scispace - formally typeset
Search or ask a question

Showing papers by "University of Copenhagen published in 2006"


Journal ArticleDOI
TL;DR: Episodic antiretroviral therapy guided by the CD4+ count significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antireteviral therapy, largely as a consequence of lowering theCD4+ cell count and increasing the viral load.
Abstract: Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. Results A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P = 0.007) and 1.7 (95% CI, 1.1 to 2.5; P = 0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). Conclusions Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352.)

1,999 citations


Journal ArticleDOI
TL;DR: Glucosinolates are sulfur-rich, anionic natural products that upon hydrolysis by endogenous thioglucosidases called myrosinases produce several different products that function as cancer-preventing agents, biopesticides, and flavor compounds.
Abstract: Glucosinolates are sulfur-rich, anionic natural products that upon hydrolysis by endogenous thioglucosidases called myrosinases produce several different products (e.g., isothiocyanates, thiocyanates, and nitriles). The hydrolysis products have many different biological activities, e.g., as defense compounds and attractants. For humans these compounds function as cancer-preventing agents, biopesticides, and flavor compounds. Since the completion of the Arabidopsis genome, glucosinolate research has made significant progress, resulting in near-complete elucidation of the core biosynthetic pathway, identification of the first regulators of the pathway, metabolic engineering of specific glucosinolate profiles to study function, as well as identification of evolutionary links to related pathways. Although much has been learned in recent years, much more awaits discovery before we fully understand how and why plants synthesize glucosinolates. This may enable us to more fully exploit the potential of these compounds in agriculture and medicine.

1,955 citations


Journal ArticleDOI
TL;DR: In this paper, a new common stratigraphic timescale for the North Greenland Ice Core Project (NGRIP) and GRIP ice cores is presented, which covers the period 7.9-14.8 kyr before present and includes the Bolling, Allerod, Younger Dryas, and early Holocene periods.
Abstract: [1] We present a new common stratigraphic timescale for the North Greenland Ice Core Project (NGRIP) and GRIP ice cores. The timescale covers the period 7.9–14.8 kyr before present and includes the Bolling, Allerod, Younger Dryas, and early Holocene periods. We use a combination of new and previously published data, the most prominent being new high-resolution Continuous Flow Analysis (CFA) impurity records from the NGRIP ice core. Several investigators have identified and counted annual layers using a multiparameter approach, and the maximum counting error is estimated to be up to 2% in the Holocene part and about 3% for the older parts. These counting error estimates reflect the number of annual layers that were hard to interpret, but not a possible bias in the set of rules used for annual layer identification. As the GRIP and NGRIP ice cores are not optimal for annual layer counting in the middle and late Holocene, the timescale is tied to a prominent volcanic event inside the 8.2 kyr cold event, recently dated in the DYE-3 ice core to 8236 years before A. D. 2000 (b2k) with a maximum counting error of 47 years. The new timescale dates the Younger Dryas-Preboreal transition to 11,703 b2k, which is 100–150 years older than according to the present GRIP and NGRIP timescales. The age of the transition matches the GISP2 timescale within a few years, but viewed over the entire 7.9–14.8 kyr section, there are significant differences between the new timescale and the GISP2 timescale. The transition from the glacial into the Bolling interstadial is dated to 14,692 b2k. The presented timescale is a part of a new Greenland ice core chronology common to the DYE-3, GRIP, and NGRIP ice cores, named the Greenland Ice Core Chronology 2005 (GICC05). The annual layer thicknesses are observed to be log-normally distributed with good approximation, and compared to the early Holocene, the mean accumulation rates in the Younger Dryas and Bolling periods are found to be 47 ± 2% and 88 ± 2%, respectively.

1,789 citations


Journal ArticleDOI
TL;DR: It is recommended that the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, and the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD.

