Showing papers by "University of Bergen published in 2006"

Microbial biogeography : putting microorganisms on the map

Abstract: We review the biogeography of microorganisms in light of the biogeography of macroorganisms A large body of research supports the idea that free-living microbial taxa exhibit biogeographic patterns Current evidence confirms that, as proposed by the Baas-Becking hypothesis, 'the environment selects' and is, in part, responsible for spatial variation in microbial diversity However, recent studies also dispute the idea that 'everything is everywhere' We also consider how the processes that generate and maintain biogeographic patterns in macroorganisms could operate in the microbial world

Archaea predominate among ammonia-oxidizing prokaryotes in soils

Abstract: Ammonia oxidation is the first step in nitrification, a key process in the global nitrogen cycle that results in the formation of nitrate through microbial activity. The increase in nitrate availability in soils is important for plant nutrition, but it also has considerable impact on groundwater pollution owing to leaching. Here we show that archaeal ammonia oxidizers are more abundant in soils than their well-known bacterial counterparts. We investigated the abundance of the gene encoding a subunit of the key enzyme ammonia monooxygenase (amoA) in 12 pristine and agricultural soils of three climatic zones. amoA gene copies of Crenarchaeota (Archaea) were up to 3,000-fold more abundant than bacterial amoA genes. High amounts of crenarchaeota-specific lipids, including crenarchaeol, correlated with the abundance of archaeal amoA gene copies. Furthermore, reverse transcription quantitative PCR studies and complementary DNA analysis using novel cloning-independent pyrosequencing technology demonstrated the activity of the archaea in situ and supported the numerical dominance of archaeal over bacterial ammonia oxidizers. Our results indicate that crenarchaeota may be the most abundant ammonia-oxidizing organisms in soil ecosystems on Earth.

The "Stern Review" on the Economics of Climate Change

Abstract: How much and how fast should the globe reduce greenhouse-gas emissions? How should nations balance the costs of the reductions against the damages and dangers of climate change? This question has been addressed by the recent "Stern Review on the Economics of Climate Change," which answers these questions clearly and unambiguously. We need urgent, sharp, and immediate reductions in greenhouse-gas emissions. An analysis of the "Stern Review" finds that these recommendations depend decisively on the assumption of a near-zero social discount rate. The Review's unambiguous conclusions about the need for extreme immediate action will not survive the substitution of discounting assumptions that are consistent with today's market place.

Immigrant Youth: Acculturation, Identity, and Adaptation

Abstract: Cet article presente plusieurs des principaux resultats d’une grande etude internationale sur l’acculturation et l’adaptation de jeunes immigres (âges de 13 a 18 ans) qui se sont implantes dans treize pays (N = 5,366); il y est adjoint un echantillon de jeunes nationaux (N = 2,631). La recherche s’appuyait sur trois questions centrales: comment les jeunes migrants gerent-ils le processus d’acculturation? Comment parviennent-ils a s’adapter? Et y a-t-il un lien manifeste entre la forme d’acculturation et le succes de l’adaptation? L’analyse en clusters deboucha sur quatre profils d’acculturation: integrateur, ethnique, national et diffus. L’analyse factorielle de cinq variables d’adaptation mit en evidence deux types d’adaptation: psychologique et socioculturel. Il existe une forte relation entre la facon dont les jeunes s’acculturent et leur adaptation: ceux qui presentent un profil integrateur beneficient des meilleurs indicateurs d’adaptations psychologique et socioculturelle alors que ceux souffrant d’un profil diffus ont les pires. Entre les deux, le profil ethnique presente une adaptation psychologique relativement bonne et une adaptation socioculturelle plutot pauvre, tandis que le profil national a une adaptation psychologique relativement pauvre et une adaptation socioculturelle legerement negative. Cette configuration de resultats fut en grande partie retrouvee a travers une modelisation en equation structurelle. Les consequences pour l’implantation des jeunes immigres sont claires: ils devraient etre encourages a preserver l’appartenance a leur culture d’origine tout en etablissant des liens etroits avec la societe d’accueil. This paper reports some of the main findings from a large international study of the acculturation and adaptation of immigrant youth (aged 13 to 18 years) who are settled in 13 societies (N= 5,366), as well as a sample of national youth (N= 2,631). The study was guided by three core questions: How do immigrant youth deal with the process of acculturation? How well do they adapt? Are there important relationships between how they acculturate and how well they adapt? Cluster analysis produced four distinct acculturation profiles: integration, ethnic, national, and diffuse. Factor analysis of five adaptation variables revealed two distinct forms of adaptation: psychological and sociocultural. There were substantial relationships between how youth acculturate and how well they adapt: those with an integration profile had the best psychological and sociocultural adaptation outcomes, while those with a diffuse profile had the worst; in between, those with an ethnic profile had moderately good psychological adaptation but poorer sociocultural adaptation, while those with a national profile had moderately poor psychological adaptation, and slightly negative sociocultural adaptation. This pattern of results was largely replicated using structural equation modeling. Implications for the settlement of immigrant youth are clear: youth should be encouraged to retain both a sense of their own heritage cultural identity, while establishing close ties with the larger national society.

