Roles of insulin-like growth factor binding protein-3 in gastrointestinal stromal tumors

Imatinib mesylate, a selective inhibitor of KIT, PDGFR, and Abl kinases, has shown significant success as a therapy for patients with advanced gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms of imatinib-induced cytotoxicity are not well understood. Using gene expression profiling and real-time PCR for target validation, we identified insulin-like growth factor binding protein-3 (IGFBP3) to be to be up-regulated after imatinib treatment in imatinib-sensitive GISTs. IGFBP3 is a multifunctional protein that regulates cell proliferation and survival and mediates the effects of a variety of anti-cancer agents through IGF-dependent and IGF-independent mechanisms. Therefore, we hypothesized that IGFBP3 mediates GIST cell response to imatinib. To test this hypothesis, we manipulated IGFBP3 protein levels in two KIT mutant, imatinib-sensitive GIST cell lines and assessed the resultant changes in cell viability, survival, and imatinib sensitivity. In GIST882 cells, endogenous IGFBP3 was required for cell viability. However, inhibiting imatinib-induced IGFBP3 up-regulation by RNA interference or neutralization resulted in reduced drug sensitivity, suggesting that IGFBP3 sensitizes GIST882 cells to imatinib. GIST-T1 cells, on the other hand, had no detectable levels of endogenous IGFBP3, nor did imatinib induce IGFBP3 up-regulation, in contrast to our previous findings. IGFBP3 overexpression in GIST-T1 cells reduced viability but did not induce cell death; rather, the cells became polyploid through a mechanism that may involve attenuated Cdc20 expression and securin degradation. Moreover, IGFBP3 overexpression resulted in a loss of KIT activation and decreased levels of mature KIT. Consistent with this, GIST-T1 cells overexpressing IGFBP3 were less sensitive to imatinib. Furthermore, as neither GIST882 cells nor GIST-T1 cells expressed detectable levels of IGF-1R, IGFBP3 is likely not exerting its effects by modulating IGF signaling through IGF-1R or IR/IGF-1R hybrid receptors in these cell lines. Collectively, these findings demonstrate that IGFBP3 has cell-dependent effects and would, therefore, not be an ideal marker for identifying imatinib response in GISTs. Nevertheless, our results provide preliminary evidence that IGFBP3 may have some therapeutic benefits in GISTs. ^

Studies of the expression of DNA repair related genes

This dissertation examines the biological functions and the regulation of expression of DNA ligase I by studying its expression under different conditions.^ The gene expression of DNA ligase I was induced two- to four-fold in S-phase lymphoblastoid cells but was decreased to 15% of control after administration of a DNA damaging agent, 4-nitroquinoline-1-oxide. When cells were induced into differentiation, the expression level of DNA ligase I was decreased to less than 15% of that of the control cells. When the gene of DNA ligase I was examined for tissue specific expression in adult rats, high levels of DNA ligase I mRNA were observed in testis (8-fold), intermediate levels in ovary and brain (4-fold), and low levels were found in intestine, spleen, and liver (1- to 2-fold).^ In confluent cells of normal skin fibroblasts, UV irradiation induced the gene expression of DNA ligase I at 24 and 48 h. The induction of DNA ligase I gene expression requires active p53 protein. Introducing a vector containing the wild type p53 protein in the cells caused an induction of the DNA ligase I protein 24 h after the treatment.^ Our results indicate that, in addition to the regulation by phosphorylation/dephosphorylation, cellular DNA ligase I activity can be regulated at the gene transcription level, and the p53 tumor suppresser is one of the transcription factors for the DNA ligase I gene. Also, our results suggest that DNA ligase I is involved in DNA repair as well as in DNA replication.^ Also, as an early attempt to clone the human homolog of the yeast CDC9 gene which has been shown to be involved in DNA replication, DNA repair, and DNA recombination, we have identified a human gene with mRNA of 1.7 kb. This dissertation studies the gene regulation and the possible biological functions of this new human gene by examining its expression at different stages of the cell cycle, during cell differentiation, and in cellular response to DNA damage.^ The new gene that we recently identified from human cells is highly expressed in brain and reproductive organs (BRE). This BRE gene encodes an mRNA of 1.7-1.9 kb, with an open reading frame of 1,149 bp, and gives rise to a deduced polypeptide of 383 amino acid residues. No extensive homology was found between BRE and sequences from the EMBL-Gene Banks. BRE showed tissue-specific expression in adult rats. The steady state mRNA levels were high in testis (5-6 fold), ovary and brain (3-4 fold) compared to the spleen level, but low in intestine and liver (1-2 fold). The expression of this gene is responsive to DNA damage and/or retinoic acid (RA) treatment. Treatment of fibroblast cells with UV irradiation and 4-nitroquinoline-1-oxide caused more than 90% and 50% decreases in BRE mRNA, respectively. Similar decreases in BRE expression were observed after treatment of the brain glioma cell line U-251 and the promyelocytic cell line HL-60 with retinoic acid. (Abstract shortened by UMI). ^