1,698 citations


Journal ArticleDOI
TL;DR: This paper presents a heuristic for the pickup and delivery problem based on an extension of the large neighborhood search heuristic previously suggested for solving the vehicle routing problem with time windows that is very robust and is able to adapt to various instance characteristics.
Abstract: The pickup and delivery problem with time windows is the problem of serving a number of transportation requests using a limited amount of vehicles. Each request involves moving a number of goods from a pickup location to a delivery location. Our task is to construct routes that visit all locations such that corresponding pickups and deliveries are placed on the same route, and such that a pickup is performed before the corresponding delivery. The routes must also satisfy time window and capacity constraints. This paper presents a heuristic for the problem based on an extension of the large neighborhood search heuristic previously suggested for solving the vehicle routing problem with time windows. The proposed heuristic is composed of a number of competing subheuristics that are used with a frequency corresponding to their historic performance. This general framework is denoted adaptive large neighborhood search. The heuristic is tested on more than 350 benchmark instances with up to 500 requests. It is able to improve the best known solutions from the literature for more than 50% of the problems. The computational experiments indicate that it is advantageous to use several competing subheuristics instead of just one. We believe that the proposed heuristic is very robust and is able to adapt to various instance characteristics.

1,685 citations


Journal ArticleDOI
26 Oct 2006-Nature
TL;DR: The genome sequence of the honeybee Apis mellifera is reported, suggesting a novel African origin for the species A. melliferA and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.
Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

1,673 citations


Journal ArticleDOI
TL;DR: The evidence for prescribing exercise therapy in the treatment of metabolic syndrome‐related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases, muscle, bone and joint diseases, and cancer, depression, asthma and type 1 diabetes is presented.
Abstract: Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases, including diseases that do not primarily manifest as disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise therapy in the treatment of metabolic syndrome-related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and the principles for prescribing exercise therapy are discussed, focusing on the type and amount of exercise and possible contraindications.

1,317 citations


Journal ArticleDOI
TL;DR: Moves of variation in logistic regression should be promoted in social epidemiological and public health research as efficient means of quantifying the importance of the context of residence for understanding disparities in health and health related behaviour.
Abstract: STUDY OBJECTIVE: In social epidemiology, it is easy to compute and interpret measures of variation in multilevel linear regression, but technical difficulties exist in the case of logistic regression. The aim of this study was to present measures of variation appropriate for the logistic case in a didactic rather than a mathematical way. Design and PARTICIPANTS: Data were used from the health survey conducted in 2000 in the county of Scania, Sweden, that comprised 10 723 persons aged 18-80 years living in 60 areas. Conducting multilevel logistic regression different techniques were applied to investigate whether the individual propensity to consult private physicians was statistically dependent on the area of residence (that is, intraclass correlation (ICC), median odds ratio (MOR)), the 80% interval odds ratio (IOR-80), and the sorting out index). RESULTS: The MOR provided more interpretable information than the ICC on the relevance of the residential area for understanding the individual propensity of consulting private physicians. The MOR showed that the unexplained heterogeneity between areas was of greater relevance than the individual variables considered in the analysis (age, sex, and education) for understanding the individual propensity of visiting private physicians. Residing in a high education area increased the probability of visiting a private physician. However, the IOR showed that the unexplained variability between areas did not allow to clearly distinguishing low from high propensity areas with the area educational level. The sorting out index was equal to 82%. CONCLUSION: Measures of variation in logistic regression should be promoted in social epidemiological and public health research as efficient means of quantifying the importance of the context of residence for understanding disparities in health and health related behaviour.

1,309 citations


Journal ArticleDOI
TL;DR: The Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer are identified using genome-wide location analysis in human embryonic fibroblasts.
Abstract: The Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here, we identify their target genes using genome-wide location analysis in human embryonic fibroblasts. We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions. We functionally identify 40 genes derepressed in human embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the PRC1 component, BMI-1. Interestingly, several markers of osteogenesis, adipogenesis, and chrondrogenesis are among these genes, consistent with the mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we delineate two different mechanisms for regulating PcG target genes. For genes activated during differentiation, PcGs are displaced. However, for genes repressed during differentiation, we paradoxically find that they are already bound by the PcGs in nondifferentiated cells despite being actively transcribed. Our results are consistent with the hypothesis that PcGs are part of a preprogrammed memory system established during embryogenesis marking certain key genes for repressive signals during subsequent developmental and differentiation processes.

1,289 citations


Journal ArticleDOI
TL;DR: It is shown that gadodiamide plays a causative role in nephrogenic systemic fibrosis, and seven patients became severely disabled, and one died 21 mo after exposure.
Abstract: Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.

