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Uppsala, Sweden

Uppsala University is a research university in Uppsala, Sweden, and is the oldest university in Sweden, founded in 1477. It ranks among the best universities in Northern Europe and in international rankings.The university rose to pronounced significance during the rise of Sweden as a great power at the end of the 16th century and was then given a relative financial stability with the large donation of King Gustavus Adolphus in the early 17th century. Uppsala also has an important historical place in Swedish national culture, identity and for the Swedish establishment: in historiography, literature, politics, and music. Many aspects of Swedish academic culture in general, such as the white student cap, originated in Uppsala. It shares some peculiarities, such as the student nation system, with Lund University and the University of Helsinki.Uppsala belongs to the Coimbra Group of European universities. The university has nine faculties distributed over three “disciplinary domains”. It has about 24,000 full-time students and 2,400 doctoral students. It has a teaching staff of roughly 1,800 out of a total of 6,500 employees. Twenty-five per cent of the 674 professors at the university are women. Of its turnover of SEK 5.9 billion in 2013, 30% was spent on education on basic and advanced level, while 66% was spent on research and research programs.Architecturally, Uppsala University has traditionally had a strong presence in the area around the cathedral on the western side of the River Fyris. Despite some more contemporary building developments further away from the centre, Uppsala's historic centre continues to be dominated by the presence of the university. Wikipedia.


Wolf J.B.W.,Max Planck Institute for Evolutionary Biology | Wolf J.B.W.,Uppsala University | Bryk J.,Max Planck Institute for Evolutionary Biology
BMC Genomics | Year: 2011

Background: Species with heteromorphic sex chromosomes face the challenge of large-scale imbalance in gene dose. Microarray-based studies in several independent male heterogametic XX/XY systems suggest that dosage compensation mechanisms are in place to mitigate the detrimental effects of gene dose differences. However, recent genomic research on female heterogametic ZZ/ZW systems has generated surprising results. In two bird species and one lepidopteran no evidence for a global dosage compensating mechanism has been found. The recent advent of massively parallel RNA sequencing now opens up the possibility to gauge the generality of this observation with a broader phylogenetic sampling. It further allows assessing the validity of microarray-based inference on dosage compensation with a novel technology.Results: We here expemplify this approach using massively parallel sequencing on barcoded individuals of a bird species, the European crow (Corvus corone), where previously no genetic resources were available. Testing for Z-linkage with quantitative PCR (qPCR,) we first establish that orthology with distantly related species (chicken, zebra finch) can be used as a good predictor for chromosomal affiliation of a gene. We then use a digital measure of gene expression (RNA-seq) on brain transcriptome and confirm a global lack of dosage compensation on the Z chromosome. RNA-seq estimates of male-to-female (m:f) expression difference on the Z compare well to previous microarray-based estimates in birds and lepidopterans. The data further lends support that an up-regulation of female Z-linked genes conveys partial compensation and suggest a relationship between sex-bias and absolute expression level of a gene. Correlation of sex-biased gene expression on the Z chromosome across all three bird species further suggests that the degree of compensation has been partly conserved across 100 million years of avian evolution.Conclusions: This work demonstrates that the study of dosage compensation has become amenable to species where previously no genetic resources were available. Massively parallele transcriptome sequencing allows re-assessing the degree of dosage compensation with a novel tool in well-studies species and, in addition, gain valuable insights into the generality of mechanisms across independent taxonomic group for both the XX/XY and ZZ/ZW system. © 2011 Wolf and Bryk; licensee BioMed Central Ltd.


Fantazzini D.,Moscow State University | Hook M.,Uppsala University
Energy Policy | Year: 2011

The Deepwater Horizon incident demonstrated that most of the oil left is deep offshore or in other difficult to reach locations. Moreover, obtaining the oil remaining in currently producing reservoirs requires additional equipment and technology that comes at a higher price in both capital and energy. In this regard, the physical limitations on producing the ever-increasing quantities of oil are highlighted as well as the possibility of the peak of production occurring this decade. The economics of oil supply and demand are also briefly discussed showing why the available supply is basically fixed in the short to medium term. Also, an alarm bell for economic recessions is shown to be when energy takes a disproportionate amount of total consumer expenditures. In this context, risk mitigation practices in government and business are called for. As for the former, early education of the citizenry of the risk of economic contraction is a prudent policy to minimize potential future social discord. As for the latter, all business operations should be examined with the aim of building in resilience and preparing for a scenario in which capital and energy are much more expensive than in the business-as-usual one. © 2011 Elsevier Ltd.


Increased intra-abdominal pressure (IAP) and abdominal compartment syndrome (ACS) are important clinical problems after repair of ruptured abdominal aortic aneurysms and are reviewed here. IAP >20 mm Hg occurs in approximately 50% of patients treated with open abdominal aortic aneurysm repair after rupture, and approximately 20% develop organ failure or dysfunction, fulfilling the criteria for ACS. Patients selected for endovascular aneurysm repair are often more hemodynamically stable, perhaps related to not handling the viscera or more favorable anatomy, resulting in less bleeding and, consequently, decreased risk of developing ACS. Centers that treat most patients with endovascular aneurysm repair tend to have the same proportion of ACS as after open repair. There are no randomized data on these aspects. Early nonsurgical therapy can prevent development of ACS. Medical therapy includes neuromuscular blockade and the combination of positive end-expiratory pressure, albumin, and furosemide. This proactive strategy can reduce the number of decompressive laparotomies, an important detail because treatment of ACS with open abdomen is a morbid procedure. When treatment with an open abdomen is necessary, it is important to choose a temporary abdominal closure that maintains sterile conditions during often prolonged treatment. In addition, it should prevent lateralization of the bowel wall and adhesions between the intestines and the bowel wall. Enteroatmospheric fistulae must be prevented. Many alternative methods have been suggested, but we prefer the combination of vacuum-assisted wound closure with mesh-mediated traction, which will be described. © 2012 Elsevier Inc..


Granqvist C.G.,Uppsala University
Journal of Vacuum Science and Technology B: Nanotechnology and Microelectronics | Year: 2014

Modern buildings often have large windows and glass facades in order to achieve good day-lighting and desirable indoors-outdoors contact. These glazings are challenging with regard to the buildings' energy efficiency and frequently let in or out too much energy; this phenomenon has to be balanced by energy guzzling cooling or heating. In particular, the cooling requirement has grown strongly in recent years. Chromogenic glazings, based on thermochromism or electrochromism, are emerging technologies that can regulate the inflow of visible light and solar energy between widely separated limits and create better energy efficiency than is possible with static solutions. Thermochromic thin films - in practice based on vanadium dioxide - have a transmittance of infrared solar radiation that is smaller at high temperature than at low temperature. Electrochromic multilayer structures - often incorporating nanoporous thin films of tungsten oxide and nickel oxide - are able to vary the transmittance of visible light and solar energy when a low voltage is applied for a short time so as to shuttle charge between the two oxide films. Furthermore, and importantly, the new chromogenic fenestration technologies are able to improve indoor comfort. This brief tutorial review surveys the fields of oxide-based thermochromics and electrochromics with particular attention to recent advances. © 2014 American Vacuum Society.


Blum M.G.B.,CNRS Complex Medical Engineering Laboratory | Jakobsson M.,Uppsala University
Molecular Biology and Evolution | Year: 2011

Two competing hypotheses are at the forefront of the debate on modern human origins. In the first scenario, known as the recent Out-of-Africa hypothesis, modern humans arose in Africa about 100,000-200,000 years ago and spread throughout the world by replacing the local archaic human populations. By contrast, the second hypothesis posits substantial gene flow between archaic and emerging modern humans. In the last two decades, the young time estimates - between 100,000 and 200,000 years - of the most recent common ancestors for the mitochondrion and the Y chromosome provided evidence in favor of a recent African origin of modern humans. However, the presence of very old lineages for autosomal and X-linked genes has often been claimed to be incompatible with a simple, single origin of modern humans. Through the analysis of a public DNA sequence database, we find, similar to previous estimates, that the common ancestors of autosomal and X-linked genes are indeed very old, living, on average, respectively, 1,500,000 and 1,000,000 years ago. However, contrary to previous conclusions, we find that these deep gene genealogies are consistent with the Out-of-Africa scenario provided that the ancestral effective population size was approximately 14,000 individuals. We show that an ancient bottleneck in the Middle Pleistocene, possibly arising from an ancestral structured population, can reconcile the contradictory findings from the mitochondrion on the one hand, with the autosomes and the X chromosome on the other hand. © 2010 The Author.


Rodriguez A.,Uppsala University | Rodriguez A.,Imperial College London | Rodriguez A.,Kings College London
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2010

Objective: This study aimed to replicate and extend previous work showing an association between maternal pre-pregnancy adiposity and risk for attention deficit hyperactivity disorder (ADHD) symptoms in children. Methods: A Swedish population-based prospective pregnancy-offspring cohort was followed up when children were 5 years old (N = 1,714). Mothers and kindergarten teachers rated children's ADHD symptoms, presence and duration of problems, and emotionality. Dichotomized outcomes examined difficulties of clinical relevance (top 15% of the distribution). Analyses adjusted for pregnancy (maternal smoking, depressive symptoms, life events, education, age, family structure), birth outcomes (birth weight, gestational age, infant sex) and concurrent variables (family structure, maternal depressive symptoms, parental ADHD symptoms, and child overweight) in an attempt to rule out confounding. Results: Maternal pre-pregnancy overweight and obesity predicted high inattention symptom scores and obesity was associated with a two-fold increase in risk of difficulties with emotion intensity and emotion regulation according to teacher reports. Means of maternal ratings were unrelated to pre-pregnancy body mass index (BMI). Presence and duration of problems were associated with both maternal over and underweight according to teachers. Conclusions: Despite discrepancies between maternal and teacher reports, these results provide further evidence that maternal pre-pregnancy overweight and obesity are associated with child inattention symptoms and extend previous work by establishing a link between obesity and emotional difficulties. Maternal adiposity at the time of conception may be instrumental in programming child mental health, as prenatal brain development depends on maternal energy supply. Possible mechanisms include disturbed maternal metabolic function. If maternal pre-pregnancy obesity is a causal risk factor, the potential for prevention is great. © 2009 Association for Child and Adolescent Mental Health.


Sensory properties guide the amount that people eat. In particular, food texture plays an important role in a food's 'expected satiation', which in turn affects the food-related decision making process. One hypothesis is that incongruent pairing of a textural cue with a post-ingestive outcome compromises this process, leading to poor energy compensation. Several studies examined the effect of both energy density and sensory characteristics (i.e. increased creaminess and thickness) on expectations, subjective appetite and food intake. To add to this literature, a re-analysis of data assessed whether the effect of sensory-nutrient pairings on energy intake compensation persisted after repeated exposure to a food. In this cross-over design, 27 participants consumed two preloads with 'congruent' (low-energy/liquid; high-energy/semi-solid) and two preloads with 'incongruent' (low-energy/semi-solid; high-energy/liquid) texture-nutrient combinations for nine subsequent meals, during which ad libitum intake was measured. Intake at first exposure did not differ between the low-energy (280. ±. 150. kcal) and high-energy preloads (292. ±. 183. kcal) in the incongruent conditions. By contrast, it was greater after the low-energy (332. ±. 203. kcal) than after the high-energy (236. ±. 132. kcal) preload in the congruent conditions (energy. *. incongruent/congruent, p=. 0.04). Post-exposure, this pattern changed: intake depended on the energy density of the preloads in all conditions, and was greater after low-energy preloads (day. *. energy. *. incongruent/congruent-interaction for breakfast: p=. 0.02). Thus, manipulating the sensory properties of a food influenced energy compensation and meal size, but only at initial exposure. Repeated exposure 'corrected' the initial lack of compensation observed in conditions with incongruent sensory-nutrient pairings. © 2014 Elsevier Inc.


Background:In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals—that is, resting-state brain activity—in the context of food intake are, however, less well studied.Objective:To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI).Methods:Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m- 2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m- 2), both before and 30 min after consumption of a standardized meal (~260 kcal).Results:Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups.Conclusion:Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.105. © 2016 Macmillan Publishers Limited


Granqvist C.G.,Uppsala University
Thin Solid Films | Year: 2014

Electrochromic (EC) smart windows are able to vary their throughput of visible light and solar energy by the application of an electrical voltage and are able to provide energy efficiency and indoor comfort in buildings. Section 1 explains why this technology is important and timely by first outlining today's precarious situation concerning increasing energy use and associated effects on the world's climate, and this section also underscores the great importance of enhancing the energy efficiency of buildings by letting them function more in harmony with the environment - particularly its varying temperature - than is possible with current mainstream technologies. This same chapter also surveys recent work on the energy savings and other benefits that are possible with EC-based technologies. Section 2 then provides some notes on the history of the EC effect and its applications. Section 3 presents a generic design for the oxide-based EC devices that are most in focus for present-day applications and research. This design includes five superimposed layers with a centrally-positioned electrolyte connecting two oxide films - at least one of which having EC properties - and with transparent electrical conductors surrounding the three-layer structure in the middle. It is emphasized that this construction can be viewed as a thin-film electrical battery whose charging state is manifested as optical absorption. Also discussed are six well known hurdles for the implementation of these EC devices, as well as a number of practical constructions of EC-based smart windows. Section 4 is an in-depth discussion of various aspects of EC oxides. It begins with a literature survey for 2007-2013, which updates earlier reviews, and is followed by a general discussion of optical and electronic effects and, specifically, on charge transfer absorption in tungsten oxide. Ionic effects are then treated with foci on the inherent nanoporosity of the important EC oxides and on the possibilities to accomplish further porosity by having suitable thin-film deposition parameters. A number of examples on the importance of the detailed deposition conditions are presented, and Section 4 ends with a presentation of the EC properties of films with compositions across the full tungsten-nickel oxide system. Section 5 is devoted to transparent electrical conductors and electrolytes, both of which are necessary in EC devices. Detailed surveys are given of transparent conductors comprising doped-oxide semiconductors, coinage metals, nanowire meshes and other alternatives, and also of electrolytes based on thin films and on polymers. Particular attention is devoted to electrolyte functionalization by nanoparticles. Section 6 considers one particular device construction: A foil that is suitable for glass lamination and which, in the author's view, holds particular promise for low-cost large-area implementation of EC smart windows. Device data are presented, and a discussion is given of quality assessment by use of 1/f noise. The "battery-type" EC device covered in the major part of this critical review is not the only alternative, and Section 7 consists of brief discussions of a number of more or less advanced alternatives such as metal hydrides, suspended particle devices, polymer-dispersed liquid crystals, reversible electroplating, and plasmonic electrochromism based on transparent conducting oxide nanoparticles. Finally, Section 8 provides a brief summary and outlook. The aim of this critical review is not only to paint a picture of the state-of-the-art for electrochromics and its applications in smart windows, but also to provide ample references to current literature of particular relevance and thereby, hopefully, an easy entrance to the research field. © 2014 Elsevier B.V.


Edelaar P.,CSIC - Donana Biological Station | Bjorklund M.,Uppsala University
Molecular Ecology | Year: 2011

The comparison between neutral genetic differentiation (FST) and quantitative genetic differentiation (QST) is commonly used to test for signatures of selection in population divergence. However, there is an ongoing discussion about what FST actually measures, even resulting in some alternative metrics to express neutral genetic differentiation. If there is a problem with FST, this could have repercussions for its comparison with QST as well. We show that as the mutation rate of the neutral marker increases, FST decreases: a higher within-population heterozygosity (He) yields a lower FST value. However, the same is true for QST: a higher mutation rate for the underlying QTL also results in a lower QST estimate. The effect of mutation rate is equivalent in QST and FST. Hence, the comparison between QST and FST remains valid, if one uses neutral markers whose mutation rates are not too high compared to those of quantitative traits. Usage of highly variable neutral markers such as hypervariable microsatellites can lead to serious biases and the incorrect inference that divergent selection has acted on populations. Much of the discussion on FST seems to stem from the misunderstanding that it measures the differentiation of populations, whereas it actually measures the fixation of alleles. In their capacity as measures of population differentiation, Hedricks GST and Josts D reach their maximum value of 1 when populations do not share alleles even when there remains variation within populations, which invalidates them for comparisons with QST. © 2011 Blackwell Publishing Ltd.


The ruff is a Palearctic wader with a spectacular lekking behavior where highly ornamented males compete for females. This bird has one of the most remarkable mating systems in the animal kingdom, comprising three different male morphs (independents, satellites and faeders) that differ in behavior, plumage color and body size. Remarkably, the satellite and faeder morphs are controlled by dominant alleles. Here we have used whole-genome sequencing and resolved the enigma of how such complex phenotypic differences can have a simple genetic basis. The Satellite and Faeder alleles are both associated with a 4.5-Mb inversion that occurred about 3.8 million years ago. We propose an evolutionary scenario where the Satellite chromosome arose by a rare recombination event about 500,000 years ago. The ruff mating system is the result of an evolutionary process in which multiple genetic changes contributing to phenotypic differences between morphs have accumulated within the inverted region. © 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Jakobsson M.,Uppsala University | Edge M.D.,Stanford University | Rosenberg N.A.,Stanford University
Genetics | Year: 2013

FST is frequently used as a summary of genetic differentiation among groups. It has been suggested that FST depends on the allele frequencies at a locus, as it exhibits a variety of peculiar properties related to genetic diversity: higher values for biallelic singlenucleotide polymorphisms (SNPs) than for multiallelic microsatellites, low values among high-diversity populations viewed as substantially distinct, and low values for populations that differ primarily in their profiles of rare alleles. A full mathematical understanding of the dependence of FST on allele frequencies, however, has been elusive. Here, we examine the relationship between FST and the frequency of the most frequent allele, demonstrating that the range of values that FST can take is restricted considerably by the allelefrequency distribution. For a two-population model, we derive strict bounds on FST as a function of the frequency M of the allele with highest mean frequency between the pair of populations. Using these bounds, we show that for a value of M chosen uniformly between 0 and 1 at a multiallelic locus whose number of alleles is left unspecified, the mean maximum FST is ~0.3585. Further, FST is restricted to values much less than 1 when M is low or high, and the contribution to the maximum FST made by the most frequent allele is on average ~0.4485. Using bounds on homozygosity that we have previously derived as functions of M, we describe strict bounds on FST in terms of the homozygosity of the total population, finding that the mean maximum FST given this homozygosity is 1 2 ln 2 ≈ 0.3069. Our results provide a conceptual basis for understanding the dependence of FST on allele frequencies and genetic diversity and for interpreting the roles of these quantities in computations of FST from population-genetic data. Further, our analysis suggests that many unusual observations of FST, including the relatively low FST values in high-diversity human populations from Africa and the relatively low estimates of FST for microsatellites compared to SNPs, can be understood not as biological phenomena associated with different groups of populations or classes of markers but rather as consequences of the intrinsic mathematical dependence of FST on the properties of allele-frequency distributions. © 2013 by the Genetics Society of America.


Carlsson M.E.,Uppsala University
Palliative and Supportive Care | Year: 2012

Objective: The aim of the present pilot study was to investigate insomnia, sleep quality, and daytime sleepiness in relatives of dying patients cared for at home. Method: The study has a descriptive, comparative, and cross-sectional design. The sample consisted of relatives of patients cared for through palliative home care in Uppsala County on 3 specific days. Relatives completed a questionnaire consisting of demographic questions, and items from the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Richard Campell Sleep Questionnaire (RCSQ). Results: Seventy-five relatives answered the questionnaire. The average total ISI score was 9.6, with 23% reporting moderate or severe clinical insomnia. The mean sleep duration was 6.5 hours, the mean assessed need of sleep was 8 hours, and the mean discrepancy was 1 hour. The total mean ESS score was 5.6 and only 15% of respondents reported excessive daytime sleepiness. Four percent scored very poor sleep quality, whereas 39% scored very good sleep quality (RCSQ). Two general age-and gender-related patterns were observed. Negative correlations were found between age and sleep problems, with younger relatives reporting more insomnia problems and more daytime sleepiness than did older relatives. The other general pattern was that womens' sleep quality was significantly inferior to that of men. A significant positive correlation was found between ISI and ESS, but not between RCSQ and ESS. Significance of results: The picture of the relatives' sleep condition is fairly complex. A minority reported clinical insomnia problems or excessive daytime sleepiness, and 73% reported getting less sleep than they wanted. © 2012 Cambridge University Press.


Black-Schaffer A.M.,NORDITA | Black-Schaffer A.M.,Uppsala University | Balatsky A.V.,Los Alamos National Laboratory
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

Topological insulators (TIs) are said to be stable against nonmagnetic impurity scattering due to suppressed backscattering in the Dirac surface states. We solve a lattice model of a three-dimensional TI in the presence of strong potential impurities and find that both the Dirac point and low-energy states are significantly modified: Low-energy impurity resonances are formed that produce a peak in the density of states near the Dirac point, which is destroyed and split into two nodes that move off center. The impurity-induced states penetrate up to ten layers into the bulk of the TI. These findings demonstrate the importance of bulk states for the stability of TIs and how they can destroy the topological protection of the surface. © 2012 American Physical Society.


Black-Schaffer A.M.,Uppsala University | Balatsky A.V.,Los Alamos National Laboratory
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

Using a three-dimensional microscopic lattice model of a strong topological insulator (TI) we study potential impurities and vacancies in surface, subsurface, and bulk positions. For all impurity locations we find impurity-induced resonance states with energy proportional to the inverse of the impurity strength, although the impurity strength needed for a low-energy resonance state increases with the depth of the impurity. For strong impurities and vacancies as deep as 15 layers into the material, resonance peaks will appear at and around the Dirac point in the surface energy spectrum, splitting the original Dirac point into two nodes located off-center. Furthermore, we study vacancy clusters buried deep inside the bulk and find zero-energy resonance states for both single and multiple-site vacancies. Only fully symmetric multiple-site vacancy clusters show resonance states expelled from the bulk gap. © 2012 American Physical Society.


Introduction: The small tyrosine kinase inhibitor Imatinib Mesylate (Gleevec) protects against diabetes, but it is not known how. Areas covered: It has been suggested that islet amyloid and fibrotic deposits promote beta-cell failure and death, leading to Type-2 diabetes. As Imatinib is known to possess anti-fibrotic/amyloid properties, in for example systemic sclerosis and mouse models for Alzheimer's disease, the present review will discuss the possibility that Imatinib acts, at least in part, by ameliorating islet hyalinization and its consequences in the pathogenesis of Type-2 diabetes. Expert opinion: A better understanding of how Imatinib counteracts Type-2 diabetes will possibly help to clarify the pathogenic role of islet amyloid and fibrosis, and hopefully lead to improved treatment of the disease. © Informa UK, Ltd.


Malqvist M.,Uppsala University
Global health action | Year: 2011

Neonatal mortality is a major health problem in low and middle income countries and the rate of improvement of newborn survival is slow. This article is a review of the PhD thesis by Mats Målqvist, titled 'Who can save the unseen - Studies on neonatal mortality in Quang Ninh province, Vietnam,' from Uppsala University. The thesis aims to investigate structural barriers to newborn health improvements and determinants of neonatal death. The findings reveal a severe under-reporting of neonatal deaths in the official health statistics in Quang Ninh province in northern Vietnam. The neonatal mortality rate (NMR) found was four times higher than what was reported to the Ministry of Health. This underestimation of the problem inhibits adequate interventions and efforts to improve the survival of newborns and highlights the invisibility of this vulnerable group. The findings of the thesis also point at an inequity in survival chances based on ethnicity of the mother. Newborns of ethnic minority mothers were at a twofold risk of dying within the first 4 weeks of life compared to their peers belonging to the hegemonic group of Kinh (OR 2.08, 95% CI: 1.39-3.10). This increased risk was independent of maternal education and household economic status. Neonatal mortality was also associated with home deliveries, non-attendance to antenatal care and distance to the health care facilities. However, ethnic minority mothers still had an increased risk of experiencing a neonatal death even if they attended antenatal care, delivered at, or lived close to a health facility. This example of ethnic inequity highlights the importance to target those most in need.


Balkestahl L.C.,Uppsala University
Acta Physica Polonica B | Year: 2015

The decay η → π+π-π0 is studied with the KLOE detector, at the DAΦNE e+e- collider. Using a data sample corresponding to an integrated luminosity of 1.6 fb-1, a new study of the Dalitz plot is presented. © 2015 ACTA PHYSICA POLONICA B.


Af Wahlberg A.E.,Uppsala University
Transportation Research Part F: Traffic Psychology and Behaviour | Year: 2011

New ways of educating offending drivers are being introduced, notably e-learning. This type of education has rarely been tested for its safety effects before. An e-learning course for offending young drivers was therefore evaluated as to its effects upon offence and self-reported collision rates. Significant reductions in number of offences and penalty points were found for an e-learning group, while this was not the case for drivers who had been fined only, or had taken a more traditional solely class-room based educational scheme. The e-learners also reported a larger reduction in collision involvement than a random control group, although a regression to the mean effect could not be ruled out. The results seem to indicate a positive effect of the e-learning course for young driving offenders. This conclusion, however, is to be interpreted in relation to the weak association between penalty points and collisions, and the low validity of self-reported collision involvement data. The present results lend further support to the use of e-learning driver improvement courses, although the most important type of data, recorded collisions, is still missing. © 2011 Elsevier Ltd. All rights reserved.


Ashoorioon A.,Uppsala University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

In double-field inflation, which exploits two scalar fields, one of the fields rolls slowly during inflation whereas the other field is trapped in a meta-stable vacuum. The nucleation rate from the false vacuum to the true one becomes substantial enough that triggers a first order phase transition and ends inflation. We revisit the question of first order phase transition in an "extended" model of hybrid inflation, realizing the double-field inflationary scenario, and correctly identify the parameter space that leads to a first order phase transition at the end of inflation. We compute the gravitational wave profile which is generated during this first order phase transition. Assuming instant reheating, the peak frequency falls in the 1 GHz to 10 GHz frequency band and the amplitude varies in the range 10-11 ≲ ΩGWh2 ≲ 10-8, depending on the value of the cosmological constant in the false vacuum. For a narrow band of vacuum energies, the first order phase transition can happen after the end of inflation via the violation of slow-roll, with a peak frequency that varies from 1 THz to 100 THz. For smaller values of cosmological constant, even though inflation can end via slow-roll violation, the universe gets trapped in a false vacuum whose energy drives a second phase of eternal inflation. This range of vacuum energies do not lead to viable inflationary models, unless the value of the cosmological constant is compatible with the observed value, M~10-3 eV. © 2015 The Author.


Westermark B.,Uppsala University
Upsala Journal of Medical Sciences | Year: 2014

The platelet-derived growth factor (PDGF) family of mitogens exerts vital functions during embryonal development, e.g. in the central nervous system, where PDGF drives the proliferation of oligodendrocyte precursors. PDGF and PDGF receptors are co-expressed in human glioblastoma (GBM). Whether an aberrant activation of the PDGF receptor pathway is a driving force in glioma development has remained an open question. In experimental animals, overexpression of PDGF has convincingly been shown to induce tumors, both in wild-type animals (marmoset, rat, mouse) and in mice with targeted deletions of suppressor genes, e.g. Tp53 or Ink4A. Targeting the PDGF receptor in tumor-bearing mice leads to growth inhibition and reversion of the transformed phenotype. Findings of PDGF receptor amplification or mutations in human GBM are strong indicators of a causative role of the PDGF receptor pathway. However, clinical trials using PDGF receptor antagonists have been disappointing. In conclusion, a PDGF receptor profile may be a biomarker for a subgroup of GBM originating from a PDGF receptor-responsive cell. Although compelling experimental and clinical evidence supports the notion that the PDGF receptor pathway is a driver in GBM, formal proof is still missing. © 2014 Informa Healthcare.


Flinkfeldt M.,Uppsala University
Sociology of Health and Illness | Year: 2011

An inherent part of the general understanding of illness is that it is incapacitating, making those who are ill unable to do things that they would normally do. Staying at home from work is a common consequence, and what 'ill' people do while at home then becomes accountable. This article explores online discourse about the kinds of activities people engage in when on sick leave. It employs a discursive psychological framework for analysis, drawing heavily on conversation analysis. A Swedish internet forum thread on sick leave is examined, focusing on how the participants describe and account for the things they do when staying home from work due to illness. The analysis suggests that the participants' accounts of their activities delicately manage the legitimacy of their sick leave. In examining how this is done in practice, the analysis makes visible the balancing act between being ill enough to stay home from work and well enough for other activities. In the context of recent debates in Sweden and elsewhere about the legitimacy of sick leave in different situations, the analysis of how legitimacy is actually negotiated is an important concern, making visible the moral work of being on sick leave. © 2011 The Author. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.


Gustavsson I.,Uppsala University
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2011

Most procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media. To evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA Elute Micro card and biopsy analysis. A total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays. All samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2-3 (CIN 2-3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis. The Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing. Copyright © 2011 Elsevier B.V. All rights reserved.


Together with large biobanks of human samples, medical registries with aggregated data from many clinical centers are vital parts of an infrastructure for maintaining high standards of quality with regard to medical diagnosis and treatment. The rapid development in personalized medicine and pharmaco-genomics only underscores the future need for these infrastructures. However, registries and biobanks have been criticized as constituting great risks to individual privacy. In this article, I suggest that quality with regard to diagnosis and treatment is an inherent, morally normative requirement of health care, and argue that quality concerns in this sense may be balanced with privacy concerns. © 2012 Springer Science+Business Media B.V.


