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Following the collapse of the communist regime in 1989, Bulgaria has undergone dramatic political, economic and social transformations. The transition process of the past two decades was characterized by several reforms to support democratisation of the political system and the functioning of a free-market economy. Since 1992, Switzerland has been active in Bulgaria providing assistance to the transition process, with support to Sustainable Management of Natural Resources (SMNR) starting in 1995. The SMNR Capitalisation of Experiences (CapEx) took place between March and September 2007, in the context of SDC phasing out its programmes in Bulgaria by the end of 2007 due to the country’s accession to the European Union. The CapEx exercise has culminated in the identification of 17 lessons learned. In the view of the CapEx team, many of these lessons are relevant for countries that are in the process of joining the EU, facing similar democratisation challenges as Bulgaria. Overall, the Swiss SMNR projects have been effective entry points to support areas that are crucial to democratic transitions, namely participation in public goods management, decentralisation, human capacity development in research and management, and preparation for EU membership. The specificity of the Swiss support stems from an approach that combines a long-term commitment with a clear thematic focus (forestry, biodiversity conservation and organic agriculture). The multistakeholder approach and diversification of support between local, regional and national levels are also important elements that contributed to make a difference in relation to other donors supporting the Bulgarian transition. At the institutional level, there are a number of challenges where the contribution of SMNR activities was only modest, namely improving the legal framework and creating more transparency and accountability, both of which are time and resource-consuming processes. In addition, the emergence of competent and sustainable non-government organisations (NGOs) is a complex process that requires support to membership based organisations, a challenge that was hardly met in the case of SMNR. Finally, reform of government institutions involved in management of natural resources is difficult to achieve via project support only, as it requires leverage and commitment at the level of policy dialogue. At the programme management level, the CapEx team notes that corruption was not systematically addressed in SMNR projects, indicating that more attention should be given to this issue at the outset of any new project.

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A Framework for a Consultation Process: Transboundary cooperation and sustainable water management is urgently needed in the up-stream/down-stream situation of the Umbeluzi River Basin between the Kingdom of Swaziland and the Republic of Mozambique. Thus, the Joint Water Commission (JWC) of the two riparian countries initiated the Umbeluzi River Basin Initiative (URBI) with the objective to develop a joint management plan of the river basin. In response to the request by SADC as well as SDC, a collaboration within CDE’s Eastern and Southern Africa Partnership Programme ESAPP was agreed upon. The project’s general objective is to provide conceptual and methodological support in the design of a consultative process with the aim to assure the participation of all water users within the river basin.

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BACKGROUND Newborn screening for CF started 01/2011 in Switzerland. We investigated the parents' opinions about the information received, their feelings, and overall approval of the screening. METHODS This is a prospective questionnaire survey of all parents of positively screened children. Parents were phoned by CF-centres and invited for diagnostic investigations. They completed a questionnaire after the visit to the CF-centre. RESULTS From 2011-2013, 246 families received the questionnaire and 138 (56%) replied. Of these 77 (60%) found the information received at birth satisfactory; 124 (91%) found the information provided in the CF-centre satisfactory. Most parents (n=98, 78%) felt troubled or anxious when the CF-centre called, 51 (38%) remained anxious after the visit. Most parents (n=122; 88%) were satisfied with the screening, 4 (3%) were not, and 12 (9%) were unsure. CONCLUSIONS The smooth organisation of the screening process, with personal information by a CF specialist and short delays between this information and the final diagnostic testing, might have contributed to reduce anxiety among parents. Most families were grateful that their child had been screened, and are happy with the process.

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Neurons exploit local mRNA translation and retrograde transport of transcription factors to regulate gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high-mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuron-like cells and of hippocampal neurons, where it has the potential to be translated, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth, while HMGN5 overexpression induces neurite outgrowth and chromatin decompaction; these effects are dependent on growth cone localization of Hmgn5 mRNA. We suggest that the localization and local translation of transcripts coding for epigenetic factors couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.