Tunicates and not cephalochordates are the closest living relatives of vertebrates

Abstract: Tunicates or urochordates (appendicularians, salps and sea squirts), cephalochordates (lancelets) and vertebrates (including lamprey and hagfish) constitute the three extant groups of chordate animals. Traditionally, cephalochordates are considered as the closest living relatives of vertebrates, with tunicates representing the earliest chordate lineage. This view is mainly justified by overall morphological similarities and an apparently increased complexity in cephalochordates and vertebrates relative to tunicates. Despite their critical importance for understanding the origins of vertebrates, phylogenetic studies of chordate relationships have provided equivocal results. Taking advantage of the genome sequencing of the appendicularian Oikopleura dioica, we assembled a phylogenomic data set of 146 nuclear genes (33,800 unambiguously aligned amino acids) from 14 deuterostomes and 24 other slowly evolving species as an outgroup. Here we show that phylogenetic analyses of this data set provide compelling evidence that tunicates, and not cephalochordates, represent the closest living relatives of vertebrates. Chordate monophyly remains uncertain because cephalochordates, albeit with a non-significant statistical support, surprisingly grouped with echinoderms, a hypothesis that needs to be tested with additional data. This new phylogenetic scheme prompts a reappraisal of both morphological and palaeontological data and has important implications for the interpretation of developmental and genomic studies in which tunicates and cephalochordates are used as model animals.

Genome-wide analysis of mammalian promoter architecture and evolution

Abstract: Mammalian promoters can be separated into two classes, conserved TATA box-enriched promoters, which initiate at a well-defined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

Cohort profile: The Norwegian Mother and Child Cohort Study (MoBa)

Abstract: The Norwegian Mother and Child Cohort Study (MoBa) was planned in the 1990s partly by researchers at the Medical Birth Registry of Norway (MBRN) 1 and partly by researchers at the National Institute of Public Health (from 2002 comprising MBRN as well as other institutions and renamed the Norwegian Institute of Public Health (NIPH). The study had a long planning phase involving many scientists who contributed ideas that helped to design questionnaires and to structure the biobank, which is described in detail elsewhere. 2 Collaboration was established with the Danish Birth Cohort Study, 3

The epidemiology of multiple sclerosis in Europe.

Abstract: Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100,000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35-64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100,000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies.

ALICE: Physics Performance Report, Volume II

Abstract: ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark–gluon plasma in nucleus–nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries.The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb–Pb collisions (dNch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus–nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies.The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC.Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate.The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517–1763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators.The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton–proton, proton–nucleus, and nucleus–nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes.

