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Search Results: 1 - 10 of 31003 matches for " Fridtjof Thomas "
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Modulation of Oxidative Stress Responses by Vitamin E, or Vitamin A plus Vitamin C Treatment in Human Retinal Pigment Epithelial Cells  [PDF]
Jinggang Yin, Christina S. Winborn, Fridtjof Thomas, Quynh T. Tran, John C. Lang, Edward Chaum
Natural Science (NS) , 2015, DOI: 10.4236/ns.2015.712056
Abstract: The purpose of this study was to characterize the potential of vitamins to protect the retinal pig-ment epithelium (RPE) from oxidative stress (OS). We have previously shown that OS induces the expression of AP1 transcription factors (FOSB, CFOS and ATF3), but is modulated by pretreatment with vitamin C (200 μM). We propose that OS-induced AP1 expression can be used as a biomarker of OS to test the efficacy of vitamins to limit the impact of OS in the RPE. Here we examined the efficacy of vitamin E or combined vitamin A plus vitamin C to modulate OS-induced AP1 expression in the RPE. We pretreated human ARPE-19 cells with vitamin E (0 - 7.5 μM) or with combined vitamin A (10 or 15 μM) plus vitamin C (50 or 100 μM) for 3 days prior to exposure to 500 μM H2O2 OS for 1 - 4 h. AP1 expression was assessed using
Parental ages and levels of DNA methylation in the newborn are correlated
Ronald M Adkins, Fridtjof Thomas, Frances A Tylavsky, Julia Krushkal
BMC Medical Genetics , 2011, DOI: 10.1186/1471-2350-12-47
Abstract: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels.These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.DNA methylation is a normal, heritable epigenetic modification that down-regulates the expression of approximately 1/3 of human genes [1-3] and is key to the allele-specific imprinting of genes [4]. DNA methylation also plays an important role in disease. For example, overall DNA hypomethylation accompanied by gene-specific hypermethylation is a hallmark of cancer [5]. Additionally, shifts in DNA methylation patterns appear to be involved in the normal aging process and increase in disease susceptibility [6]. Indeed, there is ample evidence for characteristic changes in the patterns of DNA methylation with age.The earliest data supporting progressive changes in DNA methylation patterns with age came from global studies of blood that demonstrated lower levels of methylation in older individuals [7] and greater differences in methylation in older monozygotic twins [8]. Christensen et al. [9] examined 217 tissues sampled from a range of non-diseased solid tissues and blood. In
Expression Levels of Obesity-Related Genes Are Associated with Weight Change in Kidney Transplant Recipients
Ann Cashion, Ansley Stanfill, Fridtjof Thomas, Lijing Xu, Thomas Sutter, James Eason, Mang Ensell, Ramin Homayouni
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059962
Abstract: Background The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain. Methodology/Principal Findings A secondary data analysis was done on a subgroup (n = 26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes classifications identified metabolic pathways that were enriched in this dataset. Furthermore, GeneIndexer literature mining analysis identified a subset of genes that are highly associated with obesity in the literature and Ingenuity pathway analysis revealed several significant gene networks associated with metabolism and endocrine function. Polymorphisms in several of these genes have previously been linked to obesity. Conclusions/Significance We have successfully identified a set of molecular pathways that taken together may provide insights into the mechanisms of weight gain in kidney transplant recipients. Future work will be done to determine how these pathways may contribute to weight gain.
A High Resolution Genome-Wide Scan of HNF4α Recognition Sites Infers a Regulatory Gene Network in Colon Cancer
Fridtjof Weltmeier, Juergen Borlak
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021667
Abstract: The hepatic nuclear factor HNF4α is a versatile transcription factor and controls expression of many genes in development, metabolism and disease. To delineate its regulatory gene network in colon cancer and to define novel gene targets a comprehensive genome-wide scan was carried out at a resolution of 35 bp with chromatin IP DNA obtained from the human colon carcinoma cell line Caco-2 that is a particularly rich source of HNF4α. More than 90% of HNF4α binding sites were mapped as promoter distal sequences while enhancer elements could be defined to foster chromatin loops for interaction with other promoter-bound transcription factors. Sequence motif analysis by various genetic algorithms evidenced a unique enhanceosome that consisted of the nuclear proteins ERα, AP1, GATA and HNF1α as cooperating transcription factors. Overall >17,500 DNA binding sites were identified with a gene/binding site ratio that differed >6-fold between chromosomes and clustered in distinct chromosomal regions amongst >6600 genes targeted by HNF4α. Evidence is presented for nuclear receptor cross-talk of HNF4α and estrogen receptor α that is recapitulated at the sequence level. Remarkably, the Y-chromosome is devoid of HNF4α binding sites. The functional importance of enrichment sites was confirmed in genome-wide gene expression studies at varying HNF4α protein levels. Taken collectively, a genome-wide scan of HNF4α binding sites is reported to better understand basic mechanisms of transcriptional control of HNF4α targeted genes. Novel promoter distal binding sites are identified which form an enhanceosome thereby facilitating RNA processing events.
Norwegian Residential Energy Demand: Coordinated use of a System Engineering and a Macroeconomic Model
Tor A Johnsen,Fridtjof F. Unander
Modeling, Identification and Control , 1996, DOI: 10.4173/mic.1996.3.2
Abstract: In Norway, the system engineering model MARKAL and the macroeconomic model MSG-EE are both used in studies of national CO2 controlling strategies. MARKAL is a linear programming model that calculates a composite set of technologies necessary to meet demand and environmental constraints at minimised total energy expenditure. MSG-EE is an applied general equilibrium model including the link between economic activity, energy demand and emissions to air. MSG-EE has a theory consistent description of the link between income, prices and energy demand, but the representation of technological improvements is simple. MARKAL has a sophisticated description of future energy technology options, but includes no feedback to the general economy. A project for studying the potential for a coordinated use of these two models was initiated and funded by the Norwegian Research Council (NFR). This paper gives a brief presentation of the two models. Results from independent model calculations show that MARKAL gives a signficant lower residential energy demand than MSG-EE does. This is explained by major differences in modelling approach. A first attempt of coordinating the residential energy demand in the models is reported. This attempt shows that implementing results from MARKAL, in MSG-EE for the residential sector alone gives little impact on the general economy. A further development of an iteration procedure between the models should include all energy using sectors.
Infatuation and Lovesickness on Sleep Quality and Dreams in Adolescence  [PDF]
Angelika A. Schlarb, Nathalie Brock, Fridtjof W. Nussbeck, Merle Cla?en
Health (Health) , 2017, DOI: 10.4236/health.2017.91010
Abstract: Background: Infatuation and lovesickness are widespread and significant experiences in adolescence. Less is known about the connection between infatuation/lovesickness and sleep. The few studies, examining the link between infatuation and sleep quality show inconsistent results. The link between lovesickness and sleep as well as the link between infatuation/lovesickness and dreams has not been investigated yet. The aim of this study was to examine whether infatuation and lovesickness are linked to sleep quality and dreams in adolescents. Methods: A self-assessment online questionnaire was constructed to assess adolescents’ infatuation, lovesickness, sleep quality and dreams. In total, data of 630 adolescents and young adults (150 males, 480 females; aged 16 - 21) were analyzed in this study. Results: Infatuation did not relate to overall sleep quality and dreams. Sleep disturbances, as a component of overall sleep quality, were more frequent in infatuated adolescents. Adolescents currently suffering from lovesickness reported a significantly lower sleep quality, more negative dreams and nightmares. Furthermore, nightmares influenced them more strongly the next day. Conclusions: The associations between infatuation/lovesickness and sleep provide evidence for the far reaching effects of infatuation and lovesickness in adolescents’ lives. The fact that lovesickness leads to lower sleep quality and more negative dreams should be integrated in new approaches of insomnia treatment.
Change in Access to Prescribed Medication following an Episode of Deliberate Self-Poisoning: A Multilevel Approach
Bergljot Gjelsvik, Fridtjof Heyerdahl, Daniel Lunn, Keith Hawton
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098086
Abstract: Objective Patients with a history of deliberate self-poisoning (DSP) are prescribed a greater amount of medication than the general public. DSP is the most robust risk factor for repeat episodes of DSP and subsequent death by suicide, and one might therefore expect that access to prescribed medication would be reduced following an episode of DSP. However, it is unclear whether access to prescribed medication changes after an episode of DSP. The objectives of this study were to investigate changes in 1) overall, psychotropic, non-psychotropic and the psychotropic subgroup antidepressant prescribed medication availability in DSP patients following an episode of DSP, 2) prescribing of the medication ingested in the episode, and 3) potential effects of gender, age and repeater status on such change. Methods The design was longitudinal. We included 171 patients admitted for DSP between January 2006 and March 2007. Data on patients' prescriptions prior to admission were retrieved from The Norwegian Prescription Database. The outcome measure was the difference between medication load in the year following compared to the year prior to the DSP episode. Results There was a significant increase in total medication load following DSP, including both psychotropic and non-psychotropic medication. Antidepressant medication load remained stable. There was a tendency for access to drugs ingested in the episode to increase following the episode, albeit not significantly. Medication load increased with age across all medication groups irrespective of time period and gender. Conclusions The findings show that physicians do not curb prescribing to patients who have recently deliberately self-poisoned. Moreover, they highlight the need for cautious and judicious prescribing for these patients, in combination with psychological and social interventions.
Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study
Christopher S. Carlson ,Tara C. Matise,Kari E. North,Christopher A. Haiman,Megan D. Fesinmeyer,Steven Buyske,Fredrick R. Schumacher,Ulrike Peters,Nora Franceschini,Marylyn D. Ritchie,David J. Duggan,Kylee L. Spencer,Logan Dumitrescu,Charles B. Eaton,Fridtjof Thomas,Alicia Young,Cara Carty,Gerardo Heiss,Loic Le Marchand,Dana C. Crawford,Lucia A. Hindorff,Charles L. Kooperberg,for the PAGE Consortium
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001661
Abstract: The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging.
Fatal poisonings in Oslo: a one-year observational study
Mari A Bjornaas, Brita Teige, Knut E Hovda, Oivind Ekeberg, Fridtjof Heyerdahl, Dag Jacobsen
BMC Emergency Medicine , 2010, DOI: 10.1186/1471-227x-10-13
Abstract: Fatal and non-fatal acute poisonings in subjects aged ≥16 years in Oslo (428 198 inhabitants) were included consecutively in an observational multi-centre study including the ambulance services, the Oslo Emergency Ward (outpatient clinic), and hospitals, as well as medico-legal autopsies from 1st April 2003 to 31st March 2004. Characteristics of fatal poisonings were examined, and a comparison of toxic agents was made between fatal and non-fatal acute poisoning.In Oslo, during the one-year period studied, 103 subjects aged ≥16 years died of acute poisoning. The annual mortality rate was 24 per 100 000. The male-female ratio was 2:1, and the mean age was 44 years (range 19-86 years). In 92 cases (89%), death occurred outside hospital. The main toxic agents were opiates or opioids (65% of cases), followed by ethanol (9%), tricyclic anti-depressants (TCAs) (4%), benzodiazepines (4%), and zopiclone (4%). Seventy-one (69%) were evaluated as accidental deaths and 32 (31%) as suicides. In 70% of all cases, and in 34% of suicides, the deceased was classified as drug or alcohol dependent. When compared with the 2981 non-fatal acute poisonings registered during the study period, the case fatality rate was 3% (95% C.I., 0.03-0.04). Methanol, TCAs, and antihistamines had the highest case fatality rates; 33% (95% C.I., 0.008-0.91), 14% (95% C.I., 0.04-0.33), and 10% (95% C.I., 0.02-0.27), respectively.Three per cent of all acute poisonings were fatal, and nine out of ten deaths by acute poisonings occurred outside hospital. Two-thirds were evaluated as accidental deaths. Although case fatality rates were highest for methanol, TCAs, and antihistamines, most deaths were caused by opiates or opioids.Deaths by acute poisoning are mainly suicides or consequences of substance use disorders. The majority of deaths attributed to substance use disorder are considered accidental, i.e. death was not the intended outcome [1]. However, a post-mortem determination of the intention behind a fa
Mechanical control of vibrational states in single-molecule junctions
Youngsang Kim,Hyunwook Song,Florian Strigl,Hans-Fridtjof Pernau,Takhee Lee,Elke Scheer
Physics , 2010,
Abstract: We report on inelastic electron tunneling spectroscopy measurements carried out on single molecules incorporated into a mechanically controllable break-junction of Au and Pt electrodes at low temperature. Here we establish a correlation between the molecular conformation and conduction properties of a single-molecule junction. We demonstrate that the conductance through single molecules crucially depends on the contact material and configuration by virtue of their mechanical and electrical properties. Our findings prove that the charge transport via single molecules can be manipulated by varying both the molecular conformation (e.g., trans or gauche) and the contact material.
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