Simple global self-ratings of health (SRH) have become increasingly used in national and international public health monitoring, and in recent decades recommended as a standard part of health surveys. Monitoring developments in population health requires identification and use of health measures, valid in relation to targets for population health. The aim of the present study was to investigate associations between SRH and sick leave, disability pension, hospital admissions, and mortality, adjusted for effects of significant covariates, in a large population-based cohort. The analyses were based on screening data from eight population-based cohorts in southern and central Sweden, and on official register data regarding sick-leave, disability pension, hospital admissions, and death, with little or no data loss. Sampling was performed 1973-2003. The study population consisted of 11,880 women and men, age 25-99 years, providing 14,470 observations. Information on SRH, socio-demographic data, lifestyle variables and somatic and psychological symptoms were obtained from questionnaires. There was a significant negative association between SRH and sick leave (Beta -13.2, p<0.0001, and -9.5, p<0.01, in women and men, respectively), disability pension (Hazard ratio 0.77, p<0.0001 and 0.76, p<0.0001, in women and men, respectively), and mortality, adjusted for covariates. SRH was also significantly associated with hospital admissions in men (Hazard ratio 0.87, p<0.0001), but not in women (Hazard ratio 0.96, p0.20). Associations between SRH on the one hand, and sick leave, disability pension, hospital admission, and mortality, on the other, were robust during the follow-up period. SRH had strong predictive validity in relation to use of social insurance facilities and health care services, and to mortality. Associations were strong and robust during follow-up.


Flores S.C.,Uppsala University
Nucleic Acids Research | Year: 2014

Determining the conformational rearrangements of large macromolecules is challenging experimentally and computationally. Case in point is the ribosome; it has been observed by high-resolution crystallography in several states, but many others are known only from low-resolution methods including cryo-electron microscopy. Combining these data into dynamical trajectories that may aid understanding of its largest-scale conformational changes has so far remained out of reach of computational methods. Most existing methods either model all atoms explicitly, resulting in often prohibitive cost, or use approximations that lose interesting structural and dynamical detail. In this work, I introduce Internal Coordinate Flexible Fitting, which uses full atomic forces and flexibility in limited regions of a model, capturing extensive conformational rearrangements at low cost. I use it to turn multiple low-resolution density maps, crystallographic structures and biochemical information into unified all-atoms trajectories of ribosomal translocation. Internal Coordinate Flexible Fitting is three orders of magnitude faster than the most comparable existing method. © 2013 The Author(s).


Schilcher J.,Linkoping University | Michaelsson K.,Uppsala University | Aspenberg P.,Linkoping University
New England Journal of Medicine | Year: 2011

Background Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. Methods In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. Results The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariableadjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). Conclusions These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small. (Funded by the Swedish Research Council.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Poropat S.F.,Uppsala University
GFF | Year: 2013

The Museum of Evolution in Uppsala acquired a number of sauropod specimens under the tenure of Professor Carl Wiman. The most intensely studied of these are two partial skeletons, PMU 24705 (formerly PMU R 233) and PMU 24706 (formerly PMU R 234), excavated in Shandong (Shantung) Province, China, by Otto Zdansky, which form the basis for the species Euhelopus zdanskyi. These specimens were acquired by the Museum of Evolution in the 1920s and remain the subject of much interest among sauropod workers. The cranial anatomy, classification and the age of Euhelopus have been the subject of some debate. Other Chinese sauropod material in the Museum of Evolution collection includes three vertebrae (one cervical, one dorsal and one caudal) and an incomplete femur. The caudal vertebra has been recently referred to Diplodocoidea by some researchers and to Titanosauriformes by others. Incomplete sauropod remains, which may represent the topotype material of Alamosaurus sanjuanensis (the only named post-Cenomanian North American sauropod to date) in the Museum of Evolution collection from New Mexico, coupled with specimens from North American museums, may help resolve the validity of A. sanjuanensis as a taxon and the "sauropod hiatus" as either a real phenomenon or an artefact of the fossil record. The palaeontological significance of the Museum of Evolution's sauropod collection cannot be overstated. These important specimens continue to be a crucial resource for studies concerning sauropod taxonomy, phylogenetic systematics, evolution and functional morphology. © 2013 Copyright OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint, 2013.


Ganesan G.,Uppsala University
IEEE Signal Processing Magazine | Year: 2011

In this article, we highlight the subspace approach to portfolio analysis. We focus on equities and show that the subspace approach leads to the decomposition of a portfolio in terms of the range space and the orthogonal subspace of systematic risk factors. The subspace decomposition helps us to decompose the performance of a portfolio in terms of a modified information coefficient, the portfolio risk, and market volatilities (one temporal and one cross-sectional). © 2011 IEEE.


Nilsson C.,Center for Clinical Research | Valachis A.,Uppsala University
Radiotherapy and Oncology | Year: 2015

Purpose The purpose of this meta-analysis is to summarize the current evidence on the role of boost and the efficacy of hypofractionated radiotherapy in patients with ductal cancer in situ (DCIS) after surgery and grade the quality of evidence. Materials and methods A comprehensive systematic electronic search through MEDLINE and the Cochrane Library as well as through the major international congresses' proceedings was conducted. Studies were considered eligible if they investigated the efficacy of hypofractionated vs. standard radiotherapy or the efficacy of boost vs. no boost in patients with DCIS. The outcome of interest was the number of local recurrences. Pooled estimates were calculated by using standard meta-analytic procedures. Results Thirteen trials were considered eligible and were further analyzed. No difference in the risk of local recurrence was observed between the patients that received boost vs. no boost in the general cohort (12 studies, 6943 patients; Odds Ratio (OR): 0.91, 95% confidence interval (CI): 0.77-1.08, very low level of evidence). However, we found a reduced risk for local recurrence when boost was administered in patients with positive margins compared to no boost (6 studies, 811 patients; OR: 0.56, 95% CI: 0.36-0.87, very low level of evidence). No difference in local recurrence rate between patients who received hypofractionated versus standard radiotherapy was observed (4 studies, 2534 patients; OR: 0.78, 95% CI: 0.58-1.03, low level of evidence). Conclusion Hypofractionated radiotherapy seems to be a safe option in patients with DCIS after breast-conserving surgery while the addition of boost reduces the risk for local recurrence in the presence of positive margins. However, the level of evidence for these observations ranges between very low and low and the results of the ongoing randomized trials are necessary to confirm the results with higher level of evidence. © 2015 Elsevier Ireland Ltd. All rights reserved.


Herbert-Read J.,Uppsala University
Current Biology | Year: 2015

A new study has decoded which birds become leaders in homing pigeon flocks, finding an unexpected benefit of leadership: faster birds emerge as leaders, and these leaders learn more about their environment than their followers. © 2015 Elsevier Ltd All rights reserved.


There has been extensive traffic of male-biased genes out of the mammalian and Drosophila X-chromosomes, and there are also reports of an under-representation of male-biased genes on the X. This may reflect an adaptive process driven by natural selection where an autosomal location of male-biased genes is favored since male genes are only exposed to selection one-third of the time when X-linked. However, there are several alternative explanations to "out-of-the-X" gene movement, including mutational bias and a means for X-linked genes to escape meiotic sex chromosome inactivation (MSCI) during spermatogenesis. As a critical test of the hypothesis that genomic relocation of sex-biased genes is an adaptive process, I examined the emergence, and loss, of genes on the chicken Z-chromosome, i.e., a female heterogametic system (males ZZ, females ZW). Here, the analogous prediction would be an emergence of male-biased genes onto, not a loss from, the Z-chromosome because Z is foundmore often in males than autosomes are. I found that genes expressed in testis but not in ovary are highly over-represented among genes that have emerged on the Z-chromosome during avian evolution. Moreover, genes with male-biased expression are similarly over-represented among new Z-chromosomal genes. Interestingly, genes with female-biased expression have more often moved from than to the Z-chromosome. These observations show that male and female heterogametic organisms display opposing directionalities in the emergence and loss of sex-biased genes on sex chromosomes. This is consistent with theoretical models on the evolution of sexually antagonistic genes in which new mutations are at least partly dominant. © 2011 by Cold Spring Harbor Laboratory Press.


Hellqvist M.,Uppsala University
Quaternary International | Year: 2014

The usage history of a natural spring deposit in associated glacial till was investigated via analysis of coleopteran remains found in peat. This material was recovered during archaeological excavations in a spring outflow in south central Sweden. The geographical region of southern Sweden has been heavily affected by uplift following the terminal glaciation (Weichselian) in Scandinavia, with the study area for this project having risen above sea level about 1200 BC. The spring was found in connection to the northern part of a large settlement and religious area, dating from the Younger Bronze Age and Pre Roman Iron Age (1100-300 BC). However, the area has been used for agricultural land up until the present day. Sampling was conducted for interpretation of the usage history of the site, with the insect fragments showing exceptional preservation as a result of unusual conditions in the sediments. 14C-dating from the lower to upper part of the spring yielded a stratigraphic range of 670-870 to 660-810 AD respectively. A half-circle boulder construction provides clear evidence that the spring was used early in prehistory, probably during the Bronze Age, and potentially excavated at irregular periods. The coleopteran assemblage was dominated by beetles indicative of open landscapes, grazing land, and forested environments. This closely resembles the vegetation setting of today, in which the spring is situated on the border between arable land and mixed deciduous and coniferous forest. A high frequency of carabid beetles suggests that the spring may have functioned as a pitfall trap, and correlated well with the relative inorganic to organic compound composition of the ground conditions. The spring was probably abandoned in the late Iron Age (600-800 AD). Identification of two red-listed threatened species that are not present in the current fauna implies that radical change in the agricultural landscape over the last 1200 years could be negatively affecting diversity dynamics within the local fauna. © 2014 Elsevier Ltd and INQUA.


Torabi A.,University of Bergen | Zarifi Z.,Uppsala University
International Journal of Rock Mechanics and Mining Sciences | Year: 2014

Cataclastic bands and their mechanical properties within two mineralogically different sandstones have been studied. In order to investigate the propagation energy of these bands, we have used dynamic elastic moduli calculated from laboratory measurements of ultrasonic velocities using a portable ultrasonic measuring system. As a product of cataclasis and compaction, elastic moduli (uniaxial compressive and shear moduli) of the bands are different from their corresponding host rocks leading to heterogeneity and anisotropy within sandstone reservoirs. Poisson's ratio decreases in the cataclastic bands of sandstone with high quartz content as a result of compaction, while it increases within cataclastic bands of sandstone with high clay and phyllosilicate content (more than 30%). Using the calculated propagation energy rates, we investigate which mode of deformation can be more dominant in the setting of our samples, propagation of deformation band as a result of strain hardening within the cataclastic band or crack propagation inside the deformation band due to strain softening prior to the propagation of band. We further estimate the maximum length of cracks inside a deformation band which can precede further growth of the deformation band. © 2013 Elsevier Ltd.


Seder D.B.,Uppsala University
Critical Care Medicine | Year: 2015

OBJECTIVES:: To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care.DESIGN:: Retrospective review of registry data.SETTING:: Cardiac arrest receiving centers in Europe and the United States from 2002 to 2012.PATIENTS:: Two thousand five hundred thirty-two cardiac arrest survivors 18 years or older enrolled in the International Cardiac Arrest Registry.INTERVENTIONS:: None.MEASUREMENTS AND MAIN RESULTS:: Eighty-eight percent of patients underwent therapeutic hypothermia and 471 (18%) exhibited myoclonus. Patients with myoclonus had longer time to professional cardiopulmonary resuscitation (8.6 vs 7.0 min; p < 0.001) and total ischemic time (25.6 vs 22.3 min; p < 0.001) and less often presented with ventricular tachycardia/ventricular fibrillation, a witnessed arrest, or had bystander cardiopulmonary resuscitation. Electroencephalography demonstrated myoclonus with epileptiform activity in 209 of 374 (55%), including status epilepticus in 102 of 374 (27%). Good outcome (Cerebral Performance Category 1–2) at hospital discharge was noted in 9% of patients with myoclonus, less frequently in myoclonus with epileptiform activity (2% vs 15%; p < 0.001). Patients with myoclonus with good outcome were younger (53.7 vs 62.7 yr; p < 0.001), had more ventricular tachycardia/ventricular fibrillation (81% vs 46%; p < 0.001), shorter ischemic time (18.9 vs 26.4 min; p = 0.003), more witnessed arrests (91% vs 77%; p = 0.02), and fewer “do-not-resuscitate” orders (7% vs 78%; p < 0.001). Life support was withdrawn in 330 of 427 patients (78%) with myoclonus and poor outcome, due to neurological futility in 293 of 330 (89%), at 5 days (3–8 d) after resuscitation. With myoclonus and good outcome, median ICU length of stay was 8 days (5–11 d) and hospital length of stay was 14.5 days (9–22 d).CONCLUSIONS:: Nine percent of cardiac arrest survivors with myoclonus after cardiac arrest had good functional outcomes, usually in patients without associated epileptiform activity and after prolonged hospitalization. Deaths occurred early and primarily after withdrawal of life support. It is uncertain whether prolonged care would yield a higher percentage of good outcomes, but myoclonus of itself should not be considered a sign of futility. Copyright © by 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


Kouyoumdjian J.A.,Laboratorio Of Investigacao Neuromuscular | Stalberg E.V.,Uppsala University
Clinical Neurophysiology | Year: 2011

Objectives: The aim of this study was to estimate the jitter parameters in healthy controls in stimulated Orbicularis Oculi (OOc) muscle using concentric needle electrode (CNE). Methods: Fifty healthy subjects, 13 males and 37 females (21-56. years, mean age of 38 ± 9.2. years) were studied. The zygomatic branch of facial nerve was stimulated with a bar electrode. Jitter was expressed as the mean consecutive difference (MCD). Filter settings 1000. Hz-10. kHz. Results: The mean MCD from individual studies (n = 50, Gaussian distribution) was 21.5 ± 1.99 μs (median = 21 μs), ranging from 17.8 to 26 μs (upper limit, 97.5%, 25.5 μs). The mean and median MCD from all potentials (n = 1500, non-Gaussian distribution) were 21.6 and 21 μs, ranging from 7.1 to 39 μs (upper limit, 97.5%, 33.4 μs). Conclusions: Suggested practical limits in the OOc for mean MCD was 26 μs and for outliers 34 μs. Significance: Stimulation jitter recordings with CNE could be used in practice but borderline findings should be judged with great caution until larger database obtained with uniform setting available. © 2010 International Federation of Clinical Neurophysiology.


In Henri Lefebvre's work, abstract space entails qualitatively new ways of envisioning and strategically arranging the sites within which capital accumulation and everyday life are to unfold. This paper sets out to delineate how this premise can be profitably used to decipher contested tactics of primitive accumulation. Arguing from a particular case-nineteenth-century reclamation of mires on the island of Gotland, Sweden-the paper explores how primitive accumulation was made possible through the conjunction of three spatialities, representing three key lines of struggle over abstract space. The abstraction and avowed homogeneity of space was produced and regulated by concurrent ideological maneuvers against customary practice, leveled by scientific discourse, and pursued through a legally endorsed material transformation of nature. © 2014 Antipode Foundation Ltd.


One often-highlighted contemporary phenomenon in the pharmaceuticals industry is the use of "tiered pricing", where essential medicines are sold more cheaply in low-income than high-income countries to widen access. With economists having for decades championed the applicability of such pricing to pharmaceuticals, this could be interpreted as a textbook case of "economic performativity"-the economic world increasingly conforming to economic models. In reality, however, tiered pharmaceutical pricing remains rare. Yet this article nonetheless urges retention of the performativity concept, albeit suitably reworked. For, insofar as the industry demonstrates nominal commitment to the model and to the social principles associated with it, it performs valuable political work. Moreover, it does help perform the pharmaceutical economy, by reproducing it in its existing form: repeatedly questioning the model's workability, Western manufacturers are able to continue to avoid putting it widely into practice and, in the process, jeopardizing the profits generated by conventional pricing. © 2014 Antipode Foundation Ltd.


Faldt G.,Uppsala University | Wilkin C.,University College London
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

Evidence has recently been presented for the existence of a dibaryon of mass 2380 MeV/c2 and width 70 MeV/c2, which decays strongly into the dπ0π0 channel [M. Bashkanov, et al., Phys. Rev. Lett. 102 (2009) 052301; P. Adlarson, et al., arXiv:1104.0123]. The decay rate of such a hypothesised dibaryon into the {pn}I=0π0π0 channel is estimated in a weakly model-dependent way by using final state interaction theory. It is shown that, if the resonance exists, it should show up as strongly in this channel as in dπ0π0. The sum of the two decay modes would saturate most of the inelasticity predicted in the relevant partial waves in the 2380 MeV/c2 region. © 2011 Elsevier B.V.


Liivat A.,Uppsala University
Solid State Ionics | Year: 2012

Cation mixing has been demonstrated experimentally in the Li-ion battery cathode material Li2FeSiO4. This feature is investigated here using DFT calculations. It is shown that full reversal of Li/Fe site occupations is energetically favoured on delithiation for all three electrochemically active Li2FeSiO4 polymorphs. The common layered topology in the arrangement of SiO4 and FeO4 tetrahedra in all three polymorphs transforms into a 3D-framwork. Calculations show here that such a change in structure leads to a lowering of electrochemical insertion potential from ~ 3.1 to ~ 2.8 V, in good agreement with experimental data. Calculations also predict the correct anisotropy in the cell expansion on delithiation on Li/Fe site reversals. Partial mixing of Li and Fe site occupations is energetically less favourable, which supports a two-phase transformation mechanism. © 2012 Elsevier B.V.


Sundberg S.,Uppsala University | Sundberg S.,Swedish University of Agricultural Sciences
Ecography | Year: 2013

While patterns of spore dispersal from single sources at short distances are fairly well known, information about 'spore rain' from numerous sources and at larger spatial scales is generally lacking. In this study, I sampled spore rain using a novel method consisting of 0.25-0.5 m2 cotton cloth traps at nine sites in the boreo-nemoral vegetation zone in eastern Sweden during two seasons, using Sphagnum spores as a model. Traps were located in various landscapes (mainland, islands). Additional trapping was done in an arctic area (Svalbard) without spore production. Spore densities were tested against distance from the nearest source and area of sources (open peatlands) within different radii around each site (5, 10, 20, 50, 100, 200, 300, 400 km). The cloth method appeared reliable when accounting for precipitation losses, retaining approximately 20-60% of the spores under the recorded amounts of precipitation. Estimated spore densities ranged from 6 million m-2 and season within a large area source, via regional deposition of 50 000-240 000 spores m-2, down to 1000 m-2 at Svalbard. Spore rain for all sites was strongly related to distance from the nearest source, but when excluding samples taken within a source peatland, the amount of sources within 200 km was most important. Spores were larger at isolated island sites, indicating that a higher proportion originated from distant, humid areas. Immense amounts of Sphagnum spores are dispersed across regional distances annually in boreal areas, explaining the success of the genus to colonise nutrient poor wetlands. The detectable deposition at Svalbard indicates that about 1% of the regional spore rain has a trans- or intercontinental origin. The regional spore rain, originating from numerous sources in the landscape, is probably valid for most organisms with small diaspores and provides a useful insight in ecology, habitat restoration and conservation planning. © 2012 The Authors.


Lindahl U.,Uppsala University
Matrix Biology | Year: 2014

The concept of "proteoglycans" as discrete molecules surfaced some 40. years ago, out of previously muddled notions of the extracellular matrix. Core proteins were gradually recognized as molecular entities, distinct with regard to location, substitution with glycosaminoglycan (GAG) chains and biological function. This development is surveyed, with brief outline of methodological approaches, biosynthesis, and functional aspects. Special emphasis is given to the impact of genomics on the field. Some outstanding unresolved issues are emphasized, including regulation of GAG biosynthesis and the specificity of GAG-protein interactions. © 2014 unknown.


Bjorkman S.,Uppsala University
Haemophilia | Year: 2013

The principles of pharmacokinetic (PK) dose tailoring in clinical practice, using limited blood sampling and Bayesian PK analysis, have been described for factor VIII (FVIII). This study applied the same procedure to recombinant FIX (rFIX), i.e. population PK modelling and the use of a simplified (one-compartment) model to describe only the terminal part of the coagulation factor vs. time curve. Data from a previous study on rFIX in 56 patients (4-56 years, 18-133 kg) were used to define a three-compartment population PK model. The average FIX clearance was 8.4 mL h-1 kg-1. Elimination half-life ranged between 14 and 27 h. Data obtained from 24 h after the infusion were found to define the terminal phase of FIX disposition. Doses to produce a target trough FIX level (set at 0.01 IU mL-1) at 72 h predicted by the Bayesian analysis, with blood sampling at either 24, 48 and 72 h or at only 24 and 48 h, were within -40% to +67% of those predicted using the three-compartment model, and within -57% to +125% for targeting a level at 96 h. These errors were lower than the overall interindividual variance in dose requirements. As three-compartment models are needed to characterize the PK of both plasma-derived FIX and rFIX, simplification to a one-compartment model is less straightforward than for FVIII, and the methodology should be investigated further before clinical application. Limited blood sampling and Bayesian analysis could still, however, be potentially useful for targeting rFIX trough levels during prophylaxis. © 2013 John Wiley & Sons Ltd.


Drabsch Y.,Leiden University | Ten Dijke P.,Leiden University | Ten Dijke P.,Uppsala University
Cancer and Metastasis Reviews | Year: 2012

The transforming growth factor-β (TGF-β) system signals via protein kinase receptors and SMAD mediators to regulate a large number of biological processes. Alterations of the TGF-β signalling pathway are implicated in human cancer. Prior to tumour initiation and early during progression, TGF-β acts as a tumour suppressor; however, at later stages, it is often a tumour promoter. Knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of cancer progression, invasion, metastasis and epithelial-to-mesenchymal transition. Furthermore, several molecular targets with great potential in therapeutic interventions have been identified. This review discusses the TGF-β signalling pathway, its involvement in cancer and current therapeutic approaches. © 2012 Springer Science+Business Media, LLC.


Larsson S.,Uppsala University | Hannink G.,Radboud University Nijmegen
Injury | Year: 2011

More than a decade has passed since the first injectable bone substitutes were introduced for use in orthopaedic trauma, and over recent years the number of commercial products has increased dramatically. Despite the fact that these bone substitutes have been on the market for many years, knowledge amongst potential users on how and when they might be useful is still fairly limited. Most injectable bone substitutes belong to one of two major groups: by far the largest group contains products based on various calcium phosphate (CP) mixtures, whilst the smaller group consists of calcium sulphate (CS) compounds. Following mixing, the CP or CS paste can be injected into - for instance - a fracture space for augmentation as an alternative to bone graft, or around a screw for augmentation if the bone is weak. Within minutes an in situ process makes the substitute hard; the mechanical strength in compression resembles that of cancellous bone, whereas the strength in bending and shear is lower. Over time, CP products undergo remodelling through a cell-mediated process that seems to mimic the normal bone remodelling, whilst CS products are dissolved through a faster process that is not cell-mediated. For CP, a number of clinical studies have shown that it can be useful for augmentation of metaphyseal fractures when a space is present. Randomised studies have verified that CP works especially well in tibial plateau fractures when compared with conventional bone grafting. So far the number of clinical studies on CS products is very low. Development at present seems to be heading towards premixed or directly mixed products as well as new compounds that contain fibres or other components to enhance bending and shear strength. Products that are based on combinations of CP and CS are also being developed to combine the fast-dissolving CS with the stronger and more slowly remodelling CP. Injectable bone substitutes, and especially CS, have also been targeted as potentially good carriers for antibiotics and growth factors. © 2011 Published by Elsevier Ltd.


Hook M.,Uppsala University | Tang X.,China University of Petroleum - Beijing
Energy Policy | Year: 2013

Future scenarios with significant anthropogenic climate change also display large increases in world production of fossil fuels, the principal CO2 emission source. Meanwhile, fossil fuel depletion has also been identified as a future challenge. This chapter reviews the connection between these two issues and concludes that limits to availability of fossil fuels will set a limit for mankind's ability to affect the climate. However, this limit is unclear as various studies have reached quite different conclusions regarding future atmospheric CO2 concentrations caused by fossil fuel limitations. It is concluded that the current set of emission scenarios used by the IPCC and others is perforated by optimistic expectations on future fossil fuel production that are improbable or even unrealistic. The current situation, where climate models largely rely on emission scenarios detached from the reality of supply and its inherent problems are problematic. In fact, it may even mislead planners and politicians into making decisions that mitigate one problem but make the other one worse. It is important to understand that the fossil energy problem and the anthropogenic climate change problem are tightly connected and need to be treated as two interwoven challenges necessitating a holistic solution. © 2012 Elsevier Ltd.


Olovsson M.,Uppsala University
American Journal of Reproductive Immunology | Year: 2011

Problem: Endometriosis is a very complex disease that profoundly affects the quality of life of many women. Method of study: A review of the relationships between the female immune system and the occurrence and development of endometriosis. Results: Function and dysfunction of the female immune system plays important roles in the initiation and progression of the disease and its relation to infertility and cancer. Conclusions: Owing to obvious associations between endometriosis and the immune system, future treatment strategies might be based on immunological concepts and methods. © 2011 John Wiley & Sons A/S.


Tan J.,University of Western Ontario | Berg M.,Uppsala University
Journal of the American Academy of Dermatology | Year: 2013

Case definitions are critical in epidemiologic research. However, modern disease indicators must now consider complex data from gene-based research along with traditional clinical parameters. Rosacea is a skin disorder with multiple signs and symptoms. In individuals, these features may be multiple or one may predominate. While studies on the epidemiology of rosacea have previously been sparse, there has been a recent increase in research activity. A broader body of epidemiological information that includes a greater variety of countries beyond Northern Europe and general population-based demographics is needed. As there are operational issues in current case definitions of rosacea subtypes - rationalization and standardization - universal consistent applications in future research is also imperative. Further improvement in disease definition combining new research information along with clinical pragmatism should increase the accuracy of rosacea case ascertainment and facilitate further epidemiological research. © 2013 by the American Academy of Dermatology, Inc.


Black-Schaffer A.M.,Uppsala University
Physical Review Letters | Year: 2012

We investigate the effect of edges on the intrinsic d-wave superconducting state in graphene doped close to the van Hove singularity. While the bulk is in a chiral d x2-y2+id xy state, the order parameter at any edge is enhanced and has d x2-y2-symmetry, with a decay length strongly increasing with weakening superconductivity. No graphene edge is pair breaking for the d x2-y2 state, and there are no localized zero-energy edge states. We find two chiral edge modes which carry a spontaneous, but not quantized, quasiparticle current related to the zero-energy momentum. Moreover, for realistic values of the Rashba spin-orbit coupling, a Majorana fermion appears at the edge when tuning a Zeeman field. © 2012 American Physical Society.


Klose T.,Uppsala University | McLoughlin T.,Max Planck Institute For Gravitationsphysik
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We formulate a set of consistency conditions appropriate to worldsheet form factors in the massive, integrable but nonrelativistic, light-cone gauge fixed AdS5×S5 string theory. We then perturbatively verify that these conditions hold, at tree level in the near-plane-wave limit and to one loop in the near-flat (Maldacena-Swanson) limit, for a number of specific cases. We further study the form factors in the weakly coupled dual description, verifying that the relevant conditions naturally hold for the one-loop Heisenberg spin chain. Finally, we note that the near-plane-wave expressions for the form factors, when further expanded in small momentum or, equivalently, large charge density, reproduce the thermodynamic limit of the spin-chain results at leading order. © 2013 American Physical Society.


Manzetti S.,Fjordforsk A.S. Midtun | Manzetti S.,Uppsala University | Ghisi R.,University of Padua
Marine Pollution Bulletin | Year: 2014

Antibiotics have been used as medical remedies for over 50. years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment. © 2014 Elsevier Ltd.


Rubensson E.H.,Uppsala University
Journal of Chemical Theory and Computation | Year: 2011

As it stands, density matrix purification is a powerful tool for linear scaling electronic structure calculations. The convergence is rapid and depends only weakly on the band gap. However, as will be shown in this letter, there is room for improvements. The key is to allow for nonmonotonicity in the recursive polynomial expansion. On the basis of this idea, new purification schemes are proposed that require only half the number of matrix-matrix multiplications compared to previous schemes. The speedup is essentially independent of the location of the chemical potential and increases with decreasing band gap. © 2011 American Chemical Society.


Widersten M.,Uppsala University
Current Opinion in Chemical Biology | Year: 2014

Hydrolytic enzymes play important roles as biocatalysts in chemical synthesis. The chemical versatility and structurally sturdy features of Candida antarctica lipase B has placed this enzyme as a common utensil in the synthetic tool-box. In addition to catalyzing acyl transfer reactions, a number of promiscuous activities have been described recently. Some of these new enzyme activities have been amplified by mutagenesis. Epoxide hydrolases are of interest due to their potential as catalysts in asymmetric synthesis. This current update discusses recent development in the engineering of lipases and epoxide hydrolases aiming to generate new biocatalysts with refined features as compared to the wild-type enzymes. Reported progress in improvements in reaction atom economy from dynamic kinetic resolution or enantioconvergence is also included. © 2014 Elsevier Ltd.


