Luovuus ja itsetuntemus ohjaajantyössä

This research deals with obstacles and opportunities with respect to creativity. It mainly focuses on the author's most meaningful discoveries as an individual and a professional in the field of theatre during the past two years of her education. The research is a description of that transitional phase in her life. Firstly, the research discusses creativity and presence. Secondly, it describes the author personally and professionally and compares her earlier and current ways of working. It contemplates the obstacles and opportunities considering her self-knowledge and creativity, and disucsses the problems she has faced on the way to freedom and well-being. Following this, the author presents the tools for increasing her creativity, self-knowledge and body awareness in theatre work: the Gestalt Method, Acting with the Inner Partner and the Authentic Movement. She discusses the relativity between overall well-being in life and the quality of theatre work. The final section of the present research discusses the process of directing the play Suurin on rakkaus in 2006. It deals with issues such as self-knowledge in directing, group management, the importance of terror and excitement in directing and ways of enduring both. The conclusion explanes the reasons behind the author's capability of working with small groups, with creative and passionate theatre workers. It also lists the benefits of exploring one's passions, cooperating with enthusiastic and creative artists and the pursuit for balance in art and in everyday life.

A Dethroned King? The Limits of State Infrastructural Power in France

Since the 1980s in Western Europe, centralized states' control over subnational territories has been deeply affected by processes of Europeanization and regionalization. These changes have raised the issue of state territorial restructuring in a particular fashion: what capacity have formerly centralized states retained to steer and control subnational territories? The article draws on Mann's concept of infrastructural power, which refers to the state's capacity to exercise control and implement political decisions over the national territory. The article applies the two main operationalizations of the concept, namely the capability of the state to exercise control and the weight of the state in the subnational territories. Empirically, the article focuses on the French state in two policy sectors (education and housing). Although France is a most likely case, this article challenges this expectation, and shows the limits of the French state's infrastructural power over the subnational territories since the late 1980s.

Alu expression in human cell lines and their retrotranspositional potential.

BACKGROUND: The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as 'source elements' can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous genome-wide analyses from normal and transformed cell lines identified multiple Alu loci occupied by pol III factors, making them candidate source elements. FINDINGS: Analysis of the data from these genome-wide studies determined that the majority of pol III-bound Alus belonged to the older subfamilies Alu S and Alu J, which varied between cell lines from 62.5% to 98.7% of the identified loci. The pol III-bound Alus were further scored for estimated retrotransposition potential (ERP) based on the absence or presence of selected sequence features associated with Alu retrotransposition capability. Our analyses indicate that most of the pol III-bound Alu loci candidates identified lack the sequence characteristics important for retrotransposition. CONCLUSIONS: These data suggest that Alu expression likely varies by cell type, growth conditions and transformation state. This variation could extend to where the same cell lines in different laboratories present different Alu expression patterns. The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies. Our observations suggest that in an in vivo scenario, the contribution of Alu activity on somatic genetic damage may significantly vary between individuals and tissues.

Rôle de la MGMT et implications cliniques dans les tumeurs cérébrales [Role of MGMT and clinical applications in brain tumours]

Glioblastoma multiforme is the most common and most malignant primary brain tumour with a dismal prognosis. The advent of new chemotherapies with alkylating agents crossing the blood-brain barrier, like temozolomide, have permitted to notably ameliorate the survival of a subgroup of patients. Improved outcome was associated with epigenetic silencing of the MGMT (O6-methylguanin methyltransferase) gene by promotor methylation, thereby blocking its repair capability, thus rendering the alkylating agents more effective. This particularity can be tested by methylation specific PCR on resected tumour tissue, best on fresh frozen biopsies, and allows identification of patients more susceptible to respond favourably to the treatment.

Iowa's Rural Alzheimer's Demonstration Project, July 1, 2004 - June 31, 2007

The Iowa Department of Elder Affairs, in collaboration with the Iowa Department of Elder Affairs (IDEA) and the University of Iowa College of Nursing (UI CON), has been engaged in developing and evaluating community based services for persons with dementia in the state of Iowa over the past 7 years under two grants form the Administration on Aging. In the current grant period, the involved agencies have completed a collaborative effort aimed to increase the capacity of Adult Day Health and Respite (ADR) providers in serving persons with dementia. Adult day services and respite care were identified by participants in the initial grant through various processes and service providers as important components of caring for persons with dementia and that there was a gap of these services in the state. Therefore, adult day and respite services were chosen as a target for the second AoA grant. The focus, in particular, was to enhance capacity to care for persons with later stages of the disease and those in rural settings as well as to begin to develop services that are more responsive to emerging minority populations. The process of the grant provided the state with a rich amount of information about the status of Iowa’s Adult Day Service providers in general and in regard to provision of dementia specific services, as well as valuable insights into the capability of rural communities to serve persons with dementia and their caregivers at home. Final Performance Report

Drivers and sources of supply flexibility: An exploratory study

Purpose - There has been much research on manufacturing flexibility, but supply chain flexibility is still an under-investigated area. This paper focuses on supply flexibility, the aspects of flexibility related to the upstream supply chain. Our purpose is to investigate why and how firms increase supply flexibility.Methodology/Approach An exploratory multiple case study was conducted. We analyzed seven Spanish manufacturers from different sectors (automotive, apparel, electronics and electrical equipment).Findings - The results show that there are some major reasons why firms need supply flexibility (manufacturing schedule fluctuations, JIT purchasing, manufacturing slack capacity, low level of parts commonality, demand volatility, demand seasonality and forecast accuracy), and that companies increase this type of flexibility by implementing two main strategies: to increase suppliers responsiveness capability and flexible sourcing . The results also suggest that the supply flexibility strategy selected depends on two factors: the supplier searching and switching costs and the type of uncertainty (mix, volume or delivery).Research limitations - This paper has some limitations common to all case studies, such as the subjectivity of the analysis, and the questionable generalizability of results (since the sample of firms is not statistically significant).Implications - Our study contributes to the existing literature by empirically investigating which are the main reasons for companies needing to increase supply flexibility, how they increase this flexibility, and suggesting some factors that could influence the selection of a particular supply flexibility strategy.

Label-free cytotoxicity screening assay by digital holographic microscopy

Abstract We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.

Caracterização Geológica e Geotécnica das Unidades Litológicas da Cidade da Praia (Santiago - Cabo Verde)

Este trabalho produz uma avaliação das características geológicas e geotécnicas de um território da ilha de Santiago, Cabo Verde, incidindo sobre a cidade da Praia e a área envolvente. Os objectivos principais do trabalho são a representação cartográfica das unidades litológicas, com uma proposta de coluna litológica sintética, a correlação com as unidades geológicas definidas por outros autores, bem como a realização de um conjunto de ensaios in situ e análises laboratoriais visando a caracterização dos parâmetros físicos e mecânicos das diferentes unidades litológicas definidas para a área em estudo. É efectuada uma compilação sobre as principais investigações geológicas realizadas em Cabo Verde, desde o séc. XIX até a actualidade, assim como a descrição das características geológicas da ilha de Santiago e dos principais processos de formação e evolução das formas de relevo e dos recursos naturais (hídricos e solos). A pesquisa incluiu uma revisão dos conceitos descritivos de caracterização dos vulcanitos e vulcanoclastitos presentes e compreendeu a redefinição das unidades litológicas da região, a respectiva representação cartográfica na escala 1: 10.000 (com maior detalhe do que a informação pré-existente) e o levantamento de campo dos principais alinhamentos estruturais. São igualmente apresentados os resultados do tratamento das bandas espectrais de imagens de satélite que suportam a definição das unidades litológicas, bem como dos principais alinhamentos tectónicos que afectam as unidades da área de estudo. Para a caracterização das diferentes unidades litológicas com base nas propriedades in situ, recorreu-se a perfis-tipo, estabelecendo uma descrição das características mineralógicas, petrográficas, texturais e estruturais das materiais presentes. Os materiais foram igualmente ensaiados in situ e amostrados para uma caracterização laboratorial. Os resultados dos ensaios geotécnicos, geomecânicos, mineralógicos e de radioactividade natural permitiram refinar a cartografia proposta e estabelecer parâmetros de comportamento para as 30 unidades litológicas consideradas, a partir de intervalos de valores não homogéneos, contudo representativos da variabilidade observada. Com base nestes resultados são apresentados valores indicativos de aptidão dos materiais, nomeadamente para fundações de edifícios, aterros, construção e potencial hidrogeológico.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Draft environmental report on Cape Verde

Faced with recurrent drought and famine during five centuries of human occupation, the small and densely populated Cape Verde Islands have a history of severe environmental problems. The arid climate and steep, rocky terrain provide scant resources for traditional subsistance farming under the best conditions, and in years of low rainfall the failure of rainfed crops causes massive food shortages. Agricultural use of steep slopes where rainfall is highest has led to soil erosion, as has removal of the island's vegetation for fuel and livestock. Pressure on the vegetation is particularly severe in dry years. International aid can provide relief from famine, and the introduction of modern agricultural and conservation techniques can improve the land and increase yield, but it is unlikely that Cape Verde can ever be entirely self -sufficient in food. Ultimately, the solution of Cape Verde's economic and environmental problems will probably require the development of productive urban jobs so the population can shift away from the intensive and destructive use of land for subsistance farming. In the meantime, the people of Cape Verde can best be served by instituting fundamental measures to conserve and restore the land so that it can be used to its fullest potential. The primary environmental problems in Cape Verde today are: 1. Soil degradation. Encouraged by brief but heavy rains and steep slopes, soil erosion is made worse by lack of vegetation. Soils are also low in organic matter due to the practice of completely removing crop plants and natural vegetation for food, fuel or livestock feed. 2. Water shortage. Brief and erratic rainfall in combination with rapid runoff makes surface water scarce and difficult to use. Groundwater supplies can be better developed but capabilities are poorly known and the complex nature of the geological substrate makes estimation difficult. Water is the critical limiting factor to the agricultural capability of the islands. 3. Fuel shortage. Demand for fuel is intense and has resulted in the virtual elimination of native vegetation. Fuelwood supplies are becoming more and more scarce and costly. Development of managed fuelwood plantations and alternate energy sources is required. 4. Inappropriate land use. Much of the land now used for raising crops or livestock is too steep or too arid for these purposes, causing erosion and destruction of vegetation. Improving yield in more appropriate areas and encouraging less damaging uses of the remaining marginal lands can help to alleviate this problem.

The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild

BACKGROUND: The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas.RESULTS: We successfully identified the causal genetic variant for Snowflake's albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake's parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla.CONCLUSIONS: In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost.

Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.

In adult mammals, neural progenitors located in the dentate gyrus retain their ability to generate neurons and glia throughout lifetime. In rodents, increased production of new granule neurons is associated with improved memory capacities, while decreased hippocampal neurogenesis results in impaired memory performance in several memory tasks. In mouse models of Alzheimer's disease, neurogenesis is impaired and the granule neurons that are generated fail to integrate existing networks. Thus, enhancing neurogenesis should improve functional plasticity in the hippocampus and restore cognitive deficits in these mice. Here, we performed a screen of transcription factors that could potentially enhance adult hippocampal neurogenesis. We identified Neurod1 as a robust neuronal determinant with the capability to direct hippocampal progenitors towards an exclusive granule neuron fate. Importantly, Neurod1 also accelerated neuronal maturation and functional integration of new neurons during the period of their maturation when they contribute to memory processes. When tested in an APPxPS1 mouse model of Alzheimer's disease, directed expression of Neurod1 in cycling hippocampal progenitors conspicuously reduced dendritic spine density deficits on new hippocampal neurons, to the same level as that observed in healthy age-matched control animals. Remarkably, this population of highly connected new neurons was sufficient to restore spatial memory in these diseased mice. Collectively our findings demonstrate that endogenous neural stem cells of the diseased brain can be manipulated to become new neurons that could allow cognitive improvement.

SOCS3 Transactivation by PPARγ Prevents IL-17-Driven Cancer Growth.

Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4 T cells derived from mice fed a DHA-enriched diet displayed less capability to differentiate into TH17 cells. In two different mouse models of cancer, DHA prevented tumor outgrowth and angiogenesis in an IL-17-dependent manner. Altogether, our results uncover a novel molecular pathway by which PPARγ-induced SOCS3 expression prevents IL-17-mediated cancer growth. Cancer Res; 73(12); 3578-90. ©2013 AACR.

Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.

Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis.

Aproximaciones al estudio de la interacción individuo-paisaje a modo de evocacion comunicativa intrapersonal (2a. parte)

El análisis de la interacción individuo-paisaje presenta numerosas perspectivas de estudio vinculadas a la generación e interpretación de simbolismos e imaginarios. La capacidad significante y/o de evocación comunicativa del paisaje encuentra, en la comunicación intrapersonal, una argumentación relevante en el proceso de construcción de un aparato teórico que permita estudiar el proceso de apropiación y vivencia del paisaje en términos de manifestación comunicativa. El despliegue de un aparato teórico que permita interpretar el mensaje del paisaje así como descodificar su discurso intangible, representa el objetivo principal de la investigación que se presenta a continuación.