Identification and characterization of cellular genes differentially expressed in a subset of tumors with non -functional WT1

Wilms tumor (WT) or nephroblastoma is a genetically heterogeneous pediatric renal tumor that accounts for 6–7% of all childhood cancers in the U.S. WT1, located at 11p13, is the sole WT gene cloned to date. Additional genomic regions containing genes that play a role in the development of Wilms tumor include 11p15, 7p, 16q, 1p, 17q and 19q. This heterogeneity has made it extremely difficult to develop an understanding of the pathways involved in the development of WT, even in the 5–20% of tumors that show mutations at the WT1 locus. My research addresses this gap in our current comprehension of the development of WT. ^ I have used two complementary approaches to extend the current understanding of molecular changes involved in the development of WT. In order to minimize complexities due to genetic heterogeneity, I confined my analysis to the WT1 pathway by assessing those genetically defined tumors that carry WT1 mutations. WT1 encodes a zinc finger transcription factor, and in vitro studies have identified many genes that are potentially regulated in vivo by WT1. However, there is very little in vivo data that suggests that they are transcriptionally regulated endogenously by WT1. In one approach I assessed the role of WT1 in the in vivo regulation of PDGFA and IGF2, two genes that are strong contenders for endogenous regulation by WT1. Using primary tissue samples, I found no correlation between the level of RNA expression of WT1 with either PDGFA or IGF2, suggesting that WT1 does not play a critical role in their expression in either normal kidney or WT. ^ In a parallel strategy, using differential display analysis I compared global gene expression in a subset of tumors with known homozygous inactivating WT1 mutations (WT1-tumors) to the gene expression in a panel of appropriate control tissues (fetal kidney, normal kidney, rhabdoid tumor and pediatric renal cell carcinoma). Transcripts that are aberrantly expressed in this subset of Wilms tumors are candidates for endogenous transcriptional regulation by WT1 as well as for potentially functioning in the development of WT. By this approach I identified several differentially expressed transcripts. I further characterized two of these transcripts, identifying a candidate WT gene in the process. I then performed a detailed analysis of this WT candidate gene, which maps to 7p. Future studies will shed more light on the role of these differentially expressed genes in WT. ^

Oceanography during TYDEMAN cruise DCM (DeepChlorMax) to the Equatorial Atlantic

The cruise with RV Tydeman was devoted to study permanently stratified plankton systems in the (sub)tropical ocean, which are characterised by a deep chlorophyll peak between 80 and 150 m. To minimise lateral effects by horizontal transport of nutrients and organic matter from river outflow and upwelling regions, stations were selected in the middle of the North Atlantic Ocean between the continents of America and Africa. (5 - 35° N and 50 - 15° W). Here the vertical distributions of light and nutrients control the abundance and growth of autotrophic algae in the thermically stratified water column. This phytoplankton is numerically dominated by the prokaryotic picoplankters Synechococcus spp. and Prochlorococcus spp., which are smaller than 2 ?m. The productivity of the 100 to 150 m deep euphotic zone can be high, because a high heterotrophic/autotrophic biomass ratio induces a rapid regeneration of nutrients and inorganic carbon. Primary grazers are mainly micro-organisms such as heterotrophic nannoflagellates and ciliates, which feed on the small algae and on bacteria. Heterotrophic bacteria can outnumber the autotrophic algae, because their number is related to the substrate pools of dissolved and particulate dead organic matter. These DOC and detritus pools reach equilibrium at a concentration, where the rate of their production (proportional to algal biomass) equals their mineralisation and sinking rate (proportional to the concentration and weight of POC and detritus). At a relatively low value of the weight-specific loss rates, the equilibrium concentration of these carbon pools and their load of bacteria can be high. The bacterial productivity is proportional to the mineralisation rate, which in a steady state can never be higher than the rate of primary production. Hence the ratio in turnover rate of bacteria and autotrophs tends to be reciprocally proportional to their biomass ratio.