1,284 citations


Journal ArticleDOI
TL;DR: A strong association between immunodeficiency and risk of liver-related death was found and long-term follow-up is required to investigate whether clinically significant treatment-associated liver- related mortality will develop.
Abstract: Background An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. Methods We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. Results There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02). Conclusions Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.

Journal ArticleDOI
TL;DR: There are major individual differences in the physical demands of players during a game related to physical capacity and tactical role in the team, and these differences should be taken into account when planning the training and nutritional strategies of top-class players, who require a significant energy intake during a week.
Abstract: In soccer, the players perform intermittent work. Despite the players performing low-intensity activities for more than 70% of the game, heart rate and body temperature measurements suggest that the average oxygen uptake for elite soccer players is around 70% of maximum (VO(2max). This may be partly explained by the 150 - 250 brief intense actions a top-class player performs during a game, which also indicates that the rates of creatine phosphate (CP) utilization and glycolysis are frequently high during a game. Muscle glycogen is probably the most important substrate for energy production, and fatigue towards the end of a game may be related to depletion of glycogen in some muscle fibres. Blood free-fatty acids (FFAs) increase progressively during a game, partly compensating for the progressive lowering of muscle glycogen. Fatigue also occurs temporarily during matches, but it is still unclear what causes the reduced ability to perform maximally. There are major individual differences in the physical demands of players during a game related to physical capacity and tactical role in the team. These differences should be taken into account when planning the training and nutritional strategies of top-class players, who require a significant energy intake during a week.

Book
01 Jan 2006
TL;DR: In this paper, a model and relations in economics and economics and Econometrics are discussed. But the authors focus on the Cointegration rank and do not discuss the relationship between the model and the model.
Abstract: BRIDGING ECONOMICS AND ECONOMETRICS 1 Introduction 2 Models and Relations in Economics and Econometrics 3 The Probability Approach in Econometrics and the VAR SPECIFYING THE VAR MODEL 4 The Unrestricted VAR 5 The Cointegrated VAR Model 6 Deterministic Components in the I(1) Model 7 Estimation in the I(1) Model 8 Determination of Cointegration Rank TESTING HYPOTHESES ON COINTEGRATION 9 Recursive Tests of Constancy 10 Testing Restrictions on Beta 11 Testing Restrictions on Alpha IDENTIFICATION 12 Identification of the Long-Run Structure 13 Identification of the Short-Run Structure 14 Identification of Common Trends 15 Identification of a Structural MA Model THE I(2) MODEL 16 Analyzing I(2) Data with the I(1) Model 17 The I(2) Model: specification and estimation 18 Testing Hypotheses in the I(2) Model A METHODOLOGICAL APPROACH 19 Specific-to-General and General-to-Specific 20 Wage, Price, and Unemployment Dynamics 21 Foreign Transmission Effects: Denmark versus Germany 22 Collecting the Threads Appendix A: The Asymptotic Tables for Cointegration Rank

Journal ArticleDOI
TL;DR: The present review will provide a thorough update in this area of inflammatory diseases, specifically Crohn's disease and Blau syndrome, and familial cold autoinflammatory syndrome, Muckle–Wells syndrome and chronic infantile neurological cutaneous and articular syndrome.
Abstract: Inflammation is part of the non-specific immune response that occurs in reaction to any type of bodily injury. In some disorders, the inflammatory process - which under normal conditions is self-limiting - becomes continuous and chronic inflammatory diseases might develop subsequently. Pattern recognition molecules (PRMs) represent a diverse collection of molecules responsible for sensing danger signals, and together with other immune components they are involved in the first line of defence. NALP3 and NOD2, which belong to a cytosolic subgroup of PRMs, dubbed Nod-like-receptors (NLRs), have been associated recently with inflammatory diseases, specifically Crohn's disease and Blau syndrome (NOD2) and familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous and articular syndrome (NALP3). The exact effects of the defective proteins are not fully understood, but activation of nuclear factor (NF)-kappaB, transcription, production and secretion of interleukin (IL)-1beta and activation of the inflammasome are some of the processes that might hold clues, and the present review will provide a thorough update in this area.