Corotating solar wind streams and recurrent geomagnetic activity: A review

Abstract: [1] Solar wind fast streams emanating from solar coronal holes cause recurrent, moderate intensity geomagnetic activity at Earth. Intense magnetic field regions called Corotating Interaction Regions or CIRs are created by the interaction of fast streams with upstream slow streams. Because of the highly oscillatory nature of the GSM magnetic field z component within CIRs, the resultant magnetic storms are typically only weak to moderate in intensity. CIR-generated magnetic storm main phases of intensity Dst < −100 nT (major storms) are rare. The elongated storm “recovery” phases which are characterized by continuous AE activity that can last for up to 27 days (a solar rotation) are caused by nonlinear Alfven waves within the high streams proper. Magnetic reconnection associated with the southward (GSM) components of the Alfven waves is the solar wind energy transfer mechanism. The acceleration of relativistic electrons occurs during these magnetic storm “recovery” phases. The magnetic reconnection associated with the Alfven waves cause continuous, shallow injections of plasma sheet plasma into the magnetosphere. The asymmetric plasma is unstable to wave (chorus and other modes) growth, a feature central to many theories of electron acceleration. It is noted that the continuous AE activity is not a series of substorm expansion phases. Arguments are also presented why these AE activity intervals are not convection bays. The auroras during these continuous AE activity intervals are less intense than substorm auroras and are global (both dayside and nightside) in nature. Owing to the continuous nature of this activity, it is possible that there is greater average energy input into the magnetosphere/ionosphere system during far declining phases of the solar cycle compared with those during solar maximum. The discontinuities and magnetic decreases (MDs) associated with interplanetary Alfven waves may be important for geomagnetic activity. In conclusion, it will be shown that geomagnetic storms associated with high-speed streams/CIRs will have the same initial, main, and “recovery” phases as those associated with ICME-related magnetic storms but that the interplanetary causes are considerably different.

Pathways of carbon assimilation and ammonia oxidation suggested by environmental genomic analyses of marine Crenarchaeota.

Abstract: Marine Crenarchaeota represent an abundant component of oceanic microbiota with potential to significantly influence biogeochemical cycling in marine ecosystems. Prior studies using specific archaeal lipid biomarkers and isotopic analyses indicated that planktonic Crenarchaeota have the capacity for autotrophic growth, and more recent cultivation studies support an ammonia-based chemolithoautotrophic energy metabolism. We report here analysis of fosmid sequences derived from the uncultivated marine crenarchaeote, Cenarchaeum symbiosum, focused on the reconstruction of carbon and energy metabolism. Genes predicted to encode multiple components of a modified 3-hydroxypropionate cycle of autotrophic carbon assimilation were identified, consistent with utilization of carbon dioxide as a carbon source. Additionally, genes predicted to encode a near complete oxidative tricarboxylic acid cycle were also identified, consistent with the consumption of organic carbon and in the production of intermediates for amino acid and cofactor biosynthesis. Therefore, C. symbiosum has the potential to function either as a strict autotroph, or as a mixotroph utilizing both carbon dioxide and organic material as carbon sources. From the standpoint of energy metabolism, genes predicted to encode ammonia monooxygenase subunits, ammonia permease, urease, and urea transporters were identified, consistent with the use of reduced nitrogen compounds as energy sources fueling autotrophic metabolism. Homologues of these genes, recovered from ocean waters worldwide, demonstrate the conservation and ubiquity of crenarchaeal pathways for carbon assimilation and ammonia oxidation. These findings further substantiate the likely global metabolic importance of Crenarchaeota with respect to key steps in the biogeochemical transformation of carbon and nitrogen in marine ecosystems.

Subtypes of mild cognitive impairment in parkinson's disease: Progression to dementia

Abstract: The aim of this study was to establish the rate of progression from mild cognitive impairment (MCI) to dementia in patients with Parkinson's disease (PD). PD patients without dementia were recruited in 1997 from an ongoing prospective epidemiological study. The assessment included neurological and psychiatric examinations, a clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia, and a battery of neuropsychological tests. PD was diagnosed according to established criteria, dementia was diagnosed according to the DSM-III-R criteria, and subtypes of MCI were classified according to modified Petersen's criteria. Seventy-two nondemented PD patients were included. A total of 34 were cognitively intact, whereas 38 were diagnosed with MCI (amnestic, n = 6; single nonmemory domain, n = 17; multiple domains slightly impaired, n = 15). Fifty-nine patients (82%) completed follow-up examination 4 years later, and 18 (62%) of the patients with MCI and 6 (20%) of the cognitively intact PD patients were demented (P = 0.001). Single domain nonmemory MCI and multiple domains slightly impaired MCI were associated with later development of dementia (P = 0.003; P = 0.04), whereas amnestic MCI subtype was not (P = 0.76). We conclude that patients with PD and MCI had a higher risk of developing dementia than cognitively intact PD patients, suggesting that MCI in PD is an early manifestation of dementia. However, these findings should be interpreted with caution due to the relatively small number of subjects included in this study.

Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer

Abstract: Breast cancer is a leading cause of cancer-death among women, where the clinicopathological features of tumors are used to prognosticate and guide therapy. DNA copy number alterations (CNAs), which occur frequently in breast cancer and define key pathogenetic events, are also potentially useful prognostic or predictive factors. Here, we report a genome-wide array-based comparative genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a patient cohort with locally advanced disease. Statistical analysis links distinct cytoband loci harboring CNAs to specific clinicopathological parameters, including tumor grade, estrogen receptor status, presence of TP53 mutation, and overall survival. Notably, distinct spectra of CNAs also underlie the different subtypes of breast cancer recently defined by expression-profiling, implying these subtypes develop along distinct genetic pathways. In addition, higher numbers of gains/losses are associated with the "basal-like" tumor subtype, while high-level DNA amplification is more frequent in "luminal-B" subtype tumors, suggesting also that distinct mechanisms of genomic instability might underlie their pathogenesis. The identified CNAs may provide a basis for improved patient prognostication, as well as a starting point to define important genes to further our understanding of the pathobiology of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat

Cognitive Behavioral Therapy vs Zopiclone for Treatment of Chronic Primary Insomnia in Older Adults A Randomized Controlled Trial

Abstract: Context Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking.

The Cenozoic palaeoenvironment of the Arctic Ocean.

Abstract: The history of the Arctic Ocean during the Cenozoic era (0–65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm ‘greenhouse’ world, during the late Palaeocene and early Eocene epochs, to a colder ‘icehouse’ world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent ~14 Myr, we find sedimentation rates of 1–2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (~3.2 Myr ago) and East Antarctic ice (~14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (~45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at ~49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (~55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

Search for neutral MSSM Higgs bosons at LEP

Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.

The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

Abstract: The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Low-level laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials.

Abstract: Objective: The aim of this study was to review the biological and clinical short-term effects of low-level laser therapy (LLLT) in acute pain from soft-tissue injury. Background Data: It is unclear if and how LLLT can reduce acute pain. Methods: Literature search of (i) controlled laboratory trials investigating potential biological mechanisms for pain relief and (ii) randomized placebo-controlled clinical trials which measure outcomes within the first 7 days after acute soft-tissue injury. Results: There is strong evidence from 19 out of 22 controlled laboratory studies that LLLT can modulate inflammatory pain by reducing levels of biochemical markers (PGE2, mRNA Cox 2, IL-1β, TNFα), neutrophil cell influx, oxidative stress, and formation of edema and hemorrhage in a dosedependent manner (median dose 7.5 J/cm2, range 0.3–19 J/cm2). Four comparisons with non-steroidal anti-inflammatory drugs (NSAIDs) in animal studies found optimal doses of LLLT and NSAIDs to be equally effective. Seven randomized placebo...

The "Stern Review" on the Economics of Climate Change

Abstract: How much and how fast should the globe reduce greenhouse-gas emissions? How should nations balance the costs of the reductions against the damages and dangers of climate change? This question has been addressed by the recent "Stern Review on the Economics of Climate Change," which answers these questions clearly and unambiguously We need urgent, sharp, and immediate reductions in greenhouse-gas emissions An analysis of the "Stern Review" finds that these recommendations depend decisively on the assumption of a near-zero social discount rate The Review's unambiguous conclusions about the need for extreme immediate action will not survive the substitution of discounting assumptions that are consistent with today's market place

Guidelines for treatment of autoimmune neuromuscular transmission disorders.

Abstract: Background: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert–Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs syndrome). Methods: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts. Conclusions: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non-thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long-term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4-Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short-term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).

