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Search Results: 1 - 10 of 1557 matches for " Ole Kristensen "
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Coping and return to work: Measurement and theoretical issues
Magnus Odéen,Lars Ole Kristensen,Holger Ursin
Norsk Epidemiologi , 2010,
Abstract: Sick leave and early departure from the workforce have serious adverse effects on both individuals and society. Motivation and coping are both important when attempting to return to work. In this article, we wanted to test if either of two coping instruments could predict return to work. Response outcome expectancies as defined in the Cognitive Activation Theory of Stress (CATS) (Ursin & Eriksen, 2004) were measured by the CODE scale (Eriksen et al., 1997) and general self-efficacy was measured by the generalized self-efficacy scale (GSE) (Schwarzer & Jerusalem, 1995). The instruments were tested in one group of rehabilitation patients (N= 135) and one group of disability pensioners (N=85), who participated in return to work interventions in randomised controlled trials. None of the instruments could predict return to work at any point of measurement. Less than 10% of the theoretical range of the scales was used. The scales appear to measure a concept that is more stable than their underlying theory predicts, and they can not predict an important outcome. Results indicate that caution is advised when making inferences from these instruments to their underlying theories.
Crystal Structures of the Human G3BP1 NTF2-Like Domain Visualize FxFG Nup Repeat Specificity
Tina Vognsen, Ingvar Runár M?ller, Ole Kristensen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080947
Abstract: Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded form of the G3BP1 NTF2-like domain was solved in two crystal forms to resolutions of 1.6 and 3.3 ? in space groups P212121 and P6322 based on two different constructs, residues 1–139 and 11–139, respectively. Crystal packing of the N-terminal residues against a symmetry related molecule in the P212121 crystal form might indicate a novel ligand binding site that, however, remains to be validated. The crystal structures give insight into the nuclear transportation mechanisms of G3BP and provide a basis for future structure based drug design.
Bioinformatics and Structural Characterization of a Hypothetical Protein from Streptococcus mutans: Implication of Antibiotic Resistance
Jie Nan, Erik Brostromer, Xiang-Yu Liu, Ole Kristensen, Xiao-Dong Su
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007245
Abstract: As an oral bacterial pathogen, Streptococcus mutans has been known as the aetiologic agent of human dental caries. Among a total of 1960 identified proteins within the genome of this organism, there are about 500 without any known functions. One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families. Phylogenetic studies showed that SMU.440 is related to a particular ecological niche and conserved specifically in some oral pathogens, due to lateral gene transfer. The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance. The structure determination of SMU.440 revealed that it shares the same fold and a similar pocket as polyketide cyclases, which indicated that it is very likely to bind some polyketide-like molecules. From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein. Besides, the combination of multiple methods in this study can be used as a general approach for functional studies of a protein with unknown function.
Mobile City- og sprogguides. Nye forbindelser mellem formelle og uformelle l ringsmilj er
Mads Bo Kristensen,Niels Ole Ankerstjerne,Anne Chresteria Neutsky-Wulff,Herluf Schelde
L?ring og Medier , 2009,
Abstract: Denne artikel pr senterer og diskuterer et m-l ringsdidaktisk scenarie til fremmedsprogsundervisning p videreg ende uddannelser. Scenariet er et bud p , hvordan mobilen og web 2.0 kan inddrages i undervisningen. Scenariet kaldes for Mobil city- og sprogguides og er en kombination af mobilt internet, GPS, Google Maps og geotagging. Fokus er p , hvordan mobilen og nettet med deres nye udviklinger kan anvendes til at skabe forbindelser mellem det formelle undervisningsrum og de uformelle l ringssituationer uden for rummet. Disse mobile og internetbaserede forbindelser er med til at "guide" den studerende ind i fremmedsproget og de kontekster, det skabes i. Artiklen pr senterer et eksempel p , hvordan Mobile city- og sprogguides kan anvendes p en studietur til et af fremmedsprogenes storbyer.
A Novel Heavy Domain Antibody Library with Functionally Optimized Complementarity Determining Regions
Ole Aalund Mandrup, Niels Anton Friis, Simon Lykkemark, Jesper Just, Peter Kristensen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076834
Abstract: Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.