Journal ArticleDOI
TL;DR: It is argued that increased attention to the problems identified and challenges discussed may strengthen studies of usability and usability research.
Abstract: How to measure usability is an important question in HCI research and user interface evaluation. We review current practice in measuring usability by categorizing and discussing usability measures from 180 studies published in core HCI journals and proceedings. The discussion distinguish several problems with the measures, including whether they actually measure usability, if they cover usability broadly, how they are reasoned about, and if they meet recommendations on how to measure usability. In many studies, the choice of and reasoning about usability measures fall short of a valid and reliable account of usability as quality-in-use of the user interface being studied. Based on the review, we discuss challenges for studies of usability and for research into how to measure usability. The challenges are to distinguish and empirically compare subjective and objective measures of usability; to focus on developing and employing measures of learning and retention; to study long-term use and usability; to extend measures of satisfaction beyond post-use questionnaires; to validate and standardize the host of subjective satisfaction questionnaires used; to study correlations between usability measures as a means for validation; and to use both micro and macro tasks and corresponding measures of usability. In conclusion, we argue that increased attention to the problems identified and challenges discussed may strengthen studies of usability and usability research.

Journal ArticleDOI
25 May 2006-Nature
TL;DR: In this article, the authors show that long-duration γ-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. But they also show that the host galaxies of the long-drone bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae.
Abstract: When massive stars exhaust their fuel, they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration γ-ray burst. One would then expect that these long γ-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the γ-ray bursts are far more concentrated in the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long γ-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration γ-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long γ-ray bursts are relatively rare in galaxies such as our own Milky Way.

Journal ArticleDOI
TL;DR: The International Headache Classification Committee has worked out the more inclusive criteria for CM and MOH and it is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication over use.
Abstract: After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Journal ArticleDOI
TL;DR: A main objective of this review is to endorse the view that the glutamate/GABA‐glutamine cycle must be seen as a bi‐directional transfer of not only carbon units but also nitrogen units.
Abstract: Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and γ-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA-glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA-glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi-directional transfer of not only carbon units but also nitrogen units.

Journal ArticleDOI
TL;DR: Pectin is a high value functional food ingredient widely used as a gelling agent and stabilizer and it is also an abundant, ubiquitous and multifunctional component of the cell walls of all land plants as mentioned in this paper.
Abstract: Pectin is a high value functional food ingredient widely used as a gelling agent and stabilizer. It is also an abundant, ubiquitous and multifunctional component of the cell walls of all land plants. Food scientists and plant scientists therefore share a common goal to better understand the structure and functionalities of pectic polymers at the molecular level. The basic properties of pectin have been known for nearly 200 years, but recently there has been tremendous progress in our understanding of the very complex fine structure of pectic polymers and pectinolytic enzymes. This has been made possible by synergies between plant and food research and by the application of a range of state-of-the-art techniques including enzymatic fingerprinting, mass spectrometry, NMR, molecular modelling, and monoclonal antibodies. With this increased knowledge comes the prospect of novel applications. Producers are beginning to develop a new generation of sophisticated designer pectins with specific functionalities. Moreover, the ability to manipulate pectin in planta would have a major impact on fruit and vegetable quality and processing, as well as on pectin production.

Journal ArticleDOI
TL;DR: SimMAP has been developed to implement stochastic character mapping that is useful to both molecular evolutionists, systematists, and bioinformaticians and enables users to address questions that require mapping characters onto phylogenies using a probabilistic approach that does not rely on parsimony.
Abstract: Character mapping on phylogenies has played an important, if not critical role, in our understanding of molecular, morphological, and behavioral evolution. Until very recently we have relied on parsimony to infer character changes. Parsimony has a number of serious limitations that are drawbacks to our understanding. Recent statistical methods have been developed that free us from these limitations enabling us to overcome the problems of parsimony by accommodating uncertainty in evolutionary time, ancestral states, and the phylogeny. SIMMAP has been developed to implement stochastic character mapping that is useful to both molecular evolutionists, systematists, and bioinformaticians. Researchers can address questions about positive selection, patterns of amino acid substitution, character association, and patterns of morphological evolution. Stochastic character mapping, as implemented in the SIMMAP software, enables users to address questions that require mapping characters onto phylogenies using a probabilistic approach that does not rely on parsimony. Analyses can be performed using a fully Bayesian approach that is not reliant on considering a single topology, set of substitution model parameters, or reconstruction of ancestral states. Uncertainty in these quantities is accommodated by using MCMC samples from their respective posterior distributions.