A binary level set model and some applications to Mumford-Shah image segmentation

Abstract: In this paper, we propose a PDE-based level set method. Traditionally, interfaces are represented by the zero level set of continuous level set functions. Instead, we let the interfaces be represented by discontinuities of piecewise constant level set functions. Each level set function can at convergence only take two values, i.e., it can only be 1 or -1; thus, our method is related to phase-field methods. Some of the properties of standard level set methods are preserved in the proposed method, while others are not. Using this new method for interface problems, we need to minimize a smooth convex functional under a quadratic constraint. The level set functions are discontinuous at convergence, but the minimization functional is smooth. We show numerical results using the method for segmentation of digital images.

Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1

Abstract: Background The autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In autoimmune polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity and chronic candidiasis can associate with thymomas as well. Patients with these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising type I interferon (IFN)–α and IFN-ω, which are secreted signalling proteins of the cytokine superfamily involved in both innate and adaptive immunity. Methods and Findings We tested for serum autoantibodies to type I IFNs and other immunoregulatory cytokines using specific binding and neutralisation assays. Unexpectedly, in 60/60 Finnish and 16/16 Norwegian APS1 patients with both AIRE alleles mutated, we found high titre neutralising immunoglobulin G autoantibodies to most IFN-α subtypes and especially IFN-ω (60% homologous to IFN-α)—mostly in the earliest samples. We found lower titres against IFN-β (30% homologous to IFN-α) in 23% of patients; two-thirds of these (from Finland only) also had low titres against the distantly related “type III IFN” (IFN-λ1; alias interleukin-29). However, autoantibodies to the unrelated type II IFN, IFN-γ, and other immunoregulatory cytokines, such as interleukin-10 and interleukin-12, were much rarer and did not neutralise. Neutralising titres against type I IFNs averaged even higher in patients with APS1 than in patients with thymomas. Anti–type I IFN autoantibodies preceded overt candidiasis (and several of the autoimmune disorders) in the informative patients, and persisted for decades thereafter. They were undetectable in unaffected heterozygous relatives of APS1 probands (except for low titres against IFN-λ1), in APS2 patients, and in isolated cases of the endocrine diseases most typical of APS1, so they appear to be APS1-specific. Looking for potentially autoimmunising cell types, we found numerous IFN-α+ antigen-presenting cells—plus strong evidence of local IFN secretion—in the normal thymic medulla (where AIRE expression is strongest), and also in normal germinal centres, where it could perpetuate these autoantibody responses once initiated. IFN-α2 and IFN-α8 transcripts were also more abundant in antigen-presenting cells cultured from an APS1 patient's blood than from age-matched healthy controls. Conclusions These apparently spontaneous autoantibody responses to IFNs, particularly IFN-α and IFN-ω, segregate like a recessive trait; their high “penetrance” is especially remarkable for such a variable condition. Their apparent restriction to APS1 patients implies practical value in the clinic, e.g., in diagnosing unusual or prodromal AIRE-mutant patients with only single components of APS1, and possibly in prognosis if they prove to predict its onset. These autoantibody responses also raise numerous questions, e.g., about the rarity of other infections in APS1. Moreover, there must also be clues to autoimmunising mechanisms/cell types in the hierarchy of preferences for IFN-ω, IFN-α8, IFN-α2, and IFN-β and IFN-λ1.

Strongly interacting low-viscosity matter created in relativistic nuclear collisions.

Abstract: Substantial collective flow is observed in collisions between large nuclei at BNL RHIC (Relativistic Heavy Ion Collider) as evidenced by single-particle transverse momentum distributions and by azimuthal correlations among the produced particles. The data are well reproduced by perfect fluid dynamics. A calculation of the dimensionless ratio of shear viscosity eta to entropy density s by Kovtun, Son, and Starinets within anti-de Sitter space/conformal field theory yields eta/s=variant Planck's over 2pi/4pikB, which has been conjectured to be a lower bound for any physical system. Motivated by these results, we show that the transition from hadrons to quarks and gluons has behavior similar to helium, nitrogen, and water at and near their phase transitions in the ratio eta/s. We suggest that experimental measurements can pinpoint the location of this transition or rapid crossover in QCD.