Static conductivity of charged domain wall in uniaxial ferroelectric-semiconductors

Using Landau-Ginzburg-Devonshire theory we calculated numerically the static conductivity of both inclined and counter domain walls in the uniaxial ferroelectrics-semiconductors of n-type. We used the effective mass approximation for the electron and holes density of states, which is valid at arbitrary distance from the domain wall. Due to the electrons accumulation, the static conductivity drastically increases at the inclined head-to-head wall by 1 order of magnitude for small incline angles theta pi/40 by up 3 orders of magnitude for the counter domain wall (theta=pi/2). Two separate regions of the space charge accumulation exist across an inclined tail-to-tail wall: the thin region in the immediate vicinity of the wall with accumulated mobile holes and the much wider region with ionized donors. The conductivity across the tail-to-tail wall is at least an order of magnitude smaller than the one of the head-to-head wall due to the low mobility of holes, which are improper carries. The results are in qualitative agreement with recent experimental data for LiNbO3 doped with MgO.Comment: 20 pages, 6 figures, 1 appendi

"Jobben vår er å gå på skolen, på en måte." : En kritisk drøfting av elevens rolle i skoleorganisasjonen.

I denne oppgaven er temaet elevens rolle i skoleorganisasjonen, og i hvilken grad den er påvirket av bestemte politiske ideer. Problemstillingen er: Hva kjennetegner elevens rolle i skoleorganisasjonen? Hvordan kan man forstå elevrollen i sammenheng med markedsorienterte ideer? Elevrollen blir her studert med utgangspunkt i organisasjonsteori. Studien er basert på to sett kvalitative data: Dokumentanalyse av offentlige dokumenter som ligger til grunn for styring og politikkutforming i skolen, nærmere bestemt de to siste grunnskolereformene i 1997 og 2006 (hhv. Reform 97 og Kunnskapsløftet), og et lite utvalg av andre relevante offentlige utredninger. I tillegg er det gjennomført elleve intervjuer med elever og lærere ved ti forskjellige skoler. Funnene peker i retning av spenninger i elevrollen, som man kan knytte til ulike politiske målsetninger. Dokumentanalysen viser at de nasjonale retningslinjene i grunnskolen inneholder motstridende normer for og forventninger til elevene. Reform 97 har et klart fokus mot demokratisk dannelse, til tross for datidens inntreden av markedstenkning i offentlig sektor. Det er en langt tydeligere vekting av markedsorienterte ideer i Kunnskapsløftet enn i Reform og et sterkt fokus på kvantitative målinger og individuell prestasjon. I intervjuene kommer det fram at elever og lærere opplever normene og forventningene fra forrige reform i 1997 som relevante i sin daglige aktivitet. Kunnskapsløftets resultat- og prestasjonsfokus, derimot, oppleves som belastende av begge grupper. Ved å bruke institusjonell teori analyserer jeg funnene ut fra to ulike perspektiver – myteperspektiv og kulturperspektiv. Dette viser hvordan elevrollen har blitt påvirket av markedsorienterte ideer, på bakgrunn av hvilke ideer som har blitt innført, og hvordan lærerne som offentlige tjenestepersoner har mottatt disse ideene. Videre peker jeg på hvordan det ser ut til å utvikle seg en felles passendelogikk mellom elever og lærere, med utgangspunkt i aspekter begge gruppene oppfatter som utfordringer ved elevrollen. Det rettes et ekstra blikk mot elevens demokratiske rett til medvirkning som bruker og borger, og hvordan markedsorienterte prinsipper for opplæringen kan være problematiske i et demokratisk perspektiv. Dette settes også i sammenheng med styring og utvikling av skolen

Long-term work outcomes and the efficacy of multidisciplinary rehabilitation programs on labor force participation in cancer patients - a protocol for a longitudinal prospective cohort study

Background. Many cancer survivors experience late effects of cancer treatment and therefore struggle to return to work. Norway provides rehabilitation programs to increase labor force participation for cancer survivors after treatment. However, the extent to which such programs affect labor force participation has not been appropriately assessed. This study aims to investigate i) labor force participation, sick leave and disability rates among cancer survivors up to 10 years after being diagnosed with cancer and identify comorbidities contributing to long-term sick leave or disability pensioning; ii) how type of cancer, treatment modalities, employment sectors and financial- and sociodemographic factors may influence labor force participation; ii) how participation in rehabilitation programs among cancer survivor affect the long-term labor force participation, the number of rehospitalizations and incidence of comorbidities. Design and methods. Information from four medical, welfare and occupational registries in Norway will be linked to information from 163,279 cancer cases (15.68 years old) registered in the Norwegian Cancer Registry from 2004 to 2016. The registries provide detailed information on disease characteristics, comorbidities, medical and surgical treatments, occupation, national insurance benefits and demographics over a 10-year period following a diagnosis of cancer. Expected impact of the study for Public Health. The study will provide important information on how treatment, rehabilitation and sociodemographic factors influence labor force participation among cancer survivors. Greater understanding of work-related risk factors and the influence of rehabilitation on work-participation may encourage informed decisions among cancer patients, healthcare and work professionals and service planners.publishedVersio

Molecular mechanisms of CharcotMarie-Tooth neuropathy linked to mutations in human myelin protein P2