Journal Article
TL;DR: Extended exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response, and exercise training may reduce basalIL-6 production as well as the magnitude of the acute exercise IL- 6 response by counteracting several potential stimuli of IL-8.
Abstract: It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of activating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. However, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Furthermore, exercise training may reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6 response by counteracting several potential stimuli of IL-6. Accordingly, a decreased plasma IL-6 concentration at rest as well as in response to exercise appears to characterize normal training adaptation.

Journal ArticleDOI
TL;DR: Evaluated and confirmed efficacy and safety of electrochemotherapy with bleomycin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malignant melanoma and other malignancies in a multicenter study.
Abstract: Purpose: To evaluate and confirm efficacy and safety of electrochemotherapy with bleomycin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malignant melanoma and other malignancies in a multicenter study. Patients and methods: This was a two year long prospective non-randomised study on 41 patients evaluable for response to treatment and 61 evaluable for toxicity. Four cancer centers enrolled patients with progressive cutaneous and subcutaneous metastases of any histologically proven cancer. The skin lesions were treated by electrochemotherapy, using application of electric pulses to the tumours for increased bleomycin or cisplatin delivery into tumour cells. The treatment was performed using intravenous or intratumoural drug injection, followed by application of electric pulses generated by a Cliniporator TM using plate or needle electrodes. Tumour response to electrochemotherapy as well as possible sideeffects with respect to the treatment approach, tumour histology and location of the tumour nodules and electrode type were evaluated. Results: An objective response rate of 85% (73.7% complete response rate) was achieved on the electrochemotherapy treated tumour nodules, regardless of tumour histology, and drug used or route of its administration. At 150 days after the treatment (median follow up was 133 days and range 60‐380 days) local tumour control rate for electrochemotherapy was 88% with bleomycin given intravenously, 73% with bleomycin given intratumourally and 75% with cisplatin given intratumourally, demonstrating that all three approaches were

Journal ArticleDOI
20 Jul 2006-Nature
TL;DR: In addition to identifying GASC1 as a histone trimethyl demethylase, this work suggests a model for how this enzyme might be involved in cancer development, and proposes it as a target for anti-cancer therapy.
Abstract: Methylation of lysine and arginine residues on histone tails affects chromatin structure and gene transcription. Tri- and dimethylation of lysine 9 on histone H3 (H3K9me3/me2) is required for the binding of the repressive protein HP1 and is associated with heterochromatin formation and transcriptional repression in a variety of species. H3K9me3 has long been regarded as a 'permanent' epigenetic mark. In a search for proteins and complexes interacting with H3K9me3, we identified the protein GASC1 (gene amplified in squamous cell carcinoma 1), which belongs to the JMJD2 (jumonji domain containing 2) subfamily of the jumonji family, and is also known as JMJD2C. Here we show that three members of this subfamily of proteins demethylate H3K9me3/me2 in vitro through a hydroxylation reaction requiring iron and alpha-ketoglutarate as cofactors. Furthermore, we demonstrate that ectopic expression of GASC1 or other JMJD2 members markedly decreases H3K9me3/me2 levels, increases H3K9me1 levels, delocalizes HP1 and reduces heterochromatin in vivo. Previously, GASC1 was found to be amplified in several cell lines derived from oesophageal squamous carcinomas, and in agreement with a contribution of GASC1 to tumour development, inhibition of GASC1 expression decreases cell proliferation. Thus, in addition to identifying GASC1 as a histone trimethyl demethylase, we suggest a model for how this enzyme might be involved in cancer development, and propose it as a target for anti-cancer therapy.