Invasive plants may compete with native species for abiotic factors as light, space and nutrients, and have also been shown to affect native pollination interactions. Studies have mainly focused on how invasive plants affect pollinator behaviour, i.e. attraction of pollinators to or away from native flowers. However, when an invasive plant provides resources utilized by native pollinators this could increase pollinator population sizes and thereby pollination success in natives. Effects mediated through changes in pollinator population sizes have been largely ignored in previous studies, and the dominance of negative interactions suggested by meta-analyses may therefore be biased. We investigated the impact of the invasive Lupinus polyphyllus on pollination in the native Lotus corniculatus using a study design comparing invaded and uninvaded sites before and after the flowering period of the invasive. We monitored wild bee abundance in transects, and visit rate and seed production of potted Lotus plants. Bumblebee abundance increased 3.9 times in invaded sites during the study period, whereas it was unaltered in uninvaded sites. Total visit rate per Lotus plant increased 2.1 times in invaded sites and decreased 4.4 times in uninvaded sites. No corresponding change in seed production of Lotus was found. The increase in visit rate to Lotus was driven by an increase in solitary bee visitation, whereas mainly bumblebees were observed to visit the invasive Lupinus. The mechanism by which the invasive increases pollinator visit rates to Lotus could be increased availability of other flower resources for solitary bees when bumblebees forage on Lupinus. © 2013 Springer-Verlag Berlin Heidelberg.


Li J.-P.,Uppsala University
Progress in Molecular Biology and Translational Science | Year: 2010

The glucuronyl C5 epimerase (HSepi) is one of the modification enzymes involved in biosynthesis of heparan sulfate (HS) and heparin, catalyzing the epimerization of d-glucuronic acid (GlcA) to l-iduronic acid (IdoA) at polymer level. IdoA is critical for HS and heparin to interact with protein ligands, because of its flexible conformation. Although the enzyme recognizes both GlcA and IdoA as substrates catalyzing a reversible reaction of the hexuronic acids in vitro, the reaction appears irreversible in vivo. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality accompanied with kidney agenesis, premature lung, and skeletal malformations, demonstrating that the single gene coded enzyme is essential for animal development. Elimination of the enzyme resulted in abnormal HS and heparin structure that completely lacks IdoA residues. Loss of 2-O-sulfation due to lacking IdoA in HS chains appears compensated by increased N- and O-sulfation of the glucosamine residues. Recombinant HSepi is used to generate HS/heparin related compounds having potential to be used for therapeutic purposes. © 2010 Elsevier Inc. All rights reserved.


Ekstrand J.,Uppsala University
Computer Physics Communications | Year: 2011

We give an introduction to the Mathematica package Lambda, designed for calculating λ-brackets in both vertex algebras, and in SUSY vertex algebras. This is equivalent to calculating operator product expansions in two-dimensional conformal field theory. The syntax of λ-brackets is reviewed, and some simple examples are shown, both in component notation, and in N=1 superfield notation. © 2010 Elsevier B.V. All rights reserved.


Berg J.,Uppsala University | Nordstrom J.,Linkoping University
Journal of Computational Physics | Year: 2011

In this paper we prove stability of Robin solid wall boundary conditions for the compressible Navier-Stokes equations. Applications include the no-slip boundary conditions with prescribed temperature or temperature gradient and the first order slip-flow boundary conditions. The formulation is uniform and the transitions between different boundary conditions are done by a change of parameters. We give different sharp energy estimates depending on the choice of parameters.The discretization is done using finite differences on Summation-By-Parts form with weak boundary conditions using the Simultaneous Approximation Term. We verify convergence by the method of manufactured solutions and show computations of flows ranging from no-slip to almost full slip. © 2011 Elsevier Inc.


Skjanes K.,Norwegian Institute for Agricultural And Environmental Research Bioforsk | Rebours C.,Norwegian Institute for Agricultural And Environmental Research Bioforsk | Lindblad P.,Uppsala University
Critical Reviews in Biotechnology | Year: 2013

Green microalgae for several decades have been produced for commercial exploitation, with applications ranging from health food for human consumption, aquaculture and animal feed, to coloring agents, cosmetics and others. Several products from green algae which are used today consist of secondary metabolites that can be extracted from the algal biomass. The best known examples are the carotenoids astaxanthin and β-carotene, which are used as coloring agents and for health-promoting purposes. Many species of green algae are able to produce valuable metabolites for different uses; examples are antioxidants, several different carotenoids, polyunsaturated fatty acids, vitamins, anticancer and antiviral drugs. In many cases, these substances are secondary metabolites that are produced when the algae are exposed to stress conditions linked to nutrient deprivation, light intensity, temperature, salinity and pH. In other cases, the metabolites have been detected in algae grown under optimal conditions, and little is known about optimization of the production of each product, or the effects of stress conditions on their production. Some green algae have shown the ability to produce significant amounts of hydrogen gas during sulfur deprivation, a process which is currently studied extensively worldwide. At the moment, the majority of research in this field has focused on the model organism, Chlamydomonas reinhardtii, but other species of green algae also have this ability. Currently there is little information available regarding the possibility for producing hydrogen and other valuable metabolites in the same process. This study aims to explore which stress conditions are known to induce the production of different valuable products in comparison to stress reactions leading to hydrogen production. Wild type species of green microalgae with known ability to produce high amounts of certain valuable metabolites are listed and linked to species with ability to produce hydrogen during general anaerobic conditions, and during sulfur deprivation. Species used today for commercial purposes are also described. This information is analyzed in order to form a basis for selection of wild type species for a future multi-step process, where hydrogen production from solar energy is combined with the production of valuable metabolites and other commercial uses of the algal biomass. © 2013 Informa Healthcare USA, Inc.


Fornberg B.,University of Colorado at Boulder | Lehto E.,Uppsala University
Journal of Computational Physics | Year: 2011

Radial basis functions (RBFs) are receiving much attention as a tool for solving PDEs because of their ability to achieve spectral accuracy also with unstructured node layouts. Such node sets provide both geometric flexibility and opportunities for local node refinement. In spite of requiring a somewhat larger total number of nodes for the same accuracy, RBF-generated finite difference (RBF-FD) methods can offer significant savings in computer resources (time and memory). This study presents a new filter mechanism, allowing such gains to be realized also for purely convective PDEs that do not naturally feature any stabilizing dissipation. © 2010 Elsevier Inc.


We introduce the so far most efficient attack against the Kirchhoff-law-Johnsonnoise (KLJN) secure key exchange system. This attack utilizes the lack of exact thermal equilibrium in practical applications and is based on cable resistance losses and the fact that the Second Law of Thermodynamics cannot provide full security when such losses are present. The new attack does not challenge the unconditional security of the KLJN scheme, but it puts more stringent demands on the security/privacy enhancing protocol than for any earlier attack. In this paper we present a simple defense protocol to fully eliminate this new attack by increasing the noise-temperature at the side of the smaller resistance value over the noise-temperature at the side with the greater resistance. It is shown that this simple protocol totally removes Eve's information not only for the new attack but also for the old Bergou-Scheuer-Yariv attack. The presently most efficient attacks against the KLJN scheme are thereby completely nullified. © 2014 by the authors.


Primetzhofer D.,Uppsala University
Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms | Year: 2014

Electronic energy loss of hydrogen ions in HfO2 was investigated in a wide energy range in the medium and low energy ion scattering regime. Experiments by Time-Of-Flight Medium-Energy Ion Scattering (TOF-MEIS) with proton and deuteron projectiles were performed in backscattering geometry for nm-films of HfO2 on Si with an ultrathin SiO2 interface layer prepared by ALD. At energies around the stopping maximum excellent agreement is found with earlier results from Behar et al. (2009) [45] and theoretical predictions. Towards lower energies discrepancies between experiment and calculations increase slightly. The low energy data exhibits excellent velocity proportionality and indicates the absence of clear effects due to distinct electronic states. Thus, no apparent velocity threshold can be extrapolated from the experiments within the uncertainty of present data. The magnitude of the energy loss is discussed in terms of a free-electron model and compared with the expected electron densities from plasmon frequencies. © 2013 Elsevier B.V. All rights reserved.


Mydosh J.A.,Leiden University | Oppeneer P.M.,Uppsala University
Philosophical Magazine | Year: 2014

Throughout the past three decades, the hidden order (HO) problem in URu2Si2 has remained a hot topic in the physics of strongly correlated electron systems with well over 600 publications related to this subject. Presently in 2014, there has been significant progress in combining various experimental results embedded within electronic structure calculations using density functional theory (DFT) to give a consistent description of the itinerant behaviour of the HO transition and its low temperature state. Here, we review six different experiments: ARPES, quantum oscillations, neutron scattering, RXD, optical spectroscopy and STM/STS. We then establish the consistencies among these experiments when viewed through the Fermi-surface nesting, folding and gapping framework as predicted by DFT. We also discuss a group of other experiments (torque, cyclotron resonance, NMR and XRD) that are more controversial and are presently in a transition state regarding their interpretation as rotational symmetry breaking and dotriacontapole formation. There are also a series of recent exotic experiments (Raman scattering, polar Kerr effect and ultrasonics) that require verification, yet they offer new insights into the HO symmetry breaking and order parameter. We conclude with some constraining comments on the microscopic models that rely on localized 5f-U states and strong Ising anisotropy for explaining the HO transition, and with an examination of different models in the light of recent experiments. © 2014 Taylor & Francis.


Stalberg E.,Uppsala University
Annals of the New York Academy of Sciences | Year: 2012

Because of certain restrictions in medical praxis, reusable materials are only allowed in some countries. This also applies to electrodes for electromyography; the special single-fiber electromyography electrode must be replaced. This article gives some details of the possibilities of using an alternative-a small concentric needle electrode. Practical hints, reference values, and the application in diagnostic work for myasthenia gravis are summarized. © 2012 New York Academy of Sciences.


Iversen C.,Uppsala University
British Journal of Social Psychology | Year: 2014

Social psychologists interested in social interaction have, in recent years, addressed the ways that people negotiate 'who is entitled to know what' across a variety of conversational settings. Using recordings of interviews conducted as a part of a Swedish national evaluation of interventions for abused children, the current article examines how children navigate knowledge and its moral implications. The analysis focuses on a particular question ('What do you believe [the perpetrator] thinks about what he has done'), which draws on the psychological concept of mentalization: the cognitive ability to picture others' mental states based on their behaviour. The findings suggest that the concept of mentalization fails to account for the moral properties of knowing someone's thoughts: The perpetrator, most often the child's father, must be believable - recognized as both credible and knowable - for the children to claim access to his thoughts. The interviewees used contrastive constructions in claims of (no) access to their fathers' thoughts as they simultaneously contested idiomatic knowledge that undermined their claims. The article contributes to recent developments in discursive social psychology concerning how subjectivity, in particular, epistemic stance, is managed in institutional interaction, and continues the discursive psychological project of respecifying concepts such as mentalization. © 2013 The British Psychological Society.


Acosta S.,Skane University Hospital | Bjorck M.,Uppsala University
British Journal of Surgery | Year: 2014

Background: Diagnosis of acute mesenteric ischaemia in the early stages is now possible with modern computed tomography (CT), using intravenous contrast enhancement and imaging in the arterial and/or portal venous phase. The availability of CT around the clock means that more patients with acute mesenteric ischaemia may be treated with urgent intestinal revascularization. Methods: This was a review of modern treatment strategies for acute mesenteric ischaemia. Results: Endovascular therapy has become an important alternative, especially in patients with acute thrombotic superior mesenteric artery (SMA) occlusion, where the occlusive lesion can be recanalized either antegradely from the femoral or brachial artery, or retrogradely from an exposed SMA after laparotomy, and stented. Aspiration embolectomy, thrombolysis and open surgical embolectomy, followed by on-table angiography, are the treatment options for embolic SMA occlusion. Endovascular therapy may be an option in the few patients with mesenteric venous thrombosis who do not respond to anticoagulation therapy. Laparotomy is needed to evaluate the extent and severity of visceral organ ischaemia, which is treated according to the principles of damage control surgery. Conclusion: Modern treatment of acute mesenteric ischaemia involves a specialized approach that considers surgical and, increasingly, endovascular options for best outcomes. © 2013 BJS Society Ltd.


Lindgren T.,Uppsala University
Building and Environment | Year: 2010

A case of suspected indoor ammonia contamination from concrete was investigated in an airline company office in Beijing. A standardized questionnaire on indoor environment perceptions, medical symptoms and psychosocial work environment was distributed to all staff, and compared with a reference group of office workers from the same company in Stockholm. Temperature, relative humidity, formaldehyde, volatile organic compounds (VOC), ammonia, and carbon dioxide were measured both in Beijing and Stockholm. In Beijing mould and bacteria were also measured. Totally 95% (N = 14) participated. The Beijing staff reported a higher rate of complaints regarding poor work satisfaction, and work stress as compared to the Stockholm reference group. In the total material (N = 203) the psychosocial environment was related to general symptoms (headache and tiredness) but not odour perception or mucous membrane symptoms. Controlling for age, smoking habits, and psychosocial work environment the Beijing staff had more complaints on unpleasant odour and mucous membrane symptoms. An increased indoor concentration of ammonia (3-6 ppm) and benzene (26.8 μg/m3) was measured in the indoor air in the Beijing office, as compared to the office in Stockholm (<0.1 ppm ammonia and 0.4 μg/m3 benzene). The ammonia contamination in the Beijing office was confirmed, the probable source being additives in the concrete. The ammonia level was well below the Swedish threshold limit values (TLV) (25 ppm). In addition the exposure to benzene, an indicator of traffic exhaust pollution was high both indoors and outdoors in Beijing, possible related to increased levels of odour complaints and mucous membrane irritation. © 2009 Elsevier Ltd. All rights reserved.


Cheng S.,Ericsson AB | Wu Z.,Uppsala University
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field. This journal is © The Royal Society of Chemistry 2012.


Betsholtz C.,Uppsala University | Betsholtz C.,Karolinska Institutet
Nature Genetics | Year: 2015

How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma. © 2015 Nature America, Inc. All rights reserved.


Garcia-Bennett A.E.,Uppsala University
Nanomedicine | Year: 2011

Although ordered mesoporous silica materials have been studied for almost 20 years, their utilization within life science applications is relatively new and unexplored. An increasing number of researchers are transcending their respective fields in order to bridge the knowledge gap between materials chemistry and biotechnology, and to exploit the potential of mesoporous materials. Their intricate porosity with order in the nanoscale translates into high surface areas above 1000 m 2/g, high selectivity for the encapsulation of biorelevant molecules as well as controlled surface chemistry. Their uses in pharmaceutics to improve drug formulation, drug bioavailability, mitigate drug toxicity and in cellular targeting, through controlled drug delivery strategies, have been shown. The incorporation of a high concentration of fluorescent and nuclear markers within their pores, whilst retaining good diffusion through their porous matrix, has shown them to be ideal candidates for sensing devices, in immunoassays such as flow cytometry and for their use in novel theranostic applications. This article aims to bring to the forefront some of the most important properties of mesoporous materials, which prove advantageous for their use in nanomedical applications and to highlight some of the potential areas into which the field may now emerge. © 2011 Future Medicine Ltd.


Torres S.,Uppsala University
Ageing and Society | Year: 2015

The globalisation of international migration has increased the ethnic diversity of most ageing populations across the Western world. This has implications for gerontological research, policy and practice, and puts our understandings of ethnicity to the test. This paper presents the different perspectives that inform ethnicity scholarship (the essentialist/primordial perspective, the structuralist/circumstantialist perspective and social constructionism) and suggests that the way in which we regard ethnicity has implications for how gerontological research is designed, how policies for old age are formulated and how gerontological practice is shaped. Through a review of contemporary gerontological research on ethnicity published in some of gerontology's main journals, the paper discusses some of the trends observed and concludes that most research seems to be informed by essentialism and structuralism. This suggests that the gerontological imagination on ethnicity has yet to be informed by the latest developments in ethnicity scholarship. The paper therefore urges gerontologists to broaden their understanding of ethnicity and suggests that much could be gained if we were to let the social constructionist perspective on ethnicity and the notion of intersectionality be sources of inspiration for the gerontological imagination on ethnicity. Copyright © Cambridge University Press 2014.


Gredeback G.,Uppsala University | Daum M.M.,University of Zurich
Child Development Perspectives | Year: 2015

In this article, we review recent evidence of infants' early competence in perceiving and interpreting the actions of others. We present a theoretical model that decomposes the timeline of action perception into a series of distinct processes that occur in a particular order. Once an agent is detected, covert attention can be allocated to the future state of the agent (priming), which may lead to overt gaze shifts that predict goals (prediction). Once these goals are achieved, the consequence of the agents' actions and the manner in which the actions were performed can be evaluated (evaluation). We propose that all of these processes have unique requirements, both in terms of timing and cognitive resources. To understand more fully the rich social world of infants, we need to pay more attention to the temporal structure of social perception and ask what information is available to infants and how this changes over time. © 2015 The Authors.


Nordstrom J.,Linkoping University | Berg J.,Uppsala University
Computers and Fluids | Year: 2013

This paper deals with conjugate heat transfer problems for the time-dependent compressible Navier-Stokes equations. One way to model conjugate heat transfer is to couple the Navier-Stokes equations in the fluid with the heat equation in the solid. This requires two different physics solvers. Another way is to let the Navier-Stokes equations govern the heat transfer in both the solid and in the fluid. This simplifies calculations since the same physics solver can be used everywhere.We show by energy estimates that the continuous problem is well-posed when imposing continuity of temperature and heat fluxes by using a modified L2-equivalent norm. The equations are discretized using finite difference on summation-by-parts form with boundary- and interface conditions imposed weakly by the simultaneous approximation term. It is proven that the scheme is energy stable in the modified norm for any order of accuracy.We also show what is required for obtaining the same solution as when the unsteady compressible Navier-Stokes equations are coupled to the heat equation. The differences between the two coupling techniques are discussed theoretically as well as studied numerically, and it is shown that they are indeed small. © 2012 Elsevier Ltd.


Mossberg M.,Karlstad University | Soderstrom T.,Uppsala University
IEEE Transactions on Automatic Control | Year: 2011

A covariance matching approach for continuous-time errors-in-variables problems is considered. The noise-free input signal is not explicitly modeled and is only assumed to be a stationary process. It is described how three different systems of equations in the model parameters are obtained and how the parameters are estimated based on these systems of equations. The approach is illustrated by some numerical studies. © 2006 IEEE.


Belyaev A.K.,Uppsala University | Belyaev A.K.,Max Planck Institute for Astrophysics
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

A model approach is derived for estimates of cross sections and rate coefficients in low-energy inelastic collisions of hydrogen atoms and negative ions with other atoms and positive ions, which are of astrophysical interests. The approach is based on the asymptotic method for electronic molecular structure determination and on the branching probability current method for a nonadiabatic nuclear dynamical treatment. The derived approach is applied to low-energy Al + H and Al+ + H- inelastic collisions. It is shown that the processes with the largest values of cross sections and rates are the excitation and de-excitation ones between the Al(3d) and Al(4p) states in collisions with H, as well as the ion-pair formation and the mutual neutralization processes between these states and the ionic state; the second largest cross sections correspond to the similar processes involving the Al(4s) state. The mechanisms of the processes are discussed in detail. © 2013 American Physical Society.


Litsarev M.S.,Uppsala University
Computer Physics Communications | Year: 2013

A description of the DEPOSIT computer code is presented. The code is intended to calculate total and m-fold electron-loss cross-sections (m is the number of ionized electrons) and the energy T(b) deposited to the projectile (positive or negative ion) during a collision with a neutral atom at low and intermediate collision energies as a function of the impact parameter b. The deposited energy is calculated as a 3D integral over the projectile coordinate space in the classical energy-deposition model. Examples of the calculated deposited energies, ionization probabilities and electron-loss cross-sections are given as well as the description of the input and output data. © 2012 Elsevier B.V. All rights reserved.


The lithium amide derived from the chiral diamine (1R,3S,4S)-3-(1- pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane, has been reported to catalytically deprotonate cyclohexene oxide and other epoxides, yielding chiral allylic alcohols in excellent enantiomeric excess. In this work, 6Li, 1H and 13C NMR spectroscopy have been used to study the aggregation of the chiral lithium amide in THF and the influence on the aggregation by the addition of additives, such as 1,8-diazabicyclo-[5.4.0]undec- 7-ene (DBU). The activated complex under catalytic deprotonation of cyclohexene oxide, that is, with excess Li-DBU and free DBU, is built from one monomer of the chiral lithium amide, one molecule of epoxide and one additional molecule of DBU. The reaction order (-0.97) obtained for the bulk base Li-DBU shows an inverse dependence on the concentration, suggesting a deaggregation of the initial mixed dimer to a monomer-based transition state containing a monomer of the lithium amide. © 2010 Elsevier Ltd. All rights reserved.


Ohlsson Sax O.,Uppsala University | Stefanski Jr. B.,City University London
Journal of High Energy Physics | Year: 2011

Building on arXiv:0912.1723 [1], in this paper we investigate the AdS 3/CFT2 correspondence using integrability techniques. We present an all-loop Bethe Ansatz (BA) for strings on AdS3× S3×S3×S1, with symmetry d(2, 1; α) 2, valid for all values of ?. This construction requires an ?-dependent scaling of the Zhukovsky map. We investigate the weakly-coupled limit of this BA and of the all-loop BA for strings on AdS3 ×S3×T4. We construct integrable short-range spin-chains and Hamiltonians that correspond to these weakly-coupled BAs. The spin-chains are alternating and homogenous, respectively. The alternating spin-chain can be regarded as giving some of the first hints about the unknown CFT2 dual to string theory on AdS3×S 3×S3×S1. We show that, in the α → 1 limit, the integrable structure of the d(2, 1; α) 2 model is non-singular and keeps track of not just massive but also massless modes. This provides a way of incorporating massless modes into the integrability machinery of the AdS3/CFT2 correspondence. © 2011 SISSA.


Forstmeier W.,Max Planck Institute for Ornithology (Seewiesen) | Schielzeth H.,Max Planck Institute for Ornithology (Seewiesen) | Schielzeth H.,Uppsala University
Behavioral Ecology and Sociobiology | Year: 2011

Fitting generalised linear models (GLMs) with more than one predictor has become the standard method of analysis in evolutionary and behavioural research. Often, GLMs are used for exploratory data analysis, where one starts with a complex full model including interaction terms and then simplifies by removing non-significant terms. While this approach can be useful, it is problematic if significant effects are interpreted as if they arose from a single a priori hypothesis test. This is because model selection involves cryptic multiple hypothesis testing, a fact that has only rarely been acknowledged or quantified. We show that the probability of finding at least one 'significant' effect is high, even if all null hypotheses are true (e. g. 40% when starting with four predictors and their two-way interactions). This probability is close to theoretical expectations when the sample size (N) is large relative to the number of predictors including interactions (k). In contrast, type I error rates strongly exceed even those expectations when model simplification is applied to models that are over-fitted before simplification (low N/k ratio). The increase in false-positive results arises primarily from an overestimation of effect sizes among significant predictors, leading to upward-biased effect sizes that often cannot be reproduced in follow-up studies ('the winner's curse'). Despite having their own problems, full model tests and P value adjustments can be used as a guide to how frequently type I errors arise by sampling variation alone. We favour the presentation of full models, since they best reflect the range of predictors investigated and ensure a balanced representation also of non-significant results. © 2010 The Author(s).


Ronnblom L.,Uppsala University
Upsala Journal of Medical Sciences | Year: 2011

Many patients with systemic autoimmune diseases have signs of a continuous production of type I interferon (IFN) and display an increased expression of IFN-α-regulated genes. The reason for the on-going IFN-α synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA or RNA-containing autoantigens. Such interferogenic ICs are internalized via the FcγRIIa expressed on pDCs, reach the endosome, and stimulate Toll-like receptor (TLR)-7 or-9, which subsequently leads to IFN-α gene transcription. Variants of genes involved in both the IFN-α synthesis and response have been linked to an increased risk to develop systemic lupus erythematosus (SLE) and other autoimmune diseases. Among these autoimmunity risk genes are IFN regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I IFN receptor. Several other gene variants in the IFN signaling pathway also confer an increased risk to develop an autoimmune disease. The observations that IFN-α therapy can induce autoimmunity and that many autoimmune conditions have an on-going type I IFN production suggest that the type I IFN system has a pivotal role in the etiopathogenesis of these diseases. Possible mechanisms behind the dysregulated type IFNsystem in autoimmune diseases and how the IFN-α produced can contribute to the development of an autoimmune process will be reviewed. © 2011 Informa Healthcare.


Berg J.,Uppsala University | Nordstrom J.,Linkoping University
Journal of Computational Physics | Year: 2013

In this paper we derive well-posed boundary conditions for a linear incompletely parabolic system of equations, which can be viewed as a model problem for the compressible Navier-Stokes equations. We show a general procedure for the construction of the boundary conditions such that both the primal and dual equations are well-posed. The form of the boundary conditions is chosen such that reduction to first order form with its complications can be avoided. The primal equation is discretized using finite difference operators on summation-by-parts form with weak boundary conditions. It is shown that the discretization can be made energy stable, and that energy stability is sufficient for dual consistency. Since reduction to first order form can be avoided, the discretization is significantly simpler compared to a discretization using Dirichlet boundary conditions. We compare the new boundary conditions with standard Dirichlet boundary conditions in terms of rate of convergence, errors and discrete spectra. It is shown that the scheme with the new boundary conditions is not only far simpler, but also has smaller errors, error bounded properties, and highly optimizable eigenvalues, while maintaining all desirable properties of a dual consistent discretization. © 2012 Elsevier Inc.


Hyolithids with helens and an operculum, and a second species of loricate cycloneuralian, Sirilorica pustulosa sp. nov., are described from the Sirius Passet Lagerstätte (early Cambrian; Cambrian Series 2, Stage 3) of Peary Land, North Greenland. An ethmophylloid archaeocyathan and a species of the bivalved arthropod Isoxys are described in open nomenclature. The association of trace fossils with body fossils is discussed.


Ekeblad S.,Uppsala University
Advances in Experimental Medicine and Biology | Year: 2010

Pancreatic endocrine tumours can cause hormonal symptoms by oversecretion of hormones. They are less aggressive than exocrine pancreatic cancer, but carry a variable prognosis. The tumours are either sporadic or hereditary, as part of the multiple endocrine neoplasia type 1 syndrome. Despite the rarity of these tumours, they evoke significant interest in the research community and important advances have been made over the past years. This chapter provides an overview of the tumours and recent advances in the field. Hereditary forms of pancreatic endocrine tumours are caused by mutations in the MEN1 gene. Menin, the protein encoded by this gene, has been shown to interact with numerous transcription factors and proteins involved in cell-cycle control, shedding some light on the importance of the protein. Several genes have been shown to be up- or down-regulated, suggesting candidates to be further evaluated for a role in tumourigenesis. Several advances have been made in prognostication; a tumour-node-metastasis system has been evaluated and seems to have prognostic value, and several new molecular prognostic markers are under evaluation. It is hoped that the tumournode- metastasis system and other prognostic markers will be adopted in clinical routine and improve prognostication and treatment choices. Surgery is still the only cure, but several new palliative drugs and interventions are in use or under investigation. Radiofrequency ablation is increasingly used for liver metastases, and a number of new chemotherapy drugs are being tested. Despite improvements in treatment, no clear improvement in survival has been demonstrated. © Springer Science+Business Media B.V. 2010.


Ekblom R.,Uppsala University
Journal of Animal Ecology | Year: 2016

(Figure presented.) In the endangered Scottish chough (Pyrrhocorax pyrrhocorax) population, a lethal blindness syndrome is found to be caused by a deleterious recessive allele. Photo: Gordon Yates. In Focus: Trask, A.E., Bignal, E.M., McCracken, D.I., Monaghan, P., Piertney, S.B. & Reid, J.M. (2016) Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. Journal of Animal Ecology, 85, 879–891. In this issue of Journal of Animal Ecology, Trask et al. () report on a strange, lethal, blindness that regularly affects chicks of an endangered bird population. The authors show that the inheritance mode of this blindness disease precisely matches the expectations of a recessive deleterious mutation. Intriguingly, there is also an indication that the disease-causing variant might be maintained in the population by balancing selection, due to a selective advantage for heterozygotes. Could this finding have consequences for conservation actions implemented for the population?. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society


Basu S.,Uppsala University | Basu S.,Uppsala University Hospital
Molecules and Cells | Year: 2010

Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids, especially prostaglandin F2α (PGF 2α) and F2-isoprostanes are endogenous compounds that are involved both in physiology and the above mentioned pathologies. These compounds are biosynthesized mainly from esterified arachidonic acid through both enzymatic and non-enzymatic free radical-catalysed reactions in vivo, respectively. They have shown to possess potent biological activities in addition to their application as biomarkers of oxidative stress and inflammation. Recent advancement of methodologies has made it possible to quantify these compounds more reliably and apply them in various in vivo studies successfully. Today, experimental and clinical studies have revealed that both PGF2α and F2-isoprostanes are involved in severe acute or chronic inflammatory conditions such as rheumatic diseases, asthma, risk factors of atherosclerosis, diabetes, ischemia-reperfusion, septic shock and many others. These evidences promote that assessment of bioactive PGF 2α and F2-isoprostanes simultaneously in body fluids offers unique non-invasive analytical opportunity to study the function of these eicosanoids in physiology, oxidative stress-related and inflammatory diseases, and also in the determination of potency of various radical scavengers, anti-inflammatory compounds, drugs, antioxidants and diet. © 2010 The Korean Society for Molecular and Cellular Biology and Springer Netherlands.


