Phase behaviour of DNA in presence of DNA-binding proteins

To characterize the thermodynamical equilibrium of DNA chains interacting with a solution of non-specific binding proteins, a Flory-Huggins free energy model was implemented. We explored the dependence on DNA and protein concentrations of the DNA collapse. For physiologically relevant values of the DNA-protein affinity, this collapse gives rise to a biphasic regime with a dense and a dilute phase; the corresponding phase diagram was computed. Using an approach based on Hamiltonian paths, we show that the dense phase has either a molten globule or a crystalline structure, depending on the DNA bending rigidity, which is influenced by the ionic strength. These results are valid at the thermodynamical equilibrium and should therefore be consistent with many biological processes, whose characteristic timescales range typically from 1 ms to 10 s. Our model may thus be applied to biological phenomena that involve DNA-binding proteins, such as DNA condensation with crystalline order, which occurs in some bacteria to protect their chromosome from detrimental factors; or transcription initiation, which occurs in clusters called transcription factories that are reminiscent of the dense phase characterized in this study.Comment: 20 pages, 9 figures, accepted for publication at The Biophysical Journa

On Restricting Real-Valued Genotypes in Evolutionary Algorithms

Real-valued genotypes together with the variation operators, mutation and crossover, constitute some of the fundamental building blocks of Evolutionary Algorithms. Real-valued genotypes are utilized in a broad range of contexts, from weights in Artificial Neural Networks to parameters in robot control systems. Shared between most uses of real-valued genomes is the need for limiting the range of individual parameters to allowable bounds. In this paper we will illustrate the challenge of limiting the parameters of real-valued genomes and analyse the most promising method to properly limit these values. We utilize both empirical as well as benchmark examples to demonstrate the utility of the proposed method and through a literature review show how the insight of this paper could impact other research within the field. The proposed method requires minimal intervention from Evolutionary Algorithm practitioners and behaves well under repeated application of variation operators, leading to better theoretical properties as well as significant differences in well-known benchmarks

Towards an Optimized Dichotic-Listening Paradigm

Dikotisk lytting (DL) er en veletablert non-invasiv test, ofte brukt til å undersøke hemisfærisk dominans for tale og språkprosessering. Til tross for den utbredte bruken både innen forskning og diagnostikk, tydes det på at DL-paradigmer har lidd av middelmådig reliabilitet, et problem som utvilsomt svekker konklusjoner trukket fra testenes målinger. I denne forstand tok den aktuelle studien sikte på å designe og evaluere et nytt DL-paradigme, optimalisert for reliabel vurdering av hemisfæriske forskjeller i taleprosessering. Etter en omfattende litteraturgjennomgang ble designfunksjoner foreslått. Disse var basert på de viktigste eksperimentelle faktorene kjent for å tilføye systematisk bias til oppgaveutførelsen eller for å påvirke tilfeldig feilvarians. Et sentralt designprinsipp var å redusere oppgaveinduserte kognitive krav i forsøket på å undersøke stimulusdrevne lateralitetsestimater. De viktigste designfunksjonene som ble implementert inkluderte bruken av stopp-konsonant vokalstavelser (CV) som stimulansmateriale, et enkelt stimuluspar i hver prøve, og en enkel, fri tilbakekalling som responsinstruksjon. Friske, høyrehendte unge og middelaldrende voksne (N = 50) deltok i en test-retestevaluering av en verbal og en manuell responsformatversjon av paradigmet. Uavhengig av responsformat, avslørte intra- klassekorrelasjonskoeffisientene (ICC) «gode» til «utmerkede» reliabilitetsestimater for hele paradigmet. De aktuelle resultatene indikerer at det foreliggende paradigmet kan tilby et effektivt alternativ til eksisterende paradigmer, både i eksperimentelle og kliniske områder.Masteroppgave i psykologiMAPSYK360INTL-SVINTL-MNINTL-HFINTL-PSYKINTL-MEDMAPS-PSYKINTL-KMDINTL-JU

Phase Locking Between Fiske and Flux-Flow Modes in Coupled Sine-Gordon Systems

We investigate nonlinear resonant modes in coupled sine-Gordon systems with open boundary conditions. The system models coupled Josephson junctions with boundary conditions representing the situation where an external magnetic field is applied. The so-called Fiske modes are found to exist in phase-locked states where the equivalent voltages across the individual coupled Josephson junctions are either identical or identical with opposite signs. The analysis covers all Fiske modes including the flux-flow region. We present a comprehensive comparison between results on analytical treatment and direct numerical simulations of the coupled field equations