This article has an erratum: Doi 10.1038/s41598-017-18751-7Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies. Recently, three CMT1-associated point mutations (I43N, T51P, and I52T) were discovered in the abundant peripheral myelin protein P2. These mutations trigger abnormal myelin structure, leading to reduced nerve conduction velocity, muscle weakness, and distal limb atrophy. P2 is a myelin-specific protein expressed by Schwann cells that binds to fatty acids and membranes, contributing to peripheral myelin lipid homeostasis. We studied the molecular basis of the P2 patient mutations. None of the CMT1-associated mutations alter the overall folding of P2 in the crystal state. P2 disease variants show increased aggregation tendency and remarkably reduced stability, T51P being most severe. In addition, P2 disease mutations affect protein dynamics. Both fatty acid binding by P2 and the kinetics of its membrane interactions are affected by the mutations. Experiments and simulations suggest opening of the beta barrel in T51P, possibly representing a general mechanism in fatty acid-binding proteins. Our findings demonstrate that altered biophysical properties and functional dynamics of P2 may cause myelin defects in CMT1 patients. At the molecular level, a few malformed hydrogen bonds lead to structural instability and misregulation of conformational changes related to ligand exchange and membrane binding.Peer reviewe

Therapeutic drug monitoring in inflammatory bowel disease : implementation, utilization, and barriers in clinical practice in Scandinavia

Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p 10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.Peer reviewe

Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile

Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77-0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSCPeer reviewe

A possible role for HLA-G in development of uteroplacental acute atherosis in preeclampsia

HLA-G, a non-classical HLA molecule expressed by extravillous trophoblasts, plays a role in the maternal immune tolerance towards fetal cells. HLA-G expression is regulated by genetic polymorphisms in the 3' untranslated region (3'UTR). Low levels of HLA-G in the maternal circulation and placental tissue are linked to preeclampsia. Our objective was to investigate whether variants of the 3'UTR of the HLA-G gene in mother and fetus are associated with acute atherosis, a pregnancy specific arterial lesion of the decidua basalis that is prevalent in preeclampsia. Paired maternal and fetal DNA samples from 83 normotensive and 83 preeclamptic pregnancies were analyzed. We sequenced the part of the HLA-G 3'UTR containing a 14-bp insertion/deletion region and seven single nucleotide polymorphisms (SNPs). Associations with acute atherosis were tested by logistic regression. The frequency of heterozygosity for the 14-bp polymorphism (Ins/Del) and the +3142 SNP (C/G) variant in the fetus are associated with acute atherosis in preeclampsia (66.7 % vs. 39.6 %, p = 0.039, and 69.0 % vs. 43.4 %, p = 0.024). Furthermore, the fetal UTR-3 haplotype, which encompasses the 14-bp deletion and the +3142G variant, is associated with acute atherosis in preeclampsia (15 % vs. 3.8 %, p = 0.016). In conclusion, HLA-G polymorphisms in the fetus are associated with acute atherosis. We hypothesize that these polymorphisms lead to altered HLA-G expression in the decidua basalis, affecting local feto-maternal immune tolerance and development of acute atherosis

Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells

Background: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs). CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. Methodology/Principal Findings: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression of other atRA catabolizing enzymes in the cells. Conclusions/Significance: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1 splice variant in health and disease

Modeling of dielectric hysteresis loops in ferroelectric semiconductors with charged defects

We have proposed the phenomenological description of dielectric hysteresis loops in ferroelectric semiconductors with charged defects and prevailing extrinsic conductivity. Exactly we have modified Landau-Ginsburg approach and shown that the macroscopic state of the aforementioned inhomogeneous system can be described by three coupled equations for three order parameters. Both the experimentally observed coercive field values well below the thermodynamic one and the various hysteresis loop deformations (constricted and double loops) have been obtained in the framework of our model. The obtained results quantitatively explain the ferroelectric switching in such ferroelectric materials as thick PZT films.Comment: 21 pages, 10 figures, sent to Journal of Physics: Condensed Matte

Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail

Schwann cells myelinate selected axons in the peripheral nervous system (PNS) and contribute to fast saltatory conduction via the formation of compact myelin, in which water is excluded from between tightly adhered lipid bilayers. Peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine-4 Sottas syndrome (DSS), are incurable demyelinating conditions that result in pain, decrease in muscle mass, and functional impairment. Many Schwann cell proteins, which are directly involved in the stability of compact myelin or its development, are subject to mutations linked to these neuropathies. The most abundant PNS myelin protein is protein zero (P0); point mutations in this transmembrane protein cause CMT subtype 8 1B and DSS. P0 tethers apposing lipid bilayers together through its extracellular immunoglobulin-like domain. Additionally, P0 contains a cytoplasmic tail (P0ct), which is membrane-associated and contributes to the physical properties of the lipid membrane. Six CMT- and DSS-associated missense mutations have been reported in P0ct. We generated recombinant disease mutant variants of P0ct and characterized them using biophysical methods. Compared to wild-type P0ct, some mutants have negligible differences in function and folding, while others highlight functionally important amino acids within P0ct. For example, the D224Y variant of P0ct induced tight membrane multilayer stacking. Our results show a putative molecular basis for the hypermyelinating phenotype observed in patients with this particular mutation and provide overall information on the effects of disease-linked mutations in a flexible, membrane-binding protein segment. Using neutron reflectometry, we additionally show that P0ct embeds deep into a lipid bilayer, explaining the observed effects of P0ct on the physical properties of the membrane