Background and Aims Initial release height and settling speed of diaspores are biologically controlled components which are key to modelling wind dispersal. Most Sphagnum (peat moss) species have explosive spore liberation. In this study, how capsule and spore sizes affect the height to which spores are propelled were measured, and how spore size and spore number of discharged particles relate to settling speed in the aspherical Sphagnum spores. Methods Spore discharge and spore cloud development were filmed in a closed chamber (nine species). Measurements were taken from snapshots at three stages of cloud development. Settling speed of spores (14 species) and clusters were timed in a glass tube. Key Results The maximum discharge speed measured was 3·6 m s-1. Spores reached a maximum height of 20 cm (average: 15 cm) above the capsule. The cloud dimensions at all stages were related positively to capsule size (R2 = 0·58-0·65). Thus species with large shoots (because they have large capsules) have a dispersal advantage. Half of the spores were released as singles and the rest as clusters (usually two to four spores). Single spores settled at 0·84-1·86 cm s -1, about 52 slower than expected for spherical spores with the same diameters. Settling speed displayed a positive curvilinear relationship with spore size, close to predictions by Stokes' law for spherical spores with 68 of the actual diameters. Light-coloured spores settled slower than dark spores. Settling speed of spore clusters agrees with earlier studies. Effective spore discharge and small, slowly settling spores appear particularly important for species in forested habitats. Conclusions The spore discharge heights in Sphagnum are among the greatest for small, wind-dispersed propagules. The discharge heights and the slow settling of spores affect dispersal distances positively and may help to explain the wide distribution of most boreal Sphagnum species.


Glimelius B.,Uppsala University
World Journal of Gastroenterology | Year: 2013

In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a locoregional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.


Maklakov A.A.,Uppsala University
Current Biology | Year: 2013

Fruit flies selected to reproduce on the fifth day of adult life for many generations remarkably keep on living for six weeks, showing no change in lifespan. A mutation-accumulation experiment suggests that the same genes confer high early-life fitness and long life. © 2013 Elsevier Ltd.


The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [11C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.Molecular Psychiatry advance online publication, 1 December 2015; doi:10.1038/mp.2015.180. © 2015 Macmillan Publishers Limited


Bergman E.,Uppsala University
Journal of clinical pharmacology | Year: 2010

The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95% confidence interval, 1.14-2.15). The interaction was less pronounced in this single-dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 μM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.


Heldin C.-H.,Uppsala University
Recent Results in Cancer Research | Year: 2010

Pericytes are smooth muscle-like cells found in close contact with the endothelium in capillaries, where they regulate the morphology and function of the vessels. During vessel formation, platelet-derived growth factor-BB (PDGF-BB) is required for the recruitment and differentiation of pericytes. Tumor vessels display abnormal morphology and increased endothelial proliferation, resulting in leaky, tortuous vessels that are often poorly perfused. These vessels typically display decreased pericyte density, and the tumor-associated pericytes often express abnormal markers and show abnormal morphology. Anti-angiogenic therapy targeting pro-angiogenic growth factor pathways has been applied to a broad range of solid tumors with varying results. Studies utilizing mouse models indicate that the presence of pericytes protect endothelial cells against inhibition of vascular endothelial growth factor (VEGF) signaling. Simultaneous inhibition of PDGF receptors on pericytes therefore improves the effect of VEGF inhibitors on endothelial cells and enhances anti-angiogenic therapy. © 2010 Springer-Verlag Berlin Heidelberg.


Hughes D.,Uppsala University
IUBMB Life | Year: 2014

The overuse and misuse of antibiotics over many years has selected a high frequency of resistance among medically important bacterial pathogens. The evolution of resistance is complex, frequently involving multiple genetic alterations that minimize biological fitness costs and/or increase the resistance level. Resistance is selected at very low drug concentrations, such as found widely distributed in the environment, and this selects for resistant mutants with a high fitness. Once resistance with high fitness is established in a community it is very difficult to reduce its frequency. Addressing the problem of resistance is essential if we are to ensure a future where we can continue to enjoy effective medical control of bacterial infections. This will require several actions including the discovery and development of novel antibiotics, the creation of a continuous pipeline of drug discovery, and the implementation of effective global antibiotic stewardship to reduce the misuse of antibiotics and their release into the environment. © 2014 IUBMB Life, 66(8):521-529, 2014 © 2014 International Union of Biochemistry and Molecular Biology.


Giordanetto F.,Astrazeneca | Giordanetto F.,Taros Chemicals GmbH and Co. KG | Kihlberg J.,Astrazeneca | Kihlberg J.,Uppsala University
Journal of Medicinal Chemistry | Year: 2014

Macrocycles are ideal in efforts to tackle "difficult" targets, but our understanding of what makes them cell permeable and orally bioavailable is limited. Analysis of approximately 100 macrocyclic drugs and clinical candidates revealed that macrocycles are predominantly used for infectious disease and in oncology and that most belong to the macrolide or cyclic peptide class. A significant number (N = 34) of these macrocycles are administered orally, revealing that oral bioavailability can be obtained at molecular weights up to and above 1 kDa and polar surface areas ranging toward 250 Å2. Moreover, insight from a group of "de novo designed" oral macrocycles in clinical studies and understanding of how cyclosporin A and model cyclic hexapeptides cross cell membranes may unlock wider opportunities in drug discovery. However, the number of oral macrocycles is still low and it remains to be seen if they are outliers or if macrocycles will open up novel oral druggable space. © 2013 American Chemical Society.


Burman R.,Uppsala University
Biopolymers | Year: 2010

Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v., 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v., 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC5o values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2-3 days; lower doses were without complications.


Buckwheat food is a good source of antioxidants, e.g. rutin, and other beneficial substances. Here we investigated the effects of the intake of common buckwheat (low rutin content) and tartary buckwheat cookies (high rutin content) on selected clinical markers. A double blind crossover study was performed among female day-care centre staffs (N = 62) from five day-care centres. Participants were randomly divided into two groups. The first group initially consumed four common buckwheat cookies per day (16.5 mg rutin equivalents/day) for two weeks, while the second group consumed four tartary buckwheat cookies per day (359.7 mg rutin equivalents/day). Then the groups switched their type of cookies and consumed them for another two weeks. We monitored selected clinical markers related to cardiovascular disease and lower airway inflammation, lung function, and subjective breathing difficulties in the staffs. Intake of tartary buckwheat cookies reduced the serum level of myeloperoxidase (MPO) by a factor 0.84 (p = 0.02). When grouping the two types of buckwheat cookies together, there was a reduction of total serum cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001) during the study period, with improved lung vital capacity (p < 0.001). The degree of reduction in total and HDL cholesterol levels was similar in staffs with low and high body mass index (cut off 25). In conclusion, intake of tartary buckwheat cookies with high level of the antioxidant rutin may reduce levels of MPO, an indicator of inflammation. Moreover, intake of both types of buckwheat cookies may lower cholesterol levels.


Aldskogius H.,Uppsala University
Frontiers in Bioscience - Scholar | Year: 2011

Microglia respond rapidly to injury of peripheral nerve axons (axotomy). This response is integrated into the responses of the injured neurons, i.e. processes for neuron survival, axon regeneration and restoration of target contact. The microglial response is also integrated in changes in presynaptic terminals on axotomized motor or autonomic neurons and in changes in the central terminals of peripherally axotomized sensory neurons. Microglia also has an established role in interacting with astrocytes to shape their response to peripheral axotomy. Axotomy models in mice have demonstrated a role for microglia in regulating the entry of lymphocytes into motor nuclei or sensory areas following peripheral axotomy. Whether this is a universal component of peripheral nerve injury remains to be determined. Under certain circumstances, microglia activated by axotomy are major contributors to CNS pathology, e.g. in models of neuropathic pain. However, the general roles played by microglia after peripheral nerve injury are still incompletely understood. Early proposals that the microglial reaction to peripheral nerve injury is preparatory for the eventuality of neuron degeneration may still have relevance.


Aspers P.,Uppsala University
Social Studies of Science | Year: 2015

Ontology, and in particular, the so-called ontological turn, is the topic of a recent themed issue of Social Studies of Science (Volume 43, Issue 3, 2013). Ontology, or metaphysics, is in philosophy concerned with what there is, how it is, and forms of being. But to what is the science and technology studies researcher turning when he or she talks of ontology? It is argued that it is unclear what is gained by arguing that ontology also refers to constructed elements. The ‘ontological turn’ comes with the risk of creating a pseudo-debate or pseudo-activity, in which energy is used for no end, at the expense of empirical studies. This text rebuts the idea of an ontological turn as foreshadowed in the texts of the themed issue. It argues that there is no fundamental qualitative difference between the ontological turn and what we know as constructivism. © 2014, © The Author(s) 2014.


Kvashnina K.O.,European Synchrotron Radiation Facility | Butorin S.M.,Uppsala University | Martin P.,CEA Cadarache Center | Glatzel P.,European Synchrotron Radiation Facility
Physical Review Letters | Year: 2013

We report here the first direct observation of U(V) in uranium binary oxides and analyze the gradual conversion of the U oxidation state in the mixed uranium systems. Our finding clarifies previous contradicting results and provides important input for the geological disposal of spent fuel, recycling applications, and chemistry of uranium species. © 2013 American Physical Society.


Vasaitis L.,Uppsala University
European Journal of Internal Medicine | Year: 2016

IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a »capsule-like rim» surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD. © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.


Palsson G.K.,Uppsala University
Nature communications | Year: 2012

Because of its light weight and small size, hydrogen exhibits one of the fastest diffusion rates in solid materials, comparable to the diffusion rate of liquid water molecules at room temperature. The diffusion rate is determined by an intricate combination of quantum effects and dynamic interplay with the displacement of host atoms that is still only partially understood. Here we present direct observations of the spatial and temporal changes in the diffusion-induced concentration profiles in a vanadium single crystal and we show that the results represent the experimental counterpart of the full time and spatial solution of Fick's diffusion equation. We validate the approach by determining the diffusion rate of hydrogen in a single crystal vanadium (001) film, with net diffusion in the [110] direction.


Nordstrom P.,Umea University | Michaelsson K.,Uppsala University | Gustafson Y.,Umea University | Nordstrom A.,Umea University
Annals of Neurology | Year: 2014

Objective To investigate the association between traumatic brain injuries (TBIs) and the risk of young onset dementia (YOD), that is, dementia before 65 years of age. Methods The study cohort comprised 811,622 Swedish men (mean age = 18 years) conscripted for military service between 1969 and 1986. TBIs, dementia, and covariates were extracted from national registers. Time-dependent exposures using Cox proportional hazard regression models were evaluated. Results During a median follow-up period of 33 years, there were 45,249 men with at least 1 TBI in the cohort. After adjustment for covariates, 1 mild TBI (hazard ratio [HR] = 1.0, 95% confidence interval [CI] = 0.5-2.0), at least 2 mild TBIs (HR = 2.5, 95% CI = 0.8-8.1), or 1 severe TBI (HR = 0.7, 95% CI = 0.1-5.2) were not associated with Alzheimer dementia (AD). Other types of dementia were strongly associated with the risk of 1 mild TBI (HR = 3.8, 95% CI = 2.8-5.2), at least 2 mild TBIs (HR = 10.4, 95% CI = 6.3-17.2), and 1 severe TBI (HR = 11.4, 95% CI = 7.4-17.5) in age-adjusted analysis. However, these associations were largely attenuated after adjustment for covariates (1 mild TBI: HR = 1.7; at least 2 mild TBIs: HR = 1.7; 1 severe TBI: HR = 2.6; p < 0.05 for all). Interpretation In the present study, we found strong associations between YOD of non-AD forms and TBIs of different severity. These associations were, however, markedly attenuated after multivariate adjustment. Ann Neurol 2014;75:374-381 © 2014 American Neurological Association.


Moczydlowska M.,Uppsala University | Nagovitsin K.E.,Russian Academy of Sciences
Precambrian Research | Year: 2012

A new assemblage of morphologically complex, ornamented and large organic-walled microfossils (acritarchs) from the Ura Formation in the Patom Uplift, East Siberia, is identified and taxonomically described as a continuation of the previous studies (Nagovitsin et al., 2004; Sergeev et al., 2011). Nine new species and three new genera are recognised; 10 other species are known from occurrences in the Ediacaran strata of Australia, China, the Siberian Platform (SP), and the East European Platform (EEP). The new species are morphologically advanced phenotypes, showing innovative elements of vesicle ornamentation and variable symmetry, and internal bodies within zygotic cyst-like vesicles that are indicative of the sexual reproduction stage of the microorganism. The morphological features and the preliminarily recognised cell wall ultrastructure are characteristic of phytoplankton; thus the described microfossils are identified as green microalgae. The relative age of the Ura assemblage, by comparison to microfossil records elsewhere and estimated in the regional geologic context of the Dalniaya Taiga (containing the Ura Formation) and the Zhuya (overlying) groups, is suggested to be early Ediacaran. Radiation of the Ura-type microorganisms pre-dates the records of Ediacaran microbiota from Australia (the Pertatataka association/Ediacaran Complex Acanthomorphic Palynoflora), the Siberian Platform (Khamaka-type assemblages), and the EEP (Vychegda association) but is preceded by the appearance of certain species recorded in China at the base of the Doushantuo Formation. The stratigraphic ranges of genera co-occurring in these palaeocontinents (Appendisphaera, Cavaspina, Ceratosphaeridium, Gyalosphaeridium, Labruscasphaeridium, Multifronsphaeridium, Tanarium, and Variomargosphaeridium) are extended by their lower record in the Patom Uplift and may span a major portion of the Ediacaran Period. The refined stratigraphic distribution of microfossils may provide a means for zoning the entire Ediacaran System in addition to the upper zones established in Australia. © 2011 Elsevier B.V.


Sletvold N.,Norwegian University of Science and Technology | Gren J.A.,Uppsala University
Ecology | Year: 2011

Pollinators may mediate selection on traits affecting pollinator attraction and effectiveness, and while nonadditive effects of traits influencing the two components of pollination success are expected when seed production is pollen limited, they have been little studied. In a factorial design, we manipulated one putative attraction trait (number of flowers) and one putative efficiency trait (spur length) previously shown to be subject to pollinatormediated selection in the deceptive orchid Dactylorhiza lapponica. Removal of half of the flowers reduced pollen removal, proportion of flowers receiving pollen, fruit set, and fruit mass compared to unmanipulated plants, while spur-tip removal increased fruit set and fruit mass but did not affect pollen removal or proportion of flowers receiving pollen. The effect of spurtip removal on fruit mass was stronger among plants with intact number of flowers compared to plants with experimentally reduced number of flowers. The results demonstrate that number of flowers and spur length are direct targets of selection and may affect female fitness nonadditively. More generally, they show that the adaptive value of a given trait can depend on floral context and illustrate how experimental approaches can advance our understanding of the evolution of trait combinations. © 2011 by the Ecological Society of America.


Arthropods show two kinds of developmental mode. In the so-called long germ developmental mode (as exemplified by the fly Drosophila), all segments are formed almost simultaneously from a preexisting field of cells. In contrast, in the so-called short germ developmental mode (as exemplified by the vast majority of arthropods), only the anterior segments are patterned similarly as in Drosophila, and posterior segments are added in a single or double segmental periodicity from a posterior segment addition zone (SAZ). The addition of segments from the SAZ is controlled by dynamic waves of gene activity. Recent studies on a spider have revealed that a similar dynamic process, involving expression of the segment polarity gene (SPG) hedgehog (hh), is involved in the formation of the anterior head segments. The present study shows that in the myriapod Glomeris marginata the early expression of hh is also in a broad anterior domain, but this domain corresponds only to the ocular and antennal segment. It does not, like in spiders, represent expression in the posterior adjacent segment. In contrast, the anterior hh pattern is conserved in Glomeris and insects. All investigated myriapod SPGs and associated factors are expressed with delay in the premandibular (tritocerebral) segment. This delay is exclusively found in insects and myriapods, but not in chelicerates, crustaceans and onychophorans. Therefore, it may represent a synapomorphy uniting insects and myriapods (Atelocerata hypothesis), contradicting the leading opinion that suggests a sister relationship of crustaceans and insects (Pancrustacea hypothesis). In Glomeris embryos, the SPG engrailed is first expressed in the mandibular segment. This feature is conserved in representatives of all arthropod classes suggesting that the mandibular segment may have a special function in anterior patterning. © Springer-Verlag 2012.


Janszky I.,Karolinska Institutet | Ahnve S.,Karolinska Institutet | Lundberg I.,Uppsala University | Hemmingsson T.,Karolinska Institutet
Journal of the American College of Cardiology | Year: 2010

Objectives: The purpose of this study was to investigate the long-term cardiac effects of depression and anxiety assessed at a young age, when reverse causation is not feasible. Background: Most prospective studies found a relatively strong association between depression and subsequent coronary heart disease (CHD). However, almost exclusively, only middle-age or older participants were examined, and subclinical atherosclerosis might contribute to the observed association. The prospective association between anxiety and CHD was less evident in previous studies and has been subjected to similar methodological concerns on the possibility for a reverse causation. Methods: In a nationwide survey, 49,321 young Swedish men, 18 to 20 years of age, were medically examined for military service in 1969 and 1970. All the conscripts were seen by a psychologist for a structured interview. Conscripts reporting or presenting any psychiatric symptoms were seen by psychiatrists. Depression and anxiety was diagnosed according to International Classification of Diseases-8th Revision (ICD-8). Data on well-established CHD risk factors and potential confounders were also collected (i.e., anthropometrics, diabetes, blood pressure, smoking, alcohol consumption, physical activity, socioeconomic position, family history of CHD, and geographic area). Participants were followed for CHD and for acute myocardial infarction for 37 years. Results: Multiadjusted hazard ratios associated with depression were 1.04 (95% confidence interval [CI]: 0.70 to 1.54), 1.03 (95% CI: 0.65 to 1.65), for CHD and for acute myocardial infarction, respectively. The corresponding multiadjusted hazard ratios for anxiety were 2.17 (95% CI: 1.28 to 3.67) and 2.51 (95% CI: 1.38 to 4.55). Conclusions: In men, aged 18 to 20 years, anxiety as diagnosed by experts according to ICD-8 criteria independently predicted subsequent CHD events. In contrast, we found no support for such an effect concerning early-onset depression in men. © 2010 American College of Cardiology Foundation.


Ullman G.,Uppsala University
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

We have developed a method combining microfluidics, time-lapsed single-molecule microscopy and automated image analysis allowing for the observation of an excess of 3000 complete cell cycles of exponentially growing Escherichia coli cells per experiment. The method makes it possible to analyse the rate of gene expression at the level of single proteins over the bacterial cell cycle. We also demonstrate that it is possible to count the number of non-specifically DNA binding LacI-Venus molecules using short excitation light pulses. The transcription factors are localized on the nucleoids in the cell and appear to be uniformly distributed on chromosomal DNA. An increase in the expression of LacI is observed at the beginning of the cell cycle, possibly because some gene copies are de-repressed as a result of partitioning inequalities at cell division. Finally, a size-growth rate uncertainty relation is observed where cells living in rich media vary more in the length at birth than in generation time, and the opposite is true for cells living in poorer media.


Amin K.,Uppsala University | Amin K.,University of Sulaimani
Respiratory Medicine | Year: 2012

The histochemical characteristics of human basophils and tissue mast cells were described over a century ago by Paul Ehrlich. When mast cells are activated by an allergen that binds to serum IgE attached to their FcεRI receptors, they release cytokines, eicosanoids and their secretory granules. Mast cells are now thought to exert critical proinflammatory functions, as well as potential immunoregulatory roles, in various immune disorders through the release of mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases (chymase and tryptase). The aim of this review is to describe the role of mast cells in allergic inflammation. Mast cells interact directly with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been shown to have inhibitory effects on mast cell degranulation and mediator release. This review shows that mast cells play an active role in such diverse diseases as asthma, rhinitis, middle ear infection, and pulmonary fibrosis. In conclusion, mast cells may not only contribute to the chronic airway inflammatory response, remodeling and symptomatology, but they may also have a central role in the initiation of the allergic immune response, that is providing signals inducing IgE synthesis by B-lymphocytes and inducing Th2 lymphocyte differentiation. © 2011 Elsevier Ltd. All rights reserved.


Mathot L.,Uppsala University | Stenninger J.,Karolinska Institutet
Cancer Science | Year: 2012

The so-called "seed and soil" hypothesis proposed by Stephen Paget in 1889 to explain the metastatic behavior of cancer cells and the homing of certain cancers to "selected" sites has been a well-recognized phenomenon for over a century. What advances have been made to increase our understanding of this phenomenon and what does it really implicate in terms of targets for therapy? © 2011 Japanese Cancer Association.


Lindas A.-C.,University of Stockholm | Chruszcz M.,University of South Carolina | Bernander R.,University of Stockholm | Valegard K.,Uppsala University
Acta Crystallographica Section D: Biological Crystallography | Year: 2014

The crystal structure of the archaeal actin, crenactin, from the rod-shaped hyperthermophilic (optimal growth at 90°C) crenarchaeon Pyrobaculum calidifontis is reported at 3.35 Å resolution. Despite low amino-acid sequence identity, the three-dimensional structure of the protein monomer is highly similar to those of eukaryotic actin and the bacterial MreB protein. Crenactin-specific features are also evident, as well as elements that are shared between crenactin and eukaryotic actin but are not found in MreB. In the crystal, crenactin monomers form right-handed helices, demonstrating that the protein is capable of forming filament-like structures. Monomer interactions in the helix, as well as interactions between crenactin and ADP in the nucleotide-binding pocket, are resolved at the atomic level and compared with those of actin and MreB. The results provide insights into the structural and functional properties of a heat-stable archaeal actin and contribute to the understanding of the evolution of actin-family proteins in the three domains of life. © 2014 International Union of Crystallography.


Terschlusen C.,Justus Liebig University | Leupold S.,Uppsala University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

The decays of narrow light vector mesons into pseudoscalar mesons and dileptons are calculated to leading order in a recently proposed scheme which treats pseudoscalar and vector mesons on equal footing. Since all required parameters have been determined by other reactions the presented approach gains predictive power for the considered processes. The decay of the ω-meson into pion and dimuon agrees reasonably well with the available experimental data concerning form factor, single-differential decay width and partial decay width. As well do the partial decay width of the Φ-meson into a pion and a dielectron and of the η-meson into an ω-meson and a dielectron. The decay properties of the Φ-meson into η-meson and dimuon or dielectron and of the Φ-meson into η-meson and dimuon are predicted. © 2010 Elsevier B.V.


Roth J.R.,University of California at Davis | Andersson D.I.,Uppsala University
Cell | Year: 2012

A multistep process of gene amplification, mutation, and reduction allows poxvirus to overcome host antiviral defenses. The mechanism speeds genetic adaptation and promises to be broadly applicable in many biological settings. © 2012 Elsevier Inc.


Cheng S.,Advanced Technology | Wu Z.,Uppsala University
Advanced Functional Materials | Year: 2011

This article describes the implementation and characterization of a new self-contained large-area wireless strain sensor, operating around 1.5 GHz, based on the concept of multi-layer microfluidic stretchable radiofrequency electronics (μFSRFEs). Compared to existing solutions, the presented integrated strain sensor is capable of remotely detecting repeated high tensile dynamic strains of up to 15% over very large surfaces or movable parts, and gets rid of all hardwiring to external storage or data processing equipment. Unlike conventional electronic devices, the major part of the sensor is a mechanically reconfigurable and reversibly deformable patch antenna, which consists of two layers of liquid metal alloy filled microfluidic channels in a silicone elastomer. A simplified radiofrequency (RF) transmitter composed of miniaturized rigid active integrated circuits (ICs) associated with discrete passive components was assembled on a flexible printed circuit board (FPCB) and then heterogeneously integrated to the antenna. The elastic patch antenna can withstand repeated mechanical stretches while still maintaining its electrical function to some extent, and return to its original state after removal of the stress. Additionally, its electrical characteristics at frequency of operation are highly sensitive to mechanical strains. Consequently, not only is this antenna a radiator for transmitting and receiving RF signals like any other conventional antennas, but also acts as a reversible large-area strain sensor in the integrated device. Good electrical performance of the standalone antenna and the RF transmitter sub-module was respectively verified by experiments. Furthermore, a personal computer (PC)-assisted RF receiver for receiving and processing the measured data was also designed, implemented, and evaluated. In the real-life demonstration, the integrated strain sensor successfully monitored periodically repeated human body motion, and wirelessly transmitted the measured data to the custom-designed receiver at a distance of 5m in real-time. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Klose T.,Uppsala University | McLoughlin T.,Max Planck Institute For Gravitationsphysik
Journal of High Energy Physics | Year: 2012

We consider worldsheet correlation functions for strings in AdS 5×S 5 using a light-cone gauge for the worldsheet theory. We compute the saddle-point approximation to three-point functions of BMN vertex operators, all with large charges, by explicitly finding the intersection of three euclidean BMN strings. We repeat this calculation for non-BPS circular winding strings extended along a great circle of the S 5, though in this case the appropriate form of the vertex operator is uncertain. Furthermore, we compute the spectrum of fluctuations about euclidean BMN strings for generic boundary conditions, and show that the spectrum depends only on the total charge and not the details of the string configuration. We extend our considerations to include near-BMN vertex operators and through the evaluation of the string path integral make contact with the light-cone string field theory calculations of gauge theory three-point structure constants. © 2012 SISSA.


Kenward B.,Uppsala University
Proceedings. Biological sciences / The Royal Society | Year: 2011

In over-imitation, children copy even elements of a goal-directed action sequence that appear unnecessary for achieving the goal. We demonstrate in 4-year olds that the unnecessary action is specifically associated with the goal, not generally associated with the apparatus. The unnecessary action is performed flexibly: 4-year olds usually omit it if it has already been performed by an adult. Most 5-year olds do not verbally report the unnecessary action as necessary when achieving the goal, although most of them report an equivalent but necessary action as necessary. Most 5-year olds explain the necessary action in functional terms, but are unsure as to the function of the unnecessary action. These verbal measures do not support the hypothesis that children over-imitate primarily because they encode unnecessary actions as causing the goal even in causally transparent systems. In a causally transparent system, explanations for over-imitation fitting the results are that children are ignorant of the unnecessary action's purpose, and that they learn a prescriptive norm that it should be carried out. In causally opaque systems, however, for children and for adults, any action performed before achieving the goal is likely to be inferred as causally necessary-this is not over-imitation, but ordinary causal learning.


Korall P.,Uppsala University | Pryer K.M.,Duke University
Journal of Biogeography | Year: 2014

Aim: Scaly tree ferns, Cyatheaceae, are a well-supported group of mostly tree-forming ferns found throughout the tropics, the subtropics and the south-temperate zone. Fossil evidence shows that the lineage originated in the Late Jurassic period. We reconstructed large-scale historical biogeographical patterns of Cyatheaceae and tested the hypothesis that some of the observed distribution patterns are in fact compatible, in time and space, with a vicariance scenario related to the break-up of Gondwana. Location: Tropics, subtropics and south-temperate areas of the world. Methods: The historical biogeography of Cyatheaceae was analysed in a maximum likelihood framework using Lagrange. The 78 ingroup taxa are representative of the geographical distribution of the entire family. The phylogenies that served as a basis for the analyses were obtained by Bayesian inference analyses of mainly previously published DNA sequence data using MrBayes. Lineage divergence dates were estimated in a Bayesian Markov chain Monte Carlo framework using beast. Results: Cyatheaceae originated in the Late Jurassic in either South America or Australasia. Following a range expansion, the ancestral distribution of the marginate-scaled clade included both these areas, whereas Sphaeropteris is reconstructed as having its origin only in Australasia. Within the marginate-scaled clade, reconstructions of early divergences are hampered by the unresolved relationships among the Alsophila, Cyathea and Gymnosphaera lineages. Nevertheless, it is clear that the occurrence of the Cyathea and Sphaeropteris lineages in South America may be related to vicariance, whereas transoceanic dispersal needs to be inferred for the range shifts seen in Alsophila and Gymnosphaera. Main conclusions: The evolutionary history of Cyatheaceae involves both Gondwanan vicariance scenarios as well as long-distance dispersal events. The number of transoceanic dispersals reconstructed for the family is rather few when compared with other fern lineages. We suggest that a causal relationship between reproductive mode (outcrossing) and dispersal limitations is the most plausible explanation for the pattern observed. © 2013 The Authors Journal of Biogeography Published by John Wiley & Sons Ltd.


Styring S.,Uppsala University
Ambio | Year: 2012

The world needs new, environmentally friendly and renewable fuels to allow an exchange from fossil fuels. The fuel must be made from cheap and 'endless' resources that are available everywhere. The new research area on solar fuels, which are made from solar energy and water, aims to meet this demand. The paper discusses why we need a solar fuel and why electricity is not enough; it proposes solar energy as the major renewable energy source to feed from. The present research strategies, involving direct, semi-direct and indirect approaches to produce solar fuels, are overviewed. © Royal Swedish Academy of Sciences 2012.


Ellegren H.,Uppsala University
Annual Review of Ecology, Evolution, and Systematics | Year: 2013

Rapidly accumulating genome sequence information in birds, which show several unique genomic features, provides novel insights into evolutionary genomics. The avian karyotype with numerous microchromosomes has remained stable during evolution, although frequent intrachromosomal inversions have occurred. Avian sex chromosome evolution, representing the best characterized ZW system to date, follows patterns seen in other organisms but has the notable exception of incomplete dosage compensation. Recombination is unevenly distributed in the avian genome; it occurs at very high rates in microchromosomes, a consequence of an obligate crossing over in even small chromosomes, and has highly elevated rates near chromosome ends. Moreover, a heterogeneous landscape of recombination feeds significant heterogeneity in base composition via GC-biased gene conversion. A uniform molecular clock is not applicable to birds, and ample evidence for substitution rate heterogeneity both among lineages and within genomes exists. Observed genome-wide levels of nucleotide diversity in birds are in the range of 10-2-10-3. © Copyright ©2013 by Annual Reviews. All rights reserved.


Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.


Alfoldi J.,The Broad Institute of MIT and Harvard | Lindblad-Toh K.,The Broad Institute of MIT and Harvard | Lindblad-Toh K.,Uppsala University
Genome Research | Year: 2013

When the human genome project started, the major challenge was how to sequence a 3 billion letter code in an organized and cost-effective manner. When completed, the project had laid the foundation for a huge variety of biomedical fields through the production of a complete human genome sequence, but also had driven the development of laboratory and analytical methods that could produce large amounts of sequencing data cheaply. These technological developments made possible the sequencing of many more vertebrate genomes, which have been necessary for the interpretation of the human genome. They have also enabled large-scale studies of vertebrate genome evolution, as well as comparative and human medicine. In this review, we give examples of evolutionary analysis using a wide variety of time frames - from the comparison of populations within a species to the comparison of species separated by at least 300 million years. Furthermore, we anticipate discoveries related to evolutionary mechanisms, adaptation, and disease to quickly accelerate in the coming years. © 2013, Published by Cold Spring Harbor Laboratory Press.


Hellqvist B.,Uppsala University
Journal of the American Society for Information Science and Technology | Year: 2010

This article studies citation practices in the arts and humanities from a theoretical and conceptual viewpoint, drawing on studies from fields like linguistics, history, library & information science, and the sociology of science. The use of references in the humanities is discussed in connection with the growing interest in the possibilities of applying citation analysis to humanistic disciplines. The study shows how the use of references within the humanities is connected to concepts of originality, to intellectual organization, and to searching and writing. Finally, it is acknowledged that the use of references is connected to stylistic, epistemological, and organizational differences, and these differences must be taken into account when applying citation analysis to humanistic disciplines. © 2009 ASIS&T.


Dimberg A.,Uppsala University
Biochemical Society Transactions | Year: 2014

Glioblastoma is characterized by microvascular proliferation and a highly abnormal dysfunctional vasculature. The glioblastoma vessels differ significantly from normal brain vessels morphologically, functionally and molecularly. The present review provides a brief overview of the current understanding of the formation, functional abnormalities and specific gene expression of glioblastoma vessels and the consequences of vascular abnormalization for the tumour microenvironment. © 2014 Biochemical Society.


Sundbom M.,Uppsala University
World Journal of Gastroenterology | Year: 2014

The history of bariatric surgery is investigational. Dedicated surgeons have continuously sought for an ideal procedure to relieve morbidly obese patients from their burden of comorbid conditions, reduced life expectancy and low quality of life. The ideal procedure must have low complication risk, both in short- and long term, as well as minimal impact on daily life. The revolution of laparoscopic techniques in bariatric surgery is described in this summary. Advances in minimal invasive techniques have contributed to reduced operative time, length of stay, and complications. The development in bariatric surgery has been exceptional, resulting in a dramatic increase of the number of procedures performed world wide during the last decades. Although, a complex bariatric procedure can be performed with operative mortality no greater than cholecystectomy, specific procedure-related complications and other drawbacks must be taken into account. The evolution of laparoscopy will be the legacy of the 21st century and at present, day-care surgery and further reduction of the operative trauma is in focus. The impressive effects on comorbid conditions have prompted the adoption of minimal invasive bariatric procedures into the field of metabolic surgery. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Koch S.,Uppsala University | Koch S.,Max Planck Institute of Molecular Physiology
Biochemical Society Transactions | Year: 2012

VEGFs (vascular endothelial growth factors) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in adults. This family of five mammalian ligands acts through three RTKs (receptor tyrosine kinases). In addition, co-receptors such as NRPs (neuropilins) associate with the ligand-receptor signalling complex and modulate the output. Therapeutics to block several of the VEGF signalling components as well as NRP function have been developed with the aim of halting blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. The present review outlines the current understanding of NRPs in relation to blood and lymphatic vessel biology. ©The Authors Journal compilation ©2012 Biochemical Society.


Svanberg I.,Uppsala University
Acta Societatis Botanicorum Poloniae | Year: 2012

This paper is a review of the actual gathering and use of wild edible plants in the 18th and 19th centuries, with a brief concluding discussion on the present day use of wild plants as food within Sweden. The peasants and the nomads in pre-industrial Sweden utilised very few wild plant taxa as food. Many even despised the wild fruits and green plants. Some plants and fruits were earlier mostly eaten fresh on the spot, or gathered for consumption in bread, gruel or soup. Other fruits were dried or preserved in other ways. In times of food shortages the amount of wild plants increased in the diet, but still the peasantry and nomads were often able to use fish and game to provide enough nutrients. With access to cheap sugar in the early 20th century wild fruits (Vaccinium myrtillus L., V. vitis-idaea L., and Rubus chamaemorus L.) increased in importance, especially among urban-dwellers and within food industry. In the last few decades fungi have also become part of the urban diet. Fifty years ago working class people gathered only Cantharellus cibarius (Fr.) and occasionally Boletus edulis Bull. Nowadays more taxa are utilised within the Swedish households, and especially the easy to pick Cantharellus tubaeformis (Pers.) has become very popular recently. Harvesting fruits and mushrooms in the forests is a popular pastime for many urban people, but also a source of income for immigrants and especially foreign seasonal labour. The only traditional green wild food plant that is regularly eaten in contemporary Sweden is Urtica dioica L. © The Author(s) 2012.


Tengholm A.,Uppsala University
Upsala Journal of Medical Sciences | Year: 2012

Insulin secretion from pancreatic β-cells is tightly regulated by glucose and other nutrients, hormones, and neural factors. The exocytosis of insulin granules is triggered by an elevation of the cytoplasmic Ca concentration ([Ca]i) and is further amplified by cyclic AMP (cAMP). Cyclic AMP is formed primarily in response to glucoincretin hormones and other Gs-coupled receptor agonists, but generation of the nucleotide is critical also for an optimal insulin secretory response to glucose. Nutrient and receptor stimuli trigger oscillations of the cAMP concentration in β-cells. The oscillations arise from variations in adenylyl cyclase-mediated cAMP production and phosphodiesterase-mediated degradation, processes controlled by factors like cell metabolism and [Ca]i. Protein kinase A and the guanine nucleotide exchange factor Epac2 mediate the actions of cAMP in β-cells and operate at multiple levels to promote exocytosis and pulsatile insulin secretion. The cAMP signaling system contains important targets for pharmacological improvement of insulin secretion in type 2 diabetes. © 2012 Informa Healthcare.


Falck-Ytter T.,Karolinska Institutet | Falck-Ytter T.,Uppsala University
Journal of Neurophysiology | Year: 2012

In support for the direct-matching hypothesis, Ambrosini et al. (2011) recently reported that goal-directed saccades during action observation were modulated by manipulations of basic motor information. This finding indicates that motor programs, activated by low-level visual descriptions of others' actions, are involved in predicting other people's action goals. Here, I put this result into a broader context, review alternative interpretations, and suggest strategies for future studies. © 2012 the American Physiological Society.


Kish L.B.,Texas A&M University | Granqvist C.G.,Uppsala University
Quantum Information Processing | Year: 2014

A simple and general proof is given for the information theoretic (unconditional) security of the Kirchhoff-law–Johnson-noise key exchange system under practical conditions. The unconditional security for ideal circumstances, which is based on the second law of thermodynamics, is found to prevail even under slightly non-ideal conditions. This security level is guaranteed by the continuity of functions describing classical physical linear, as well as stable non-linear, systems. Even without privacy amplification, Eve’s probability for successful bit guessing is found to converge toward 0.5—i.e., the perfect security level—when ideal conditions are approached. © 2014, Springer Science+Business Media New York.


Stalberg E.,Uppsala University
Muscle and Nerve | Year: 2011

The macro electromyography method was developed in the 1980s. Since then, technical modifications have been made, and a number of conditions have been explored. This study is a methodological introduction and an update of findings in some nerve-muscle disorders. The spike component of a motor unit potential (MUP) recorded by a concentric or monopolar needle electromyography (EMG) electrode is generated primarily by fibers within 1-2 mm of the needle recording area. Given that a MUP's typical anatomical reach is 5-15 mm in diameter, it follows that conventional EMG is unable to record activity from the entire motor unit. Such information could promote understanding of muscle in health and disease. Macro EMG, with its large recording area, appears to provide this information by recording the activity from most of the fibers in a given motor unit. The value of combining macro EMG with single-fiber EMG and conventional EMG recordings is discussed. © 2011 American Association of Neuromuscular and Electrodiagnostic Medicine.


Atig M.F.,Uppsala University
Leibniz International Proceedings in Informatics, LIPIcs | Year: 2010

In this paper, we address the verification problem of ordered multi-pushdown systems: A multistack extension of pushdown systems that comes with a constraint on stack operations such that a pop can only be performed on the first non-empty stack. First, we show that for an ordered multi-pushdown system the set of all predecessors of a regular set of configurations is an effectively constructible regular set. Then, we exploit this result to solve the global model checking which consists in computing the set of all configurations of an ordered multi-pushdown system that satisfy a given w-regular property (expressible in linear-time temporal logics or the linear-time μ-calculus). As an immediate consequence of this result, we obtain an 2ETIME upper bound for the model checking problem of w-regular properties for ordered multi-pushdown systems (matching its lower-bound). © Mohamed Faouzi Atig.


Feuk L.,Uppsala University
Genome Medicine | Year: 2010

Significant advances have been made over the past 5 years in mapping and characterizing structural variation in the human genome. Despite this progress, our understanding of inversion variants is still very restricted. While unbalanced variants such as copy number variations can be mapped using array-based approaches, strategies for characterization of inversion variants have been limited and underdeveloped. Traditional cytogenetic approaches have long been able to identify microscopic inversion events, but discovery of submicroscopic events has remained elusive and largely ignored. With the advent of pairedend sequencing approaches, it is now possible to map inversions across the human genome. Based on the paired-end sequencing studies published to date, it is now feasible to make a first map of inversions across the human genome and to use this map to explore the characteristics and distribution of this form of variation. The current map of inversions indicates that many remain to be identified, especially in the smaller size ranges. This review provides an overview of the current knowledge about human inversions and their contribution to human phenotypes. Further characterization of inversions should be considered as an important step towards a deeper understanding of human variation and genome dynamics.© 2010 BioMed Central Ltd.


Eriksson O.,Uppsala University | Alavi A.,University of Pennsylvania
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2012

Clinical islet transplantation is being investigated as a permanent cure for type 1 diabetes mellitus (T1DM). Currently, intraportal infusion of islets is the favoured procedure, but several novel implantation sites have been suggested. Noninvasive longitudinal methodologies are an increasingly important tool for assessing the fate of transplanted islets, their mass, function and early signs of rejection. This article reviews the approaches available for islet graft imaging by positron emission tomography and progress in the field, as well as future challenges and opportunities. © Springer-Verlag 2011.


Antoni G.,Uppsala University
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2015

The development of positron emission tomography (PET) from being an exclusive and expensive research tool at major research institutes to a clinically useful modality found at most major hospitals around the world is largely dependent on radiochemistry and synthesis technology achievements by a few pioneer researchers starting their PET careers 40 to 50years ago. Especially, the introduction of [11C]methyl iodide resulted in a quantum jump in the history of PET tracer development enabling the smooth labelling of a multitude of useful tracers. A more recent and still challenging methodological improvement is transition metal mediated 11C-carbonylations, having a large synthetic potential that has, however, not yet been realized in the clinical setting. This mini-review focuses on the history of carbon-11 radiochemistry and related technology developments and the role this played in PET tracer developments, especially emphasizing radiolabelling of endogenous compounds. A few examples will be presented of how the use of radiolabelled endogenous substances have provided fundamental information of in vivo biochemistry using the concept of position-specific labelling in different positions in the same molecule. Copyright © 2015 John Wiley & Sons, Ltd.


Hogman M.,Uppsala University
Journal of Breath Research | Year: 2012

Extended NO analysis is a promising tool in different diseases where NO metabolism is altered. One single exhalation cannot give insight to the NO production in the respiratory system; rather the use of multiple exhalation flows can give the alveolar levels (C ANO), airway wall concentration (C awNO) and the diffusion rate of NO (D awNO). Increased values of CANO are shown in COPD, systemic sclerosis, hepatopulmonary syndrome and in severe asthma. In asthma the C awNO and D awNO are increased leading to an increase in bronchial NO flux (J′ awNO). Low levels of J′ awNO are seen in cystic fibrosis, primary ciliary dyskinesia and in smoking subjects. More studies are needed to evaluate the clinical usefulness of the extended NO analysis, similar to what has been done in systemic sclerosis where a cut-off value has been identified predicting pulmonary function deterioration. © 2012 IOP Publishing Ltd.


Background:Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.Methods:AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.Results:AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.Conclusions:AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.British Journal of Cancer advance online publication 31 March 2016. doi:10.1038/bjc.2016.42 www.bjcancer.com. © 2016 Cancer Research UK


Arnqvist G.,Uppsala University | Tuda M.,Kyushu University
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Although males and females share much of the same genome, selection is often distinct in the two sexes. Sexually antagonistic loci will in theory cause a gender load in populations, because sex-specific selection on a given trait in one sex will compromise the adaptive evolution of the same trait in the other sex. However, it is currently not clear whether such intralocus sexual conflict (ISC) represents a transient evolutionary state, where conflict is rapidly resolved by the evolution of sexual dimorphism (SD), or whether it is a more chronic impediment to adaptation. All else being equal, ISC should manifest itself as correlated evolution between population fitness and SD in traits expressed in both sexes. However, comparative tests of this prediction are problematic and have been unfeasible. Here, we assess the effects of ISC by comparing fitness and SD across distinct laboratory populations of seed beetles that should be well adapted to a shared environment. We show that SD in juvenile development time, a key life-history trait with a history of sexually antagonistic selection in this model system, is positively related to fitness. This effect is due to a correlated evolution between population fitness and development time that is positive in females but negative in males. Loosening the genetic bind between the sexes has evidently allowed the sexes to approach their distinct adaptive peaks. © 2009 The Royal Society.


Savolainen O.,University of Oulu | Lascoux M.,Uppsala University | Merila J.,University of Helsinki
Nature Reviews Genetics | Year: 2013

It is increasingly important to improve our understanding of the genetic basis of local adaptation because of its relevance to climate change, crop and animal production, and conservation of genetic resources. Phenotypic patterns that are generated by spatially varying selection have long been observed, and both genetic mapping and field experiments provided initial insights into the genetic architecture of adaptive traits. Genomic tools are now allowing genome-wide studies, and recent theoretical advances can help to design research strategies that combine genomics and field experiments to examine the genetics of local adaptation. These advances are also allowing research in non-model species, the adaptation patterns of which may differ from those of traditional model species. © 2013 Macmillan Publishers Limited.


Liu Y.,Uppsala University
Molecular & cellular proteomics : MCP | Year: 2011

Western blotting is a powerful and widely used method, but limitations in detection sensitivity and specificity, and dependence upon high quality antibodies to detect targeted proteins, are hurdles to overcome. The in situ proximity ligation assay, based on dual antibody recognition and powerful localized signal amplification, offers increased detection sensitivity and specificity, along with an ability to identify complex targets such as phosphorylated or interacting proteins. Here we have applied the in situ proximity ligation assay mechanism in Western blotting. This combination allowed the use of isothermal rolling circle amplification of DNA molecules formed in target-specific ligation reaction, for 16-fold or greater increase in detection sensitivity. The increased specificity because of dual antibody recognition ensured highly selective assays, detecting the specific band when combinations of two cross-reactive antitubulin antibodies were used (i.e. both producing distinct nonspecific bands in traditional Western blotting). We also demonstrated detection of phosphorylated platelet-derived growth factor receptor β by proximity ligation with one antibody directed against the receptor and another directed against the phosphorylated tyrosine residue. This avoided the need for stripping and re-probing the membrane or aligning two separate traditional blots. We demonstrate that the high-performance in situ proximity ligation-based Western blotting described herein is compatible with detection via enhanced chemiluminescence and fluorescence detection systems, and can thus be readily employed in any laboratory.


Andersson L.,Uppsala University | Andersson L.,Swedish University of Agricultural Sciences
Current Opinion in Genetics and Development | Year: 2013

The phenotypic diversity in domestic animals provides a unique opportunity to study genotype-phenotype relationships. The identification of causal mutations provides an insight into what types of mutations have contributed to phenotypic evolution in domestic animals. Whole genome sequencing has revealed that fixation of null alleles that inactivate genes, which are essential under natural conditions but disadvantageous on the farm, has not been a common mechanism for genetic adaptation in domestic animals. Numerous examples have been revealed where structural changes cause specific phenotypic effects by altering transcriptional regulation. An emerging feature is also the evolution of alleles by the accumulation of several consecutive mutations which affect gene function. © 2013 Elsevier Ltd.


Wehling T.O.,University of Bremen | Black-Schaffer A.M.,Uppsala University | Balatsky A.V.,NORDITA | Balatsky A.V.,Los Alamos National Laboratory
Advances in Physics | Year: 2014

A wide range of materials, like d-wave superconductors, graphene, and topological insulators, share a fundamental similarity: their low-energy fermionic excitations behave as massless Dirac particles rather than fermions obeying the usual Schrödinger Hamiltonian. This emergent behavior of Dirac fermions in condensed matter systems defines the unifying framework for a class of materials we call "Dirac materials." In order to establish this class of materials, we illustrate how Dirac fermions emerge in multiple entirely different condensed matter systems and we discuss how Dirac fermions have been identified experimentally using electron spectroscopy techniques (angle-resolved photoemission spectroscopy and scanning tunneling spectroscopy). As a consequence of their common low-energy excitations, this diverse set of materials shares a significant number of universal properties in the low-energy (infrared) limit. We review these common properties including nodal points in the excitation spectrum, density of states, specific heat, transport, thermodynamic properties, impurity resonances, and magnetic field responses, as well as discuss many-body interaction effects. We further review how the emergence of Dirac excitations is controlled by specific symmetries of the material, such as time-reversal, gauge, and spin-orbit symmetries, and how by breaking these symmetries a finite Dirac mass is generated. We give examples of how the interaction of Dirac fermions with their distinct real material background leads to rich novel physics with common fingerprints such as the suppression of back scattering and impurity-induced resonant states. © 2014 Taylor & Francis.


Budd G.E.,Uppsala University
Current Genomics | Year: 2013

The certain fossil record of animals begins around 540 million years ago, close to the base of the Cambrian Period. A series of extraordinary discoveries starting over 100 years ago with Walcott's discovery of the Burgess Shale has accelerated in the last thirty years or so with the description of exceptionally-preserved Cambrian fossils from around the world. Such deposits of "Burgess Shale Type" have been recently complemented by other types of exceptional preservation. Together with a remarkable growth in knowledge about the environments that these early animals lived in, these discoveries have long exerted a fascination and strong influence on views on the origins of animals, and indeed, the nature of evolution itself. Attention is now shifting to the period of time just before animals become common, at the base of the Cambrian and in the preceding Ediacaran Period. Remarkable though the Burgess Shale deposits have been, a substantial gap still exists in our knowledge of the earliest animals. Nevertheless, the fossils from this most remarkable period of evolutionary history continue to exert a strong influence on many aspects of animal evolution, not least recent theories about developmental evolution. ©2013 Bentham Science Publishers.


For most of the 20th century, the Nile River has been the source of political tensions and low-intensity conflicts among three of its major riparian countries (Ethiopia, Sudan and Egypt). However, since the late 1990s, the Nile basin countries-with the encouragement and support of the international community-have made some attempts to establish basin-wide cooperative institutions. This process of engagement and collaboration is presently under severe stress due to increasing demand and decreasing supply of water resources in the basin. This situation may be complicated further by the global climate change, which is anticipated to result in long-term changes in the volume and pattern of runoff in the Nile River system. Moreover, the emergence of China as a major player in the power politics of the Nile basin has facilitated a number of unilateral initiatives for large-scale water development projects. In this context, this paper critically examines the survival and sustainability of water cooperation endeavours in the Nile basin as the river faces challenges from the global climate change and shifting regional geo-politics. © 2011 IAHS Press.


Phillipson M.,Uppsala University | Kubes P.,University of Calgary
Nature Medicine | Year: 2011

Here we focus on how neutrophils have a key regulatory role in vascular inflammation. Recent studies using advanced imaging techniques have yielded new insights into the mechanisms by which neutrophils contribute to defense against bacterial infections and also against sterile injury. In these settings, neutrophils are recruited by various mechanisms depending on the situation. We also describe how these processes may be disrupted in systemic infections, with a particular emphasis on mouse models of sepsis. Neutrophils are often immobilized in the lungs and liver during systemic infections, and this immobilization may be a mechanism through which bacteria can evade the innate immune response or allow neutrophils to form neutrophil extracellular traps that trap and kill bacteria in blood. The platelet is also an important player in sepsis, and we describe how it collaborates with neutrophils in the formation of neutrophil extracellular traps. © 2011 Nature America, Inc. All rights reserved.


Sjoqvist E.,Uppsala University
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2010

The concept of relative state is used to introduce geometric phases that originate from correlations in states of composite quantum systems. In particular, we identify an entanglement-induced geometric phase in terms of a weighted average of geometric phase factors associated with a decomposition that define the entanglement of formation. An explicit procedure to calculate the entanglement-induced geometric phase for qubit pairs is put forward. We illustrate it for maximally entangled mixed states (MEMS) of two qubits. © 2010 Elsevier B.V. All rights reserved.


Early Cambrian acritarchs from the Lukati Formation of Estonia are described, based on new material, and their biological affinities reviewed. The phenotypical variants and the inferred function of their vesicles are indicative for recognising zygotic/resting cysts and vegetative cells. They represent the Chlorophytes in the class Prasinophyceae, which reproduce asexually (forming resting phycoma cysts), and Chlorophyceae, which reproduce sexually (zygotic cysts). Some species had a complex life cycle, with alternating vegetative and reproductive generations that differed morphologically. Based on acritarch records from the Baltica palaeocontinent, of which the Lukati Formation assemblage is a part, and the global PhytoPal Taxonomic Database (PhytoPal Project, Leverhulme Trust, Leicester University, 2003-2006), the early Cambrian diversification of phytoplankton is reviewed. The initial Cambrian diversification, and a recovery after the end-Ediacaran extinction, was rapid and exhibited a stepwise pattern of radiation episodes covering short intervals equivalent to biochrons lasting a few million years, estimated from the numerical ages of the strata containing them and the current time scale of the early Cambrian. However, the first appearance datum (FAD) of new species within the biozones/biochrons appears in a succession rather than at one stratigraphical level, indicating true biological speciations. The only genera surviving from the Proterozoic Eon are Leiosphaeridia, Tasmanites, Pterospermella and Pterospermopsimorpha; these are Lazarus genera radiating new species in the early Cambrian. All other Cambrian genera and species are new, morphologically innovative, and much smaller. © 2011 AASP - The Palynological Society.


Af Wahlberg A.E.,Uppsala University
Journal of Safety Research | Year: 2010

Introduction: Offending drivers are often re-educated, but these courses have seldom been shown to have any safety effects. Method: An on-line improvement course for offending drivers below the age of 25 was evaluated with several driver inventories. Results: The drivers reported higher levels of aggression, stress, sensation seeking, drunk driving, and driving violations, six months after the course than before. However, these levels were lower than those of controls, indicating that the initially low levels for the education group were due to socially desirable responding, as measured by a lie scale, an effect that waned after the course. Discussion: The results can be interpreted as a positive effect of the education, although this conclusion is tentative and not in agreement with all effects in the data. Impact on industry: The results are in disagreement with previous evaluation studies using the same or similar instruments, and show the need to include controls for social desirability in self-report studies. © 2010 National Safety Council and Elsevier Ltd.


Demandt M.H.,Uppsala University
Conservation Genetics | Year: 2010

Genetic drift, together with natural selection and gene flow, affects genetic variation and is the major source of changes in allele frequencies in small and isolated populations. Temporal shifts in allele frequencies at five polymorphic loci were used to estimate the amount of genetic drift in an isolated population of perch (Perca fluviatilis L.) and roach (Rutilus rutilus L.). Here, I used the populations from the Biotest basin at Forsmark, Sweden, to investigate genetic diversity between 1977 and 2000, during which time the population can be considered to be totally isolated from other populations. Microsatellite data reveal stable levels of gene diversity over time for both species. Estimates of genetic differentiation (FST) showed a significant divergence between 1977 and 2000 for both perch and roach. A positive correlation between genetic distance and time was found (Mantel test, perch: r = 0.724, P = 0.0112; roach: r = 0.59, P = 0.036). Estimates of effective population size (Ne) differed with a factor six between two different estimators (NeEstimator and TempoFS) applying the temporal method. Ratios of Ne/N ranged between 10-2 and 10-3, values normally found in marine species. Despite low Ne the populations have not lost their evolutionary potential due to drift. But two decades of isolation have lead to isolation by time for populations of perch and roach, respectively. © Springer Science+Business Media B.V. 2010.


The half-life of factor VIII (FVIII) increases with the age of the patient, while studies on recombinant factor IX (rFIX) and factor VIIa (rFVIIa) have not demonstrated corresponding age-related changes. The purpose of this analysis was to relate the changes in FVIII and rFIX pharmacokinetics (PK) with age to developmental changes in body size and fluid volumes and explain why the elimination half-life of FVIII, but not of rFIX, would change with age, and to consider how the findings could be applied prospectively to other coagulation factors. Published PK data for FVIII from 186 patients aged 1-74 years and for rFIX from 56 patients aged 4-56 years were used. The relationships of FVIII and rFIX clearance (CL) with body weight could be described by allometric expressions. Relative changes in CL with age or weight were similar for FVIII and rFIX. The age-related change in volume of distribution at steady state (Vss) of rFIX was parallel to the change in CL in the children while for FVIII the change was much less pronounced. Elimination half-life was clearly age-dependent for FVIII while only a very weak trend could be seen for rFIX. Limited data suggest that rFVIIa in this respect resembles rFIX, with parallel changes in CL and Vss producing insignificant change in half-life. To what extent the elimination half-life of a coagulation factor would show a correlation with age can in principle be predicted from the characteristics of its CL and distribution. © 2013 John Wiley & Sons Ltd.


Collins G.S.,University of Oxford | Michaelsson K.,Uppsala University
Current Osteoporosis Reports | Year: 2012

Osteoporotic fractures, including hip fractures, are a global health concern associated with significant morbidity and mortality as well as a major economic burden. Identifying individuals who are at an increased risk of osteoporotic fracture is an important challenge to be resolved. Recently, multivariable prediction tools have been developed to assist clinicians in the management of their patients by calculating their 10-year risk of fracture (FRAX, QFracture, Garvan) using a combination of known risk factors. These prediction models have revolutionized the way clinicians assess the risk of fracture. Studies evaluating the performance of prediction models in this and other areas of medicine have, however, been characterized by poor design, methodological conduct, and reporting. We examine recently developed fracture prediction models and critically discuss issues in their design, validation, and transparency. © Springer Science+Business Media, LLC 2012.


Falck-Ytter T.,Uppsala University
Biology Letters | Year: 2010

Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goaldirected actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others' actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand-object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS. © 2009 The Royal Society.


Despite the importance of the emotional attachment to land among landowners affected by Soviet collectivisation, relatively few studies have focused on this question. In Estonia, the land restitution process in the 1990s made it possible to return nationalised property to its former owners or their heirs. Many of these now live abroad or in other parts of the country. This paper shows that the opportunity to own restituted property may create strong emotional bonds to land. This study also attempts to discuss what these bonds mean to different categories of landowners and how this can affect attitudes to land and plans for the future. The study is based on a postal survey and interviews. One implication of a strong attachment to land can be reluctance to sell the land. A group of absentee owners wants to keep the land as preventive owners without using it. This non-active land ownership has implications for the area, with its potential for tourism and second homes. A historically rooted emotional attachment to land among owners of restituted property is most common among the locals and the Swedish owners. Memories associated with the land in question are identified as one important aspect of the evolvement of such emotional bonds. On the basis of the results I argue that those among the next generation of absentee owners who lack these kinds of memories could be more inclined to sell family land in the future. © 2010 Elsevier B.V.