Disease Activity in Inflammatory Bowel Disease Is Associated with Increased Risk of Myocardial Infarction, Stroke and Cardiovascular Death – A Danish Nationwide Cohort Study
S?ren Lund Kristensen, Ole Ahlehoff, Jesper Lindhardsen, Rune Erichsen, Gunnar Vagn Jensen, Christian Torp-Pedersen, Ole Haagen Nielsen, Gunnar Hilmar Gislason, Peter Riis Hansen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056944
Abstract: Purpose Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD. Methods In a nationwide Danish population-based setting, a cohort of patients with incident IBD between 1996 and 2009 were identified in national registers. Hospitalizations with IBD as primary diagnosis, initiation of biological treatment and dispensed prescriptions of corticosteroids were all used as surrogate markers for disease activity, with flares classified as the first 120 days after diagnosis of IBD, and 120 days after a new corticosteroid prescription, biological treatment or IBD hospitalization, respectively. Continued corticosteroid prescriptions or IBD hospitalizations were defined as persistent activity, and periods free of such events were defined as remissions. Poisson regression was used to examine risk of MI, stroke, and cardiovascular death using a matched population-based comparison cohort as reference Results We identified 20,795 IBD patients with a mean age of 40.3 years that were matched according to age and sex with 199,978 controls. During the study period, there were 365 patients with MI, 454 with stroke, and 778 with cardiovascular death. Patients with IBD had an overall increased risk of MI (rate ratio [RR] 1.17 [95% confidence interval 1.05–1.31]), stroke (RR 1.15 [1.04–1.27], and cardiovascular death (RR 1.35 [1.25–1.45]). During flares and persistent IBD activity the RRs of MI increased to 1.49 (1.16–1.93) and 2.05 (1.58–2.65), the RRs of stroke to 1.53 (1.22–1.92) and 1.55 (1.18–2.04) and for cardiovascular death 2.32 (2.01–2.68) and 2.50 (2.14–2.92). In remission periods, the risk of MI, stroke and cardiovascular death was similar to controls. Conclusion Inflammatory bowel disease is associated with increased risk of MI, stroke, and cardiovascular death during periods with active disease.
QT Measurement and Heart Rate Correction during Hypoglycemia: Is There a Bias?
Toke Folke Christensen,Jette Randl?v,Leif Engmann Kristensen,Ebbe Eldrup,Ole Kristian Hejlesen,Johannes Jan Struijk
Cardiology Research and Practice , 2010, DOI: 10.4061/2010/961290
Abstract: Introduction. Several studies show that hypoglycemia causes QT interval prolongation. The aim of this study was to investigate the effect of QT measurement methodology, heart rate correction, and insulin types during hypoglycemia. Methods. Ten adult subjects with type 1 diabetes had hypoglycemia induced by intravenous injection of two insulin types in a cross-over design. QT measurements were done using the slope-intersect (SI) and manual annotation (MA) methods. Heart rate correction was done using Bazett’s (QTcB) and Fridericia’s (QTcF) formulas. Results. The SI method showed significant prolongation at hypoglycemia for QTcB (42(6)?ms; ) and QTcF (35(6)?ms; ). The MA method showed prolongation at hypoglycemia for QTcB (7(2)?ms, ) but not QTcF. No difference in ECG variables between the types of insulin was observed. Discussion. The method for measuring the QT interval has a significant impact on the prolongation of QT during hypoglycemia. Heart rate correction may also influence the QT during hypoglycemia while the type of insulin is insignificant. Prolongation of QTc in this study did not reach pathologic values suggesting that QTc prolongation cannot fully explain the dead-in-bed syndrome. 1. Introduction The introduction of human insulin in the 1990s led to an increase in the number of sudden nocturnal deaths of young people with type I diabetes. This specific type of death in diabetes was termed the “dead in bed” syndrome and it was hypothesized that the deaths were caused by hypoglycemia [1]. The pathophysiological mechanisms behind the deaths are still not understood although circumstantial evidence suggests that they are cases of fatal cardiac arrhythmia. The proposed proarrhythmic effect of hypoglycemia is thought to be mediated by sympathoadrenal activation and hypokalaemia [2]. It has been reported that insulin-induced hypoglycemia affects repolarization of the cardiac cells in both healthy subjects [3, 4] and people with diabetes [5–7]. The altered repolarization is notable on the electrocardiogram (ECG) as a flattened T wave [4, 6] and a prolonged heart rate-corrected QT interval (QTc) [3, 5]. A prolonged QTc is associated with an increased risk of sudden cardiac death [8, 9], and QTc has thus been the primary variable investigated in studies of the proarrhythmic effect of hypoglycemia. The degree of QTc prolongation during clamped hypoglycemia ranges from 5?ms [6] to 60?ms [3] with one study reporting a prolongation of 156?ms [5]. Thus, in some studies the prolongation of QTc is seen to be insignificant while other studies show a
Linear and non-linear dependencies between copy number aberrations and mRNA expression reveal distinct molecular pathways in breast cancer
Hiroko K Solvang, Ole Lingj?rde, Arnoldo Frigessi, Anne-Lise B?rresen-Dale, Vessela N Kristensen
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-197