La expresión génica hipotalámica de la enzima Citocromo P450scc en ratas hembras es regulada positivamente por estrógeno y negativamente por progesterona

Los neuroesteroides son potentes moléculas modulatorias sintetizadas en sistema nervioso central y cuya actividad se restringe a dicho ámbito. En su síntesis participan enzimas del grupo del citocromo P450 (CP450) enzimas que no pertenecen a dicho grupo. En este trabajo se estudia la expresión génica de CP450scc a nivel de hipotálamo medio basal (HMB) de ratas hembra en diferentes condiciones hormonales, y se lo relaciona con su eventual regulación a través de esteroides gonadales, particularmente estrógenos y progesterona. Se proporciona evidencia de que existe una expresión diferencial en HMB, y que dicha expresión se encuentra positivamente modulada por estrógenos, y negativamente modulada por progesterona.

Methodologies for estimating abortion incidence and abortion-related morbidity: a review.

The objective of the following chapters is to contribute to addressing these data quality issues by improving research on the measurement of abortion incidence and abortion related morbidity. To do so, they provide over- views of existing methods of and approaches to estimating abortion incidence and morbidity. The volume supplies detailed descriptions and examples of key methods. Its goal is to provide a clear understanding of the relative merits of available study designs to quantify abortion incidence and abortion related morbidity. Information on methodologies will greatly assist researchers worldwide in carrying out studies on these topics, particularly in settings where abortion is legally restricted.

Paleomagnetic of lower Cretaceous sediments from the Argo and Gascoyne Abyssal Plain

Lower Cretaceous sediments were sampled for magnetostratigraphy at three sites. ODP Site 765 and DSDP Site 261, in the Argo Abyssal Plain, consist primarily of brownish-red to gray claystone having hematite and magnetite carriers of characteristic magnetization. ODP Site 766, in the Gascoyne Abyssal Plain, consists mainly of dark greenish-gray volcaniclastic turbidites with magnetite as the carrier of characteristic magnetization. Progressive thermal demagnetization (Sites 765 and 261) or alternating field demagnetization (Site 766) yielded well-defined polarity zones and a set of reliable paleolatitudes. Magnetic polarity chrons were assigned to polarity zones using biostratigraphic correlations. Late Aptian chron M"-1"r, a brief reversed-polarity chron younger than MOr, is a narrow, 40-cm feature delimited in Hole 765C. Early Aptian reversed-polarity chron MOr is also present in Hole 765C. Polarity chrons Mir through M3r were observed in the Barremian of all three sites. Valanginian and Hauterivian polarity chrons can be tentatively assigned to polarity zones only in Hole 766A. The paleolatitude of this region remained at 35° to 37°S from the Berriasian through the Aptian. During this interval, there was approximately 16° of clockwise rotation, with the oriented sample suites of Site 765 displaying a Berriasian declination of 307° to an Aptian declination of 323°. These results are consistent with the interpolated Early Cretaceous apparent polar wander for Australia, but indicate that this region was approximately 5? farther north than predicted.

Optimization of the silicon subcell for III-V on silicon multijunction solar cells: key differences with conventional silicon technology

Dual-junction solar cells formed by a GaAsP or GaInP top cell and a silicon (Si) bottom cell seem to be attractive candidates to materialize the long sought-for integration of III-V materials on Si for photovoltaic (PV) applications. Such integration would offer a cost breakthrough for PV technology, unifying the low cost of Si and the efficiency potential of III-V multijunction solar cells. The optimization of the Si solar cells properties in flat-plate PV technology is well-known; nevertheless, it has been proven that the behavior of Si substrates is different when processed in an MOVPE reactor In this study, we analyze several factors influencing the bottom subcell performance, namely, 1) the emitter formation as a result of phosphorus diffusion; 2) the passivation quality provided by the GaP nucleation layer; and 3) the process impact on the bottom subcell PV properties.

Análisis de la técnica de recarga artificial en la Cubeta de Sant Andreu de la Barca (Barcelona)