Moczydlowska M.,Uppsala University
Journal of Paleontology | Year: 2010

Light microscopy studies on new materials and museum collections of early Cambrian organic-walled microfossils, informally called acritarchs, provide the observations on phenetic features that permit a comparison to certain Modern microalgae and the recognition of various developmental stages in their life cycle. The microfossils derive from various depositional settings in Estonia, Australia, Greenland, Sweden, and Poland. The exceptionally preserved microfossils reveal the internal body within the vesicle, the endocyst, and the process of releasing the endocyst from the cyst. Vegetative cells, cysts, and endocysts are distinguished, and the hypothetical reconstruction of a complex life cycle with the alternation of sexual and asexual generations is proposed. Acritarchs from the Skiagia-plexus are cysts, and likely zygotes in the sexual generation, which periodically rested as "benthic plankton." Some microfossils of the Leiosphaeridia-plexus that are inferred to be vegetative cells were planktonic and probably haplobiontic. These form-taxa may belong to a single biological species, or a few closely related species, and represent the developmental stages and alternating generations in a complex life cycle that is expressed by polymorphic, sphaero- and acanthomorphic acritarchs. The morphological resemblance and diagnostic cell wall ultrastructure with the trilaminar sheath structure known from earlier studies suggest that the early Cambrian microfossils are the ancestral representatives and/or early lineages to the Modern class Chlorophyceae and the orders Volvocales and Chlorococcales. © 2010 The Paleontological Society.


Hedenstierna G.,Uppsala University
Minerva Anestesiologica | Year: 2012

Te recording of esophageal pressure (Pes) in supine position as a substitute for pleural pressure is difficult and fraught with potential errors. Pes is affected by the: 1) elastance and weight of the lung; 2) elastance and weight of the rib cage; 3) weight of the mediastinal organs; 4) elastance and weight of the diaphragm and abdomen; 5) elastance of the esophageal wall; and 6) elastance of the esophageal balloon (if filled with too much air). If the purpose is to measure lung compliance in the intensive care patient, reasonably useful information might be obtained by measuring airway pressure alone, considering chest wall compliance to be a weight that is forced away by the ventilation. Such weight requires a constant pressure for displacement. Te transpulmonary pressure, whether calculated with Pes or by another measure of abdominal pressure, may guide in PEEP titration. It may also enable calculation of stresses applied to the lung and these may be more important in guiding an optimal ventilator setting than an optimum compliance or oxygenation of blood. Diaphragm function can be estimated by esophageal minus gastric pressure and with even more precision, when combined with diaphragm electromyography. © 2012 EDIZIONI MINERVA MEDICA.


The analytic signal concept can be applied to gravity gradient tensor data in three dimensions. Within the gravity gradient tensor, the horizontal and vertical derivatives of gravity vector components are Hilbert transform pairs. Three analytic signal functions then are introduced along x-, y-, and z-directions. The amplitude of the first vertical derivative of the analytic signals in x- and y-directions enhances the edges of causative bodies. The directional analytic signals are homogenous and satisfy Euler's homogeneity equation. The application of directional analytic signals to Euler deconvolution on generic models demonstrates their ability to locate causative bodies. One of the advantages of this method is that it allows the automatic identification of the structural index from solving three Euler equations derived from the gravity gradient tensor for a collection of data points in a window. The other advantage is a reduction of interference effects from neighboring sources by differentiation of the directional analytic signals in x-, y-, and z-directions. Application of the method is demonstrated on gravity gradient tensor data in the Vredefort impact structure, South Africa. © 2010 Society of Exploration Geophysicists.


Krokhotin A.,Uppsala University
The Journal of chemical physics | Year: 2012

A heterodimer consisting of two or more different kinds of proteins can display an enormous number of distinct molecular architectures. The conformational entropy is an essential ingredient in the Helmholtz free energy and, consequently, these heterodimers can have a very complex phase structure. Here, it is proposed that there is a state of proteins, in which the different components of a heterodimer exist in different phases. For this purpose, the structures in the protein data bank (PDB) have been analyzed, with radius of gyration as the order parameter. Two major classes of heterodimers with their protein components coexisting in different phases have been identified. An example is the PDB structure 3DXC. This is a transcriptionally active dimer. One of the components is an isoform of the intra-cellular domain of the Alzheimer-disease related amyloid precursor protein (AICD), and the other is a nuclear multidomain adaptor protein in the Fe65 family. It is concluded from the radius of gyration that neither of the two components in this dimer is in its own collapsed phase, corresponding to a biologically active protein. The UNRES energy function has been utilized to confirm that, if the two components are separated from each other, each of them collapses. The results presented in this work show that heterodimers whose protein components coexist in different phases, can have intriguing physical properties with potentially important biological consequences.


Af Wahlberg A.E.,Uppsala University
Journal of Safety Research | Year: 2011

Problem: It has been claimed that exposure to risk of road traffic accidents (usually conceptualized as mileage) is curvilinearly associated with crashes (i.e., the increase in number of crashes decreases with increased mileage). However, this effect has been criticized as mainly an artifact of self-reported data. Method: To test the proposition that self-reported accidents create part of the curvilinearity in data by under-reporting by high-accident drivers, self-reported and recorded collisions were plotted against hours of driving for bus drivers. Results: It was found that the recorded data differed from self-reported information at the high end of exposure, and had a more linear association with the exposure measure as compared to the self-reported data, thus supporting the hypothesis. Discussion: Part of the previously reported curvilinearity between accidents and exposure is apparently due to biased methods. Also, the interpretation of curvilinearity as an effect of exposure upon accidents was criticized as unfounded, as the causality may just as well go the other way. Impact on industry: The question of how exposure associates with crash involvement is far from resolved, and everyone who uses an exposure metric (mileage, time, induced) should be careful to investigate the exact properties of their variable before using it. © 2011 National Safety Council and Elsevier Ltd. All rights reserved.


Soderstrom T.,Uppsala University | Mossberg M.,Karlstad University
Automatica | Year: 2011

A system identification method for errors-in-variables problems based on covariance matching was recently proposed. In the first step, a small amount of covariances of noisy inputoutput data are computed, and then a parametric model is fitted to these covariances. In this paper, the method is further analyzed and the asymptotic accuracy of the parameter estimates is derived. An explicit algorithm for computing the asymptotic covariance matrix of the parameter estimates is given, and the identification method is shown to be asymptotically statistically efficient assuming that the given information is the computed covariances. As an important byproduct, an efficient algorithm is presented for computing the covariance matrix of the computed inputoutput covariances. © 2010 Elsevier Ltd. All rights reserved.


Andersson D.I.,Uppsala University
Clinical Microbiology and Infection | Year: 2015

The methods used today by academic researchers and the pharmaceutical industry to assess the risk of emergence of resistance, for example during development of new antibiotics or when assessing an old antibiotic, are sub-optimal. Even though easy to perform, the presently used serial passage procedures, minimal prevention concentration measurements and determination of mutation rates in vitro are generally providing inadequate knowledge for risk assessment and making decisions to continue/discontinue drug development. These methods need to be complemented and replaced with more relevant methods such as determination of whether resistance genes already pre-exist in various metagenomes, and the likelihood that these genes can transfer into the relevant pathogens and be stably maintained. Furthermore, to determine the risk of emergence of mutationally conferred resistance the fitness effect of the resistance mechanism is key, as this parameter will determine the ability of the resistant mutants to be maintained and enriched in the host after they have emerged. This information combined with knowledge of bacterial population sizes and growth and killing dynamics at relevant infection sites should allow for better forecasting of the risk of resistance emerging in clinical settings. © 2015 European Society of Clinical Microbiology and Infectious Diseases.


A large (maximum length 80mm), tubular, corset-like problematic fossil from the early Cambrian (Cambrian Series 2, Stage 3) Sirius Passet Lagerstätte of North Greenland is interpreted as the lorica of an ancestral loriciferan. In addition to the double circlet of 7 plates composing the lorica, Sirilorica carlsbergi new genus, new species also preserves up to six multicuspidate cuticular denticles that are similar in shape to the pharyngeal teeth of priapulid worms, although their location is suggestive of scalids. Whilst traditionally placed as a sister group of priapulid worms within Vinctiplicata (Scalidophora), recent molecular sequence data suggest that loriciferans might be more closely related to nematomorphs. The limited morphological information available from Sirilorica is consistent with this interpretation, placing the Sirius Passet fossil within the total-group of Loricifera, within the Loricifera Nematomorpha clade. © 2010 The Paleontological Society.


Francis R.M.,Uppsala University
Molecular Ecology Resources | Year: 2016

The pophelper r package and web app are software tools to aid in population structure analyses. They can be used for the analyses and visualization of output generated from population assignment programs such as admixture, structure and tess. Some of the functions include parsing output run files to tabulate data, estimating K using the Evanno method, generating files for clumpp and functionality to create barplots. These functions can be streamlined into standard r analysis workflows. The latest version of the package is available on github (https://github.com/royfrancis/pophelper). An interactive web version of the pophelper package is available which covers the same functionalities as the r package version with features such as interactive plots, cluster alignment during plotting, sorting individuals and ordering of population groups. © 2016 John Wiley & Sons Ltd.


Nordblad P.,Uppsala University
Physica Scripta | Year: 2013

What does the equilibrium atomic, molecular or spin configuration of a glass phase look like? Is there only one unique equilibrium configuration or are there infinitely many configurations of equal energy? The processes and mechanisms governing the path towards equilibrium, i.e. the dynamics of glassy systems, provide insights to these questions. Here we discuss the intrinsic dynamics of different glassy magnets: of spin-glasses, frustrated ferromagnets, superspin-glasses and other nanostructured systems with competing ferro- and antiferromagnetic interactions and randomness in their spatial distribution. This paper is intended as a brief update on some unsolved problems and the current empirical status in the field of disordered and frustrated magnetism. © 2013 The Royal Swedish Academy of Sciences.


Summary: Plasma-derived (pd) and recombinant (r) factor IX (FIX) differ in pharmacokinetic (PK) properties. These differences and their clinical implications have been debated since the introduction of rFIX. The aim of this review was to describe the comparative disposition of pdFIX and rFIX and will for this purpose begin with an overview of population PK modelling. In contrast to the model-independent method, a population PK model can analyse sparse data sets obtained in various settings, provide parameter values that can be used to predict coagulation factor levels with any kind of single or multiple dosing and include statistical analysis of variation between individuals. Population modelling has also clearly demonstrated the difference in PK between pdFIX and rFIX. Their distribution characteristics influence the FIX coagulant activity (FIX:C) level vs. time curve during the early hours after infusion. In vivo recovery and elimination half-life are consequently not adequate descriptors of the effective PK of FIX, and for new analogues with modified PK, differences in distribution might be clinically important. Calculated doses to maintain 1% trough levels during twice-weekly prophylactic treatment are considerably higher with rFIX than with pdFIX and roughly correspond to dosing in clinical studies. However, the putative relationship between FIX:C trough level and therapeutic outcome has never been confirmed in a clinical trial. Comparative studies on prophylaxis with different types of FIX are needed. © 2013 John Wiley & Sons Ltd.


Lundberg M.,Uppsala University | Borowski T.,Polish Academy of Sciences
Coordination Chemistry Reviews | Year: 2013

Mononuclear non-heme iron enzymes perform a wide range of chemical reactions. Still, the catalytic mechanisms are usually remarkably similar, with formation of a key oxoferryl (Fe(IV)O) intermediate through two well-defined steps. First, two-electron reduction of dioxygen occurs to form a peroxo species, followed by OO bond cleavage. Even though the peroxo species have different chemical character in various enzyme families, the analogies between different enzymes in the group make it an excellent base for investigating factors that control metal-enzyme catalysis. We have used density-functional theory to model the complete chemical reaction mechanisms of several enzymes, e.g., for aromatic and aliphatic hydroxylation, chlorination, and oxidative ring-closure. Reactivity of the Fe(IV)O species is discussed with focus on electronic and steric factors determining the preferred reaction path. Various spin states are compared, as well as the two reaction channels that stem from involvement of different frontier molecular orbitals of Fe(IV)O. Further, the two distinctive species of Fe(IV)O, revealed by Mössbauer spectroscopy, and possibly relevant for specificity of aliphatic chlorination, can be identified. The stability of the modeling results have been analyzed using a range of approaches, from active-site models to multi-scale models that include classical free-energy contributions. Large effects from an explicit treatment of the protein matrix (∼10kcal/mol) can be observed for O 2 binding, electron-transfer and product release. © 2012 Elsevier B.V..


Black-Schaffer A.M.,Uppsala University | Balatsky A.V.,NORDITA | Balatsky A.V.,Los Alamos National Laboratory
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

We study and classify the proximity-induced superconducting pairing in a topological insulator (TI)-superconductor (SC) hybrid structure for SCs with different symmetries. The Dirac surface state gives a coupling between spin-singlet and spin-triplet pairing amplitudes as well as pairing that is odd in frequency for p-wave SCs. We also find that all SCs induce pairing that is odd in both frequency and orbital (band) index, with oddness in frequency and orbital index being completely interchangeable. The different induced pairing amplitudes significantly modify the density of states in the TI surface layer. © 2013 American Physical Society.


D'Arcy P.,Karolinska Institutet | Linder S.,Karolinska Institutet | Linder S.,Uppsala University
Clinical Cancer Research | Year: 2014

The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS coupled with the clinical success of bortezomib for the treatment of multiple myeloma have made the UPS an obvious target for drug development. Deubiquitinases (DUB) are components of the UPS that encompass a diverse family of ubiquitin isopeptidases that catalyze the removal of ubiquitin moieties from target proteins or from polyubiquitin chains, resulting in altered signaling or changes in protein stability. Increasing evidence has implicated deregulation of DUB activity in the initiation and progression of cancer. The altered pattern of DUB expression observed in many tumors can potentially serve as a clinical marker for predicting disease outcome and therapy response. The finding of DUB overexpression in tumor cells suggests that they may serve as novel targets for the development of anticancer therapies. Several specific and broad-spectrum DUB inhibitors are shown to have antitumor activity in preclinical in vivo models with low levels of systemic toxicity. Future studies will hopefully establish the clinical potential for DUB inhibitors as a strategy to treat cancer. © 2014 American Association for Cancer Research.


Dudai Y.,Weizmann Institute of Science | Evers K.,Uppsala University
Neuron | Year: 2014

Simulation is a powerful method in science and engineering. However, simulation is an umbrella term, and its meaning and goals differ among disciplines. Rapid advances in neuroscience and computing draw increasing attention to large-scale brain simulations. What is the meaning of simulation, and what should the method expect to achieve? We discuss the concept of simulation from an integrated scientific and philosophical vantage point and pinpoint selected issues that are specific to brain simulation. Are we on the long and winding road to simulation of the human brain? Dudai and Evers provide a realistic conjoint view of a neuroscientist and a philosopher on the concept of simulation and its complex pragmatics in brain research. © 2014 Elsevier Inc.


Nyberg F.,Uppsala University
Neuropharmacology | Year: 2014

Over the past years it has become evident that repeated exposure to a variety of psychoactive stimulants, like amphetamine, cocaine, MDMA (3,4-methylenedioxy-N-methylamphetamine), methylphenidate and nicotine may produce profound behavioral changes as well as structural and neurochemical alterations in the brain that may persist long after drug administration has ceased. These stimulants have been shown to produce long-lasting enhanced embranchments of dendrites and increasing spine density in brain regions linked to behavioral sensitization and compulsive patterns characteristic of drug seeking and drug addiction. In this regard, addiction to stimulant drugs represents a compulsory behavior that includes drug seeking, drug use and drug craving, but is also characterized as a cognitive disorder. In this article, recent findings regarding the impact of central stimulants on plasticity in brain regions of relevance for addictive behavior will be highlighted. A particular focus will be given to changes in neuroplasticity that occur in areas related to memory and cognition. Possible routes for the reversal of altered brain plasticity will also be discussed. This article is part of the Special Issue entitled 'CNS Stimulants'. © 2014 Elsevier Ltd.


Malmborg H.,Uppsala University
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2013

The urge to facilitate the atrial fibrillation (AF) ablation procedure has led to the development of new ablation catheters specifically designed as 'one-shot tools' for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficacy, safety, and procedure times for two such catheters using different energy sources. One hundred and ten patients, referred for ablation of paroxysmal or persistent AF, were randomized to treatment with either the cryoballoon or the circular multipolar duty-cycled radiofrequency-based pulmonary vein ablation catheter (PVAC). Complete PVI was achieved in 98 vs. 93% patients in the cryoballoon and PVAC group, respectively, with complication rates of 8 vs. 2% (P = 0.2). Complete freedom from AF, without antiarrhythmic drugs, after one single ablation procedure was seen in 46% in the cryoballoon vs. 34% after 12 months (P = 0.2). Procedure times were comparable, but fluoroscopy time was shorter for the cryoballoon (32 ± 16 min) than for the PVAC procedures (47 ± 17 min) (P < 0.001). A significant improvement of quality of life (QoL) and arrhythmia-related symptoms was seen in both groups after ablation. Both catheters proved comparably effective and safe in achieving acute PVI, apart from the shorter fluoroscopy times achieved with the cryoballoon. At follow-up, there was no statistically significant difference between the groups regarding freedom from AF and clinical success. The QoL increased to the same levels as for the general Swedish population in both groups.


Kuutmann K.,Uppsala University | Hilsenroth M.J.,Adelphi University
Clinical Psychology and Psychotherapy | Year: 2012

This study explored the amount of in-session focus on the patient-therapist relationship during early treatment with patient pre-treatment interpersonal style, personality pathology, patient ratings of session process and outcome. The sample consisted of 76 outpatients engaged in short-term psychodynamic psychotherapy. Results showed that higher levels of pre-treatment personality pathology and interpersonal problems were positively related to a greater focus on the patient-therapist relationship early in treatment. This was especially true for patients with a cold/distant interpersonal style and low self-esteem. Moreover, these two patient pre-treatment characteristics demonstrated a significant change over the course of therapy. These post-treatment changes also demonstrated a significant relationship with greater early treatment focus on the patient-therapist relationship. In addition, we found an interaction effect between quality of object relations (i.e., higher levels of object relations) and greater early treatment focus on the patient-therapist relationship with subsequent changes in patient cold/distant interpersonal problems. Greater in-session focus on the therapeutic relationship was not significantly related to patient ratings of session process. Implications for clinical practice and future research are discussed. © 2011 John Wiley & Sons, Ltd.


Kallen J.,Uppsala University
Journal of High Energy Physics | Year: 2011

We generalize the framework introduced by Kapustin et al. for doing path integral localization in Chern-Simons theory to work on any Seifert manifold. This is done by topologically twisting the supersymmetric theory considered by Kapustin et al., after which the theory takes a cohomological form. We also consider Wilson loops which wrap the fiber directions and compute their expectation values. We discuss the relation with other approaches to exact path integral calculations in Chern-Simons theory. © SISSA 2011.


De Boer J.,University of Amsterdam | Kulaxizi M.,Uppsala University | Parnachevc A.,University of Barcelona
Journal of High Energy Physics | Year: 2011

We study entanglement entropies of simply connected surfaces in field theories dual to Lovelock gravities. We consider Gauss-Bonnet and cubic Lovelock gravities in detail. In the conformal case the logarithmic terms in the entanglement entropy are governed by the conformal anomalies of the CFT; we verify that the holographic calculations are consistent with this property. We also compute the holographic entanglement entropy of a slab in the Gauss-Bonnet examples dual to relativistic and non-relativistic CFTs and discuss its properties. Finally, we discuss features of the entanglement entropy in the backgrounds dual to renormalization group flows between fixed points and comment on the implications for a possible c-theorem in four spacetime dimensions.


Barklem P.S.,Uppsala University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2016

A theoretical method is presented for the estimation of cross sections and rates for excitation and charge-transfer processes in low-energy hydrogen-atom collisions with neutral atoms, based on an asymptotic two-electron model of ionic-covalent interactions in the neutral atom-hydrogen-atom system. The calculation of potentials and nonadiabatic radial couplings using the method is demonstrated. The potentials are used together with the multichannel Landau-Zener model to calculate cross sections and rate coefficients. The main feature of the method is that it employs asymptotically exact atomic wave functions, which can be determined from known atomic parameters. The method is applied to Li+H, Na+H, and Mg+H collisions, and the results compare well with existing detailed full-quantum calculations. The method is applied to the astrophysically important problem of Ca+H collisions, and rate coefficients are calculated for temperatures in the range 1000-20 000 K. © 2016 American Physical Society.


Ronnblom L.,Uppsala University | Elkon K.B.,University of Washington
Nature Reviews Rheumatology | Year: 2010

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving most immune cells. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. Among these are B-cell activating factor, which promotes B-cell survival and autoantibody production, interferon-α, which acts as an immune adjuvant, and tumor necrosis factor, which contributes to organ inflammation. This knowledge, in combination with the successful use of anti-TNF treatment in rheumatoid arthritis, has spurred the development of several biologic agents targeting different cytokines or their receptors in SLE. Consequently, many trials of anticytokine therapies for SLE are underway. Although most of these trials are small or in early phases, the results of some large studies have also been reported. In this Review, we discuss the rationale for anticytokine therapies in SLE and review agents currently in use, and those being developed and tested experimentally. We present the results from published trials and discuss the tentative conclusions that can be drawn regarding the efficacy of the new agents. Finally, we provide suggestions for the future of treatment for SLE, including new therapeutic strategies. © 2010 Macmillan Publishers Limited. All rights reserved.


Ossipov D.A.,Uppsala University
Expert Opinion on Drug Delivery | Year: 2015

Introduction: Bisphosphonates (BPs) were introduced 45 years ago as anti-osteoporotic drugs and during the last decade have been utilized as bone-targeting groups in systemic treatment of bone diseases. Very recently, strategies of chemical immobilization of BPs in hydrogels and nanocomposites for bone tissue engineering emerged. These strategies opened new applications of BPs in bone tissue engineering.Areas covered: Conjugates of BPs to different drug molecules, imaging agents, proteins and polymers are discussed in terms of specific targeting to bone and therapeutic affect induced by the resulting prodrugs in comparison with the parent drugs. Conversion of these conjugates into hydrogel scaffolds is also presented along with the application of the resulting materials for bone tissue engineering.Expert opinion: Calcium-binding properties of BPs can be successfully extended via different conjugation strategies not only for purposes of bone targeting, but also in supramolecular assembly affording either new nanocarriers or bulk nanocomposite scaffolds. Interaction between carrier-linked BPs and drug molecules should also be considered for the control of release of these molecules and their optimized delivery. Bone-targeting properties of BP-functionalized nanomaterials should correspond to bone adhesive properties of their bulk analogs. © 2015 © Informa UK, Ltd.


Minahan J.A.,Uppsala University
Journal of High Energy Physics | Year: 2011

We discuss supergraphs and their relation to "chiral functions" in N = 4 Super Yang-Mills. Based on the magnon dispersion relation and an explicit three-loop result of Sieg's we make an all loop conjecture for the rational contributions of certain classes of supergraphs. We then apply superspace techniques to the "cubic" branch of Leigh-Strassler N = 1 superconformal theories. We show that there are order 2 L/L single trace operators of length L which have zero anomalous dimensions to all loop order in the planar limit. We then compute the anomalous dimensions for another class of single trace operators we call one-pair states. Using the conjecture we can find a simple expression for the rational part of the anomalous dimension which we argue is valid at least up to and including five-loop order. Based on an explicit computation we can compute the anomalous dimension for these operators to four loops. © SISSA 2011.


Abnormally developing embryos (ADEs) of the common pill millipede Glomeris marginata have been investigated by means of nuclear staining and mRNA in situ hybridization. It showed that all ADEs represent cases of Duplicitas posterior, which means that the posterior body pole is duplicated. The severity of the duplication ranges from duplicated posterior trunk segments in one specimen to an almost completely duplicated specimen that only shares the very anterior head region. Remarkably, none of the encountered ADEs represents a case of Duplicitas anterior (duplicated anterior pole) or a case of Duplicitas cruciata (cruciate duplication with two anterior and two posterior poles). This observation is discussed in the light of earlier reports on G. marginata ADEs that claim to have found these abnormalities. The lack of any other axial abnormality aside from D. posterior implies that early axis determination in G. marginata, and possibly myriapods in general, underlies the developmental mechanisms that prevent the formation of any other type of axial duplication. It is proposed that the formation of D. posterior-type embryos could be caused by the formation of two instead of only one posterior cumulus early during development. © 2012 Springer-Verlag Berlin Heidelberg.


Abbott J.K.,Uppsala University
Proceedings of the Royal Society B: Biological Sciences | Year: 2011

Intra-locus sexual conflict results when sex-specific selection pressures for a given trait act against the intra-sexual genetic correlation for that trait. It has been found in a wide variety of taxa in both laboratory and natural populations, but the importance of intra-locus sexual conflict and sexually antagonistic genetic variation in hermaphroditic organisms has rarely been considered. This is not so surprising given the conceptual and theoretical association of intra-locus sexual conflict with sexual dimorphism, but there is no a priori reason why intra-locus sexual conflict cannot occur in hermaphroditic organisms as well. Here, I discuss the potential for intra-locus sexual conflict in hermaphroditic animals and review the available evidence for such conflict, and for the existence of sexually antagonistic genetic variation in hermaphrodites. I argue that mutations with asymmetric effects are particularly likely to be important in mediating sexual antagonism in hermaphroditic organisms. Moreover, sexually antagonistic genetic variation is likely to play an important role in inter-individual variation in sex allocation and in transitions to and from gonochorism (separate sexes) in simultaneous hermaphrodites. I also describe how sequential hermaphrodites may experience a unique form of intra-locus sexual conflict via antagonistic pleiotropy. Finally, I conclude with some suggestions for further research. © 2010 The Royal Society.


Odeen A.,Uppsala University | Hastad O.,Swedish University of Agricultural Sciences
BMC Evolutionary Biology | Year: 2013

Background: Colour vision in birds can be categorized into two classes, the ultraviolet (UVS) and violet sensitive (VS). Their phylogenetic distributions have traditionally been regarded as highly conserved. However, the complicated nature of acquiring spectral sensitivities from cone photoreceptors meant that until recently, only a few species had actually been studied. Whether birds are UVS or VS can nowadays be inferred from a wide range of species via genomic sequencing of the UV/violet SWS1 cone opsin gene. Results: We present genomic sequencing results of the SWS1 gene from 21 avian orders. Amino acid residues signifying UV sensitivity are found in the two most important spectral tuning sites 86 and 90 of Pteroclidiformes and Coraciiformes, in addition to the major clades, Palaeognathae, Charadriiformes, Trogoniformes, Psittaciformes and Passeriformes, where they where previously known to occur. We confirm that the presumed UVS-conferring amino acid combination F86, C90 and M93 is common to Palaeognathae and unique to this clade, despite available spectrometric evidence showing the ostrich retina to be VS. Conclusions: By mapping our results together with data from previous studies on a molecular phylogeny we show that avian colour vision shifted between VS and UVS at least 14 times. Single nucleotide substitutions can explain all these shifts. The common ancestor of birds most likely had a VS phenotype. However, the ancestral state of the avian SWS1 opsin's spectral tuning sites cannot be resolved, since the Palaeognathae are F86, C90 while the Neognathae are ancestrally S86, S90. The phylogenetic distribution of UVS and VS colour vision in birds is so complex that inferences of spectral sensitivities from closely related taxa should be used with caution. © 2013 Ödeen and Håstad; licensee BioMed Central Ltd.


Leproult R.,University of Chicago | Leproult R.,Free University of Colombia | Holmback U.,University of Chicago | Holmback U.,Uppsala University | Van Cauter E.,University of Chicago
Diabetes | Year: 2014

Shift workers, who are exposed to irregular sleep schedules resulting in sleep deprivation and misalignment of circadian rhythms, have an increased risk of diabetes relative to day workers. In healthy adults, sleep restriction without circadian misalignment promotes insulin resistance. To determine whether the misalignment of circadian rhythms that typically occurs in shift work involves intrinsic adverse metabolic effects independently of sleep loss, a parallel group design was used to study 26 healthy adults. Both interventions involved 3 inpatient days with 10-h bedtimes, followed by 8 inpatient days of sleep restriction to 5 h with fixed nocturnal bedtimes (circadian alignment) or with bedtimes delayed by 8.5 h on 4 of the 8 days (circadian misalignment). Daily total sleep time (SD) during the intervention was nearly identical in the aligned and misaligned conditions (4 h 48 min [5 min] vs. 4 h 45 min [6 min]). In both groups, insulin sensitivity (SI) significantly decreased after sleep restriction, without a compensatory increase in insulin secretion, and inflammation increased. In male participants exposed to circadian misalignment, the reduction in SI and the increase in inflammation both doubled compared with those who maintained regular nocturnal bedtimes. Circadian misalignment that occurs in shift work may increase diabetes risk and inflammation, independently of sleep loss. © 2014 by the American Diabetes Association.


Black-Schaffer A.M.,Uppsala University
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

We show that the intrinsic chiral (dx2-y2±id xy)-wave superconducting pairing in doped graphene is significantly strengthened in the core region of a doubly quantized s-wave superconducting vortex produced in a graphene-superconductor hybrid structure. The chiral d-wave state is induced by the proximity effect, which transfers the center-of-mass angular momentum of the s-wave vortex to the orbital angular momentum of the chiral d-wave Cooper pairs. The proximity effect is enhanced by the circular geometry of the vortex and we find a [1+ (T-T c,J)2]-1 temperature dependence for the chiral d-wave core amplitude, where Tc,J is its intrinsic bulk transition temperature. We further propose to detect the chiral d-wave state by studying the temperature dependence of the low-energy local density of states in the vortex core, which displays a sudden radial change as a function of the strength of the d-wave core state. © 2013 American Physical Society.


