Growth and replication : exploring facade subdivision based on natural processes

Generative methods for subdivision of building façades are presented in this thesis through a series of case studies exploring methods of stochastic generation, tiling and tessellation and branching structures.  In each of these studies, a method of generative design based on natural phenomena of growth and replication is described algorithmically.

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).

Replication Data Management,needs and solutions: an initial evaluation of conceptual approaches for integrating heterogeneous replication study data

Replication Data Management (RDM) aims at enabling the use of data collections from several iterations of an experiment. However, there are several major challenges to RDM from integrating data models and data from empirical study infrastructures that were not designed to cooperate, e.g., data model variation of local data sources. [Objective] In this paper we analyze RDM needs and evaluate conceptual RDM approaches to support replication researchers. [Method] We adapted the ATAM evaluation process to (a) analyze RDM use cases and needs of empirical replication study research groups and (b) compare three conceptual approaches to address these RDM needs: central data repositories with a fixed data model, heterogeneous local repositories, and an empirical ecosystem. [Results] While the central and local approaches have major issues that are hard to resolve in practice, the empirical ecosystem allows bridging current gaps in RDM from heterogeneous data sources. [Conclusions] The empirical ecosystem approach should be explored in diverse empirical environments.

Replication types: towards a shared taxonomy

Context: The software engineering community is becoming more aware of the need for experimental replications. In spite of the importance of this topic, there is still much inconsistency in the terminology used to describe replications. Objective: Understand the perspectives of empirical researchers about various terms used to characterize replications and propose a consistent taxonomy of terms. Method: A survey followed by plenary discussion during the 2013 International Software Engineering Research Network meeting. Results: We propose a taxonomy which consolidates the disparate terminology. This taxonomy had a high level of agreement among workshop attendees. Conclusion: Consistent terminology is important for any field to progress. This work is the first step in that direction. Additional study and discussion is still necessary.

Understanding replication of experiments in software engineering: a classification

Context: Replication plays an important role in experimental disciplines. There are still many uncertain- ties about how to proceed with replications of SE experiments. Should replicators reuse the baseline experiment materials? How much liaison should there be among the original and replicating experiment- ers, if any? What elements of the experimental configuration can be changed for the experiment to be considered a replication rather than a new experiment? Objective: To improve our understanding of SE experiment replication, in this work we propose a classi- fication which is intend to provide experimenters with guidance about what types of replication they can perform. Method: The research approach followed is structured according to the following activities: (1) a litera- ture review of experiment replication in SE and in other disciplines, (2) identification of typical elements that compose an experimental configuration, (3) identification of different replications purposes and (4) development of a classification of experiment replications for SE. Results: We propose a classification of replications which provides experimenters in SE with guidance about what changes can they make in a replication and, based on these, what verification purposes such a replication can serve. The proposed classification helped to accommodate opposing views within a broader framework, it is capable of accounting for less similar replications to more similar ones regarding the baseline experiment. Conclusion: The aim of replication is to verify results, but different types of replication serve special ver- ification purposes and afford different degrees of change. Each replication type helps to discover partic- ular experimental conditions that might influence the results. The proposed classification can be used to identify changes in a replication and, based on these, understand the level of verification.

Improved cervical smear assessment using antibodies against proteins that regulate DNA replication

Carcinoma of the cervix is one of the most common malignancies. Papanicolaou (Pap) smear tests have reduced mortality by up to 70%. Nevertheless their interpretation is notoriously difficult with high false-negative rates and frequently fatal consequences. We have addressed this problem by using affinity-purified antibodies against human proteins that regulate DNA replication, namely Cdc6 and Mcm5. These antibodies were applied to sections and smears of normal and diseased uterine cervix by using immunoperoxidase or immunofluorescence to detect abnormal precursor malignant cells. Antibodies against Cdc6 and Mcm5 stain abnormal cells in cervical smears and sections with remarkably high specificity and sensitivity. Proliferation markers Ki-67 and proliferating cell nuclear antigen are much less effective. The majority of abnormal precursor malignant cells are stained in both low-grade and high-grade squamous intraepithelial lesions. Immunostaining of cervical smears can be combined with the conventional Pap stain so that all the morphological information from the conventional method is conserved. Thus antibodies against proteins that regulate DNA replication can reduce the high false-negative rate of the Pap smear test and may facilitate mass automated screening.

Interferon γ expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity

Interferon γ (IFN-γ) has pleiotropic biological effects, including intrinsic antiviral activity as well as stimulation and regulation of immune responses. An infectious recombinant human respiratory syncytial virus (rRSV/mIFN-γ) was constructed that encodes murine (m) IFN-γ as a separate gene inserted into the G-F intergenic region. Cultured cells infected with rRSV/mIFN-γ secreted 22 μg mIFN-γ per 106 cells. The replication of rRSV/mIFN-γ, but not that of a control chimeric rRSV containing the chloramphenicol acetyl transferase (CAT) gene as an additional gene, was 63- and 20-fold lower than that of wild-type (wt) RSV in the upper and lower respiratory tract, respectively, of mice. Thus, the attenuation of rRSV/mIFN-γ in vivo could be attributed to the activity of mIFN-γ and not to the presence of the additional gene per se. The mice were completely resistant to subsequent challenge with wt RSV. Despite its growth restriction, infection of mice with rRSV/mIFN-γ induced a level of RSV-specific antibodies that, on day 56, was comparable to or greater than that induced by infection with wt RSV. Mice infected with rRSV/mIFN-γ developed a high level of IFN-γ mRNA and an increased amount of interleukin 12 p40 mRNA in their lungs, whereas other cytokine mRNAs tested were unchanged compared with those induced by wt RSV. Because attenuation of RSV typically is accompanied by a reduction in immunogenicity, expression of IFN-γ by an rRSV represents a method of attenuation in which immunogenicity can be maintained rather than be reduced.