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Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

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The Live Usability Lab provides an exciting format for demonstrating the potential of usability testing to evaluate Web resources from the patron’s perspective. A panel of librarians will use this innovative, interaction-driven method to assess iCONN, to demonstrate the potential and power of user testing, and to engage the audience by illustrating the process with live data instead of canned examples.

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Filamin is a high molecular weight (2 x 250,000) actin crosslinking protein found in a wide variety of cells and tissues. The most striking feature of filamin is its ability to crosslink F-actin filaments and cause ATP-independent gelation and contraction of F-actin solutions. The gelation of actin filaments by filamin involves binding to actin and crosslinking of the filaments by filamin self-association. In order to understand the role of filamin-actin interactions in the regulation of cytoskeletal assembly, two approaches were used. First, the structural relationship between self-association and actin-binding was examined using proteolytic fragments of filamin. Treatment of filamin with papain generated two major fragments, 90Kd and 180Kd. Upon incubation of the papain digest with F-actin and centrifugation at 100,000 x g, only the 180Kd fragment co-sedimented with F-actin. The binding of the 180Kd fragment, P180, was similar to native filamin in its sensitivity to ionic strength. Analytical gel filtration studies indicated that, unlike native filamin, P180 was monomeric and did not self-associate. Thermolysin treatment of P180 produced a 170Kd fragment, PT170, which no longer bound and co-sedimented with F-actin. These results suggested that filamin contained a discrete actin-binding domain. In order to locate the actin-binding domain, affinity purified antibodies to the papain and thermolysin sensitive regions of filamin were used in conjunction with filamin fragments generated by digestion with S. aureus V8 protease and elastase. The results indicated that the papain and thermolysin cleavage sites were close together, and, most likely, within 10Kd of one another. Taken together, these data suggest that filamin contains a discrete, internal actin-binding domain. The second approach was to use the non-crosslinking fragment P180 to develop a quantitative assay of filamin-actin binding. The binding of ('14)C-carboxyalkylated P180 was examined using the co-sedimentation assay. ('14)C-P180 binding to actin was equivalent to that of unlabelled P180 and exhibited comparable sensitivity of binding to changes in ionic strength. Within 5 min. of incubation the process had reached equilibrium. The specificity of binding was shown by the lack of binding of ('14)C-PT170. The binding of ('14)C-P180 was found to be a reversible and saturable process, with a K(,d) of 2 x 10('-7) M. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

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Radiotherapy has been a method of choice in cancer treatment for a number of years. Mathematical modeling is an important tool in studying the survival behavior of any cell as well as its radiosensitivity. One particular cell under investigation is the normal T-cell, the radiosensitivity of which may be indicative to the patient's tolerance to radiation doses.^ The model derived is a compound branching process with a random initial population of T-cells that is assumed to have compound distribution. T-cells in any generation are assumed to double or die at random lengths of time. This population is assumed to undergo a random number of generations within a period of time. The model is then used to obtain an estimate for the survival probability of T-cells for the data under investigation. This estimate is derived iteratively by applying the likelihood principle. Further assessment of the validity of the model is performed by simulating a number of subjects under this model.^ This study shows that there is a great deal of variation in T-cells survival from one individual to another. These variations can be observed under normal conditions as well as under radiotherapy. The findings are in agreement with a recent study and show that genetic diversity plays a role in determining the survival of T-cells. ^

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Cells are exposed to a variety of environmental and physiological changes including temperature, pH and nutrient availability. These changes cause stress to cells, which results in protein misfolding and altered cellular protein homeostasis. How proteins fold into their three-dimensional functional structure is a fundamental biological process with important relevance to human health. Misfolded and aggregated proteins are linked to multiple neurodegenerative diseases, cardiovascular disease and cystic fibrosis. To combat proteotoxic stress, cells deploy an array of molecular chaperones that assist in the repair or removal of misfolded proteins. Hsp70, an evolutionarily conserved molecular chaperone, promotes protein folding and helps maintain them in a functional state. Requisite co-chaperones, including nucleotide exchange factors (NEFs) strictly regulate and serve to recruit Hsp70 to distinct cellular processes or locations. In yeast and human cells, three structurally non-related cytosolic NEFs are present: Sse1 (Hsp110), Fes1 (HspBP1) and Snl1 (Bag-1). Snl1 is unique among the cytosolic NEFs as it is localized at the ER membrane with its Hsp70 binding (BAG) domain exposed to the cytosol. I discovered that Snl1 distinctly interacts with assembled ribosomes and several lines of evidence indicate that this interaction is both independent of and concurrent with binding to Hsp70 and is not dependent on membrane localization. The ribosome-binding site is identified as a short lysine-rich motif within the amino terminus of the Snl1 BAG domain distinct from the Hsp70 interaction region. In addition, I demonstrate ribosome association with the Snl1 homolog in the pathogenic fungus, Candida albicans and localize this putative NEF to a perinuclear/ER membrane, suggesting functional conservation in fungal BAG domain-containing proteins. As a first step in determining specific domain architecture in fungal BAG proteins, I present the preliminary steps of protein purification and analysis of the minimal Hsp70 binding region in in both S.cerevisiae and C. albicans Snl1. Contrary to previous in vitro evidence which showed the Fes1 NEF to interact with both cytosolic Hsp70s, Ssa and Ssb, Fes1 is shown to interact specifically with Ssa when expressed under normal cellular conditions in S. cerevisiae. This is the first reported evidence of Hsp70 binding selectivity for a cytosolic NEF, and suggests a possible mechanism to achieve specificity in Hsp70-dependent functions. Taken together, the work presented in this dissertation highlights the striking divergence among Hsp70 co-chaperones in selecting binding partners, which may correlate with their specific roles in the cell.

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El presente artículo pretende contribuir en el abordaje del análisis cualitativo, de la información que fue recolectada durante el proceso de investigación, con un grupo poblacional de estudiantes Sordos usuarios de Lengua de Señas colombiana en proceso de transición entre la educación media y vida laboral y/o educación superior. Para tal cometido, se llevaron a cabo procesos de indagación previos, tanto a nivel teórico como práctico, con respecto a la temática de orientación vocacional y proyecto de vida, diseñando así un trabajo de campo, que finalmente concluyó en una propuesta pedagógico-formativa que pretende fortalecer el proyecto de vida de los jóvenes Sordos usuarios de la lengua de Señas colombiana en la educación media.

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En el presente trabajo se evaluaron 4 casos clínicos de pacientes con riesgo de caries pero que poseían molares sin lesiones, a los cuales se les colocó selladores de fosas y fisuras: en dos pacientes con resina y en dos pacientes con ionómero de vidrio. Los mismos fueron controlados en su permanencia en boca, los de resina en 6 meses y los de ionómero en 2 años, no encontrándose diferencias clínicas entre los materiales utilizados, debido a la diferencia en el tiempo de control de los mismos. Paralelamente, se realizó un trabajo in vitro con dos grupos de 10 molares cada uno, tratados el grupo 1 con sellador a base de resina y el grupo 2 con sellador de ionómero de vidrio. Luego de someter las muestras a la acción de un colorante (azul de metileno) se seccionaron longitudinalmente y se observaron en una lupa estereoscópica para ver si el colorante había penetrado o no por la interfase sellador/esmalte. No se encontraron diferencias estadísticamente significativas (a>0.05) entre los grupos analizados.