Journal ArticleDOI
TL;DR: Sprint performance is reduced both temporarily during a game and at the end of a soccer game, the latter finding may be explained by low glycogen levels in individual muscle fibers.
Abstract: Purpose: To examine muscle and blood metabolites during soccer match play and relate it to possible changes in sprint performance. Methods: Thirty-one Danish fourth division players took part in three friendly games. Blood samples were collected frequently during the game, and muscle biopsies were taken before and after the game as well as immediately after an intense period in each half. The players performed five 30-m sprints interspersed by 25-s recovery periods before the game and immediately after each half (N = 11) or after an intense exercise period in each half (N = 20). Results: Muscle lactate was 15.9 ± 1.9 and 16.9 ± 2.3 mmol·kg-1 d.w. during the first and second halves, respectively, with blood lactate being 6.0 ± 0.4 and 5.0 ± 0.4 mM, respectively. Muscle lactate was not correlated with blood lactate (r2 = 0.06-0.25, P >0.05). Muscle glycogen decreased (P < 0.05) from 449 ± 23 to 255 ± 22 mmol·kg-1 d.w. during the game, with 47 ± 7% of the muscle fibers being completely or almost empty of glycogen after the game. Blood glucose remained elevated during the game, whereas plasma FFA increased (P < 0.05) from 0.45 ± 0.05 to 1.37 ± 0.23 mM. Mean sprint time was unaltered after the first half, but longer (P < 0.05) after the game (2.8 ± 0.7%) as well as after intense periods in the first (1.6 ± 0.6%) and second halves (3.6 ± 0.5%). The decline in sprint performance during the game was not correlated with muscle lactate, muscle pH, or total glycogen content. Conclusion: Sprint performance is reduced both temporarily during a game and at the end of a soccer game. The latter finding may be explained by low glycogen levels in individual muscle fibers. Blood lactate is a poor indicator of muscle lactate during soccer match play.

Journal ArticleDOI
TL;DR: This paper focuses on welfare as the absence of suffering in fish, arguing that complex animals with sophisticated behaviour, such as fish, probably have the capacity for suffer ing, though this may be different in degree and kind from the human experience of this state.
Abstract: Human beings may affect the welfare of fish through fisheries, aquaculture and a number of other activities. There is no agreement on just how to we igh the concern for welfare of fish against the hum an interests involved, but ethical frameworks exist th at suggest how this might be approached. Different definitions of animal welfare focus on an animal's condition, on its subjective experience o f that condition and/or on whether it can lead a natu ral life. These provide different, legitimate, pers pectives, but the approach taken in this paper is to focus on welfare as the absence of suffering. An unresolved and controversial issue in discussion s about animal welfare is whether non-human animals exposed to adverse experiences such as physical injury or confinement experience what humans would call suffering. The neocortex, which in huma ns is an important part of the neural mechanism tha t generates the subjective experience of suffering, i s lacking in fish and non-mammalian animals, and it has been argued that its absence in fish indicates that fish cannot suffer. However, a strong alternative view is that complex animals with sophisticated behaviour, such as fish, probably have the capacity for suffer ing, though this may be different in degree and kind fro m the human experience of this state. Recent empirical studies support this view and show that painful stimuli are, at least, strongly avers ive to fish. Consequently, injury or experience of othe r harmful conditions is a cause for concern in term s of welfare of individual fish. There is also growing e vidence that fish can experience fear-like states a nd that they avoid situations in which they have experience d adverse conditions.

Journal ArticleDOI
TL;DR: The Greenland Ice Core Chronology 2005, GICC05, is extended back to 42 ka b2k (before 2000 AD), i.e. to the end of Greenland Stadial 11.5 years as mentioned in this paper.