Purpose of review: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) constitute a diverse group of neoplasms arising from the diffuse neuroendocrine cell system. During the last 2 years a new classification system, the WHO 2010, has come into clinical practice together with Tumor Nodes Metastases (TNM) staging and grading systems, developed by the European Neuroendocrine Tumor Society/American Joint Cancer Committee. At the same time new targeted agents have been developed for treatment of GEP-NETs and it is important discuss these new agents in relation to the classification and staging system. Recent findings: The current article is reviewing the most important clinical trials of targeting agents within the field of neuroendocrine tumors. Tyrosine kinase inhibitors as well as PI3 kinase mTOR inhibitors have been applied in the treatment of neuroendocrine tumors. Summary: Sunitinib and everolimus have recently been registered for treatment of pancreatic neuroendocrine tumors worldwide. The role of these new targeted agents in the treatment algorithm of neuroendocrine tumors will be discussed. A large number of phase I and phase II trials have been performed in GEP-NETs with rather limited results and no significant impact on the clinical management of patients with GEP-NETs. However, there are two phase III trials that have completely changed the treatment landscape for pancreatic neuroendocrine tumors, e.g., sunitinib and everolimus demonstrating an increased progression free survival of 11 vs. 5 months for the placebo group. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Janssen R.,Uppsala University
Evolution and Development | Year: 2011

All trunk segments in the pill millipede Glomeris marginata (Myriapoda: Diplopoda) are initially patterned genetically, (as visualized by the embryonic expression pattern of the even-skipped gene) and formed morphologically, (as visualized by 4-6-diamidin-2-phenylindol stained embryos) in a single segmental period. In addition, formation of every nascent trunk segment concerns ventral as well as dorsal segmental units. Only after the formation of the nascent posterior trunk segments, the dorsal segmental units of two adjacent segments fuse to form a single dorsal segmental unit that subsequently covers two ventral leg-bearing segmental units. The formation of a diplosegmental unit, or in short a diplosegment, is thus the result of dorsal fusion of embryonic tissue and not the result of any splitting-process or fusion of dorsal tergites. The new data also argue against heterochrony as a primary causative factor for the formation of the diplosegments during the formation of dorsal versus ventral segmental units. Furthermore, no evidence was found supporting the hypothesis that anterior trunk segments in diplopods represent degenerate diplosegments. Two possible scenarios arise from the ontogenetic data presented here, whether this represents an ancestral feature of the diplopods, or alternatively if they represent an isolated case only found in Glomeris (and close relatives). If the former is the case, my work may provide an impressive example of Haeckel's recapitulation theory. © 2011 Wiley Periodicals, Inc.


Kuzenko S.M.,University of Western Australia | Tartaglino-Mazzucchelli G.,Uppsala University
Journal of High Energy Physics | Year: 2011

Long ago, Achúcarro and Townsend discovered that in three dimensions (3D) N-extended anti-de Sitter (AdS) supergravity exists in several incarnations, which were called the (p, q) AdS supergravity theories with non-negative integers p ≥ q such that N = p + q. Using the superspace approach to 3D N-extended supergravity developed in arXiv:1101.4013, we present three superfield formulations for N = 2 supergravity that allow for well defined cosmological terms and supersymmetric AdS solutions. The conformal compensators corresponding to these theories are respectively: (i) a chiral scalar multiplet; (ii) a vector multiplet; and (iii) an improved complex linear multiplet. The theories corresponding to (i) and (iii) are shown to provide two dually equivalent realizations of the (1,1) AdS supergravity, while (ii) describes the (2,0) AdS supergravity. We associate with each supergravity formulation, with and without a cosmological term, a consistent supercurrent multiplet. The supercurrents in the (1,1) and (2,0) AdS backgrounds are derived for the first time. We elaborate on rigid supersymmetric theories in (1,1) and (2,0) AdS superspaces. © SISSA 2011.


Fredriksson A.,Uppsala University
Journal of neural transmission (Vienna, Austria : 1996) | Year: 2011

Wheel-running and treadmill running physical exercise have been shown to alleviate parkinsonism in both laboratory and clinical studies. MPTP was administered to C57/BL6 mice using two different procedures: (a) administration of a double-dose regime (MPTP 2 × 20 or 2 × 40 mg/kg, separated by a 24-h interval), vehicle (saline 5 ml/kg) or saline (vehicle 2 × 5 ml/kg), and (b) administration of a single-dose weekly regime (MPTP 1 × 40 mg/kg) or saline (vehicle 1 × 5 ml/kg) repeated over 4 consecutive weeks. For each procedure, two different physical exercise regimes were followed: (a) after the double-dose MPTP regime, mice were given daily 30-min periods of wheel-running exercise over 5 consecutive days/week or placed in a cage in close proximity to the running wheels for 3 weeks. (b) Mice were either given wheel-running activity on 4 consecutive days (30-min periods) or placed in a cage nearby for 14 weeks. Behavioral testing was as follows: (a) after 3 weeks of exercise/no exercise, mice were tested for spontaneous motor activity (60 min) and subthreshold L-Dopa (5 mg/kg)-induced activity. (b) Spontaneous motor activity was measured on the fifth day during each of the each of the first 5 weeks (Tests 1-5), about 1 h before injections (first 4 weeks), and continued on the 5th days of the 6th to the 14th weeks (Tests 6-14). Subthreshold L-Dopa (5 mg/kg)-induced activity was tested on the 6th, 8th, 10th, 12th and 14th weeks. (b) Mice from the single-dose MPTP weekly regime were killed during the 15th week and striatal regions taken for dopamine analysis, whereas frontal and parietal cortex and hippocampus were taken for analysis of brain-derived neurotrophic factor (BDNF). It was shown that in both experiments, i.e., the double-dose regime and single-dose weekly regime of MPTP administration, physical activity attenuated markedly the MPTP-induced akinesia/hypokinesia in both the spontaneous motor activity and restored motor activity completely in subthreshold L-Dopa tests. Running wheel activity attenuated markedly the loss of dopamine due to repeated administrations of MPTP. BDNF protein level in the parietal cortex was elevated by the MPTP insult and increased further by physical exercise. Physical running wheel exercise alleviated both the functional and biomarker expressions of MPTP-induced parkinsonism.


Kanduri C.,Uppsala University
Advances in Experimental Medicine and Biology | Year: 2011

Accumulating evidence over the last decade has presented us with the intriguing observation that the majority of eukaryotic genomes are pervasively transcribed to encode a complex network of small and long noncoding RNAs. Long noncoding RNAs are of particular interest, as they were once thought to be restricted to housekeeping functions and are now linked to a wide variety of biological functions related to physiology, embryology and development. Emerging evidence indicates that a subset of long noncoding RNAs mediate their biological functions by using chromatin as a substrate, to index the genetic information encoded in the genome. This chapter will discuss how noncoding RNAs and the processes underlying their transcription mediate transcriptional regulation, by epigenetically regulating the structure of chromatin in various biological contexts. © 2011 Landes Bioscience and Springer Science+Business Media, LLC.


Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.


Forster A.C.,Uppsala University
Biotechnology Journal | Year: 2012

Synthetic biology is a powerful experimental approach, not only for developing new biotechnology applications, but also for testing hypotheses in basic biological science. Here, examples from our research using the best model system, Escherichia coli, are reviewed. New evidence drawn from synthetic biology has overturned several long-standing hypotheses regarding the mechanisms of transcription and translation: (i) all native aminoacyl-tRNAs are not equally efficient in translation at equivalent concentrations; (ii) accommodation is not always rate limiting in translation, and may not be for any aminoacyl-tRNA; (iii) proline is the only N-alkyl-amino acid in the genetic code not because of special suitability for protein structure, but because of its comparatively high nucleophilicity; (iv) the usages of most sense codons in E. coli do not correlate with cognate tRNA abundances and (v) class II transcriptional pausing and termination by T7 RNA polymerase cannot be assumed to occur in vivo based on in vitro data. Implications of these conclusions for the biotechnology field are discussed. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Uba K.,Uppsala University
Energy Policy | Year: 2010

A broad participation by stakeholders and an extensive reliance on expert advice are often seen as preconditions for a legitimate and successfully implemented renewable energy policy. However, we have lacked systematic data for testing this argument. This article's contribution is to examine the actors who take part in the making of Swedish energy policy with the help of data on the composition of various committees of inquiry over the last twenty years (1988-2009). Swedish renewable energy policy is often characterised with words like "pioneering" and "forerunner", suggesting that the policy-making process in this area engages many different experts and stakeholders. Our data give only some support to this argument. Results point to a noteworthy predominance of politicians, civil servants, and representatives of state agencies within the policy-process. Producers of uranium and fossils based energy have been engaged more often than producers of renewable energy. Experts have played a prominent role, but this is mostly due to the participation of expert bureaucrats rather than of scientists. The study suggests that a better understanding of the making of energy policy, both in Sweden and elsewhere, requires greater attention to the networks and role of various state employees. © 2010.


The aim was to assess the feasibility and reliability of Velikova's Content Analysis System (VCAS) and the Medical Interaction Process System (MIPS) global scale for evaluation of communication in oncology care. Seventy routine physician consultations with gastro-intestinal (GI) cancer patients were audio-recorded. Two coders applied VCAS and MIPS global scale to the consultations. VCAS captures aspects of communication like symptoms, side effects, functional issues (e.g. emotional, social, physical), health-related quality of life and medical decision making. MIPS global scale measures the total impression of the consultation, e.g. patient centredness and psychosocial focus. In total, 61 of 70 consultations were coded. The coding took twice the consultations' actual durations in minutes for VCAS. The time for coding MIPS global scale equalled the consultations length. However, the coder had then listened to the consultation twice before, coding for VCAS. Cohen's kappa for all aspects measured by VCAS varied between 0.20 and 1, mean 0.80. One category (Info on test) had a kappa of 0.20, the other categories were all above 0.60. Weighted Kappa for MIPS global scale varied between 0.25 and 0.73, mean 0.42. VCAS and MIPS global scale is a feasible combination of tools for evaluating patient-physician communication regarding content, medical decision making and global aspects of communication. VCAS showed high reliability. The MIPS global scale showed lower reliability, due to its sensitivity to the individual coders' unique values, common for all global scales. Further development of the combination of content and global instruments would be valuable. Copyright © 2010 John Wiley & Sons, Ltd.


Background Oppositional defiant disorder behaviours (ODD) and attention deficit/hyperactivity disorder symptoms (ADHD) are common disruptive childhood problems and co-occur to a large extent. In this study, prime questions were the specificity of relations between demographic factors and negative life events, respectively, and ADHD and ODD symptoms, and the role of negative life events in the relations between demographic factors and ODD and ADHD symptoms. Methods Concurrent relations between maternal education, family structure, ethnicity/immigrant background and symptoms of ADHD and ODD were investigated in a Swedish population sample of 1,200 10-year-old children (52% boys). Parents completed questionnaires containing information about demographic characteristics and negative life events and rated the child's ADHD and ODD symptoms using DSM-IV criteria. Results Low maternal education, single/step-parenthood and non-European descent were associated with higher numbers of ODD and ADHD symptoms. Regression analyses identified ethnicity as specifically associated with ODD symptoms and single/step-parenthood as specific to ADHD symptoms, while there was no specificity with regard to negative life events. Experiences of multiple negative life events were more common in families in nonoptimal circumstances. Negative life events had mainly additive effects on the level of ODD and ADHD symptoms above effects of the demographic stressors and especially conflicts between adults around the child were related to high symptom levels. The few gender effects pointed to boys as being more vulnerable than girls to non-optimal family factors expressed in relations to ODD and ADHD symptoms. Conclusion Even in an affluent and egalitarian society, children's life circumstances are related to theirmental health. Further, there seems to be somespecificity in the demographic risk factors associated withODD and with ADHD symptoms, while negative life events act as general stressors. © Springer-Verlag 2009.


Aberg M.,Uppsala University | Henning D.,Optensys Energianalys
Energy Policy | Year: 2011

The development towards more energy efficient buildings, as well as the expansion of district heating (DH) networks, is generally considered to reduce environmental impact. But the combined effect of these two progressions is more controversial. A reduced heat demand (HD) due to higher energy efficiency in buildings might hamper co-production of electricity and DH. In Sweden, co-produced electricity is normally considered to displace electricity from less efficient European condensing power plants. In this study, a potential HD reduction due to energy efficiency measures in the existing building stock in the Swedish city Linköping is calculated. The impact of HD reduction on heat and electricity production in the Linköping DH system is investigated by using the energy system optimisation model MODEST. Energy efficiency measures in buildings reduce seasonal HD variations. Model results show that HD reductions primarily decrease heat-only production. The electricity-to-heat output ratio for the system is increased for HD reductions up to 30%. Local and global CO2 emissions are reduced. If co-produced electricity replaces electricity from coal-fired condensing power plants, a 20% HD reduction is optimal for decreasing global CO2 emissions in the analysed DH system. © 2011 Elsevier Ltd.


Jonsson B.,Uppsala University
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

One of the challenges in the Connect project is to develop techniques for learning models of networked components from exploratory interaction with the component, based on analyzing messages exchanged between the component and its environment. Many approaches to this problem employ regular inference (aka. automata learning) techniques which generate modest-size finite-state models. Most communication with real-life systems involves data values being relevant to the communication context and thus influencing the observable behavior of the communication endpoints. When applying methods from the realm of automata learning, it is desirable to handle such data-occurrences. It is therefore important to extend inference techniques to handle message alphabets and state-spaces with structures containing data parameters, often with large domains. After very briefly mentioning several approaches to the problem, we give a longer account of an approach proposed by Aarts et al, which adapts ideas from of predicate abstraction, successfully used in formal verification. We illustrate the techniques by application to a simple running example, which models a simple booking service. © 2011 Springer-Verlag.


Drabsch Y.,Leiden University | Ten Dijke P.,Leiden University | Ten Dijke P.,Uppsala University
Journal of Mammary Gland Biology and Neoplasia | Year: 2011

The contribution of transforming growth factor β (TGF-β) signaling to breast cancer has been studied for more than two decades. In an early phase TGF-β may act as a tumour suppressor, while later, when cells have become resistant to its anti-mitogenic effects, the role of TGF-β switches towards malignant conversion and progression. TGF-β stimulates cell invasion and modifies the microenvironment to the advantage of cancer cells. Studies have shown that TGF-β promotes bone and lung metastasis via different mechanisms. The therapeutic strategies to target the TGF-β pathway in breast cancer are becoming increasingly clear. This review will focus on the role TGF-β in breast cancer invasion and metastasis. © 2011 The Author(s).


Skarlund M.,Uppsala University
BMC public health | Year: 2012

Many researchers have examined the effect that mental health has on reemployment opportunities amongst the unemployed, but the results are inconclusive. Our aim in this study is to investigate the effects that different aspects of mental and physical health, as well as socio-demographic, social, and economic factors, have on reemployment. A questionnaire was administered to 1,000 and answered by 502 newly registered unemployed Swedes, who were followed for one year using data from the Swedish National Labour Market Board. The differences between those reemployed and those not reemployed was analysed using stepwise logistic regression. General mental ill health amongst unemployed individuals measured by the General Health Questionnaire scale was associated with lower levels of reemployment after one year. This effect could not be explained by any of the scales measuring specific aspects of mental disease such as health-related level of function, rate of depression, burnout, or alcohol misuse. Instead being above 45, low control over one's financial situation, being an immigrant, and visiting a physician during the last three months were better predictors of failure to be reemployed. There are theoretical reasons to assume that psychological distress leads to a decreased reemployment rate amongst the unemployed. The results of this study partly endorse this hypothesis empirically, showing that general subjective mental distress decreases the rate of reemployment amongst newly unemployed individuals, although this effect was mediated by social and economic factors. Indicators of psychiatric disease had no significant effect on reemployment. The results of this study lead us to suggest the early introduction of financial counselling, psychological support, and other interventions for groups with lower reemployment rates.


Granqvist C.G.,Uppsala University
Materials Today: Proceedings | Year: 2016

Modern buildings normally have large windows and glass facades, known jointly as glazings, for achieving good day-lighting and indoors-outdoors contact. However, glazings are challenging for the buildings' energy efficiency and frequently let in or out too much energy, which has to be balanced by active cooling or heating. Cooling requirements, in particular, have soared recently. Emerging technologies based on thermochromics and/or electrochromics can regulate the inflow of visible light and solar energy between widely separated limits and yield better energy efficiency than static solutions. Thermochromic thin layers, based on vanadium dioxide, transmit less infrared solar radiation at high temperature than at low temperature. Electrochromic multilayer structures, normally based on thin films of tungsten oxide and nickel oxide, can regulate the transmittance of visible light and solar energy when a low-voltage is applied for a short time in order to move charge between the two oxide films. Importantly, the new fenestration technologies can improve indoor comfort. This brief review covers thermochromics and electrochromics and emphasizes that they are keys to a new paradigm for energy efficient buildings. © 2016 The Authors.


Styring S.,Uppsala University
Faraday Discussions | Year: 2012

This contribution was presented as the closing lecture at the Faraday Discussion 155 on artificial photosynthesis, held in Edinburgh Scotland, September 5-7 2011. The world needs new, environmentally friendly and renewable fuels to exchange for fossil fuels. The fuel must be made from cheap and "endless" resources that are available everywhere. The new research area of solar fuels aims to meet this demand. This paper discusses why we need a solar fuel and why electricity is not enough; it proposes solar energy as the major renewable energy source to feed from. The scientific field concerning artificial photosynthesis expands rapidly and most of the different scientific visions for solar fuels are briefly overviewed. Research strategies and the development of artificial photosynthesis research to produce solar fuels are overviewed. Some conceptual aspects of research for artificial photosynthesis are discussed in closer detail. © 2012 The Royal Society of Chemistry.


Dahan A.,Ben - Gurion University of the Negev | Lennernas H.,Uppsala University | Amidon G.L.,University of Michigan
Molecular Pharmaceutics | Year: 2012

The drug intestinal permeability (Peff) measure has been widely used as one of the main factors governing both the rate and/or extent of drug absorption (Fabs) in humans following oral administration. In this communication we emphasize the complexity behind and the care that must be taken with this in vivo Peff measurement. Intestinal permeability, considering the whole of the human intestine, is more complex than generally recognized, and this can lead to misjudgment regarding Fabs and Peff in various settings, e.g. drug discovery, formulation design, drug development and regulation. Setting the adequate standard for the low/high permeability class boundary, the different experimental methods for the permeability measurement, and segmental-dependent permeability throughout the human intestine due to different mechanisms are some of the main points that are discussed. Overall, the use of jejunal Peff as a surrogate for extent of absorption is sound and scientifically justified; a compound with high jejunal Peff will have high Fabs, eliminating the risk for misclassification as a BCS class I drug. Much more care should be taken, however, when jejunal Peff does not support a high-permeability classification; a thorough examination may reveal high-permeability after all, attributable to e.g. segmental-dependent permeability due to degree of ionization or transporter expression. In this situation, the use of multiple permeability experimental methods, including the use of metabolism, which except for luminal degradation requires absorption, is prudent and encouraged. © 2012 American Chemical Society.


Kazancioglu E.,Uppsala University | Alonzo S.H.,Yale University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

Mating decisions usually involve conflict of interests between sexes. Accordingly, males benefit from increased number of matings, whereas costs of mating favour a lower mating rate for females. The resulting sexual conflict underlies the coevolution of male traits that affect male mating success ('persistence') and female traits that affect female mating patterns ('resistance'). Theoretical studies on the coevolutionary dynamics of male persistence and female resistance assumed that costs of mating and, consequently, the optimal female mating rate are evolutionarily constant. Costs of mating, however, are often caused by male 'persistence' traits that determine mating success. Here, we present a model where the magnitude of costs of mating depend on, and evolve with, male persistence. We find that allowing costs of mating to depend on male persistence results in qualitatively different coevolutionary dynamics. Specifically, we find that male traits such as penis spikes that harm females are not predicted to exhibit runaway selection with female resistance, in contrast to previous theory that predicts indefinite escalation. We argue that it is essential to determine when and to what extent costs of mating are caused by male persistence in order to understand and accurately predict coevolutionary dynamics of traits involved in mating decisions. © 2012 The Royal Society.


Nik A.M.,Gothenburg University | Reyahi A.,Gothenburg University | Ponten F.,Uppsala University | Carlsson P.,Gothenburg University
Gastroenterology | Year: 2013

Background & Aims: The stem cell niche at the base of the intestinal crypts, as well as stemness and high clonogenicity in colon cancer cells, depend on Wnt signaling to β-catenin. Fibroblasts modulate the Wnt pathway in normal and neoplastic epithelial cells via unclear mechanisms. We investigated how in intestinal fibroblasts the forkhead transcription factor Foxf2 controls Wnt signaling to affect numbers of stem cells and formation and growth of adenomas in mice. Methods: We created mice with different copy numbers of Foxf2 by generating Foxf2-/+ mice and a transgenic strain, Tg(FOXF2). Adenoma formation was investigated in ApcMin/+ mice, stem cells were counted in mice with the Lgr5-enhanced green fluorescent protein knock-in allele, proliferation was measured by incorporation of bromodeoxyuridine, Foxf2 and Sfrp1 were localized by immunohistochemistry, and signaling pathways were analyzed by quantitative polymerase chain reaction and immunoblot assays. Results: Epithelial β-catenin was stabilized in Foxf2-/+ mice, resulting in increased number and size of adenomas. Tg(FOXF2) mice, however, were partially resistant to intestinal neoplasia and developed fewer and smaller adenomas; Foxf2-/+ mice developed 24-fold more tumors than Tg(FOXF2) mice. Epithelial cells of Foxf2-/+ mice also had higher numbers of Lgr5+ stem cells and greater amounts of crypt cell proliferation and expression of Myc (a target of Wnt signaling) than Tg(FOXF2) mice. Expression of Sfrp1, which encodes an extracellular inhibitor of Wnt, in fibroblasts increased with copy number of Foxf2. Conclusions: Foxf2 is a fibroblast factor that inhibits paracrine Wnt signaling and restricts the crypt stem cell niche in intestines of mice. Loss of Foxf2 promotes adenoma formation and growth. © 2013 AGA Institute.


Background: Flow-mediated vasodilation (FMD) has previously been shown to be related to cardiovascular risk factors in cross-sectional studies. The present study aims to investigate how FMD changes over time, and determine whether this change is paralleled by changes in cardiovascular risk factors. Methods: Of the participants in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 750 individuals had measurements made of FMD in the brachial artery both at the ages of 70 and 75 years. In addition, the change over the 5 years in carotid artery intima-media thickness (IMT) was monitored, as well as traditional cardiovascular risk factors. Results: While no significant change in FMD occurred during the 5-year period (+0.1%, p=0.53), large changes could be seen at the individual level. The Framingham risk score (excluding the age-variable) increased during the follow-up period (+0.54, p<0.001). This change was inversely related to the individual change in FMD (beta-0.15, 95% CI -0.29 to-0.0059, p=0.041). Of the eight individual CV risk factors tested, the change in FMD was only related to the change in LDL-cholesterol (inversely, p=0.0028). The change in FMD was not related to the change in IMT seen over the 5-year period ( p=0.41). Conclusion: While no change was seen in the mean FMD over a five-year period in elderly subjects attending both examinations despite ageing and a change in several risk factors, the individual change was mainly related to the change in LDL-cholesterol, further emphasizing the important role of lipids to determine vasoreactivity. © 2014.


Wolf J.B.W.,Uppsala University | Wolf J.B.W.,Science of Life Laboratory
Molecular Ecology Resources | Year: 2013

Genome-wide analyses and high-throughput screening was long reserved for biomedical applications and genetic model organisms. With the rapid development of massively parallel sequencing nanotechnology (or next-generation sequencing) and simultaneous maturation of bioinformatic tools, this situation has dramatically changed. Genome-wide thinking is forging its way into disciplines like evolutionary biology or molecular ecology that were historically confined to small-scale genetic approaches. Accessibility to genome-scale information is transforming these fields, as it allows us to answer long-standing questions like the genetic basis of local adaptation and speciation or the evolution of gene expression profiles that until recently were out of reach. Many in the eco-evolutionary sciences will be working with large-scale genomic data sets, and a basic understanding of the concepts and underlying methods is necessary to judge the work of others. Here, I briefly introduce next-generation sequencing and then focus on transcriptome shotgun sequencing (RNA-seq). This article gives a broad overview and provides practical guidance for the many steps involved in a typical RNA-seq work flow from sampling, to RNA extraction, library preparation and data analysis. I focus on principles, present useful tools where appropriate and point out where caution is needed or progress to be expected. This tutorial is mostly targeted at beginners, but also contains potentially useful reflections for the more experienced. © 2013 John Wiley & Sons Ltd.


Rodhe A.,Uppsala University
Hydrology and Earth System Sciences | Year: 2012

Hydrology teaching benefits from the fact that many important processes can be illustrated and explained with simple physical models. A set of mobile physical models has been developed and used during many years of lecturing at basic university level teaching in hydrology. One model, with which many phenomena can be demonstrated, consists of a 1.0-m-long plexiglass container containing an about 0.25-m-deep open sand aquifer through which water is circulated. The model can be used for showing the groundwater table and its influence on the water content in the unsaturated zone and for quantitative determination of hydraulic properties such as the storage coefficient and the saturated hydraulic conductivity. It is also well suited for discussions on the runoff process and the significance of recharge and discharge areas for groundwater. The flow paths of water and contaminant dispersion can be illustrated in tracer experiments using fluorescent or colour dye. This and a few other physical models, with suggested demonstrations and experiments, are described in this article. The finding from using models in classroom teaching is that it creates curiosity among the students, promotes discussions and most likely deepens the understanding of the basic processes. © 2012 Author(s).


This paper investigates whether family background seems to have any influence on first-time homeownership. Recent studies have indicated that it has become more difficult to become established in the housing market and such situations may increase the importance of parental wealth. In this study, parental wealth is estimated as family background information on parents' homeownership, father's socioeconomic status and single parenting. Unique cohort data for three birth cohorts suggest that there is a significant cohort effect in young adults' tenure decision. Furthermore, the results imply that parents' homeownership has become a more important predictor of the transition to first-time homeownership for those young adults facing increasing problems in the housing market. © 2011 Urban Studies Journal Limited.


Congenital ichthyosis is often associated with typical neonatal phenotypes, "Collodion baby" and "Harlequin foetus", later transforming into severe lamellar or erythrodermic ichthyosis. However, in a minority of cases the skin condition will improve spontaneously after birth, although slight scaling, xerosis, hypohidrosis and keratoderma usually persist. Some of these patients will eventually be diagnosed as suffering from self-improving collodion ichthyosis, ichthyosis prematurity syndrome, or other, even rarer, forms of ichthyosis also characterized by a phenotypic shift in early childhood. This paper summarizes newly described aetiologies for some of these diseases and discusses difficulties encountered when trying to distinguish them clinically from other types of autosomal recessive congenital ichthyosis. To remind health providers about this heterogeneous group of partially transient disorders of cornification, a new umbrella term, "pleomorphic ichthyosis", is proposed. © 2010 The Authors.


Aim: It has previously been shown that flow-mediated vasodilation is a predictor of the progression of the intima-media thickness (IMT). In the present study, the degree of endothelium-dependent vasodilation in both resistance and conduit arteries was evaluated as a predictor of the IMT and plaque progression. Methods: In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) trial (1,016 subjects all 70 years of age), the invasive forearm technique using acetylcholine administered in the brachial artery (resistance artery, EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (conduit artery, FMD) were evaluated. The IMT and number of carotid arteries with plaques (0, 1 or 2) were recorded using ultrasound at the baseline investigation and the follow-up visit conducted five years later. Results: A total of 760 subjects had valid measurements of the IMT and carotid artery plaques at both the investigations conducted at 70 and 75 years of age. Neither the FMD nor EDV significantly predicted the change in IMT over five years. However, the FMD, but not EDV, was associated with the change in carotid plaque burden during the follow-up period, independent of classical risk factors, such as gender, waist circumference, fasting blood glucose, systolic and diastolic blood pressure, HDL-and LDL-cholesterol, serum triglycerides, BMI and smoking (OR 0.81 for a 1 SD change in FMD, 95%CI 0.68 to 0.95, p=0.010). Conclusions: The FMD was found to be a predictor of changes in the carotid plaque status, but not IMT, during the 5-year follow-up period, independent of classical cardiovascular risk factors.


Svennebring A.,Uppsala University
Drug Development Research | Year: 2014

A novel concept of dose fractions, based on the distribution of total bioavailable dose between the six combinations of location and binding state in Øie-Tozer's model is suggested as a way to visualize the distribution pharmacokinetics of a drug. The concept of dose fractions provides a sharper terminology in discussions of drug distribution allowing for a more precise description of the state and location of a drug within a system. In medicinal chemistry literature, the free fraction of a drug in plasma is a commonly discussed factor affecting the exposure to free drug while tissue binding is less well addressed. The free dose fraction, defined as the fraction of the bioavailable dose existing in free form, is suggested as a potentially valuable term for such discussions. Presently, drugs with high (>95%) plasma protein binding are viewed with skepticism, the rational behind which is questioned. The plasma protein bound dose fraction defined as the fraction of the total available dose, which is bound to plasma proteins, is suggested as a measure of the risk for problems related to fluctuations in free drug exposure due to variations in the concentration of drug binding plasma protein. © 2014 Wiley Periodicals, Inc.


