Structuring institutions to exploit learning technologies: A cybernetic model

The adoption of learning technologies has not fulfilled expectation in any sector of education. Arguably, it is the structure of educational institutions which is the main obstacle. Schools, colleges and universities were designed to allow the delivery of education by the few to the many at a time when the key technology was the printed page, and many of the organizational instruments that facilitated this are still with us today: timetables, classrooms, syllabuses and so on. These permit a particular style of education to take place, but result in a system where the complexity of learning needs is ignored New technologies can provide new organizational devices that recognize this complexity. These require careful design and imply a significant restructuring of institutional organization. This paper addresses how the tools provided by management cybernetics, in particular Stafford Beer's Viable System Model, allow the analysis of structural mechanisms and how they impact on organizational complexity. It describes how these tools can be used to redesign educational organizations, including identifying key points where technologies can be used to create structures that permit a more flexible exploitation of the opportunities offered by learning technologies. The current JTAP project Toolkit for the Management of Learning is offered as an example of a set of software tools that emerge from such a cybernetic analysis

Mechanisms for establishing transcriptional competence of tissue-specific genes in pluripotent stem cells

Tissue-specific genes have been found to be epigenetically marked in embryonic stem cells by different combination of histone modifications. These marks are believed to prime genes for activation at later stages of development. Previous work has revealed the presence of one such signature on one enhancer of the mouse λ5-VpreB1 locus, which is expressed at the pro- and pre-B cell stage of B lymphocyte development. This element, which has been called Early- Transcriptional Competence Mark (ETCM), is characterised by the presence of tightly localised peaks of histone H3K4 methylation and H3K9 acetylation. However, the ETCM lacks the trimethylation of H3K27 that defines bivalent domains at many tissue-specific genes in ES cells. The results described in this thesis show that that two ES cell transcription factors, Sox2 and Foxd3, bind to the λ5-VpreB1 ETCM in ES cells. Analysis of factor binding to the λ5-VpreB1 locus at the proB cell stage of B-cell development showed that the same sequences are occupied by the B-cell specific factors Sox4 and Foxp1. Chromatin immunoprecipitation and microarray analysis (ChIP-on-Chip) showed that Sox2 and Foxd3 are bound to a number of ETCM-like elements in ES cells, as well as bivalent domains, suggesting that they are involved in the establishment and maintenance of these epigenetic marks in ES cells. Knockdown of Sox2 by siRNA confirmed its involvement in the methylation of H3K4 on these DNA regions. Based on these data, I propose a factor-relay model in which embryonic stem cell transcription factors generate epigenetic signatures at key regulatory elements of tissue-specific genes. During differentiation these proteins are replaced by related factors, which share their DNA-binding profile, and play an important role in activating tissue-specific transcription

Wave propagation in fiber composite laminates, part 2

An experimental investigation was conducted to determine the wave propagation characteristics, transient strains and residual properties in unidirectional and angle-ply boron/epoxy and graphite/epoxy laminates impacted with silicone rubber projectiles at velocities up to 250 MS-1. The predominant wave is flexural, propagating at different velocities in different directions. In general, measured wave velocities were higher than theoretically predicted values. The amplitude of the in-plane wave is less than ten percent of that of the flexural wave. Peak strains and strain rates in the transverse to the (outer) fiber direction are much higher than those in the direction of the fibers. The dynamics of impact were also studied with high speed photography

Lamination residual stresses in fiber composites

An experimental investigation was conducted to determine the magnitude of lamination residual stresses in angle-ply composites and to evaluate their effects on composite structural integrity. The materials investigated were boron/epoxy, boron/polyimide, graphite/low modulus epoxy, graphite/high modulus epoxy, graphite/polyimide and s-glass/epoxy. These materials were fully characterized. Static properties of laminates were also determined. Experimental techniques using embedded strain gages were developed and used to measure residual strains during curing. The extent of relaxation of lamination residual stresses was investigated. It was concluded that the degree of such relaxation is low. The behavior of angle-ply laminates subjected to thermal cycling, tensile load cycling, and combined thermal cycling with tensile load was investigated. In most cases these cycling programs did not have any measurable influence on residual strength and stiffness of the laminates. In the tensile load cycling tests, the graphite/polyimide shows the highest endurance with 10 million cycle runouts at loads up to 90 percent of the static strength

