predictions about their approximate equivalence. We investigated this problem by simulating data, which were then analyzed by maximum likelihood bootstrapping and Bayesian phylogenetic analysis using identical models and reoptimization of parameter values. We show that Bayesian posterior probabilities are significantly higher than corresponding nonparametric bootstrap frequencies for true clades, but also that erroneous conclusions will be made more often. These errors are strongly accentuated when the models used for analyses are underparameterized. When data are analyzed under the correct model, nonparametric bootstrapping is conservative. Bayesian posterior probabilities are also conservative in this respect, but less so.

N-Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy

Abstract: BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain na ...

Breast Cancer Following Radiotherapy and Chemotherapy Among Young Women With Hodgkin Disease

Abstract: ContextSecond cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.ObjectiveTo quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.Design, Setting, and SubjectsMatched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.Main Outcome MeasuresRelative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.ResultsBreast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P = .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P = .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.ConclusionsHormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.