Abstract: We applied the proposed method to DNA copy numbers derived from Illumina 109 K SNP-CGH arrays (using the log R values) and expression data from Agilent 44 K mRNA arrays, focusing on commonly aberrated genomic loci in a collection of 102 breast tumors. Regression analysis was used to identify the type of relationship (linear or nonlinear), and subsequent pathway analysis revealed that genes displaying a linear relationship were overall associated with substantially different biological processes than genes displaying a nonlinear relationship. In the group of genes with a linear relationship, we found significant association to canonical pathways, including purine and pyrimidine metabolism (for both deletions and amplifications) as well as estrogen metabolism (linear amplification) and BRCA-related response to damage (linear deletion). In the group of genes displaying a nonlinear relationship, the top canonical pathways were specific pathways like PTEN and PI13K/AKT (nonlinear amplification) and Wnt(B) and IL-2 signalling (nonlinear deletion). Both amplifications and deletions pointed to the same affected pathways and identified cancer as the top significant disease and cell cycle, cell signaling and cellular development as significant networks.This paper presents a novel approach to assessing the validity of the dependence of expression data on copy number data, and this approach may help in identifying the drivers of carcinogenesis.Cancer development and progression are complex processes involving a series of genetic and functional abnormalities. Joint analysis of array comparative genomic hybridization (aCGH) copy number data and microarray gene expression data may uncover biological relationships relevant to our understanding of cancer. Previous whole-genome analyses of copy number and gene expression have led to the identification of global cellular processes underlying malignant transformation and progression. In addition to basic biological applications, clinic
Gene expression analyses in breast cancer epidemiology: the Norwegian Women and Cancer postgenome cohort study
Vanessa Dumeaux, Anne-Lise B?rresen-Dale, Jan-Ole Frantzen, Merethe Kumle, Vessela N Kristensen, Eiliv Lund
Breast Cancer Research , 2008, DOI: 10.1186/bcr1859
Abstract: The Norwegian Women and Cancer (NOWAC) postgenome cohort study consists of approximately 50,000 women born between 1943 and 1957 who gave blood samples between 2003 and 2006 and filled out a two-page questionnaire. Blood was collected in such a way that RNA is preserved and can be used for gene expression analyses. The women are part of the NOWAC study consisting of 172,471 women 30 to 70 years of age at recruitment from 1991 to 2006 who answered one to three questionnaires on diet, medication use, and lifestyle. In collaboration with the Norwegian Breast Cancer Group, every NOWAC participant born between 1943 and 1957 who is admitted to a collaborating hospital for a diagnostic biopsy or for surgery of breast cancer will be asked to donate a tumor biopsy and two blood samples. In parallel, at least three controls are approached for each breast cancer case in order to obtain blood samples from at least two controls per case. The controls are drawn at random from NOWAC matched by time of follow-up and age. In addition, 400 normal breast tissues as well as blood samples will be collected among healthy women participating at the Norwegian Mammography Screening program at the Breast Imaging Center at the University Hospital of North-Norway, Troms?.The NOWAC postgenome cohort offers a unique opportunity (a) to study blood-derived gene expression profiles as a diagnostic test for breast cancer in a nested case-control design with adjustment for confounding factors related to different exposures, (b) to improve the reliability and accuracy of this approach by adjusting for an individual's genotype (for example, variants in genes coding for hormone and drug-metabolizing and detoxifying enzymes), (c) to study gene expression profiles from peripheral blood as surrogate tissue to biomonitor defined exposure (for example, hormone) and its association with disease risk (that is, breast cancer), and (d) to study gene variants (single nucleotide polymorphisms and copy number varia
Induction of Empathy by the Smell of Anxiety
Alexander Prehn-Kristensen, Christian Wiesner, Til Ole Bergmann, Stephan Wolff, Olav Jansen, Hubertus Maximilian Mehdorn, Roman Ferstl, Bettina M. Pause
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005987
Abstract: The communication of stress/anxiety between conspecifics through chemosensory signals has been documented in many vertebrates and invertebrates. Here, we investigate how chemosensory anxiety signals conveyed by the sweat of humans (N = 49) awaiting an academic examination are processed by the human brain, as compared to chemosensory control signals obtained from the same sweat donors in a sport condition. The chemosensory stimuli were pooled according to the donation condition and administered to 28 participants (14 males) synchronously to breathing via an olfactometer. The stimuli were perceived with a low intensity and accordingly only about half of the odor presentations were detected by the participants. The fMRI results (event-related design) show that chemosensory anxiety signals activate brain areas involved in the processing of social emotional stimuli (fusiform gyrus), and in the regulation of empathic feelings (insula, precuneus, cingulate cortex). In addition, neuronal activity within attentional (thalamus, dorsomedial prefrontal cortex) and emotional (cerebellum, vermis) control systems were observed. The chemosensory perception of human anxiety seems to automatically recruit empathy-related resources. Even though the participants could not attentively differentiate the chemosensory stimuli, emotional contagion seems to be effectively mediated by the olfactory system.
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