Lamination residual stresses in hybrid composites, part 1

An experimental investigation was conducted to study lamination residual stresses for various material and loading parameters. The effects of hybridization on residual stresses and residual properties after thermal cycling under load were determined in angle-ply graphite/Kevlar/epoxy and graphite/S-glass/epoxy laminates. Residual strains in the graphite plies are not appreciably affected by the type and number of hybridizing plies. Computed residual stresses at room temperature in the S-glass plies reach values up to seventy-five percent of the transverse strength of the material. Computed residual stresses in the graphite plies exceed the static strength by approximately ten percent. In the case of Kevlar plies, computed residual stresses far exceed the static strength indicating possible early failure of these plies. Static testing of the hybrids above indicates that failure is governed by the ultimate strain of the graphite plies. In thermally cycled hybrids, in general, residual moduli were somewhat lower and residual strengths were higher than initial values

LIBER 41st Annual Conference : Mobilising the Knowledge Economy for Europe

Conference Programme. 27–30 June 2012, Tart

Household Smoking Bans in Ohio

Background: Clean indoor air ordinances are being rapidly adopted across the United States to protect persons in public places from exposure to environmental tobacco smoke. The private sphere can be partially protected by adopting a household smoking ban. Objective: To analyze the prevalence and adoption patterns of household smoking bans in Ohio. Design: The 2008 Ohio Family Health Survey collected data using random-digit-dialing methodology and cell phone sampling from more than 50,000 Ohio households that provided sociodemographic and health behavior data for analysis. Respondent, household, neighborhood and regional level data were examined to determine the prevalence of adopting a total household smoking ban. Basic descriptive statistics and chi square analyses were used to determine if there were differences in ban adoption by select characteristics. Results: The variables most closely associated with the adoption of household smoking bans included higher respondent education level, and the presence of children and other adults in a household. Being a current smoker was most negatively related to the adoption of a household smoking ban. Conclusions: Public health officials have done an excellent job promoting the adoption of household smoking bans. It may now be necessary to refocus future campaigns to target those populations that have lower household smoking ban adoption rates, namely those in rural Appalachia, blacks, and smokers.No embarg