El presente proyecto pretende mostrar las posibilidades de la recarga artificial como elemento de gestión de los recursos de agua subterránea del acuífero aluvial del río Llobregat, en su sector de la Cubeta de Sant Andreu de la Barca (Barcelona), el cual es fuente de abastecimiento urbano, agrícola e industrial del entorno de Sant Andreu de la Barca. Igualmente, se revisa la efectividad de la aplicación de dicha técnica que se practica actualmente. Hace años, las condiciones naturales del río hacían posible la recarga natural de la Cubeta, pero la implantación de industrias en la zona y la regulación mediante la presa de La Baells desde el año 1976, han originado cambios en el comportamiento natural del acuífero, que se han manifestado básicamente en una disminución de la recarga natural como consecuencia de la impermeabilización de los suelos originada por la urbanización de los mismos. Se ha producido también un fenómeno de colmatación del lecho del río, al dificultarse la removilización de los materiales finos depositados en el fondo del cauce, produciendo también una disminución de la recarga al acuífero a través del lecho. Por último, la mayor demanda de suministro por parte del sector industrial ha influido negativamente en el almacenamiento del acuífero. Desde hace décadas, se lleva efectuando una recarga artificial en el lecho del río para tratar de paliar en lo posible estos efectos perjudiciales. La misma se efectúa mediante dos sistemas distintos: escarificando el lecho del río para aumentar su capacidad de infiltración, y mediante la utilización de balsas de recarga, a través de las cuales se infiltra el agua en el acuífero. El objetivo de este proyecto es analizar el efecto actual que la recarga mediante balsas está teniendo sobre el acuífero. Para ello, se utilizarán, entre otras técnicas, la elaboración de un modelo matemático con el que poder simular el efecto de la recarga. VIII ABSTRACT This project aims to show the possibilities of artificial recharge as groundwater resources management element in the alluvial aquifer of the Llobregat River, in the sector of the Basin of Sant Andreu de la Barca (Barcelona), which is a source of urban, agricultural and industrial supply of the Sant Andreu de la Barca area. Too, the effectiveness of the current implementation of this technique is reviewed. Years ago, natural river conditions made possible the natural recharge of the aquifer, but the establishment of industries in the area and the river regulation by the la Baells dam since 1976, have led to changes in the natural behavior of the aquifer, which basically are a decrease in natural recharge, because the soil has become impervious, due to land urbanization. There has been also a phenomenon of clogging of the river bed, caused by the difficult in the remobilization of fine materials deposited on the river bed, which has produced a decrease in the groundwater recharge through the river. Finally, the increase in water demand by the industrial sector, has diminished aquifer storage. For decades, artificial recharge in the river bed has been practiced to alleviate negative effects. It is done by two different systems: scratching the river bed to increase its infiltration capacity, and using recharge ponds, through which water infiltrates into the aquifer. The objective of this project is to analyze the current effect that recharge by ponds is having in the aquifer. Among other techniques, mathematical modeling has been used for simulating the effect of artificial recharge in the aquifer.

Balanced scorecard to improve strategic management control at School of Mines and Energy, Universidad Politécnica de Madrid

We studied the situation in Spanish public universities regarding the use of the Balanced Scorecard (BSC), as an instrument of control and strategic management. Also, we studied its application to the School of Mines and Energy at Universidad Politécnica de Madrid. The main advantage of the BSC is that improves the organizational structure of the workplace and the achievement of the objectives that ensure long-term success. First we review the strategy for success used in the Spanish educational system and specifically in the Spanish public universities. Then using the BSC and applying the main strategic lines for the successful management of the School of Mines and Energy at Universidad Politécnica de Madrid. The strategic lines affect all the college groups and the success of the BSC tool is to increase communication between the faculties, personal auxiliary, students and society in general that make up the university. First we performed a SWOT analysis (DAFO in Spanish) there are proposed different perspectives that focus the long-term strategic objectives. The BSC is designed based on the strategic objectives that set the direction through using indicators and initiatives, the goals are achieved up to the programmed schedule. In the perspective of teaching, objectives are set to update facilities and increase partnerships with other universities and businesses, encouraging ongoing training of staff and improved coordination and internal communication. The internal process perspective aims at improving the marketing, the promotion of the international dimension of the school through strategic alliances, better mobility for students and professors and improved teaching and research quality results. It continues with improving the image of the school between customer?s perspective, the quality perceived by students and the loyalty of the teaching staff by retaining talent. Finally, the financial perspective which should contain costs without harming the quality, improving the employability of students and achieve relevant jobs at teaching and research through international measurement standards.

Factores transcripcionales de la clase DOF en Brachypodium distachyon: caracterización molecular de BdDOF24 durante la germinación de las semillas

