Reading between the lines: attitudinal expressions in text

This is a brief overview of the starting points a project currently proposed and under evaluation by funding agencies. We discuss some of the linguistic methodology we plan to employ to idenitify and analyze attitudinal expressions in text, and touch briefly on how to evaluate our future results

Alpha Decay Hindrance Factors: A Probe of Mean Field Wave Functions

A simple model to calculate alpha-decay Hindrance Factors is presented. Using deformation values obtained from PES calculations as the only input, Hindrance Factors for the alpha-decay of Rn- and Po-isotopes are calculated. It is found that the intrinsic structure around the Fermi surface determined by the deformed mean field plays an important role in determining the hindrance of alpha-decay. The fair agreement between experimental and theoretical Hindrance Factors suggest that the wave function obtained from the energy minima of the PES calculations contains an important part of the correlations that play a role for the alpha-decay. The calculated HF that emerges from these calculations render a different interpretation than the commonly assumed n-particle n-hole picture.Comment: 7 pages, 9 figure

Three-dimensional visualisation of authentic cases in anatomy learning – An educational design study

Many studies have investigated the value of three-dimensional (3D) images in learning anatomy. However, there is a lack of knowledge about students learning processes using technology and 3D images. To understand how to facilitate and support the learning of anatomy, there is a need to know more about the student perspectives on how they can use and benefit from 3D images

Virtual patients designed for training against medical error: Exploring the impact of decision-making on learner motivation.

OBJECTIVES: Medical error is a significant cause of patient harms in clinical practice, but education and training are recognised as having a key role in minimising their incidence. The use of virtual patient (VP) activities targeting training in medical error allows learners to practice patient management in a safe environment. The inclusion of branched decision-making elements in the activities has the potential to drive additional generative cognitive processing and improved learning outcomes, but the increased cognitive load on learning risks negatively affecting learner motivation. The aim of this study is to better understand the impact that the inclusion of decision-making and inducing errors within the VP activities has on learner motivation. METHODS: Using a repeated study design, over a period of six weeks we provided undergraduate medical students at six institutions in three countries with a series of six VPs written around errors in paediatric practice. Participants were divided into two groups and received either linearly structured VPs or ones that incorporated branched decision-making elements. Having completed all the VPs, each participant was asked to complete a survey designed to assess their motivation and learning strategies. RESULTS: Our analysis showed that in general, there was no significant difference in learner motivation between those receiving the linear VPs and those who received branched decision-making VPs. The same results were generally reflected across all six institutions. CONCLUSIONS: The findings demonstrated that the inclusion of decision-making elements did not make a significant difference to undergraduate medical students' motivation, perceived self-efficacy or adopted learning strategies. The length of the intervention was sufficient for learners to overcome any increased cognitive load associated with branched decision-making elements being included in VPs. Further work is required to establish any immediate impact within periods shorter than the length of our study or upon achieved learning outcomes

Incremental dimension reduction of tensors with random index

We present an incremental, scalable and efficient dimension reduction technique for tensors that is based on sparse random linear coding. Data is stored in a compactified representation with fixed size, which makes memory requirements low and predictable. Component encoding and decoding are performed on-line without computationally expensive re-analysis of the data set. The range of tensor indices can be extended dynamically without modifying the component representation. This idea originates from a mathematical model of semantic memory and a method known as random indexing in natural language processing. We generalize the random-indexing algorithm to tensors and present signal-to-noise-ratio simulations for representations of vectors and matrices. We present also a mathematical analysis of the approximate orthogonality of high-dimensional ternary vectors, which is a property that underpins this and other similar random-coding approaches to dimension reduction. To further demonstrate the properties of random indexing we present results of a synonym identification task. The method presented here has some similarities with random projection and Tucker decomposition, but it performs well at high dimensionality only (n>10^3). Random indexing is useful for a range of complex practical problems, e.g., in natural language processing, data mining, pattern recognition, event detection, graph searching and search engines. Prototype software is provided. It supports encoding and decoding of tensors of order >= 1 in a unified framework, i.e., vectors, matrices and higher order tensors.Comment: 36 pages, 9 figure

Retained NK cell phenotype and functionality in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage non-alcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease. Here, we explored the presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD. Using 18-color-flow cytometry, substantial changes were observed in certain myeloid populations in patients as compared to controls. NK cell numbers, on the other hand, were not altered. Furthermore, only minor differences in expression of activating and inhibitory NK cell receptors were noted, with the exception of an increased expression of NKG2D on NK cells from patients with NASH. NK cell differentiation remained constant, and NK cells from these patients retain their ability to respond adequately upon stimulation. Instead, considerable alterations were observed between liver, adipose tissue, and peripheral blood NK cells, independently of disease status. Taken together, these results increase our understanding of the importance of the local microenvironment in shaping the NK cell compartment and stress the need for further studies exploring how NASH affects intrahepatic NK cells in humans.publishedVersio

Scalable In Situ Hybridization on Tissue Arrays for Validation of Novel Cancer and Tissue-Specific Biomarkers

Tissue localization of gene expression is increasingly important for accurate interpretation of large scale datasets from expression and mutational analyses. To this end, we have (1) developed a robust and scalable procedure for generation of mRNA hybridization probes, providing >95% first-pass success rate in probe generation to any human target gene and (2) adopted an automated staining procedure for analyses of formalin-fixed paraffin-embedded tissues and tissue microarrays. The in situ mRNA and protein expression patterns for genes with known as well as unknown tissue expression patterns were analyzed in normal and malignant tissues to assess procedure specificity and whether in situ hybridization can be used for validating novel antibodies. We demonstrate concordance between in situ transcript and protein expression patterns of the well-known pathology biomarkers KRT17, CHGA, MKI67, PECAM1 and VIL1, and provide independent validation for novel antibodies to the biomarkers BRD1, EZH2, JUP and SATB2. The present study provides a foundation for comprehensive in situ gene set or transcriptome analyses of human normal and tumor tissues

Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Genomics 11 (2010): 643, doi:10.1186/1471-2164-11-643.Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters. Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.This work was supported by NIH grants R01ES015912 and P42ES007381 (Superfund Basic Research Program at Boston University) (to JJS). MEJ was a Guest Investigator at the Woods Hole Oceanographic Institution (WHOI) and was supported by grants from the Swedish research council Formas and Carl Trygger's foundation. AK was a Post-doctoral Fellow at WHOI, and was supported by a fellowship from the Japanese Society for Promotion of Science (JSPS). JZ and TP were Guest Students at the WHOI and were supported by a CAPES Ph.D. Fellowship and CNPq Ph.D. Sandwich Fellowship (JZ), and by a CNPq Ph.D. Fellowship (TP), from Brazil

M402, a Novel Heparan Sulfate Mimetic, Targets Multiple Pathways Implicated in Tumor Progression and Metastasis

Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis