Option contracts for allocating water in inter-basin transfers: the case of the Tagus-Segura Basin in Spain

Users in the Mediterranean region face significant water supply risks. Water markets mechanisms can provide flexibility to water systems run in tight situations. The largest water infrastructure in the Iberian Peninsula connects the Segura and Tagus Basins. Stakeholders and politicians in the Tagus Basin have asked that water transfers between the two basins be eventually phased out. The need to increase the statutory minimum environmental flow in the middle Tagus and to meet new urban demands is going to result in a redefinition of the Transfer?s management rules, leading to a reduction in the transferable volumes. To minimise the consequences of such restrictions to irrigators in the Segura Basin who depend on the transferred volumes, we propose the establishment of water option contracts between both basins that represents an institutional innovation with respect to previous inter-basin spot market experiences. Based on the draft of the new Tagus Basin Plan, we propose both a modification of the Transfer?s management rule and an innovative inter-basin option contract. The main goal of the paper is to define this contract and evaluate it with respect to non-market scenarios. We also assess the resulting impact on environmental flows in the Tagus River and water availability for users in the Segura Basin, together with the economic impacts of such contract on both basins. Our results show that the proposed option contract would reduce the impact of a change in the transfer?s management rule, and reduce the supply risks of the recipient area.

Incorporating equity into transport planning: utility, priority and sufficiency approaches

The analysis addresses the issue of transport equity and explores three different approaches to equity in transport: utilitarianism, sufficientarianism and prioritarianism. Each approach calls for a different treatment of the benefits reaped by different population groups in the assessment of transport investments or policies. In utilitarianism, which underlies much of the current practice of transport project appraisal, all benefits receive the same weight, irrespective of the recipient of the benefits. In both sufficientarianism and prioritarianism, benefits are weighed in distinct ways, depending on the characteristics of the recipients. The three approaches are illustrated using a fictive case study, in which three different transport investment are assessed and compared to each other. Finally, the assessment of transport investments will be explored using the cost-effectiveness analysis (CEA). The CEA assesses the distributional effects of transport investments for utilitarism, sufficientarism and prioritarism approaches and addresses distinct needs associated with different population groups in respect to their transport

La casa industrializada : seis propuestas para este milenio

La Casa Industrializada supone el ideal de realizar la casa unifamiliar a través de la potencia y los procedimientos de la industria. Como tal, la casa supone un producto industrial más sujeto a la lógica de la reproducción y del consumo. Como producto de consumo la casa debe establecerse como objeto de deseo, accesible al grupo de usuarios-consumidores al que va dirigido. El sueño de la Casa Industrializada se origina en la primera Revolución Industrial y se consolida en la segunda tras la producción del Ford T y la adhesión de los padres del movimiento moderno. A lo largo de su historia se han sucedido casos de éxito y fracaso, los primeros con la realización de un producto de imagen convencional y los segundos la mayor parte de las veces dirigidos por arquitectos. El sueño de la Casa Industrializada de la mano de arquitectos está comenzando a ser una realidad en Japón, Suecia y Estados Unidos a través de marcas como MUJI, Arkitekthus y Living Homes, pero aún dista de ser un hecho extendido en nuestra sociedad. Para que este ideal se cumpla deberá ofrecer valores que permita a la sociedad hacerlo suyo. La Tesis busca analizar la historia y la metodología de la Casa Industrializada, desde el diseño a la comercialización con el fin de ofrecer esos valores en forma de propuestas para la Casa Industrializada en este milenio. La casa como producto industrial-producto de consumo supera las lógicas tradicionales de la arquitectura para operar dentro del contexto de la producción industrial y la reproducción de los objetos. En este sentido es necesario establecer no solo la forma y construcción de la casa sino los mecanismos de reproducción con sus pertinentes eficiencias. La Casa industrializada no se construye, se monta, y para ello utiliza las estrategias de la construcción en seco, la prefabricación, el uso de componentes y los materiales ligeros. Desde la lógica del consumo, la casa debe dirigirse a un determinado público, no es más la casa para todos, característica de las situaciones de crisis y de emergencia. La casa se enfrenta a un mercado segmentado, tanto en cultura, como en deseos y poderes adquisitivos. En la cuestión del diseño debe plantearse más como diseño de producto que como diseño arquitectónico. La Casa Industrializada no es el fruto de un encargo y de una acción singular, debe ofrecerse lista para adquirir y para ser reproducida. Esta reproducción se puede dar tanto en la forma de modelos cerrados o sistemas abiertos que permitan la personalización por parte de los usuarios. Desde el ámbito cultural es necesario entender que la casa es más que una máquina de habitar, es un receptor de emociones, forma parte de nuestra memoria y nuestra cultura. La casa como producto social es una imagen de nosotros mismos, define la manera en la que nos situamos en el mundo y por tanto supone una definición de estatus. En esto, la Tesis se apoya en los textos de Baudrillard y su análisis de la sociedad de consumo y el papel de los objetos y su valor como signo. La Tesis realiza un repaso de los procedimientos industriales con especial énfasis en la producción automovilística y sitúa la evolución de la Casa Industrializada en relación a la evolución de los avances en los sistemas de producción industrial y las transferencias desde las industrias del automóvil y aeronáutica. La tesis se completa con una serie de casos de estudio que parten de las primeras casas de venta por correo de principios del siglo XX, pasando por las propuestas de Gropius, Fuller, el Case Study House Program, Prouvé, Sota y acaban con la situación actual. La Casa Industrializada ha mantenido una serie de valores a lo largo de su historia, como ideal, forma un cuerpo estable de propuestas que no se ha modificado a lo largo del tiempo. Con respecto a este nuevo milenio este ideal no debe ser cambiado sino simplemente actualizado y adaptado a los métodos de producción y las necesidades, sueños y exigencias de la sociedad de hoy. ABSTRACT The industrialized House provides an ideal to manufacture the house through the power and strategies of the industry. As such, the house becomes an industrial product that respond to the logic of reproduction and consumption. As a comodity, the house must become a desirable object, accessible to the group of the consumers to which is targeted The dream of the Industrialized home is originated in the First Industrial Revolution and it is consolidated in the second one after Ford´s production of Model T and the incorporation of the principal figures of the modern movement to the ideal of making houses at the factories. Throughout history there have been cases of success and failure, the first with the completion of a product of conventional image and the second most often led by architects. Industrialized dream house made by architects is starting to become a reality in Japan, Sweden and the United States through brands such as MUJI, Arkitekthus and Living Homes, but still far from beeing a widespread fact in our society. To fulfill this ideal, it should provide values that society could accept as of their own. The Thesis seeks to analyze the history and methodology of industrialized house, from design to marketing in order to offer these values in the form of proposals for industrialized house in this millennium. The house as an industrial-product-comodity extend beyond the traditional architectural logic to operate within the context of industrial production and the reproduction of objects. In this sense it is necessary to establish not only the shape and construction of the house but the mechanisms of reproduction with its relevant efficiencies. Industrialized house is not built it is assembled, and it uses the strategies of dry construction, prefabrication, using lightweight materials and components. From the logic of consumption, the house must go to a certain audience, it is no longer the home for all that is characteristic of crisis respond and emergency. The house faces a segmented market, both in culture and desires and purchasing power. On the question of design it must be considered more like product design than architectural design. Industrialized House is not the result of a commission and a singular action, it should be offered pret-a-porter and able to be reproduced. This reproduction can be given in form of closed or open systems models that allow its customization by users. From the cultural sphere is necessary to understand that the house is more than a machine for living, is a recipient of emotions, is part of our memory and our culture. The home as a social product is an image of ourselves, defines the way in which we place ourselves in the world and therefore represents a definition of status. In this aspect, the thesis is based on the texts of Baudrillard and his analysis of consumption society and the role of objects and its value as a sign in it. The thesis makes a review of the industrial processes with emphasis on automotive production and places the evolution of industrialized House in relation to the evolution of developments in industrial production systems and transfers from the automotive and aeronautics industries. The thesis is completed with a series of case studies that starts from the first mail order houses from the early twentieth century, going through the proposal of Gropius, Fuller, the Case Study House Program, Prouvé, Sota and end up with the current situation. Industrialized House has held a series of values throughout its history, as an ideal, forms a stable corps of proposals that has not changed over time. Regarding this new millennium this ideal should not be changed but simply be updated and adapted to production methods and needs, dreams and demands of today's society.

DIVINDADES MLK E CULTO A MOLEK NOS QUADROS DA CRISE RELIGIOSA NO FINAL DA MONARQUIA DE JUDÁ (2 Reis 16,3; 17,17.31; 21,6; 23,10; KTU 1.100; 1.118; 1.161)

A dissertação é dirigida a um especial e não resolvido problema na descrição do desenvolvimento religioso de Israel. Em textos do Antigo Testamento acerca do sacrifício de humanos, há uma unidades literárias autônomas relacionadas ao culto a mOlek. Porém, alguns pesquisadores sustentam que o culto a mOlek não tem esta característica. A dissertação aspira a investigar este argumento, concentrando-se em fontes históricas (2Reis 16,3; 17,17.31; 21,6; 23,10). Discutindo fontes ugaríticas duas listas de divindades e um texto funerário nós perguntares acerca das características das divindades mLlK nas culturas cananéias. Em síntese, mOlek é uma divindade ctônica mas não é destinatária de sacrifícios humanos.(AU)

DIVINDADES MLK E CULTO A MOLEK NOS QUADROS DA CRISE RELIGIOSA NO FINAL DA MONARQUIA DE JUDÁ (2 Reis 16,3; 17,17.31; 21,6; 23,10; KTU 1.100; 1.118; 1.161)

A dissertação é dirigida a um especial e não resolvido problema na descrição do desenvolvimento religioso de Israel. Em textos do Antigo Testamento acerca do sacrifício de humanos, há uma unidades literárias autônomas relacionadas ao culto a mOlek. Porém, alguns pesquisadores sustentam que o culto a mOlek não tem esta característica. A dissertação aspira a investigar este argumento, concentrando-se em fontes históricas (2Reis 16,3; 17,17.31; 21,6; 23,10). Discutindo fontes ugaríticas duas listas de divindades e um texto funerário nós perguntares acerca das características das divindades mLlK nas culturas cananéias. Em síntese, mOlek é uma divindade ctônica mas não é destinatária de sacrifícios humanos.(AU)

Barriers to recombination between closely related bacteria: MutS and RecBCD inhibit recombination between Salmonella typhimurium and Salmonella typhi

Previous studies have shown that inactivation of the MutS or MutL mismatch repair enzymes increases the efficiency of homeologous recombination between Escherichia coli and Salmonella typhimurium and between S. typhimurium and Salmonella typhi. However, even in mutants defective for mismatch repair the recombination frequencies are 102- to 103-fold less than observed during homologous recombination between a donor and recipient of the same species. In addition, the length of DNA exchanged during transduction between S. typhimurium and S. typhi is less than in transductions between strains of S. typhimurium. In homeologous transductions, mutations in the recD gene increased the frequency of transduction and the length of DNA exchanged. Furthermore, in mutS recD double mutants the frequency of homeologous recombination was nearly as high as that seen during homologous recombination. The phenotypes of the mutants indicate that the gene products of mutS and recD act independently. Because S. typhimurium and S. typhi are ≈98–99% identical at the DNA sequence level, the inhibition of recombination is probably not due to a failure of RecA to initiate strand exchange. Instead, these results suggest that mismatches act at a subsequent step, possibly by slowing the rate of branch migration. Slowing the rate of branch migration may stimulate helicase proteins to unwind rather than extend the heteroduplex and leave uncomplexed donor DNA susceptible to further degradation by RecBCD exonuclease.