La semilla es el órgano que garantiza la propagación y continuidad evolutiva de las plantas espermatofitas y constituye un elemento indispensable en la alimentación humana y animal. La semilla de cereales acumula en el endospermo durante la maduración, mayoritariamente, almidón y proteínas de reserva. Estas reservas son hidrolizadas en la germinación por hidrolasas sintetizadas en la aleurona en respuesta a giberelinas (GA), siendo la principal fuente de energía hasta que la plántula emergente es fotosintéticamente activa. Ambas fases del desarrollo de la semilla, están reguladas por una red de factores de transcripción (TF) que unen motivos conservados en cis- en los promotores de sus genes diana. Los TFs son proteínas que han desempeñado un papel central en la evolución y en el proceso de domesticación, siendo uno de los principales mecanismos de regulación génica; en torno al 7% de los genes de plantas codifican TFs. Atendiendo al motivo de unión a DNA, éstos, se han clasificado en familias. La familia DOF (DNA binding with One Finger) participa en procesos vitales exclusivos de plantas superiores y sus ancestros cercanos (algas, musgos y helechos). En las semillas de las Triticeae (subfamilia Pooideae), se han identificado varias proteínas DOF que desempeñan un papel fundamental en la regulación de la expresión génica. Brachypodium distachyon es la primera especie de la subfamilia Pooideae cuyo genoma (272 Mbp) ha sido secuenciado. Su pequeño tamaño, ciclo de vida corto, y la posibilidad de ser transformado por Agrobacterium tumefaciens (plásmido Ti), hacen que sea el sistema modelo para el estudio de cereales de la tribu Triticeae con gran importancia agronómica mundial, como son el trigo y la cebada. En este trabajo, se han identificado 27 genes Dof en el genoma de B. distachyon y se han establecido las relaciones evolutivas entre estos genes Dof y los de cebada (subfamilia Pooideae) y de arroz (subfamilia Oryzoideae), construyendo un árbol filogenético en base al alineamiento múltiple del dominio DOF. La cebada contiene 26 genes Dof y en arroz se han anotado 30. El análisis filogenético establece cuatro grupos de genes ortólogos (MCOGs: Major Clusters of Orthologous Genes), que están validados por motivos conservados adicionales, además del dominio DOF, entre las secuencias de las proteínas de un mismo MCOG. El estudio global de expresión en diferentes órganos establece un grupo de nueve genes BdDof expresados abundantemente y/o preferencialmente en semillas. El estudio detallado de expresión de estos genes durante la maduración y germinación muestra que BdDof24, ortólogo putativo a BPBF-HvDOF24 de cebada, es el gen más abundante en las semillas en germinación de B. distachyon. La regulación transcripcional de los genes que codifican hidrolasas en la aleurona de las semillas de cereales durante la post‐germinación ha puesto de manifiesto la existencia en sus promotores de un motivo tripartito en cis- conservado GARC (GA-Responsive Complex), que unen TFs de la clase MYB-R2R3, DOF y MYBR1-SHAQKYF. En esta tesis, se ha caracterizado el gen BdCathB de Brachypodium que codifica una proteasa tipo catepsina B y es ortólogo a los genes Al21 de trigo y HvCathB de cebada, así como los TFs responsables de su regulación transcripcional BdDOF24 y BdGAMYB (ortólogo a HvGAMYB). El análisis in silico del promotor BdCathB ha identificado un motivo GARC conservado, en posición y secuencia, con sus ortólogos en trigo y cebada. La expresión de BdCathB se induce durante la germinación, así como la de los genes BdDof24 y BdGamyb. Además, los TFs BdDOF24 y BdGAMYB interaccionan en el sistema de dos híbridos de levadura e in planta en experimentos de complementación bimolecular fluorescente. En capas de aleurona de cebada, BdGAMYB activa el promotor BdCathB, mientras que BdDOF24 lo reprime; este resultado es similar al obtenido con los TFs ortólogos de cebada BPBF-HvDOF24 y HvGAMYB. Sin embargo, cuando las células de aleurona se transforman simultáneamente con los dos TFs, BdDOF24 tiene un efecto aditivo sobre la trans-activación mediada por BdGAMYB, mientras que su ortólogo BPBF-HvDOF24 produce el efecto contrario, revirtiendo el efecto de HvGAMYB sobre el promotor BdCathB. Las diferencias entre las secuencias deducidas de las proteínas BdDOF24 y BPBF-HvDOF24 podrían explicar las funciones opuestas que desempeñan en su interacción con GAMYB. Resultados preliminares con líneas de inserción de T-DNA y de sobre-expresión estable de BdGamyb, apoyan los resultados obtenidos en expresión transitoria. Además las líneas homocigotas knock-out para el gen BdGamyb presentan alteraciones