Application of multidimensional IRT models to longitudinal data

The application of multidimensional item response theory (IRT) models to longitudinal educational surveys where students are repeatedly measured is discussed and exemplified. A marginal maximum likelihood (MML) method to estimate the parameters of a multidimensional generalized partial credit model for repeated measures is presented. It is shown that model fit can be evaluated using Lagrange multiplier tests. Two tests are presented: the first aims at evaluation of the fit of the item response functions and the second at the constancy of the item location parameters over time points. The outcome of the latter test is compared with an analysis using scatter plots and linear regression. An analysis of data from a school effectiveness study in Flanders (Belgium) is presented as an example of the application of these methods. In the example, it is evaluated whether the concepts "academic self-concept," "well-being at school," and "attentiveness in the classroom" were constant during the secondary school period. \u

Semantically linking molecular entities in literature through entity relationships

Background Text mining tools have gained popularity to process the vast amount of available research articles in the biomedical literature. It is crucial that such tools extract information with a sufficient level of detail to be applicable in real life scenarios. Studies of mining non-causal molecular relations attribute to this goal by formally identifying the relations between genes, promoters, complexes and various other molecular entities found in text. More importantly, these studies help to enhance integration of text mining results with database facts. Results We describe, compare and evaluate two frameworks developed for the prediction of non-causal or 'entity' relations (REL) between gene symbols and domain terms. For the corresponding REL challenge of the BioNLP Shared Task of 2011, these systems ranked first (57.7% F-score) and second (41.6% F-score). In this paper, we investigate the performance discrepancy of 16 percentage points by benchmarking on a related and more extensive dataset, analysing the contribution of both the term detection and relation extraction modules. We further construct a hybrid system combining the two frameworks and experiment with intersection and union combinations, achieving respectively high-precision and high-recall results. Finally, we highlight extremely high-performance results (F-score > 90%) obtained for the specific subclass of embedded entity relations that are essential for integrating text mining predictions with database facts. Conclusions The results from this study will enable us in the near future to annotate semantic relations between molecular entities in the entire scientific literature available through PubMed. The recent release of the EVEX dataset, containing biomolecular event predictions for millions of PubMed articles, is an interesting and exciting opportunity to overlay these entity relations with event predictions on a literature-wide scale

Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions

<p>Abstract</p> <p>Background</p> <p>Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies.</p> <p>Results</p> <p>EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC.</p> <p>Conclusion</p> <p>This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions.</p

The mechanisms of plaster drying

International audienceWe show that the drying rate of plaster pastes is significantly lower than that expected for a pure liquid evaporating from a simple homogeneous porous medium. This effect is enhanced by the air flow velocity and the initial solid/water ratio. Further tests under various conditions and with the help of additional techniques (MRI, ESEM, Microtomography) for measuring the drying rate and local characteristics (water content, porosity) prove that this effect is due to the crystallization of gypsum ions below the sample free surface, which creates a dry region and decreases the drying rate by increasing the length of the path the vapor has to follow before reaching the free surface

Microstructural evolution of a low-alloy steel / nickel superalloy dissimilar metal weld during post-weld heat treatment

The microstructural evolution of a dissimilar metal weld (DMW) obtained by narrow-gap gas tungsten arc welding (NG-GTAW) was investigated after it was subjected to a post-weld heat treatment (PWHT). The case studied here is a joint between low-alloy steel pipes and a stainless steel steam generator using a nickel based alloy as filler material. The fusion boundary that was the focus of this work was that between the low-alloy steel (2.25Cr-1Mo) and the nickel alloy (alloy 82). The difference in matrix phase and chemical composition between the two alloys leads to a large difference in chemical potential for carbon, which is mobile at the PWHT temperature. A number of advanced characterization techniques were used to assess the gradient of composition, hardness and microstructures across the fusion line, both as welded and after PWHT. This complete analysis permits to highlight and understand the main microstructural changes occurring during the PWHT

Intramolecular locking and coumarin insertion: a stepwise approach for TADF design

