International Conference on African Successes: documenting the concept and process

Conference Paper No.

Methylation of migraine-related genes in different tissues of the rat

17β-Estradiol, an epigenetic modulator, is involved in the increased prevalence of migraine in women. Together with the prophylactic efficacy of valproate, which influences DNA methylation and histone modification, this points to the involvement of epigenetic mechanisms. Epigenetic studies are often performed on leukocytes, but it is unclear to what extent methylation is similar in other tissues. Therefore, we investigated methylation of migraine-related genes that might be epigenetically regulated (CGRP-ergic pathway, estrogen receptors, endothelial NOS, as well as MTHFR) in different migraine-related tissues and compared this to methylation in rat as well as human leukocytes. Further, we studied whether 17β-estradiol has a prominent role in methylation of these genes. Female rats (n = 35) were ovariectomized or shamoperated and treated with 17b-estradiol or placebo. DNA was isolated and methylation was assessed through bisulphite treatment and mass spectrometry. Human methylation data were obtained using the Illumina 450k genome-wide methylation array in 395 female subjects from a population-based cohort study. We showed that methylation of the Crcp, Calcrl, Esr1 and Nos3 genes is tissue-specific and that methylation in leukocytes was not correlated to that in other tissues. Interestingly, the interindividual variation in methylation differed considerably between genes and tissues. Furthermore we showed that methylation in human leukocytes was similar to that in rat leukocytes in our genes of interest, suggesting that rat may be a good model to study human DNA methylation in tissues that are difficult to obtain. In none of the genes a significant effect of estradiol treatment was observed

Технология извлечения структур знаний с использованием аппарата расширенных семантических сетей

В статье рассматривается задача извлечения из текстов естественного языка структур знаний: информационных объектов («именованных сущностей»), их свойств, связей и фактов участия в действиях. Для этих целей разработан инструментарий: язык представления знаний (расширенные семантические сети – РСС) и их обработки (язык преобразования структур – ДЕКЛ). На этой основе созданы технологии, которые обладают следующими особенностями. Из текстов извлекаются не отдельные объекты (именованные сущности), а структуры знаний, представляющие связи объектов и их участие в действиях и событиях. Для извлечения структур знаний разработан уникальный семантико-ориентированный лингвистический процессор (ЛП), осуществляющий глубинный анализ текстов ЕЯ и выявляющий десятки типов объектов вместе с их структурами. Процессор ЛП управляется лингвистическими знаниями, представляющими собой декларативные структуры и обеспечивающие быструю настройку ЛП на предметную область и язык. Основой лингвистических знаний являются правила, обладающие высокой степенью избирательности при выявлении объектов («сущностей»), средствами устранения коллизий при их применении. Это позволяет минимизировать шумы и потери.У статті розглядається задача знайдення у текстах природної мови структур знань: інформаційних об’єктів («іменованих сутностей»), їх якостей зв’язків і фактів участі у діях. Для цих цілей розроблений інструментарій: мова представлення знань (розширені семантичні мережі – РСМ) та їх обробки (мова перетворення структур – ДЕКЛ). На цій основі створені технології, що мають наступні особливості. З тестів виділяються не окремі об’єкти (іменовані сутності), а структури знань, що представляють зв’язки об’єктів та їх участь у діях та подіях. З метою виділення структур знань розроблений винятковий семантико-орієнтований лінгвістичний процесор (ЛП), що здійснює глибинний аналіз текстів ЕЯ та виявляє десятки типів об’єктів разом з їх структурами. Процесор ЛП керується лінгвістичними знаннями, які представляють собою декларативні структури та забезпечують швидке настроювання ЛП на предметну сферу та мову. Основою лінгвістичних знань є правила, що мають високий ступінь вибірковості при виявленні об’єктів («сутностей»), засобами усунення колізій при їхньому використанні. Це дозволяє мінімізувати шуми та втрати.The paper is devoted to the extracting of knowledge structures from the natural language texts, i.e. information objects (“Named Entities”), their features, relationships, and participation in the actions and events. For this purpose, the language used for knowledge representation (extended semantic networks/ESN) and tools for processing (language for structure conversion LSC) are considered. On this base, the new technologies are proposed. These technologies have the following features: extraction from the texts of knowledge structures that represent the links of named entities and their participation in actions and events. For the knowledge extraction the unique semantic-oriented language processor (LP) are designed. Processor LP provides the deep analysis of NL-texts and revealing set of objects together with their structures. Processor LP is controlled by the linguistic knowledge, which are declarative structures (on ESN) and which provides the quick tuning of LP on subject area and language, both Russian and English

Effects of chilled storage and cryopreservation of sperm, and sperm to egg ratio on fertilization success in lumpfish (Cyclopterus lumpus)

publishedVersio

Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration

Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity

Clinical profile of patients with ATP1A3 mutations in alternating hemiplegia of childhood-a study of 155 patients.

BACKGROUND: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. METHODS: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. RESULTS: In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p < 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations. CONCLUSIONS: Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trials

Diagnosis of sustainable collaboration in health promotion – a case study

<p>Abstract</p> <p>Background</p> <p>Collaborations are important to health promotion in addressing multi-party problems. Interest in collaborative processes in health promotion is rising, but still lacks monitoring instruments. The authors developed the DIagnosis of Sustainable Collaboration (DISC) model to enable comprehensive monitoring of public health collaboratives. The model focuses on opportunities and impediments for collaborative change, based on evidence from interorganizational collaboration, organizational behavior and planned organizational change. To illustrate and assess the DISC-model, the 2003/2004 application of the model to the Dutch whole-school health promotion collaboration is described.</p> <p>Methods</p> <p>The study combined quantitative research, using a cross-sectional survey, with qualitative research using the personal interview methodology and document analysis. A DISC-based survey was sent to 55 stakeholders in whole-school health promotion in one Dutch region. The survey consisted of 22 scales with 3 to 8 items. Only scales with a reliability score of 0.60 were accepted. The analysis provided for comparisons between stakeholders from education, public service and public health.</p> <p>The survey was followed by approaching 14 stakeholders for a semi-structured DISC-based interview. As the interviews were timed after the survey, the interviews were used to clarify unexpected and unclear outcomes of the survey as well.</p> <p>Additionally, a DISC-based document analysis was conducted including minutes of meetings, project descriptions and correspondence with schools and municipalities.</p> <p>Results</p> <p>Response of the survey was 77% and of the interviews 86%. Significant differences between respondents of different domains were found for the following scales: organizational characteristics scale, the change strategies, network development, project management, willingness to commit and innovative actions and adaptations. The interviews provided a more specific picture of the state of the art of the studied collaboration regarding the DISC-constructs.</p> <p>Conclusion</p> <p>The DISC-model is more than just the sum of the different parameters provided in the literature on interorganizational collaboration, organization change, networking and setting-approaches. Monitoring a collaboration based on the DISC-model yields insight into windows of opportunity and current impediments for collaborative change. DISC-based monitoring is a promising strategy enabling project managers and social entrepreneurs to plan change management strategies systematically.</p

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie