994 research outputs found

    Computational and Mathematical Modelling of the EGF Receptor System

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    This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described

    Use of the ODD-Luciferase Transgene for the Non-Invasive Imaging of Spontaneous Tumors in Mice

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    In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice

    Identification of physicochemical selective pressure on protein encoding nucleotide sequences

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    BACKGROUND: Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of amino acids into account. RESULTS: We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, γ and ω respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest. The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC) and from the abalone sperm lysine. CONCLUSION: Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties

    First report of generalized face processing difficulties in möbius sequence.

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    Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the production of that expression. Previous work has tested this theory by examining facial expression recognition in participants with Möbius sequence, a condition characterized by congenital bilateral facial paralysis. However, a mixed pattern of findings has emerged, and it has not yet been tested whether these individuals can imagine facial expressions, a process also hypothesized to be underpinned by proprioceptive feedback from the face. We investigated this issue by examining expression recognition and imagery in six participants with Möbius sequence, and also carried out tests assessing facial identity and object recognition, as well as basic visual processing. While five of the six participants presented with expression recognition impairments, only one was impaired at the imagery of facial expressions. Further, five participants presented with other difficulties in the recognition of facial identity or objects, or in lower-level visual processing. We discuss the implications of our findings for the reverse simulation model, and suggest that facial identity recognition impairments may be more severe in the condition than has previously been noted

    Introduction: Examined Live – An Epistemological Exchange Between Philosophy and Cultural Psychology on Reflection

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    Besides the general agreement about the human capability of reflection, there is a large area of disagreement and debate about the nature and value of “reflective scrutiny” and the role of “second-order states” in everyday life. This problem has been discussed in a vast and heterogeneous literature about topics such as epistemic injustice, epistemic norms, agency, understanding, meta-cognition etc. However, there is not yet any extensive and interdisciplinary work, specifically focused on the topic of the epistemic value of reflection. This volume is one of the first attempts aimed at providing an innovative contribution, an exchange between philosophy, epistemology and psychology about the place and value of reflection in everyday life. Our goal in the next sections is not to offer an exhaustive overview of recent work on epistemic reflection, nor to mimic all of the contributions made by the chapters in this volume. We will try to highlight some topics that have motivated a new resumption of this field and, with that, drawing on chapters from this volume where relevant. Two elements defined the scope and content of this volume, on the one hand, the crucial contribution of Ernest Sosa, whose works provide original and thought-provoking contributions to contemporary epistemology in setting a new direction for old dilemmas about the nature and value of knowledge, giving a central place to reflection. On the other hand, the recent developments of cultural psychology, in the version of the “Aalborg approach”, reconsider the object and scope of psychological sciences, stressing that “[h]uman conduct is purposeful”

    A systematic review of the evidence for single stage and two stage revision of infected knee replacement

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    BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

    Gene discovery in the hamster: a comparative genomics approach for gene annotation by sequencing of hamster testis cDNAs

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    BACKGROUND: Complete genome annotation will likely be achieved through a combination of computer-based analysis of available genome sequences combined with direct experimental characterization of expressed regions of individual genomes. We have utilized a comparative genomics approach involving the sequencing of randomly selected hamster testis cDNAs to begin to identify genes not previously annotated on the human, mouse, rat and Fugu (pufferfish) genomes. RESULTS: 735 distinct sequences were analyzed for their relatedness to known sequences in public databases. Eight of these sequences were derived from previously unidentified genes and expression of these genes in testis was confirmed by Northern blotting. The genomic locations of each sequence were mapped in human, mouse, rat and pufferfish, where applicable, and the structure of their cognate genes was derived using computer-based predictions, genomic comparisons and analysis of uncharacterized cDNA sequences from human and macaque. CONCLUSION: The use of a comparative genomics approach resulted in the identification of eight cDNAs that correspond to previously uncharacterized genes in the human genome. The proteins encoded by these genes included a new member of the kinesin superfamily, a SET/MYND-domain protein, and six proteins for which no specific function could be predicted. Each gene was expressed primarily in testis, suggesting that they may play roles in the development and/or function of testicular cells

    The American Experience With Desmopressin

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    Conclusive evidence of a polyuric etiology from a failure of vasopressin elevation led to a new pharmacologic approach to the treatment of childhood nocturnal enuresis. Desmopressin acetate, a vasopressin analogue, has been used successfully since 1978 to treat this condition. Desmopressin's efficacy at doses of 5 to 40 μg has been demonstrated in Europe and the United States. Similarly, its safety has been established, and it is a first-line choice for physicians worldwide.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67214/2/10.1177_000992289303200107.pd
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