ClockOME: searching for oscillatory genes in early vertebrate development

Embryo development is a dynamic process regulated in space and time. Cells must integrate biochemical and mechanical signals to generate fully functional organisms, where oscillatory gene expression plays a key role. The embryo molecular clock (EMC) is the best known genetic oscillator active in embryo segmentation, involving genes from the Notch, FGF, and WNT pathways. However, the list of cyclic genes is still incomplete mostly due to the challenges involved with studying periodic systems. Recently, such studies have become more feasible with the development of pseudo-time ordering algorithms that search for candidate oscillatory genes using large transcriptomics datasets sampled without explicit time measurements. This study aims at finding candidate oscillatory genes - ClockOME - active in early chick embryo development. Two Gallus gallus microarray transcriptomics datasets from Presomitic mesoderm (PSM), and one dataset from limb segmentation were gathered from GEO and ArrayExpress. To normalize these data from different experiments, an RData package - FrozenChicken - was developed to apply a frozen Robust MultiArray (fRMA) normalization to the data. Next the datasets were processed with Oscope (a pseudo-time ordering algorithm) to search for candidate periodic genes clustered by similar oscillatory behaviour. The clusters of predicted oscillators were then subject to functional enrichment and interaction network analyses to highlight the biological functions associated with these genes. Oscope predicted three clusters of oscillators: two in PSM (106 and 32 genes), and one in Limb (162 genes). Overall, the genes are associated with regulatory, morphological, and developmental processes. Mesp2, a gene involved with the EMC, was found in this dataset, validating the approach, however, the majority of genes are novel oscillatory candidates, associated with chromatin and transcriptional regulation, as well as protein and oxygen metabolism. The list of candidate oscillators represents a valuable resource for guided experimental validation to discover additional members of the chick EMC. Six genes have been proposed for high-priority experimental validation: SRC, PTCH1, NOTCH2, YAP1, KDR, CTR9.O desenvolvimento embrionário é um processo dinâmico que envolve alterações moleculares no espaço e no tempo. As células embrionárias são constantemente expostas a estímulos bioquímicos e mecânicos, e respondem ao ambiente em que se encontram alterando o seu programa genético. Quando corretamente integradas, estas respostas celulares culminam com o desenvolvimento bem-sucedido de um organismo funcional. Assim, a embriogénese envolve processos moleculares estritamente regulados, sendo a expressão oscilatória de genes uma das formas possíveis para a regulação do comportamento das células ao longo do tempo. O relógio molecular embrionário é um conhecido oscilador genético, e está envolvido na segmentação do tecido paraxial embrionário. O conceito de relógio molecular foi inicialmente proposto em 1976 por Cooke e Zeeman, ao qual chamaram o modelo Clock and Wavefront (Relógio e Frente de Onda)1. Este modelo foi concebido para descrever teoricamente a formação rítmica de sómitos em ambos os lados da mesoderme paraxial (PSM) nos vertebrados, e baseia-se na existência de osciladores genéticos que regulam esse processo de segmentação da PSM ao longo do tempo. Para além do relógio, como diz o nome, o modelo inclui a existência de uma frente de onda, que determina espacialmente o comportamento das células presentes na mesoderme pré-somítica (PSM). Assim, os dois mecanismos guiam a diferenciação das células da PSM, que consequentemente sofrem transformações genéticas que precedem a formação dos sómitos. A base deste relógio molecular consiste na expressão periódica de genes que fazem parte das vias moleculares Notch, FGF e WNT. Contudo, a lista de genes envolvidos no relógio embrionário ainda não se encontra completa, facto este que se deve principalmente às dificuldades experimentais relacionadas com o estudo de sistemas periódicos quando não se conhece de antemão a periodicidade/ritmo da expressão dos genes envolvidos. Com o advento de novas técnicas de transcriptómica que permitem o estudo dos valores de expressão de todos os genes simultaneamente, nomeadamente usando Microarrays, ou mais recentemente através de métodos de sequenciação, como RNA-sequencing ou Single-Cell RNA-sequencing, surge a oportunidade de procurar alargar a lista de genes com expressão oscilatória. Porém, estes métodos implicam a extração do RNA das células amostradas resultando na morte celular. Assim, este processamento inviabiliza o estudo das mesmas células ao longo do tempo, originando dados moleculares estáticos, isto é, os níveis de expressão obtidos representam uma única amostra temporal. Para o estudo de processos periódicos, seria então necessário fazer uma série temporal amostrando diferentes indivíduos ao longo do tempo de desenvolvimento, aumentando grandemente o número de amostras biológicas necessárias para resolver o ciclo de oscilação para cada gene estudado. Assim, sem informação temporal medida explicitamente, a expressão oscilatória de genes pode apenas ser estudada usando modelos matemáticos apropriados, nomeadamente através da aplicação de algoritmos de ordenação pseudo-temporal. Estes métodos ordenam as amostras ao longo do tempo de uma oscilação de forma a obter o padrão do comportamento cíclico para todos os genes cuja expressão oscila concomitantemente. Torna-se assim possível, bioinformaticamente, inferir o potencial oscilatório de genes medidos por estas técnicas de transcriptómica, sem informação temporal explícita. Deste modo, o objetivo deste estudo é encontrar novos genes oscilatórios, a que coletivamente chamamos ClockOME, que estão ativos durante as primeiras etapas do desenvolvimento embrionário (somitogénese) da galinha, nos tecidos da mesoderme présomítica (PSM), e no membro superior (Limb); tecidos estes onde o relógio molecular foi descrito, atuando como regulador temporal das alterações genéticas subjacentes. Para tal, recolheu-se 3 conjuntos de dados (datasets) de transcriptómica obtidos por microarray de dois repositórios de dados públicos: GEO (da instituição americana NCBI) e ArrayExpress (da instituição europeia EMBL-EBI). Dois datasets continham dados de mesoderme paraxial (PSM) – tecido onde ocorre a somitogénese; e um dataset de dados de obtidos do membro superior do embrião de galinha. Com o objetivo de normalizar os três datasets de forma a torná-los comparáveis (uma vez que são oriundos de processos experimentais diferentes), foi desenvolvido um pacote de R denominado “FrozenChicken: Promoting the meta-analysis of chicken microarray data” (publicado em 2021) (https://doi.org/10.1101/2021.02.25.432894). Este pacote contém dados sumarizados de 472 datasets de microarrays de embriões de galinha, tornando possível a normalização por fRMA (frozen Robust MultiArray) de microarrays de Gallus gallus. Após normalização e controlo de qualidade dos valores de expressão genética, os dados da PSM e do membro foram processados com o Oscope (algoritmo de ordenação pseudo-temporal), com o propósito de prever genes oscilatórios. Este algoritmo avalia todas as combinações de pares de genes, agrupando aqueles que apresentem padrões de expressão semelhantes, ou seja, cujos valores de expressão ao longo das amostras seguem trajetórias semelhantes, indiciando um período de oscilação potencialmente semelhante. Os clusters de genes previstos pelo Oscope foram posteriormente submetidos a uma análise de enriquecimento funcional e a uma análise de interações funcionais, com o intuito de perceber o seu potencial papel biológico, e funções moleculares subjacentes. O Oscope reportou três listas de genes potencialmente oscilatórios: dois grupos foram encontrados a partir dos dados da PSM (com 106 e 32 genes cada) e o terceiro grupo de 162 genes foi encontrado nos dados do membro superior. No total, a lista de genes que denominamos ClockOME é composta por 296 genes potencialmente oscilatórios, envolvidos em diversos mecanismos regulatórios importantes para o desenvolvimento embrionário e para a morfogénese. A maioria dos genes presentes nesta lista não estão descritos na literatura como sendo oscilatórios (novel candidates), representando, portanto, uma mais-valia para a comunidade científica que estuda o relógio molecular embrionário. Estes genes parecem estar associados a funções como remodelação da cromatina, regulação da transcrição, metabolismo proteico e metabolismo do oxigénio, sendo, portanto, bons candidatos para futura validação experimental. Notavelmente, o Oscope identificou com sucesso o Mesp2, um gene oscilatório bem descrito na literatura, mostrando assim a validade e o potencial desta abordagem teórica. Em suma, este trabalho produziu uma lista de 296 genes potencialmente oscilatórios. Com base na sua novidade e na função molecular anotada, foi proposta uma lista de seis genes candidatos de particular relevância para validação experimental no futuro próximo, nomeadamente: SRC, PTCH1, NOTCH2, YAP1, KDR, CTR9. Assim, as listas resultantes do trabalho desta tese poderão agora guiar futuras experiências laboratoriais capazes de adicionar novos interactores moleculares ao atual modelo do relógio molecular embrionário

Formulating a Regulatory Stance: The Comparative Politics of E-Cigarette Regulation in Australia, Canada and New Zealand

Depending on who is asked, electronic cigarettes (e-cigarettes) are either the worst thing to happen to the fight against tobacco or a godsent technology that will dramatically improve public health. Unlike tobacco cigarettes, where the world has converged on common regulatory policies intent on shrinking the market for those deadly products, jurisdictions diverge immensely in their regulatory goals towards e-cigarettes. Illustratively, in March 2017, the government of New Zealand announced it would legalize the sale of e-cigarettes. In February 2017, Australia’s pharmaceutical regulator rejected a proposal to legalize the sale of nicotine for use in e-cigarettes because evidence of the product’s long-term safety was lacking. Previously, the medicines regulator in each country agreed the sale of e-cigarettes with nicotine should not be legal. Within a month, two wealthy, democratic, neighboring former British colonies, with a history of being leaders in tobacco control policy, led by right-wing governments, parted company on this momentous policy issue. Why? Through a comparative study of Australia, Canada, and New Zealand, this study addresses how the concerns of public health advocates, business, bureaucrats, and politicians around e-cigarettes are translated into regulatory policy. Political science has only begun to apply its theories to the study of public health policies, and most of what drives public health policy outcomes remains poorly understood. Here, a qualitative comparative approach of three most-similar country cases is used to determine what factors enabled e-cigarette regulatory policy change or stasis. To imbue meaning to the purpose of a regulatory framework, the study introduces an organizing framework called a regulatory stance, which describes the intent of a regulatory framework to alter the size of a market in the future relative to the present. All three case countries began with a prohibitionist regulatory stance towards e-cigarettes, which intended the market for e-cigarettes should make up none of their economies. New Zealand and Canada soon adopted expansionist regulatory stances, meaning that these countries intended on growing the size of their e-cigarette markets. Australia kept its original regulatory stance. Structured by John W. Kingdon’s Multiple Streams Approach to agenda-setting, the case studies examine how and why a country’s regulatory stance towards e-cigarettes, changed or did not. I employed qualitative techniques of document collection and key informant interviews to piece together a comparative study of e-cigarette regulatory policy and politics. In the Multiple Streams Approach, the problem and policy streams must become primed before they can merge with the politics stream and open a policy window. The problem stream became primed once the current regulatory policy was deemed a failure when it was rejected by the courts as illegal, rejected by bureaucracies as not worth enforcing, or it failed to advance the fight against smoking. Next, the policy stream became primed once the public health policy community agreed on a consensus alternative regulatory stance expanding the market for e-cigarettes. Finally, the politics stream was primed when conditions in the problem and policy stream granted left-wing politicians’ permission to support a regulatory stance change favored by business groups. This freed right-wing politicians to support regulatory stance change without facing a political penalty. Once all stakeholders agreed they would benefit more by adopting the alternative regulatory stance than by continuing with the failed policy, a policy window to change the failed e-cigarette regulatory stance opened.PHDHealth Services Organization & PolicyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162993/1/acliber_1.pd

Áreas de restricción y zonas de prohibición para la explotación de aguas subterráneas. El caso de Mendoza, Argentina

El artículo aborda el crucial tema de creciente importancia del régimen jurídico de las áreas de restricción y prohibición para la explotación de aguas subterráneas en Argentina centrándose en el análisis de tres problemas jurídicos principales. Primero, la cuestión del establecimiento, declaración y creación de esas áreas y los efectos jurídicos con respecto a terceros y los requisitos de fondo y forma vinculados a la razonabilidad tanto como a la legalidad. El segundo problema analizado es la aplicación de la nueva reglamentación a situaciones jurídicas existentes donde se enfrentan principio medulares como el de irretroactividad de la ley, buena fe y confianza legítima, con el aplicación de la ley a situaciones no consolidadas o no consumadas y la inexistencia de derecho adquiridos ante la ausencia de acto administrativo. El tercer núcleo es el relativo a la determinación del ámbito espacial de la restricción, con el seccionamiento de acuíferos, sectorización o definición de áreas de manejo de aguas subterráneas dentro de un mismo acuífero, donde se invoca a veces el principio precautorio, pero al mismo tiempo la certidumbre al fijar el seccionamiento o la disponibilidad exacta en ciertos puntos para el otorgamiento de nuevos derechos. El campo analizado es especialmente problemático por la confluencia de aspectos e intereses técnicos, políticos, económicos y jurídicos, el nivel reglamentario y marco de excepcionalidad en que suele moverse y la inconsistencia, contradicción y opacidad demostrada en su accionar tanto por los particulares como por la administración y la jurisprudencia.Fil: Martin, Liber Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentin