117 research outputs found
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
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
False friends in the Fanfanyu
In the present article, a remarkable phenomenon is brought to the attention of those interested in early Chinese translations of Buddhist texts: false friends in the Fanfanyu (T54n2130). Baochang's Sanskrit-Chinese lexicon that was compiled as early as 517 AD reveals some curious examples of faux amis. In the present contribution, this case will be illustrated with references from the Shanjian lü piposha (T24n1462), a fifth century Chinese translation of the Samantapāsādikā, Buddhaghosa's commentary on the Pāli Vinaya. The fact that Baochang did not realise that this text was not translated from Sanskrit, inadvertently gave rise to some interesting jeux de mots
Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug–Drug Interactions
ABSTRACT: The hepatic organic anion transporting poly-peptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug−drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors
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
In Vitro and In Silico Strategies to Identify OATP1B1 Inhibitors and Predict Clinical Drug–Drug Interactions
Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities
In breast cancer patients, tumor metastases at distant sites are the main cause of death. However, the molecular mechanisms of metastasis of breast cancer remain unclear. It is thought that changes occurring at the level of RNA processing contribute to cancer. Alternative splicing (AS) of pre-mRNA, a key post-transcriptional mechanism allowing for the production of distinct proteins from a single gene, affects over 90% of human genes. Such splicing events are responsible for generating mRNAs that encode protein isoforms that can have very different biological properties and functions. A well-studied example is the BCL-X gene, whose two major transcript isoforms produce two proteins having antagonistic functions: the short form (BCL-XS) promotes apoptosis while the long form (BCL-XL) is anti-apoptotic. Moreover, overexpression of BCL-XL has been reported to enhance the metastatic potential of breast tumor cells in patients
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
Overexpression of PaHAP3A stimulates differentiation of ectopic embryos from maturing somatic embryos of Norway spruce
Markers associated with heading and aftermath heading in perennial ryegrass full-sib families
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