Hirt R.P.,Northumbria University | Alsmark C.,Uppsala University | Alsmark C.,National Veterinary Institute | Embley T.M.,Northumbria University
Current Opinion in Microbiology | Year: 2015

Our knowledge of the extent and functional impact of lateral gene transfer (LGT) from prokaryotes to eukaryotes, outside of endosymbiosis, is still rather limited. Here we review the recent literature, focusing mainly on microbial parasites, indicating that LGT from diverse prokaryotes has played a significant role in the evolution of a number of lineages, and by extension throughout eukaryotic evolution. As might be expected, taxonomic biases for donor prokaryotes indicate that shared habitat is a major factor driving transfers. The LGTs identified predominantly affect enzymes from metabolic pathways, but over a third of LGT are genes for putative proteins of unknown function. Finally, we discuss the difficulties in analysing LGT among eukaryotes and suggest that high-throughput methodologies integrating different approaches are needed to achieve a more global understanding of the importance of LGT in eukaryotic evolution. © 2014 The Authors.


OBJECTIVE: For a couple of decades, flow-mediated vasodilation in the brachial artery (FMD) and acetylcholine-mediated vasodilation in the forearm (EDV) have been used to assess endothelium-dependent vasodilation. During recent years a third technique, peripheral artery tonometry (PAT) using EndoPat, has been introduced. We now aimed to investigate the relationships between these techniques, and their relation to cardiovascular risk. METHODS: In the population-based Prospective investigation of Obesity, Energy and Metabolism (POEM) study conducted in individuals all aged 50 years (50% women), EDV, FMD and the reactive hyperemia index were measured in the first 222 individuals. Cardiovascular risk was assessed by the Framingham risk score. RESULTS: No significant relationships were seen between the three different tests to evaluate endothelium-dependent vasodilation. EDV (ra=-0.21, Pa=0.004) and FMD (ra=-0.19, Pa=0.004), but not PAT were significantly related to the Framingham score in an inverse way. Also sodium nitroprusside-mediated vasodilation in the forearm, reflecting endothelium-independent vasodilation (EIDV), was related to the Framingham score in an inverse way (ra=-0.30, P<0.0001). CONCLUSION: No close relationships were seen between the three tests of endothelium-dependent vasodilation, suggesting that they each contribute with unique information on vasoreactivity. EDV, EIDV and FMD, but not PAT, were related to the Framingham score, suggesting that vasoreactivity in some vascular beds are related to cardiovascular risk in middle-aged individuals. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.


Lonn P.,University of California at San Diego | Lonn P.,Uppsala University | Dowdy S.F.,University of California at San Diego
Expert Opinion on Drug Delivery | Year: 2015

Introduction: Macromolecular therapeutics, including enzymes, transcription factors, siRNAs, peptides and large synthetic molecules, can potentially be used to treat human diseases by targeting intracellular molecular pathways and modulating biological responses. However, large macromolecules have no ability to enter cells and require delivery vehicles. Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), are a diverse class of peptides that can deliver macromolecules into cells.Areas covered: In this review, we cover the uptake and usage of arginine-rich PTDs/CPPs (TAT-PTD, Penetratin/Antp and 8R). We review the endocytosis-mediated uptake of these peptides and highlight three important steps: i) cell association; ii) internalization and iii) endosomal escape. We also discuss the array of different cargos that have been delivered by cationic PTDs/CPPs as well as cellular processes and biological responses that have been modulated.Expert opinion: PTDs/CPPs have shown great potential to deliver otherwise undeliverable macromolecular therapeutics into cells for experimentation in cell culture and in animal disease models in vivo. Moreover, over 25 clinical trials have been performed predominantly using the TAT-PTD. However, more work is still needed. Endosomal escape and target-cell specificity remain two of the major future challenges. © 2015 Informa UK, Ltd.


The European Union (EU) aims at reducing its CO2 emissions and use of primary energy. The EU also aims to improve the energy efficiency in buildings and promote the use of combined heat and power (CHP) plants in district heating (DH) systems. Due to significant differences among DH systems regarding fuel use and heat production units, results for one individual DH systems are not generally valid for other DH systems. Therefore, there is a need to generally describe entire DH sectors in a way that considers the heat production plant merit-orders of the individual DH systems. Here, four models of typical DH systems are defined to represent the Swedish DH sector. A scenario for stepwise heat demand reductions due to building energy efficiency improvements is studied. The results show that heat demand reductions in Swedish DH systems generally reduce global CO2 emissions and mainly reduce the use of biomass and fossil fuels, while the use of waste and industrial waste heat (IWH) is less influenced. The results further show that in order to maximise the reduction of CO2 emissions by energy conservation in buildings, the heat production technologies of the DH system should be considered. A large share of CHP production with a high electricity-to-heat output ratio decreases the possibilities to reduce global CO2 emissions through heat demand reductions. © 2013 Elsevier Ltd.


Studies within the field of rural geography have lately to a noticeable extent enriched the theme of the creation of masculinities and femininities focussing on social constructions of the rural, as well as social constructions of gender. In this study I aim to discuss some expressed discourses of the rural in order to illuminate the power relation between the urban and the rural and the spatial implications of the construction of masculinities and femininities.Taking three Swedish television productions as a point of departure, I will argue that an urban hegemony exists and that the programmes reveal how rural masculinities are constructed. The aim is firstly to add a spatial dimension to the constructions of masculinities, and secondly to show how media builds up and emphasises a gap between the rural and the urban in these constructions. Cutting-edge media is of interest, as it is active in reproducing certain practices and also in identifying who is following the norm and who is deviating from it. The three television productions highlight the construction of rural masculinities in terms of seeking help and being 'backward'; that rural men are unequal and traditional as well as deviating and out of place. © 2011 Elsevier Ltd.


Marklof J.,University of Bristol | Strombergsson A.,Uppsala University
Communications in Mathematical Physics | Year: 2014

Previous studies of kinetic transport in the Lorentz gas have been limited to cases where the scatterers are distributed at random (e.g., at the points of a spatial Poisson process) or at the vertices of a Euclidean lattice. In the present paper we investigate quasicrystalline scatterer configurations, which are non-periodic, yet strongly correlated. A famous example is the vertex set of a Penrose tiling. Our main result proves the existence of a limit distribution for the free path length, which answers a question of Wennberg. The limit distribution is characterised by a certain random variable on the space of higher dimensional lattices, and is distinctly different from the exponential distribution observed for random scatterer configurations. The key ingredients in the proofs are equidistribution theorems on homogeneous spaces, which follow from Ratner's measure classification. © 2014 Springer-Verlag Berlin Heidelberg.


Minahan J.A.,Uppsala University
Journal of High Energy Physics | Year: 2012

We consider holographic three-point functions for operators dual to short string states at strong coupling in N = 4 super Yang-Mills. We treat the states as point-like as they come in from the boundary but as strings in the interaction region in the bulk. The interaction position is determined by saddle point, which is equivalent to conservation of the canonical momentum for the interacting particles, and leads to conservation of their conformal charges. We further show that for large dimensions the rms size of the interaction region is small compared to the radius of curvature of the AdS space, but still large compared to the string Compton wave-length. Hence, one can approximate the string vertex operators as flat-space vertex operators with a definite momentum, which depends on the conformal and R-charges of the operator. We then argue that the string vertex operator dual to a primary operator is chosen by satisfying a twisted version of Q L = Q R, up to spurious terms. This leads to a unique choice for a scalar vertex operator with the appropriate charges at the first massive level. We then comment on some features of the corresponding three-point functions, including the application of these results to Konishi operators. © 2012 SISSA.


Freyhult L.,Uppsala University
Journal of High Energy Physics | Year: 2012

We study operators in the sl(2) sector of N = 4 SYM in the generalised scaling limit, where the spin is large and the length of the operator scales with the logarithm of the spin. At leading order in the large spin expansion the scaling dimension at strong coupling is given in terms of the free energy of the O(6) model. We investigate the first subleading corrections to the scaling dimension and find that these too can be derived from the O(6) model in the strong coupling limit. © SISSA 2012.


Maklakov A.A.,Uppsala University | Lummaa V.,University of Sheffield
BioEssays | Year: 2013

Why do the two sexes have different lifespans and rates of aging? Two hypotheses based on asymmetric inheritance of sex chromosomes ("unguarded X") or mitochondrial genomes ("mother's curse") explain sex differences in lifespan as sex-specific maladaptation leading to increased mortality in the shorter-lived sex. While asymmetric inheritance hypotheses equate long life with high fitness, considerable empirical evidence suggests that sexes resolve the fundamental tradeoff between reproduction and survival differently resulting in sex-specific optima for lifespan. However, selection for sex-specific values in life-history traits is constrained by intersexual genetic correlations resulting in intra-locus sexual conflict over optimal lifespan. The available data suggest that the evolution of sexual dimorphism only partially resolves these conflicts. Sexual conflict over optimal trait values, which has been demonstrated in model organisms and in humans, is likely to play a key role in shaping the evolution of lifespan, as well as in maintaining genetic variation for sex-specific diseases. © 2013 WILEY Periodicals, Inc.


Chen D.,Shanghai JiaoTong University | Gyllensten U.,Uppsala University
Carcinogenesis | Year: 2014

The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) encodes a membrane-bound protein acting as a ligand to stimulate an activating receptor, NKG2D, expressed on the surface of essentially all human natural killer (NK), γδ T and CD8(+) αβ T cells. MICA protein is absent from most cells but can be induced by infections and oncogenic transformation and is frequently expressed in epithelial tumors. Upon binding to MICA, NKG2D activates cytolytic responses of NK and γδ T cells against infected and tumor cells expressing MICA. Therefore, membrane-bound MICA acts as a signal during the early immune response against infection or spontaneously arising tumors. On the other hand, human tumor cells spontaneously release a soluble form of MICA, causing the downregulation of NKG2D and in turn severe impairment of the antitumor immune response of NK and CD8(+) T cells. This is considered to promote tumor immune evasion and also to compromise host resistance to infections. MICA is the most polymorphic non-classical class I gene. A possible association of MICA polymorphism with genetic predisposition to different cancer types has been investigated in candidate gene-based studies. Two genome-wide association studies have identified loci in MICA that influence susceptibility to cervical neoplasia and hepatitis C virus-induced hepatocellular carcinoma, respectively. Given the current level of interest in the field of MICA gene, we discuss the genetics and biology of the MICA gene and the role of its polymorphism in cancer. Gaps in our understanding and future research needs are also discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


Edoff M.,Uppsala University
Ambio | Year: 2012

Electricity generation by photovoltaic conversion of sunlight is a technology in strong growth. The thin film technology is taking market share from the dominant silicon wafer technology. In this article, the market for photovoltaics is reviewed, the concept of photovoltaic solar energy conversion is discussed and more details are given about the present technological limitations of thin film solar cell technology. Special emphasis is given for solar cells which employ Cu(In,Ga)Se2 and Cu2ZnSn(S,Se) 4 as the sunlight-absorbing layer. © Royal Swedish Academy of Sciences 2012.


Stein M.,Uppsala University
Zoological Journal of the Linnean Society | Year: 2010

Kiisortoqia soperi gen. et sp. nov. is an arthropod species from the Early Cambrian Sirius Passet Lagerstätte of North Greenland. A head, incorporating four appendiferous segments and biramous limbs, with an anteroposteriorly compressed basipod with a spine bearing median edge, support the euarthropod affinities of K. soperi gen. et sp. nov. Similarities with 'short great appendage' arthropods, or megacheirans, like the nine-segmented endopod, and the flap- or paddle-like exopod, may be symplesiomorphies. The antennula, however, resembles in composition and size the anteroventral raptorial appendage of anomalocaridids. Thus, the morphology of K. soperi gen. et sp. nov. provides additional support for the homologization of the anomalocaridid 'great appendage' with the appendage of the antennular or deutocerebral segment of extant Euarthropoda. © 2010 The Linnean Society of London.


A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation. © 2011 The Author(s).


Cedervall Y.,Uppsala University
American journal of Alzheimer's disease and other dementias | Year: 2012

The longitudinal influences on physical capacity and habitual aerobic activity level in the early stages of Alzheimer's disease (AD) are unclear. Therefore, changes in physical capacity and aerobic activity level were evaluated. Twenty-five individuals with AD were assessed annually for 2 years, by 10-m walk test, 6-minute walk test, and timed up-and-go (TUG) single/dual tasks. Habitual aerobic activity was assessed by diary registrations. The AD group showed a lower physical capacity than controls at baseline but comparable levels of aerobic activity. During the follow-up period, physical capacity declined in the AD group, but the aerobic activity levels changed only marginally. Our results show that in the early stages of AD, people are capable of maintaining health-promoting aerobic activity levels, despite a decline in their physical capacity. Additionally, it appears that cognitive dysfunction contributes to an impaired physical capacity. The TUG tasks might, therefore, be useful for detecting early signs of cognitive impairment.


Warensjo E.,Uppsala University
Advances in food and nutrition research | Year: 2010

Dairy food comprises a range of different products with varying nutritional components. In the context of a healthy diet, dairy food may provide protection against and amelioration of chronic diseases related to obesity. These include overweight, insulin resistance/metabolic syndrome/type 2 diabetes, hypertension/stroke, and cardiovascular disease. Eliciting how dairy food may have this impact represents a challenge for modern nutritional science and requires an integration of knowledge from observational studies of population dietary patterns and disease prevalence, and experimental studies testing the effect of dairy food consumption. It also benefits from the recent identification of biomarkers of dairy fat intake and from mechanistic studies that support the plausibility of the observed effects. Future research might discriminate between types of dairy foods and focus on the synergy provided by the food matrix, rather than simply the component parts of the food. Copyright © 2010 Elsevier Inc. All rights reserved.


The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD. Copyright © 2012 Elsevier Inc. All rights reserved.


Husby A.,University of Edinburgh | Husby A.,Uppsala University | Visser M.E.,Netherlands Institute of Ecology | Kruuk L.E.B.,University of Edinburgh
PLoS Biology | Year: 2011

The amount of genetic variance underlying a phenotypic trait and the strength of selection acting on that trait are two key parameters that determine any evolutionary response to selection. Despite substantial evidence that, in natural populations, both parameters may vary across environmental conditions, very little is known about the extent to which they may covary in response to environmental heterogeneity. Here we show that, in a wild population of great tits (Parus major), the strength of the directional selection gradients on timing of breeding increased with increasing spring temperatures, and that genotype-by-environment interactions also predicted an increase in additive genetic variance, and heritability, of timing of breeding with increasing spring temperature. Consequently, we therefore tested for an association between the annual selection gradients and levels of additive genetic variance expressed each year; this association was positive, but non-significant. However, there was a significant positive association between the annual selection differentials and the corresponding heritability. Such associations could potentially speed up the rate of micro-evolution and offer a largely ignored mechanism by which natural populations may adapt to environmental changes. © 2011 Husby et al.


Arnqvist G.,Uppsala University
Evolution | Year: 2011

Recent documentations of sexually antagonistic genetic variation in fitness have spurred an interest in the mechanisms that may act to maintain such variation in natural populations. Using individual-based simulations, I show that positive assortative mating by fitness increases the amount of sexually antagonistic genetic variance in fitness, primarily by elevating the equilibrium frequency of heterozygotes, over most of the range of sex-specific selection and dominance. Further, although the effects of assortative mating by fitness on the protection conditions of polymorphism in sexually antagonistic loci were relatively minor, it widens the protection conditions under most reasonable scenarios (e.g., under heterozygote superiority when fitness is averaged across the sexes) but can also somewhat narrow the protection conditions under other circumstances. The near-ubiquity of assortative mating in nature suggests that it may contribute to upholding standing sexually antagonistic genetic variation in fitness. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution..


Lind P.M.,Uppsala University | Lind L.,Uppsala University Hospital
Atherosclerosis | Year: 2011

Background and objective: Bisphenol A (BPA) levels have previously been associated with coronary heart disease (CHD). Since CHD is an atherosclerotic disease, we investigated if circulating levels of BPA and phthalate metabolites are related to atherosclerosis in a cross-sectional study. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), the prevalence of overt plaques and echogenectity (grey scale median, GSM) of carotid artery plaques were recorded by ultrasound in both of the carotid arteries. The thickness (IMT) and echogenicity (IM-GSM) of the intima-media complex were also measured. Bisphenol A (BPA) and 10 phthalate metabolites were analyzed in serum by a API 4000 liquid chromatograph/tandem mass spectrometer. Results: Mono-methyl phthalate (MMP) was related to carotid plaques in an inverted U-shaped manner. This pattern was significant after adjustment for gender, body mass index, blood glucose, blood pressure, HDL and LDL-cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use (p=0.004). High levels of BPA, mono-isobutyl phthalate (MiBP) and MMP were associated with an echogenic IM-GSM and plaque GSM, while high levels of mono-2-ethylhexyl phthalate (MEHP) were associated with an echolucent IM-GSM and plaque GSM (p<0.0001 after adjustment). Conclusion: The phthalate metabolite MMP was related to atherosclerotic plaques in an inverted U-shaped manner independently of CV risk factors. Some phthalates and BPA were also related to the echogenicity of the plaques, suggesting a role for plaque-associated chemicals in atherosclerosis. © 2011.


Nyholm D.,Uppsala University
Parkinsonism and Related Disorders | Year: 2012

Enterally administered levodopa/carbidopa gel (Duodopa®) is used for the treatment of advanced Parkinson's disease (PD) in patients with motor fluctuations and dyskinesias. This review summarizes the current efficacy and safety data on this drug. Clinically important differences (CID) have been used to assess whether statistical improvements in symptoms translate into meaningful improvements for the patients.A PubMed search in February 2012 found 23 papers with efficacy data and 33 with safety data. Of 11 studies reporting Unified Parkinson's Disease Rating Scale (UPDRS) III scores, 10 found improvements that met the CID of 10.8 points. Of 7 studies reporting UPDRS IV scores, 5 found improvements meeting the CID of 2.3 points. Quality of life (QoL) was assessed in 6 studies using the 8- or 39-question version of the Parkinson's disease Questionnaire, and all reported improvements meeting the CID (10 points). Due to the nature of the data, it is not possible to give exact numbers for the frequency of adverse events. However, the findings seem to be in line with a previous report stating the majority of adverse events were related to the infusion system or surgical procedure rather than the drug. In conclusion, the large majority of studies have reported that Duodopa® is clinically effective in relieving the symptoms of advanced PD and improving QoL in comparison with conventional therapy. High-quality randomized trials with larger patient numbers will yield greater insights into the efficacy and safety of this treatment. © 2012 Elsevier Ltd.


Birgegard G.,Uppsala University
Best Practice and Research: Clinical Haematology | Year: 2014

Anaemia is a common finding at diagnosis in myelofibrosis, and becomes a symptomatic problem in most patients with time. There are several treatment options for specific anaemia treatment, none of which has been tested in large, randomized, controlled trials. However, as myelofibrosis is not a disease with spontaneous remissions, even non-randomized trials carry weight. In this survey, the existing evidence will be analysed, both for the commonly used treatments like erythropoiesis-stimulating agents, androgens and thalidomide and for the new drugs in the area, and conclusions will be drawn concerning standard clinical anaemia treatment in myelofibrosis, which according to evidence from studies has a 40e50% chance of response in patients with not too advanced disease. © 2014 Elsevier Ltd. All rights reserved.


Increasing attention has focused on relational spatial entities as potentially embedding renewed and alternative paths of local development. This paper discusses the intertwining of an emerging relational configuration of space and the pursuit of post-industrial development, by analysing the formation of an organisational identity. The case of NewcastleGateshead (UK) is interpreted as a brand emerging from urban collective strategy-making, involving two partner cities, thus crossing administrative borders. By suggesting the importance of the emergence of 'branded relational spaces', research results stress the active role of a collective construction of meanings and their communication in the creation of relational spatial entities. This provides an opportunity to reflect on the extent to which branding, here interpreted as collective strategy-making, goes beyond mere communication and fosters an institutionalisation of the branded space, thus influencing the way in which local development is spatially and strategically conceived. © 2013 Urban Studies Journal Limited.


Freyhult L.,Uppsala University
Letters in Mathematical Physics | Year: 2012

We review the computation of the anomalous dimension of twist operators in the planar limit of N = 4 SYM using the asymptotic Bethe ansatz and demonstrate how this quantity is obtained at weak, strong and intermediate values of the coupling constant. The anomalous dimension of twist operators in the limit of large Lorentz spin played a major role in the construction as well as in many tests of the asymptotic Bethe equations; this aspect of the story is emphasized. © 2011 Springer.


Mihranyan A.,Uppsala University
Journal of Applied Polymer Science | Year: 2011

This article represents the first attempt to summarize the knowledge about the structure and functional properties of green algae cellulose since 1885, when cellulose of algal origin was first described. Here, I systematically discuss the unique structural characteristics of Cladophora cellulose. This specific interest in Cladophora filamentous green algae is justified by unwanted global socioenvironmental problems associated with seasonal blooms by these algae. Thus, the physicochemical properties and the use of this unique material are discussed in a broad context. Several high-tech applications wherein the use of Cladophora cellulose is highly beneficial are highlighted. © 2010 Wiley Periodicals, Inc.


Quevedo D.E.,University of Newcastle | Ahlen A.,Uppsala University | Johansson K.H.,KTH Royal Institute of Technology
IEEE Transactions on Automatic Control | Year: 2013

Stochastic stability for centralized time-varying Kalman filtering over a wireless sensor network with correlated fading channels is studied. On their route to the gateway, sensor packets, possibly aggregated with measurements from several nodes, may be dropped because of fading links. To study this situation, we introduce a network state process, which describes a finite set of configurations of the radio environment. The network state characterizes the channel gain distributions of the links, which are allowed to be correlated between each other. Temporal correlations of channel gains are modeled by allowing the network state process to form a (semi-)Markov chain. We establish sufficient conditions that ensure the Kalman filter to be exponentially bounded. In the one-sensor case, this new stability condition is shown to include previous results obtained in the literature as special cases. The results also hold when using power and bit-rate control policies, where the transmission power and bit-rate of each node are nonlinear mapping of the network state and channel gains. © 1963-2012 IEEE.


Malqvist A.,Uppsala University
Multiscale Modeling and Simulation | Year: 2011

In this paper we derive a framework for multiscale approximation of elliptic problems on standard and mixed form. The method presented is based on a splitting into coarse and fine scales together with a systematic technique for approximation of the fine scale part, based on the solution of decoupled localized subgrid problems. The fine scale approximation is then used to modify the coarse scale equations. A key feature of the method is that symmetry in the bilinear form is preserved in the discrete system. Other key features are a posteriori error bounds and adaptive algorithms based on these bounds. The adaptive algorithms are used for automatic tuning of the method parameters. In the last part of the paper we present numerical examples where we apply the framework to a problem in oil reservoir simulation. © 2011 Society for Industrial and Applied Mathematics.


Klose T.,Uppsala University
Letters in Mathematical Physics | Year: 2012

We review the duality and integrability of N = 4 6 superconformal Chern-Simons theory in three dimensions and IIA superstring theory on the background Ads 4 × CP 3. We introduce both of these models and describe how their degrees of freedom are mapped to excitations of a long-range integrable spin-chain. Finally, we discuss the properties of the Bethe equations, the S-matrix and the algebraic curve that are special to this correspondence and differ from the case of N = 4 SYM theory and strings on Ads 5 × S 5. © 2011 Springer.


Minahan J.A.,Uppsala University
Letters in Mathematical Physics | Year: 2012

In this chapter of Review of AdS{pipe}CFT Integrability we introduce N = 4 Super Yang-Mills. We discuss the global superalagebra PSU(2, 2{pipe}4) and its action on gauge invariant operators. We then discuss the computation of the correlators of certain gauge invariant operators, the so-called single trace operators in the large N limit. We show that interactions in the gauge theory lead to mixing of the operators. We compute this mixing at the one-loop level and show that the problem maps to a one-dimensional spin chain with nearest neighbor interactions. For operators in the SU(2) sector we show that the spin chain is the ferromagnetic Heisenberg spin chain whose eigenvalues are determined by the Bethe equations. © 2011 Springer.


Bull J.,Uppsala University
Environment and Planning A | Year: 2011

This paper examines the material intertwinings of fish and water. It discusses how the presence of water and fish is simultaneously material and immaterial and examines how the processes and tensions between narratives of fish and water are caught up and inform human encounters with waterscapes. In particular, the paper does three things: first, it highlights the tensions between the angling literature and the practices and performances of angling. Second, it examines how fish embody the material and imaginative aspects of waterscapes, highlighting how fish are shaped to fit in or adapt to 'environmental quality' and human expectations. Third, it examines how water may be thought through as 'fishy' as made animate by the creatures that dwell there. © 2011 Pion Ltd and its Licensors.


Christophers B.,Uppsala University
Environment and Planning D: Society and Space | Year: 2011

In an attempt to resist and surmount the mystifications of commodity fetishism, scholars have gone to great lengths to trace the social and spatial pathways of various physical, consumable commodities. By contrast, there have been relatively limited efforts to similarly defetishise what Marx called the god of commodities" ömoneyöand there has been no systematic, theoretically informed consideration of what the defetishisation of money might actually entail. From an explicitly Marxian perspective this paper aims to make a modest contribution in such a direction. It has two central objectives: to demonstrate why money merits defetishisation and to explore, at a largely theoretical level, how such an exercise might proceed, what primary challenges it would confront, and where the main opportunities for progress are likely to lie. © 2011 Pion Ltd and its Licensors.


Mazorchuk V.,Uppsala University | Zhao K.,Wilfrid Laurier University | Zhao K.,Hebei University
Selecta Mathematica, New Series | Year: 2014

We propose a very general construction of simple Virasoro modules generalizing and including both highest weight and Whittaker modules. This construction enables us to classify all simple Virasoro modules that are locally finite over a positive part. To obtain those irreducible Virasoro modules, we use simple modules over a family of finite dimensional solvable Lie algebras. For one of these algebras, all simple modules are classified by R. Block and we extend this classification to the next member of the family. As a result, we recover many known but also construct a lot of new simple Virasoro modules. We also propose a revision of the setup for study of Whittaker modules. © 2013 Springer Basel.


In the last decade and across countries, changes in national intelligence policies have spurred widespread political opposition and public protest. Instances of intelligence policy change warrant close academic attention to cast light on the dynamics of policymaking in contested policy areas. In an effort to contribute to further development of a theory of policy change within the Advocacy Coalition Framework (ACF), this article analyzes the adoption of legislation in Sweden to expand the mandate for signals intelligence gathering. Three explanatory variables are derived from the ACF to explain policy change in this case: shifts in advocacy coalition membership, distribution of coalition resources, and access to policy venues. Whereas shifts in coalition membership were unrelated to policy change in this case, the case-study lends partial support to the role of resource distribution and policy venues. To promote the progress of an ACF theory of policy change, the study concludes by drawing two theoretical implications: (i) introducing hierarchical classification of coalition resources and (ii) identification of revised policy narratives and exploitative policy entrepreneurship as causal mechanisms linking external shocks to venue shifts and policy change. © 2011 Policy Studies Organization.


Hedman L.,Uppsala University
Housing Studies | Year: 2011

Neighbourhoods and cities are dynamic; their characteristics and relative positions change over time due to constant moves in and out. However, neighbourhood effect theory and most attempts to quantitatively estimate neighbourhood effects seem to treat neighbourhoods as if they were static. This paper argues that such a view is not only strange but may also result in biased estimates. Four methodological challenges are highlighted that are directly related to mobility: (1) measures of exposure time; (2) neighbourhood change; (3) selection bias; and (4) endogeneity. These are all topics worthy of scholarly interest in themselves, but also challenges that all neighbourhood effect studies must address to convincingly argue that their results are indicative of causal relationships-results of neighbourhood transmission mechanisms-and not just statistical correlations. The paper discusses how and to what extent these challenges have been met by the quantitative neighbourhood effect literature and gives directions to future research. © 2011 Taylor & Francis.


The Ugandan Anti-Homosexuality Bill of October 2009 caused an international outcry and sparked intense debate in the local and international media. Particularly contentious was its proposal to impose the death penalty for acts of 'aggravated homosexuality'. Through a quantitative content analysis of 176 items from two main daily newspapers, the government-owned New Vision and the privately-owned Daily Monitor, over the period October 2009-June 2010, combined with qualitative interviews with human rights defenders in Uganda, this study explores attempts made by local human rights advocates to influence the media's coverage of the Bill and the extent to which these attempts were successful. The study finds that while there are significant differences between the frequency of reporting on the Bill in the two newspapers, both papers devoted little editorial space to the public health and human rights concerns put forward by local human rights organizations. Despite Uganda's recent and often lauded history of openly addressing HIV/AIDS, human right organizations' attempts to highlight the Bill's potentially adverse effects on the country's ability to tackle the epidemic effectively were only partially successful and, interestingly, awarded much less attention than the potential human rights implications of the proposed change in legislation. © 2011 Taylor & Francis.


Organic substrates in reactive barrier systems are often heterogeneous material mixtures with relatively large contrasts in hydraulic conductivity and porosity over short distances. These short-range variations in material properties imply that preferential flow paths and diffusion between regio