Importance of replication in microarray gene expression studies: Statistical methods and evidence from repetitive cDNA hybridizations

We present statistical methods for analyzing replicated cDNA microarray expression data and report the results of a controlled experiment. The study was conducted to investigate inherent variability in gene expression data and the extent to which replication in an experiment produces more consistent and reliable findings. We introduce a statistical model to describe the probability that mRNA is contained in the target sample tissue, converted to probe, and ultimately detected on the slide. We also introduce a method to analyze the combined data from all replicates. Of the 288 genes considered in this controlled experiment, 32 would be expected to produce strong hybridization signals because of the known presence of repetitive sequences within them. Results based on individual replicates, however, show that there are 55, 36, and 58 highly expressed genes in replicates 1, 2, and 3, respectively. On the other hand, an analysis by using the combined data from all 3 replicates reveals that only 2 of the 288 genes are incorrectly classified as expressed. Our experiment shows that any single microarray output is subject to substantial variability. By pooling data from replicates, we can provide a more reliable analysis of gene expression data. Therefore, we conclude that designing experiments with replications will greatly reduce misclassification rates. We recommend that at least three replicates be used in designing experiments by using cDNA microarrays, particularly when gene expression data from single specimens are being analyzed.

A new method for generating point mutations in bacterial artificial chromosomes by homologous recombination in Escherichia coli

Bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), which contain large fragments of genomic DNA, have been successfully used as transgenes to create mouse models of dose-dependent diseases. They are also potentially valuable as transgenes for dominant diseases given that point mutations and/or small rearrangements can be accurately introduced. Here, we describe a new method to introduce small alterations in BACs, which results in the generation of point mutations with high frequency. The method involves homologous recombination between the original BAC and a shuttle vector providing the mutation. Each recombination step is monitored using positive and negative selection markers, which are the Kanamycin-resistance gene, the sacB gene and temperature-sensitive replication, all conferred by the shuttle plasmid. We have used this method to introduce four different point mutations and the insertion of the β-galactosidase gene in a BAC, which has subsequently been used for transgenic animal production.

Method Validation for Bacterial and Viral Analysis of Geoducks

Thesis (Master's)--University of Washington, 2016-06

Inference by replication in densely connected systems

An efficient Bayesian inference method for problems that can be mapped onto dense graphs is presented. The approach is based on message passing where messages are averaged over a large number of replicated variable systems exposed to the same evidential nodes. An assumption about the symmetry of the solutions is required for carrying out the averages; here we extend the previous derivation based on a replica-symmetric- (RS)-like structure to include a more complex one-step replica-symmetry-breaking-like (1RSB-like) ansatz. To demonstrate the potential of the approach it is employed for studying critical properties of the Ising linear perceptron and for multiuser detection in code division multiple access (CDMA) under different noise models. Results obtained under the RS assumption in the noncritical regime give rise to a highly efficient signal detection algorithm in the context of CDMA; while in the critical regime one observes a first-order transition line that ends in a continuous phase transition point. Finite size effects are also observed. While the 1RSB ansatz is not required for the original problems, it was applied to the CDMA signal detection problem with a more complex noise model that exhibits RSB behavior, resulting in an improvement in performance. © 2007 The American Physical Society.

Compression by replication

A recently introduced inference method based on system replication and an online message passing algorithm is employed to complete a previously suggested compression scheme based on a nonlinear perceptron. The algorithm is shown to approach the information theoretical bounds for compression as the number of replicated systems increases, offering superior performance compared to basic message passing algorithms. In addition, the suggested method does not require fine-tuning of parameters or other complementing heuristic techniques, such as the introduction of inertia terms, to improve convergence rates to nontrivial results. © 2014 American Physical Society.

‘Fat, four-eyed and female’ 30 years later: A replication of Harris, Harris, and Bochner’s (1982) early study of obesity stereotypes

Objective: This study aimed to replicate Harris, Harris, and Bochner’s (1982) early experiment on obesity stereotyping to examine whether negative obesity stereotypes persist and in what form.

Method: A sample of psychology students (N = 506) read a description of a target described as female or male, overweight or average weight, and wearing glasses or not, who they subsequently rated on 12 descriptors.

Results: Overweight targets were rated as significantly less active, assertive, athletic, attractive, happy, hardworking, masculine, popular, and successful than average weight targets. This negative stereotype effect of target weight was much larger than effects observed for sex or wearing glasses. There were no differences in effect sizes for target weight between this study and the original study.

Conclusions: It was concluded that the negative obesity stereotypes reported by Harris et al. have persisted over a 30-year period, despite the fact that people who are overweight are no longer a minority. Efforts are needed to challenge negative stereotyping of this group. Future research could examine why stereotypes of overweight people are resistant to change.

An approximate method for the solution of an influence function foil rolling model

Fleck and Johnson (Int. J. Mech. Sci. 29 (1987) 507) and Fleck et al. (Proc. Inst. Mech. Eng. 206 (1992) 119) have developed foil rolling models which allow for large deformations in the roll profile, including the possibility that the rolls flatten completely. However, these models require computationally expensive iterative solution techniques. A new approach to the approximate solution of the Fleck et al. (1992) Influence Function Model has been developed using both analytic and approximation techniques. The numerical difficulties arising from solving an integral equation in the flattened region have been reduced by applying an Inverse Hilbert Transform to get an analytic expression for the pressure. The method described in this paper is applicable to cases where there is or there is not a flat region.