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Se propone ampliar el registro analítico sobre el proceso de conformación del sistema político e institucional de la "Confederación" (1852-1862), atendiendo a las vinculaciones entre el poder central y San Juan. Se examinan las relaciones de negociación y conflicto que entretejieron la política de San Juan entre 1855 y 1858, al calor del desarrollo de una institución estatal nacional: la Circunscripción Militar del Oeste. Se considera en forma recíproca la articulación del poder central en el espacio provincial y los clivajes y sucesos locales y regionales que se generaron en dicho devenir. Se estudia la interacción entre el Jefe de la Circunscripción Nazario Benavides, los Gobernadores de San Juan y los poderes legislativo y ejecutivo nacionales. Además, se enmarca el tema en el proceso de institucionalización política provincial, con especial interés en la sanción de la constitución sanjuanina. Para ello, se conjuga el examen de la Circunscripción con el del Congreso con sede en la ciudad capital de la Confederación (Paraná/Entre Ríos), lo que permite proyectar las escalas analíticas de observación por fuera de la geografía sanjuanina. Se aborda así al Congreso como otro sitio institucional de cristalización de los conflictos y juegos de alianzas políticas provinciales y nacionales estudiadas.

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El artículo propone un recorrido somero por la historia de la profesionalización del escritor en Argentina, a través de la lectura de tres textos autobiográficos escritos entre finales de la década de 1880 y 1930: una causerie de Lucio V. Mansilla, el diario del viaje a París de Horacio Quiroga y las memorias de Hugo Wast. La elección apunta a leer un proceso de transformación con sus inflexiones, superposiciones, emergencias y residuos, para revisar a partir de allí las relaciones que la literatura entabla con el dinero por medio de modalidades tan diversas como el trabajo periodístico, la colaboración free-lance o la escritura de best-sellers, aunque siempre reunidas bajo una figura común: el hambre en vinculación con la escena de iniciación al mundo de las letras.

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Se propone ampliar el registro analítico sobre el proceso de conformación del sistema político e institucional de la "Confederación" (1852-1862), atendiendo a las vinculaciones entre el poder central y San Juan. Se examinan las relaciones de negociación y conflicto que entretejieron la política de San Juan entre 1855 y 1858, al calor del desarrollo de una institución estatal nacional: la Circunscripción Militar del Oeste. Se considera en forma recíproca la articulación del poder central en el espacio provincial y los clivajes y sucesos locales y regionales que se generaron en dicho devenir. Se estudia la interacción entre el Jefe de la Circunscripción Nazario Benavides, los Gobernadores de San Juan y los poderes legislativo y ejecutivo nacionales. Además, se enmarca el tema en el proceso de institucionalización política provincial, con especial interés en la sanción de la constitución sanjuanina. Para ello, se conjuga el examen de la Circunscripción con el del Congreso con sede en la ciudad capital de la Confederación (Paraná/Entre Ríos), lo que permite proyectar las escalas analíticas de observación por fuera de la geografía sanjuanina. Se aborda así al Congreso como otro sitio institucional de cristalización de los conflictos y juegos de alianzas políticas provinciales y nacionales estudiadas.

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Se propone ampliar el registro analítico sobre el proceso de conformación del sistema político e institucional de la "Confederación" (1852-1862), atendiendo a las vinculaciones entre el poder central y San Juan. Se examinan las relaciones de negociación y conflicto que entretejieron la política de San Juan entre 1855 y 1858, al calor del desarrollo de una institución estatal nacional: la Circunscripción Militar del Oeste. Se considera en forma recíproca la articulación del poder central en el espacio provincial y los clivajes y sucesos locales y regionales que se generaron en dicho devenir. Se estudia la interacción entre el Jefe de la Circunscripción Nazario Benavides, los Gobernadores de San Juan y los poderes legislativo y ejecutivo nacionales. Además, se enmarca el tema en el proceso de institucionalización política provincial, con especial interés en la sanción de la constitución sanjuanina. Para ello, se conjuga el examen de la Circunscripción con el del Congreso con sede en la ciudad capital de la Confederación (Paraná/Entre Ríos), lo que permite proyectar las escalas analíticas de observación por fuera de la geografía sanjuanina. Se aborda así al Congreso como otro sitio institucional de cristalización de los conflictos y juegos de alianzas políticas provinciales y nacionales estudiadas.