Effects of apoB-derived peptide vaccination in a murine model of systemic lupus erythematosus

OBJECTIVE: Atherosclerotic disease progression is mediated in part, by immunological mechanisms. In recent years, interest has increased towards the prospect of modulating these immune mechanisms through vaccination to ameliorate the course of disease. Patients with lupus are at a significantly higher risk for accelerated atherosclerosis and related complications. The goal of this study was to assess the outcome of immunization in mouse models of lupus, and lupus with accelerated atherosclerosis. MATERIALS/METHODS: Atherosclerosis-prone apoE^-/- mice and autoimmune gld mice were previously crossed to generate the gld.apoE^-/- mouse. Mice were treated with an apoB-100-derived vaccine, Alum (adjuvant control), or PBS control. The antibody response was determined by quantifying the amount of circulating anti-apoB100. Serum triglyceride and cholesterol levels were analyzed. Kidney tissue from gld and gld.apoE^-/- mice was processed and histologically analyzed, using glomerular tuft size as a measure of renal disease and by extension, autoimmune disease severity. Results: Immunization led to a pronounced initial antibody response that was decreased by the endpoint of the study. No significant differences in serum triglyceride or cholesterol were observed regardless of treatment. Similarly, no significant differences were observed in glomerular tuft size. Conclusion: The data suggests that immunization with an apoB-100- derived vaccine neither improves nor worsens autoimmune disease severity in the gld.apoE^-/- mouse model. It also appears that immunization is tolerated in the autoimmune background. While further study is necessary to determine the efficacy of immunization in reducing atherosclerotic disease in this model, this may be a possible therapy to lower incidence of atherosclerosis in lupus patients

Investigation of immune cells in psoriasis patients treated with infliximab

Postponed access: the file will be accessible after 2022-05-20Psoriasis is a chronic inflammatory disease that manifests in the skin affecting both sexes equally and all ages. In Norway, the prevalence reaches 11.43% in adults. Both genetics and environment factors are important in developing the disease. Comorbidities such as cardiovascular disease, psoriatic arthritis and psychiatric disorders are associated with psoriasis. Treatment of the disease depends on comorbidities and disease severity. For moderate to severe disease, the TNF-α inhibitor infliximab is approved. Even though the discovery of biologics revolutionized the treatment of autoimmune diseases, there is still a problem with relapsing disease and non-responders to treatment. Disease specific biomarkers that could help indicate who will respond to treatment and not at earlier stages are therefore required to optimize treatment. Psoriasis is a T cell mediated disease and T cell subsets such as the IL-17 secreting Th17 have been identified as important contributors to disease. However, other cell types and cytokines are also important in the pathophysiology, including dendritic cells and the cytokines TNF-α and IFN-γ. Other cell types are not as investigated in the disease mechanism, and the changes in immunophenotype after treatment are also not fully known. Continued research on these fields is therefore interesting. In this master project, flow cytometry was used to investigate immune cells in 24 psoriasis patients treated with the TNF-α inhibitor infliximab. The cells were immunophenotyped and compared to 33 healthy controls, matched for age, sex and BMI. Whilst we found no changes in frequencies of T cell populations or a trend of activated or inactivated T cells, some of the surface markers were different from the control populations. This change included a decreased expression of CD107a which was also evident on all subtypes of NK cells. NK cells did also not show a trend of increased or decreased activity, but similarly showed a changed expression of some expression markers. Both CD38 and CD27 was significantly increased in patients on CD56dim NK cells. The observations indicated continuous activation of monocytes even after treatment with an increase of frequency of intermediate monocytes, which is implicated in the cardiovascular disease was observed. On these cells, both HLA-DR and CD38 were increased, suggesting increased activity.Masteroppgave i FarmasiFARM399/05HMATF-FAR

Reacting to the Past and student motivation

This thesis investigates how Reacting to the Past (Reacting) affect student motivation in an English as a Foreign Language classroom (EFL classroom) in Norway. For the intervention I have collaborated with three fellow MA students, and we conducted an adapted version of John M. Burney and Andrew J. Auge’s (2020) Ending the Troubles in a 10th grade classroom. The findings from this study consist of quantitative and qualitative data, gathered through online surveys and semi-structured interviews. The goal of this dissertation is to test if Reacting as an innovative, student-centered, active learning pedagogy could contribute to maintenance or enhancement of student motivation. This study shows that students are more motivated for Reacting lessons compared to ordinary teaching lessons. The pedagogy gives students autonomy and responsibilities, while the social aspect contributes to a classroom environment where students are motivated to learn. Additionally, Reacting contributes to variation and creativity in the classroom, which a majority of the students seem to be motivated by. Furthermore, students saw its value and relevance to everyday life and thus were motivated to participate. Grounded in the findings of this study I would argue that Reacting does have a positive impact on student motivation, and that the pedagogy is a great way to be innovative and creative in the classroom. The students of this study saw learning as fun and engaging, and as a soon to be teacher, that is what I strive towards

Climatic variations and sediment provenance during the last 16 000 years in the North Hinlopen Trough, Svalbard

Gravity core HH18-1500GC retrieved from the Hinlopen Trough, Arctic Ocean, has been investigated in order to reconstruct the climatic evolution and ocean circulation over the last 16 000 years. The core was taken at the edge of the trough on the northern Svalbard shelf in order to be certain to reach into till, with the intent of dating the retreat of the ice sheet. The Fram Strait is located between Greenland and Svalbard, and is the main gateway for water and heat exchange to the Arctic Ocean. Reconstructing paleoceanography and paleoenvironmental changes in relation to climate change is important to predict future climate changes, as changes occurring in this area probably will affect the whole Arctic. The core was divided into 5 lithological and stratigraphic units based on grain size distribution, magnetic susceptibility, ice-rafted debris data, benthic and planktonic foraminiferal analysis and content of total carbon, total organic carbon and calcium carbonate. An age model was constructed based on AMS-14C dates and correlation with other studies. The core contains sediments from pre-Bølling (> 16 100 cal years BP), the Bølling-Allerød interstadials (16 100 – c. 13 000 cal years BP), the Younger Dryas stadial (c. 13 000 – c. 12 000 cal years BP) and the Holocene (< c. 12 000 cal years). The most recent sediments are c. 6500 cal years BP, indicating erosion or non-deposition due to strong bottom currents activity on the shelf. Five distinct pinkish layers were discovered within the Bølling-Allerød interval, correlating to increasing spectre of lightness, decreasing magnetic susceptibility and decreasing IRD content. Pink sediments were probably derived by melt water run-off from retreating glaciers, under high surface temperatures and at high sedimentation rates

An Isotopic Assessment of Late Prehistoric Interregional Warfare in the Southcentral US

Skull burials are found all over the world. The cause of such ancient Native Americans deposits often lead to disagreement among scholars torn between warfare and ancestor veneration. One skull-and-mandible deposit, representing at least 352 people (A.D. 1253-1399), was uncovered at the Crenshaw site, a multiple-mound Caddo ceremonial center in southwest Arkansas. Most previous research suggested they were victims of interregional warfare from the Southern Plains or Mississippi Valley. One previous study hypothesized that this was a Caddo burial practice which expanded during the Middle Caddo period (A.D. 1200-1500) due to the adoption of maize as a staple and a dispersed settlement pattern. A dispersed population might need such a practice to be buried at their preferred ritual center due to the inability to move large numbers of bodies. This study uses multiple methods to evaluate the purpose of this burial practice including (1) lead, strontium, carbon, and nitrogen isotope analyses for geographic origins and diet, (2) geophysical analysis of settlement patterns, and (3) analyses of biological traits. The biologically available lead method, using lead isotopes from ancient animal teeth, was developed to provide a method to assess the geographic origin of the human remains. The first large-scale lead and strontium isoscape using such samples was constructed to evaluate geographic origins. Sites targeted for sampling included those with evidence of violence from the same time period (from Arkansas, Illinois, Louisiana, Mississippi, Missouri, Oklahoma, and Texas). The stable isotope signatures show that the human remains are local to sites surrounding Crenshaw and indicate or strongly suggest they are non-local to all other tested regions. The dietary evidence indicates a maize and fish diet rather than a bison diet, consistent with southwest Arkansas and not the Southern Plains. Some aspects of the diet also suggest matrilocal intermarriage and food sharing with community and ritual leaders, consistent with Caddo cultural practices. The geophysical analysis of settlement patterning concludes that Crenshaw was among the most heavily occupied sites in the Caddo Area, if not the most, at one time. Analyses of possible ceremonial and domestic structures show that Crenshaw had a nucleated settlement pattern at least as late as the Early Caddo period (A.D. 1000-1200). It is hypothesized to have become more dispersed ca. A.D. 1200. Biological traits were compared to a nearby population in the Little River region. There were no significant differences between compared populations (locals, the skulls, or the mandibles) except the mandibles had additional tooth chipping. An analysis of mortuary patterning in the Little River region shows that there is a lack of Middle Caddo bodies at secondary mound sites nearest to Crenshaw despite the presence of mortuary structures from that time. The Caddo skull and mandible burial practice is therefore a regional burial practice associated with ancestor veneration. The ritual burial practice reflects that Crenshaw was expanding its ritual influence on previously existing surrounding sites and its ritual landscape through the dispersal of the populace around Crenshaw while the population began to adopt maize as a staple

