A critical evaluation of theories of nationalism

This thesis considers the main theoretical positions within the contemporary sociology of nationalism. These can be grouped into two basic types, primordialist theories which assert that nationalism is an inevitable aspect of all human societies, and modernist theories which assert that nationalism and the nation-state first developed within western Europe in recent centuries. With respect to primordialist approaches to nationalism, it is argued that the main common explanation offered is human biological propensity. Consideration is concentrated on the most recent and plausible of such theories, sociobiology. Sociobiological accounts root nationalism and racism in genetic programming which favours close kin, or rather to the redirection of this programming in complex societies, where the social group is not a kin group. It is argued that the stated assumptions of the sociobiologists do not entail the conclusions they draw as to the roots of nationalism, and that in order to arrive at such conclusions further and implausible assumptions have to be made. With respect to modernists, the first group of writers who are considered are those, represented by Carlton Hayes, Hans Kohn and Elie Kedourie, whose main thesis is that the nation-state and nationalism are recent phenomena. Next, the two major attempts to relate nationalism and the nation-state to imperatives specific either to capitalist societies (in the `orthodox' marxist theory elaborated about the turn of the twentieth century) or to the processes of modernisation and industrialisation (the `Weberian' account of Ernest Gellner) are discussed. It is argued that modernist accounts can only be sustained by starting from a definition of nationalism and the nation-state which conflates such phenomena with others which are specific to the modern world. The marxist and Gellner accounts form the necessary starting point for any explanation as to why the nation-state is apparently the sole viable form of polity in the modern world, but their assumption that no pre-modern society was national leaves them without an adequate account of the earliest origins of the nation-state and of nationalism. Finally, a case study from the history of England argues both the achievement of a national state form and the elucidation of crucial components of a nationalist ideology were attained at a period not consistent with any of the versions of the modernist thesis.

Evolution of lace knitting stitch patterns by genetic programming

In this paper we study the generation of lace knitting stitch patterns by using genetic programming. We devise a genetic representation of knitting charts that accurately reflects their usage for hand knitting the pattern. We apply a basic evolutionary algorithm for generating the patterns, where the key of success is evaluation. We propose automatic evaluation of the patterns, without interaction with the user. We present some patterns generated by the method and then discuss further possibilities for bringing automatic evaluation closer to human evaluation. Copyright 2007 ACM.

Solving Travelling Salesman Problem in a Simulation of Genetic Algorithms with DNA

In this paper it is explained how to solve a fully connected N-City travelling salesman problem (TSP) using a genetic algorithm. A crossover operator to use in the simulation of a genetic algorithm (GA) with DNA is presented. The aim of the paper is to follow the path of creating a new computational model based on DNA molecules and genetic operations. This paper solves the problem of exponentially size algorithms in DNA computing by using biological methods and techniques. After individual encoding and fitness evaluation, a protocol of the next step in a GA, crossover, is needed. This paper also shows how to make the GA faster via different populations of possible solutions.

Genetic Algorithm for Finding the Key’s Length and Cryptanalysis of the Permutation Cipher

In this article we discuss a possibility to use genetic algorithms in cryptanalysis. We developed and described the genetic algorithm for finding the secret key of a block permutation cipher. In this case key is a permutation of some first natural numbers. Our algorithm finds the exact key’s length and the key with controlled accuracy. Evaluation of conducted experiment’s results shows that the almost automatic cryptanalysis is possible.

Paediatric drug development:reformulation, in vitro, genomic and in vivo evaluation

Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.

Preimplantation genetic diagnosis: Analysis of gene expression, nuclear DNA and cytoplasmic DNA

Preimplantation genetic diagnosis (PGD) following in vitro fertilization (IVF) offers couples at risk for transmitting genetic disorders the opportunity to identify affected embryos prior to replacement. In particular, embryo gender determination permits screening for X-linked diseases of unknown etiology. Analysis of embryos can be performed by polymerase chain reaction (PCR) amplification of material obtained by micromanipulation. This approach provides an alternative to the termination of an established pregnancy following chorionic villi sampling or amniocentesis. ^ Lately, the focus of preimplantation diagnosis and intervention has been shifting toward an attempt to correct cytoplasmic deficiencies. Accordingly, it is the aim of this investigation to develop methods to permit the examination of single cells or components thereof for clinical evaluation. In an attempt to lay the groundwork for precise therapeutic intervention for age related aneuploidy, transcripts encoding proteins believed to be involved in the proper segregation of chromosomes during human oocyte maturation were examined and quantified. Following fluorescent rapid cycle RT-PCR analysis it was determined that the concentration of cell cycle checkpoint gene transcripts decreases significantly as maternal age increases. Given the well established link between increasing maternal age and the incidence of aneuploidy, these results suggest that the degradation of these messages in aging oocytes may be involved with inappropriate chromosome separation during meiosis. ^ In order to investigate the cause of embryonic rescue observed following clinical cytoplasmic transfer procedures and with the objective of developing a diagnostic tool, mtDNA concentrations in polar bodies and subcellular components were evaluated. First, the typical concentration of mtDNA in human and mouse oocytes was determined by fluorescent rapid cycle PCR. Some disparity was noted between the copy numbers of individual cytoplasmic samples which may limit the use of the current methodology for the clinical assessment of the corresponding oocyte. ^

Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.

Longitudinal evaluation of quality of life in 288 patients with Neurofibromatosis 2

Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype.

Sanctity of Human Life in the Context of Human Genetic Research

The study on the concept of sanctity of human life is a journey in finding out what is it said to be “human” in human life. It is an evaluation of the universal concept and the role it plays in controlling and moulding human conduct and relationships. This concept is a foundational principle of human rights law and the grundnorm of every legal system. However, of late, the challenges by way of certain advances in human genetic research had prompted the need to evaluate the significance and extent of the concept in human endeavours. Scientific advances by way of human genetic research promises significant diagnostic and therapeutic advances but at the same time pose threat to fundamental notions and assumptions on humanity, hence there is a global concern to derive common legal standards, Thus the major challenge is to analyse universal principles which can be a common criteria for evolving legal standards to control certain advances in human genetic research. Hence the relevance of the study. The study aims at analysing the content, scope, extent and limitation of the concept of sanctity of human life. In this attempt it evaluates the extent to which the concept had been accommodated by legal systems and international human rights regimes. The problem which had been undertaken in the study is the extent of intrusion made to the concept by virtue of certain advances in human genetic research.

Evaluation of male breeding population inferred from paternity analyses in the Cape Verde islands

[EN] Because of the extensive migrations of marine turtles through the ocean, many aspects of their biology have been unknown for a long time. However, much information has been recently gained from genetic studies and population monitoring of female turtles at their nesting sites. In contrast, still very little is known on the genetic diversity, population structure and dispersal patterns of the male breeding population, mainly because of the difficulty of capturing and monitoring them at sea. The aim of this study is to assess the genetic patterns of the male breeding population of the loggerhead turtle, Caretta caretta, using a non invasive approach and compare them to the female breeding population.

Increasing the power of genome wide association studies in natural populations using repeated measures : evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.

Partnering Strategies for Fitness Evaluation in a Pyramidal Evolutionary Algorithm

This paper combines the idea of a hierarchical distributed genetic algorithm with different inter-agent partnering strategies. Cascading clusters of sub-populations are built from bottom up, with higher-level sub-populations optimising larger parts of the problem. Hence higher-level sub-populations search a larger search space with a lower resolution whilst lower-level sub-populations search a smaller search space with a higher resolution. The effects of different partner selection schemes for (sub-)fitness evaluation purposes are examined for two multiple-choice optimisation problems. It is shown that random partnering strategies perform best by providing better sampling and more diversity.

Evaluation of reproductive barriers contributes to the development of novel interspecific hybrids in the Kalanchoe genus

Background: Interspecific hybridization is a useful tool in ornamental breeding to increase genetic variability and introduce new valuable traits into existing cultivars. The successful formation of interspecific hybrids is frequently limited by the presence of pre- and post-fertilization barriers. In the present study, we investigated the nature of hybridization barriers occurring in crosses between Kalanchoe species and evaluated possibilities of obtaining interspecific hybrids. Results: The qualitative and quantitative analyses of pollen tube growth in situ were performed following intra-and interspecific pollinations. They revealed occurrence of pre-fertilization barriers associated with inhibition of pollen germination on the stigma and abnormal growth of pollen tubes. Unilateral incongruity related to differences in pistil length was also observed. The pollen quality was identified as a strong factor influencing the number of pollen tubes germinating in the stigma. In relation to post-fertilization barriers, endosperm degeneration was a probable barrier hampering production of interspecific hybrids. Moreover, our results demonstrate the relation of genetic distance estimated by AFLP marker analysis of hybridization partners with cross-compatibility of Kalanchoe species. At the same time, differences in ploidy did not influence the success of interspecific crosses. Conclusions: Our study presents the first comprehensive analysis of hybridization barriers occurring within Kalanchoe genus. Reproductive barriers were detected on both, pre- and post-fertilization levels. This new knowledge will contribute to further understanding of reproductive isolation of Kalanchoe species and facilitate breeding of new cultivars. For the first time, interspecific hybrids between K. nyikae as maternal plant and K. blossfeldiana as well as K. blossfeldiana and K. marnieriana were generated.

Partnering Strategies for Fitness Evaluation in a Pyramidal Evolutionary Algorithm

This paper combines the idea of a hierarchical distributed genetic algorithm with different inter-agent partnering strategies. Cascading clusters of sub-populations are built from bottom up, with higher-level sub-populations optimising larger parts of the problem. Hence higher-level sub-populations search a larger search space with a lower resolution whilst lower-level sub-populations search a smaller search space with a higher resolution. The effects of different partner selection schemes for (sub-)fitness evaluation purposes are examined for two multiple-choice optimisation problems. It is shown that random partnering strategies perform best by providing better sampling and more diversity.

National evaluation of NHS genetics service investments: emerging issues from the cancer genetics pilots

In seeking to fulfil the ambition of the 2003 genetics white paper, Our Inheritance, Our Future, to ‘mainstream’ genetic knowledge and practices, the Department of Health provided start-up funding for pilot services in various clinical areas, including seven cancer genetics projects. To help to understand the challenges encountered by such an attempt at reconfiguring the organization and delivery of services in this field, a programme-level evaluation of the genetics projects was commissioned to consider the organizational issues faced. Using a qualitative approach, this research has involved comparative case-study work in 11 of the pilot sites, including four of the seven cancer genetics pilots. In this paper, the researchers present early findings from their work, focusing in particular on the cancer genetics pilots. They consider some of the factors that have influenced how the pilots have sought to address pre-existing sector, organizational and professional boundaries to these new ways of working. The article examines the relationship between these factors and the extent to which pilots have succeeded in setting up boundary-spanning services, dealing with human-resource issues and creating sustainable, ‘mainstreamed’ provision which attracts ongoing funding in a volatile NHS commissioning environment where funding priorities do not always favour preventive, risk-assessment services.