Journal ArticleDOI
TL;DR: In this paper, the authors show that the surface enrichment is the result of a minor amount of transport and deposition by aqueous processes on the surface of olivine-bearing basalts.
Abstract: Spirit landed on the floor of Gusev Crater and conducted initial operations on soil covered, rock-strewn cratered plains underlain by olivine-bearing basalts. Plains surface rocks are covered by wind-blown dust and show evidence for surface enrichment of soluble species as vein and void-filling materials and coatings. The surface enrichment is the result of a minor amount of transport and deposition by aqueous processes. Layered granular deposits were discovered in the Columbia Hills, with outcrops that tend to dip conformably with the topography. The granular rocks are interpreted to be volcanic ash and/or impact ejecta deposits that have been modified by aqueous fluids during and/or after emplacement. Soils consist of basaltic deposits that are weakly cohesive, relatively poorly sorted, and covered by a veneer of wind blown dust. The soils have been homogenized by wind transport over at least the several kilometer length scale traversed by the rover. Mobilization of soluble species has occurred within at least two soil deposits examined. The presence of mono-layers of coarse sand on wind-blown bedforms, together with even spacing of granule-sized surface clasts, suggest that some of the soil surfaces encountered by Spirit have not been modified by wind for some time. On the other hand, dust deposits on the surface and rover deck have changed during the course of the mission. Detection of dust devils, monitoring of the dust opacity and lower boundary layer, and coordinated experiments with orbiters provided new insights into atmosphere-surface dynamics.

Journal ArticleDOI
TL;DR: In this paper, the Granger causal relationship between foreign direct investment (FDI) and GDP in a sample of 31 developing countries covering 31 years was analyzed. And they found that FDI has a lasting impact on GDP, while GDP has no long-run impact on the FDI-to-GDP ratio.
Abstract: We analyse the Granger causal relationships between foreign direct investment (FDI) and GDP in a sample of 31 developing countries covering 31 years. Using estimators for heterogeneous panel data we find bi-directional causality between the FDI-to-GDP ratio and the level of GDP. FDI has a lasting impact on GDP, while GDP has no longrun impact on the FDI-to-GDP ratio. In that sense FDI causes growth. Furthermore, in a model for GDP and FDI as a fraction of gross capital formation (GCF) we also find long-run effects from FDI to GDP. This finding may be interpreted as evidence in favour of the hypotheses that FDI has an impact on GDP via knowledge transfers and adoption of new technology.

Journal ArticleDOI
TL;DR: It is strongly indicated that synergistic effects promote biofilm biomass and resistance of the biofilm to antimicrobial agents and bacterial invasion in multispecies biofilms.
Abstract: Most biofilms in their natural environments are likely to consist of consortia of species that influence each other in synergistic and antagonistic manners. However, few reports specifically address interactions within multispecies biofilms. In this study, 17 epiphytic bacterial strains, isolated from the surface of the marine alga Ulva australis, were screened for synergistic interactions within biofilms when present together in different combinations. Four isolates, Microbacterium phyllosphaerae, Shewanella japonica, Dokdonia donghaensis, and Acinetobacter lwoffii, were found to interact synergistically in biofilms formed in 96-well microtiter plates: biofilm biomass was observed to increase by >167% in biofilms formed by the four strains compared to biofilms composed of single strains. When exposed to the antibacterial agent hydrogen peroxide or tetracycline, the relative activity (exposed versus nonexposed biofilms) of the four-species biofilm was markedly higher than that in any of the single-species biofilms. Moreover, in biofilms established on glass surfaces in flow cells and subjected to invasion by the antibacterial protein-producing Pseudoalteromonas tunicata, the four-species biofilms resisted invasion to a greater extent than did the biofilms formed by the single species. Replacement of each strain by its cell-free culture supernatant suggested that synergy was dependent both on species-specific physical interactions between cells and on extracellular secreted factors or less specific interactions. In summary, our data strongly indicate that synergistic effects promote biofilm biomass and resistance of the biofilm to antimicrobial agents and bacterial invasion in multispecies biofilms.

Journal ArticleDOI
TL;DR: A detailed analysis of conditions for in situ detection of miRNAs in the zebrafish embryo using locked nucleic acid (LNA)-modified DNA probes is performed and expression patterns for 15 miRNA molecules in the mouse embryo are reported.
Abstract: MicroRNAs (miRNAs) are 20-23 nucleotide (nt) RNA molecules that regulate gene expression post-transcriptionally. A key step toward understanding the function of the hundreds of miRNAs identified in animals is to determine their expression during development. Here we performed a detailed analysis of conditions for in situ detection of miRNAs in the zebrafish embryo using locked nucleic acid (LNA)-modified DNA probes and report expression patterns for 15 miRNAs in the mouse embryo.