Do patients assigned to multidisciplinary examination differ from patients assigned to monodisciplinary examination at the University Hospital of Northern Norway? - The Norwegian neck and back registry 2018

Background: Back pain is a very common disability. 60-80% of the population in Norway will experience LBP during their life. 30-50% of all people report neck pain during a year. Most back pain has no pathoanatomical diagnosis and is considered a multifactorial condition where biopsychosocial factors influence pain. “Yellow flags” are used in guidelines referring to psychosocial risk-factors for chronic pain. The guideline recommends referral to a multidisciplinary rehabilitation program like a “specialized clinic in physical medicine and rehabilitation” if pain persist after 6-8 weeks. The guidelines also define a multidisciplinary team of at least two health professionals. No studies have previously investigated the patients assigned to multidisciplinary versus monodisciplinary examinations at a specialized clinic in Norway. Aims: Investigate if the patients assigned to multidisciplinary examination differ from patients assigned to monodisciplinary examination regarding patient characteristics, yellow flags, pain indicators, function level and treatment recommendations. Material and methods: Data from the Norwegian Neck and Back Registry (NNRR) were used. All patients who were examined at the University Hospital of Northern Norway (UNN) in 2018 and completed the first patient questionnaire of the NNRR were included. Final sample of 655 patients. Differences in patient characteristics were described. Binary logistic regression was used to calculate multivariable adjusted odds ratios (OR) with 95% confidence intervals (95% CI) of associations between exposure variables and being assigned to mono- or multidisciplinary examinations. Results: Patients assigned to multidisciplinary examinations were on average 5.6 years younger. Among the yellow flags describing mental health problems there were increased odds for the multidisciplinary group to report both depression (OR=2.04, 95% CI=1.09-3.80), anxiety (2.06, 95% CI=1.03-4.12) and a HSCL-10 score >1.85 indicating mental health problems (OR=1.64, 95% CI=0.96-2.77) compared to patients assigned to monodisciplinary examinations. There were also increased odds (OR=2.53, 95% CI=1.25-5.10) that the patient believed his/her pain was caused by mental problems. Among yellow flags describing comorbidities there were increased odds of stomach discomfort (OR=2.16, 95% CI=1.10-4.24), upper back pain (OR=1.74 95% CI=1.04-2.90) and shoulder pain (OR=1.85 95% CI=1.12-3.06) in the multidisciplinary group compared to the monodisciplinary group. There were increased odds (OR=2.36, 95% CI=1.20-4.64) of the patients in the multidisciplinary group using prescription pain medication more than once every week compared to the patients in the monodisciplinary group. Patients in the multidisciplinary group had lower odds (OR=0.43, 95% CI=0.24-0.76) of being recommended no treatment compared to the patients in the monodisciplinary group, while at the same time having increased odds (OR=3.1, 95% CI=1.85-5.20) of being recommended treatment for follow-up by a physician in primary care. Conclusion: This study shows that patients assigned for multidisciplinary examinations at UNN are younger than patients assigned for monodisciplinary examinations. There are also indications that patients assigned to multidisciplinary examinations suffers from more mental health problems, as well as being more likely to use pain medication requiring a prescription. The patients assigned to multidisciplinary examinations were also receiving overall more treatment recommendations from the health professionals and were especially more likely to be recommended to follow-up by a physician in primary care. There were no differences between the groups concerning pain, function and work-related variables