en anteras y polen y no producen semillas viables. ABSTRACT The seed is the plant organ of the spermatophytes responsible for the dispersion and survival in the course of evolution. In addition, it constitutes one of the most importan elements of human food and animal feed. The main reserves accumulated in the endosperm of cereal seeds through the maturation phase of development are starch and proteins. Its degradation by hydrolases synthetized in aleurone cells in response to GA upon germination provides energy, carbon and nitrogen to the emerging seedling before it acquires complete photosynthetic capacity. Both phases of seed development are controlled by a network of transcription factors (TFs) that interact with specific cis- elements in the promoters of their target genes. TFs are proteins that have played a central role during evolution and domestication, being one of the most important regulatory mechanisms of gene expression. Around 7% of genes in plant genomes encode TFs. Based on the DNA binding motif, TFs are classified into families. The DOF (DNA binding with One Finger) family is involved in specific processes of plants and its ancestors (algae, mosses and ferns). Several DOF proteins have been described to play important roles in the regulation of genes in seeds of the Triticeae tribe (Pooideae subfamily). Brachypodium distachyon is the first member of the Pooideae subfamily to be sequenced. Its small size and compact structured genome (272 Mbp), the short life cycle, small plant size and the possibility of being transformed with Agrobacterium tumefaciens (Ti-plasmid) make Brachypodium the model system for comparative studies within cereals of the Triticeae tribe that have big economic value such as wheat and barley. In this study, 27 Dof genes have been identified in the genome of B. distachyon and the evolutionary relationships among these Dof genes and those frome barley (Pooideae subfamily) and those from rice (Oryzoideae subfamily) have been established by building a phylogenetic tree based on the multiple alignment of the DOF DNA binding domains. The barley genome (Hordeum vulgare) contains 26 Dof genes and in rice (Oryza sativa) 30 genes have been annotated. The phylogenetic analysis establishes four Major Clusters of Orthologous Genes (MCOGs) that are supported by additional conserved motives out of the DOF domain, between proteins of the same MCOG. The global expression study of BdDof genes in different organs and tissues classifies BdDof genes into two groups; nine of the 27 BdDof genes are abundantly or preferentially expressed in seeds. A more detailed expression analysis of these genes during seed maturation and germination shows that BdDof24, orholog to barley BPBF-HvDof24, is the most abundantly expressed gene in germinating seeds. Transcriptional regulation studies of genes that encode hydrolases in aleurone cells during post-germination of cereal seeds, have identified in their promoters a tripartite conserved cis- motif GARC (GA-Responsive Complex) that binds TFs of the MYB-R2R3, DOF and MYBR1-SHAQKYF families. In this thesis, the characterization of the BdCathB gene, encoding a Cathepsin B-like protease and that is ortholog to the wheat Al21 and the barley HvCathB genes, has been done and its transcriptional regulation by the TFs BdDOF24 and BdGAMYB (ortholog to HvGAMYB) studied. The in silico analysis of the BdCathB promoter sequence has identified a GARC motif. BdCathB expression is induced upon germination, as well as, those of BdDof24 and BdGamyb genes. Moreover, BdDOF24 and BdGAMYB interact in yeast (Yeast 2 Hybrid System, Y2HS) and in planta (Bimolecular Fluorecence Complementation, BiFC). In transient assays in aleurone cells, BdGAMYB activates the BdCathB promoter, whereas BdDOF24 is a transcriptional repressor, this result is similar to that obtained with the barley orthologous genes BPBF-HvDOF24 and HvGAMYB. However, when aleurone cells are simultaneously transformed with both TFs, BdDOF24 has an additive effect to the trans-activation mediated by BdGAMYB, while its ortholog BPBF-HvDOF24 produces an opposite effect by reducing the HvGAMYB activation of the BdCathB promoter. The differences among the deduced protein sequences between BdDOF24 and BPBF-HvDOF24 could explain their opposite functions in the interaction with GAMYB protein. Preliminary results of T-DNA insertion (K.O.) and stable over-expression lines of BdGamyb support the data obtained in transient expression assays. In addition, the BdGamyb homozygous T-DNA insertion (K.O.) lines have anther and pollen alterations and they do not produce viable seeds.

¿Es este un proyecto de Mies? / Is this a Mies s project?

Is this a Mies?s project? Disappearances, or the art of being a Mies project Angel Borrego Several years ago I had to solve the structure of Mies House of the Werkbund exhibition of 1931 as an exercise for a course named Structures Projects in the School of Architecture of Madrid. We were offered this house as an exercise because there had been some complaints about having to calculate and deal with ?bad, real, anonymous? architecture widely recognized as such, in so far as it has been widely published, that furthermore had some ideal quality to it, a quality reinforced by the fact that it was not there anymore, one could not go and see it, old and deteriorated, all images we have of it are of a shiny new object: in fact its ideal quality was even present in that it had not even been designed to be a completely real house, as nobody ever lived there and wasn?t supposed to. It was a three dimensional representation of a house, what gave it a further flair of ideality. And it was as well the representation of an idea, and we all liked that. Last but not least, it had Mies to back it up, which promised us the remote possibility of analyzing one of his works in depth, with proper tools (this was a structures course, and we had already read, or heard, something about the importance of structures in Mies?s work.) We were lured by the possibility of reconstructing, if not the pavilion, some of the ideas leading to it. Ideas that were themselves structural, like the ?perfectly regular all columnar structure?, an ideal structure. We had a sensation that we could somehow reproduce the process and thoughts of Mies leading to the solution of a particular work, investigate him in a cuasi archaeological manner, reconstruct the project, as if being able to reconstruct one work we could reconstruct the entire Mies, and placing ourselves in his position replace him, which was to know for once where we were (1). All these thoughts, passed through our minds more or less abstractly, believe it or not, before we realized that we were supposed to imagine that the roof was also supported by the walls and that the plan was lacking two columns, which was short. We could not believe that only to make the exercise more difficult, as it was admitted, the professors would mutilate a Mies work in such a way. The exercise had lost all interest to us and there were some timid protests. The surprise came when, though admitting that the supporting walls had been their idea, the professors said they had not manipulated the plan of the house at all. Some confusion followed, since that seemed quite incredible to us, even more to professors I guess. Two of us went to the library and checkout two books, one being the ?History of Modern Architecture? (the Benevolo as it was known), from where they said to have copied the plan of the house for the exercise, and another book on Mies that included the same project. The Benevolo was actually lacking the two columns, but the other book included them, making clear our point. We were able to reorient the exercise and calculate the house just as Mies had designed it. We, the students I mean, were really happy, since we had a voice in the discipline of architecture: our own discipline since we were the ones being disciplined, and we had been allowed to freely talk our way through it. I had the nice sensation that what happened was curiously and rewardingly similar to, or a kind of metaphor for, the flowing space of the free plan, that was allowed to move through the perfectly regular structure, a most disciplined structure. As Mark Wigley has noted, discipline is intimately related to prothesis. The concept of prothesis (pro-thesis) would be already architectural as ?the act of placing before?, referring to a structure that has to be placed before anything else; it is already a structure, rather than being something added that could be removed..

Diseño del sostenimiento primario y secundario del túnel de aducción de la central hidroeléctrica Renace III

El presente proyecto trata el diseño del sostenimiento y revestimiento del túnel de aducción de la Central hidroeléctrica Renace III. Se ha diseñado un sostenimiento con el fin de cumplir de forma óptima los requisitos funcionales , estructurales y económicos, garantizando de forma primordial la seguridad y durabilidad de la construcción. A partir del conocimiento geológico-geotécnico del macizo encajante se definen mediante clasificaciones geomecánicas divisiones del terreno en función de su calidad. Para cada una de ellas se ha definido una sección tipo de sostenimiento estableciendo sus respectivas especificaciones. A la justificación del cumplimiento de los requisitos se llega mediante distintos métodos empíricos y de cálculo, operando de la misma forma a la hora de decidir el revestimiento. Por último se ha definido la impermeabilización y el plan de auscultación con el fin de garantizar la seguridad y estanqueidad del túnel. ABSTRACT The aim of this project is to design the support and lining of the adduction tunnel in Renace III Hydroelectric Plant. The support has been defined to optimize functional structural and economical demands guaranteeing the tunnel´s safety and durability. Starting with an exhaustive knowledge of the rock mass, divisions of the quality ground by using geomechanical classifications shall be done. Special support for each division has been defined through several empirical and mathematical methods, using the same process to define the lining. Finally, a waterproofing and an auscultation plan has been designed in order to provide sealing and protection