Three novel TADF (thermally activated delayed fluorescence) emitters based on the well-studied Qx-Ph-DMAC fluorophore are designed and synthesized. The photophysical properties of these materials are studied from a theoretical and experimental point of view, demonstrating the cumulative effects of multiple small modifications that combine to afford significantly improved TADF performance. First, an extra phenyl ring is added to the acceptor part of Qx-Ph-DMAC to increase the conjugation length, resulting in BQx-Ph-DMAC, which acts as an intermediate molecular structure. Next, an electron-deficient coumarin unit is incorporated to fortify the electron accepting ability, affording ChromPy-Ph-DMAC with red-shifted emission. Finally, the conjugated system is further enlarged by ‘locking’ the molecular structure, generating DBChromQx-DMAC with further red-shifted emission. The addition of the coumarin unit significantly impacts the charge-transfer excited state energy levels with little effect on the locally excited states, resulting in a decrease of the singlet–triplet energy gap. As a result, the two coumarin-based emitters show considerably improved TADF performance in 1 w/w% zeonex films when compared to the initial Qx-Ph-DMAC structure. ‘Locking’ the molecular structure further lowers the singlet–triplet energy gap, resulting in more efficient reverse intersystem crossing and increasing the contribution of TADF to the total emission

Polymorphisms in the Mn-SOD and EC-SOD Genes and Their Relationship to Diabetic Neuropathy in Type 1 Diabetes Mellitus

BACKGROUND: Oxidative stress, resulting in a marked increase in the level of oxygen free radicals (OFR), has been implicated in the etiology of diabetic neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and progression of DN, by reducing the excess of OFR and peroxide. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to DN. We investigated the role of genes encoding two antioxidant enzymes, mitochondrial (Mn-SOD) and extracellular (EC-SOD) superoxide dismutase, in DN pathogenesis in a Russian population. We studied Ala(-9)Val and Ile58Thr polymorphisms of the Mn-SOD gene and Arg213Gly dimorphism of the EC-SOD gene in type 1 diabetic patients with (n = 82) and without DN (n = 84). RESULTS: We developed and used a new polymerase chain reaction (PCR) assays for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was than digested with BshTI, Eco32I or Eco52I to detect Ala(-9)Val, Ile58Thr or Arg213Gly polymorphic site respectively. The frequencies of the Ala allele (50.6% vs. 68.5%, p < 0.002) and the Ala/Ala genotype (17.1% vs. 39.3%, p < 0.005) of the Mn-SOD gene were significantly lower in DN patients than in diabetic subjects without DN. In contrast, the Val allele (49.4% vs. 31.5%, p < 0.002) and the Val/Val genotype (15.9% vs. 2.4%, p < 0.01) were significantly more frequent in the DN patients than in the control group. CONCLUSIONS: Ala(-9)Val substitution in the Mn-SOD gene was associated with DN in a Russian populatio

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the ApcMin/+ mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in ApcMin/+ tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B∶ IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells

Continued glacial retreat linked to changing macronutrient supply along the West Antarctic Peninsula

At the West Antarctic Peninsula (WAP), continued atmospheric and oceanic warming is causing significant physical and biogeochemical changes to glaciers and the marine environment. We compare sediment sources and drivers of macronutrient distributions at two bays along the WAP during austral summer 2020, using radioactive radium and stable oxygen isotopes to trace sedimentary influences and quantify different freshwater inputs. In the Ryder Bay, where the Sheldon Glacier is marine-terminating, radium activities at the sediment-water interface indicate considerable benthic mixing. Using radium isotope activity gradients to resolve radium and macronutrient fluxes, we find buoyant meltwater proximal to the glacier drives vigorous mixing of sediment and entrainment of macronutrient deep waters, on the order of 2.0 × 105 mol d− 1 for nitrate. Conversely, in the Marian Cove, where the Fourcade Glacier terminates on land, low salinities and oxygen isotopes indicate a meltwater-rich surface layer <1 m thick and rich in sediment, and strong vertical mixing to the seafloor. A continued shift to land-terminating glaciers along the WAP may have a significant impact upon nutrient and sediment supply to the euphotic zone, with impacts upon primary productivity and carbon uptake efficiency. The future of primary production, carbon uptake, and food web dynamics is therefore linked to glacier retreat dy�namics in the many fjords along the WAP