Cuadro de mando, plataforma de gestión para el modelo EFQM

La propuesta del trabajo de fin de grado escogida por el autor del proyecto se basa en la continuación del proyecto comenzado durante la asignatura de Prácticum del pasado semestre. El nacimiento del mismo se gestó en una pequeña empresa de consultoría llamada ‘Grupo Develop’ (en la sección ‘Entidad colaboradora y ubicación’ se describe más detalladamente la organización) situada al este de Madrid, una organización con carácter de fundación y dedicada, esencialmente, al sector de la consultoría en el sector de la calidad. Grupo Develop necesitaba aprovechar la utilidad de las nuevas tecnologías para ofrecer un nuevo y mejor servicio para sus clientes mediante un proyecto que fuera dirigido y llevado a cabo por un ingeniero informático. Partiendo de este contexto se vislumbró un proyecto consistente en diseñar, desplegar, programar y mantener una plataforma-sistema informático capaz de ayudar a las organizaciones (en este caso particular la mayoría son organizaciones sin ánimo de lucro) a gestionarse mejor de acuerdo a distintos modelos de calidad como pueden ser el EFQM1 o ISO. Además, la certificación en ambos modelos son cada vez más demandados como garantía de calidad por organismos públicos y privados e incluso por los clientes. Por lo tanto, este programa debe llegar a ser una herramienta que realmente apoye a cada entidad a elaborar un diagnóstico de su gestión y, por supuesto, debe conseguir acercar a estas empresas a los certificados más prestigiosos. Desde el punto de vista de un profesional del sector de la informática, el proyecto se estructura de una forma clara en una arquitectura cliente-servidor clásica donde todas las entidades (de momento 15) han participado de forma activa y paralela al desarrollo del proyecto. Si bien es cierto que esto ha ralentizado notablemente el desarrollo del proyecto y ha requerido una sincronización entre dos proyectos paralelos (uno para el despliegue y otro para el desarrollo).---ABSTRACT---The proposal of my graduation work is a continuation of the project that I already started in the Practicum subject the first part of the academic year. The birth of that project arose in a small consulting firm (Grupo Develop) in the east of Madrid, an organization that at the same time is incorporated as a Foundation. This organization works with different NGO´s and their work covers the Quality Consulting Sector. Grupo Develop needed to use new technologies to give a new and best service to our customers through a project managed by a person trained in the computer science area. Starting from this context, Grupo Develop saw a new opportunity to create a project to design, deploy and maintain a platform-system that can help our customers (in this case the organizations are often organizations from the Third Sector) to get a best management in some Norms or Models like ISO or EFQM. Also in some cases the Certifications of any of these models are increasingly demanded as quality assurance by public entities, privates and even by clients. Therefore, this program should be a tool that helps to any organization to make a diagnosis of their management and, of course, should close to these companies to the most prestigious Certificates. From a point of view of a computer science student, the software project has a defined structure in a classic client-server model where all the organizations (15) have actively participated in parallel mode to the development of the project. It is true that the involvement of the organizations has slowed the development of the project so I had to create two projects (one for the different organizations and the other one to develop the major improvements).

CONTRIBUIÇÃO DOS CURSOS DE PÓS-GRADUAÇÃO LATO-SENSU PARA A FORMAÇÃO DE GESTORES DE COMUNICAÇÃO ORGANIZACIONAL: ESTUDO DE CASO - GESTCORP

A gestão eficiente da comunicação organizacional representa um diferencial estratégico para qualquer organização, pública ou privada. A conscientização sobre a importância do executivo que fica à frente dessa área aumentou, no entanto, a nova realidade das organizações reduziu ao mínimo o quadro de funcionários de comunicação nas empresas. Esse cenário provocou mudanças na expectativa das competências e atuação do profissional desejado. Junto com o reconhecimento, veio a exigência do mercado de trabalho em encontrar pessoas completas para exercer a função. O Gestor de Comunicação, no cumprimento de seus objetivos, necessitará de uma visão ampla e ética, que contemple ao mesmo tempo, interesses institucionais e interesses dos públicos envolvidos. A atuação profissional à frente dessa área vai requerer, de qualquer indivíduo, domínio de conhecimentos técnicos e teóricos. Habilitar pessoas para atender essa demanda tem sido objetivo de cursos oferecidos em instituições de ensino superior em todas as regiões do país. Essas iniciativas, na maioria das vezes, são promovidas no âmbito da pós-graduação lato sensu. Desse modo, parte deste estudo será dedicada a contextualizar esta modalidade de ensino no universo da pósgraduação brasileira, verificando, inclusive, dados que se referem a sua regulação junto ao MEC. Além disso, o estudo pretende conhecer o contexto e o processo de formação dos profissionais/estudantes que buscam aprimoramento por meio desses cursos. Para atender esse objetivo, analisaremos a experiência de 10 anos de realização do Gestcorp - Curso de Gestão Estratégica de Comunicação Organizacional e Relações Públicas. Trata-se de um curso de especialização oferecido pela Escola de Comunicações e Artes da USP cujo propósito é formar gestores de comunicação organizacional para atuarem em instituições públicas, privadas ou do terceiro setor. Esperamos que este estudo possa esclarecer e/ou responder algumas indagações, entre elas: Qual o perfil do público que busca a especialização em Gestão da Comunicação Organizacional? Quais temáticas estão demandando estudos nesta área? Onde podem atuar estes formandos?.(AU)