Decoding temporally encoded sensory input by cortical oscillations and thalamic phase comparators

The temporally encoded information obtained by vibrissal touch could be decoded “passively,” involving only input-driven elements, or “actively,” utilizing intrinsically driven oscillators. A previous study suggested that the trigeminal somatosensory system of rats does not obey the bottom-up order of activation predicted by passive decoding. Thus, we have tested whether this system obeys the predictions of active decoding. We have studied cortical single units in the somatosensory cortices of anesthetized rats and guinea pigs and found that about a quarter of them exhibit clear spontaneous oscillations, many of them around whisking frequencies (≈10 Hz). The frequencies of these oscillations could be controlled locally by glutamate. These oscillations could be forced to track the frequency of induced rhythmic whisker movements at a stable, frequency-dependent, phase difference. During these stimulations, the response intensities of multiunits at the thalamic recipient layers of the cortex decreased, and their latencies increased, with increasing input frequency. These observations are consistent with thalamocortical loops implementing phase-locked loops, circuits that are most efficient in decoding temporally encoded information like that obtained by active vibrissal touch. According to this model, and consistent with our results, populations of thalamic “relay” neurons function as phase “comparators” that compare cortical timing expectations with the actual input timing and represent the difference by their population output rate.

Prevention of development of autoimmune disease in BXSB mice by mixed bone marrow transplantation

Transplantations of fully allogeneic, autoimmune-resistant T-cell-depleted marrow (TCDM) plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice were carried out to investigate the ability of the mixed bone marrow transplantation (BMT) to prevent development of autoimmune disease and, at the same time, to reconstitute fully the immunity functions of heavily irradiated BXSB recipients. Male BXSB mice were engrafted with mixed TCDM from both allogeneic, autoimmune-resistant BALB/c mice and syngeneic, autoimmune-prone BXSB mice. BMT with mixed TCDM from both resistant and susceptible strains of mice (mixed BMT) prolonged the median life span and inhibited development of glomerulonephritis in BXSB mice. BMT with mixed TCDM also prevented the formation of anti-DNA antibodies that is typically observed in male mice of this strain. Moreover, mixed BMT reconstituted primary antibody production in BXSB recipients, so that no annoying immunodeficiencies that are regularly observed in fully allogeneic chimeras were present in the recipient of the mixed TCDM. These findings indicate that transplanting allogeneic, autoimmune-resistant TCDM plus syngeneic, autoimmune-prone TCDM into lethally irradiated BXSB mice prevents development of autoimmune disease in this strain of mice. In addition, this dual BMT reconstitutes the immunity functions and avoids the immunodeficiencies that occur regularly in fully allogeneic chimeras after total-body irradiation.

Posttranscriptional modification of retroviral primers is required for late stages of DNA replication

During reverse transcription of retroviral RNA, synthesis of (−) strand DNA is primed by a cellular tRNA that anneals to an 18-nt primer binding site within the 5′ long terminal repeat. For (+) strand synthesis using a (−) strand DNA template linked to the tRNA primer, only the first 18 nt of tRNA are replicated to regenerate the primer binding site, creating the (+) strand strong stop DNA intermediate and providing a 3′ terminus capable of strand transfer and further elongation. On model HIV templates that approximate the (−) strand linked to natural modified or synthetic unmodified tRNA3Lys, we find that a (+) strand strong stop intermediate of the proper length is generated only on templates containing the natural, modified tRNA3Lys, suggesting that a posttranscriptional modification provides the termination signal. In the presence of a recipient template, synthesis after strand transfer occurs only from intermediates generated from templates containing modified tRNA3Lys. Reverse transcriptase from Moloney murine leukemia virus and avian myoblastosis virus shows the same requirement for a modified tRNA3Lys template. Because all retroviral tRNA primers contain the same 1-methyl-A58 modification, our results suggest that 1-methyl-A58 is generally required for termination of replication 18 nt into the tRNA sequence, generating the (+) strand intermediate, strand transfer, and subsequent synthesis of the entire (+) strand. The possibility that the host methyl transferase responsible for methylating A58 may provide a target for HIV chemotherapy is discussed.

Substantial narrowing of the Niemann–Pick C candidate interval by yeast artificial chromosome complementation

Niemann–Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11–12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.

Production of identical sextuplet mice by transferring metaphase nuclei from four-cell embryos

Mouse clones were produced by serial nuclear transfer commencing with the transfer of four-cell nuclei at metaphase into unfertilized ooplasts. The donor four-cell-stage nuclei were synchronized in metaphase with nocodazole. The oocytes receiving a four-cell nucleus at metaphase formed two nuclei after artificial activation and inhibition of cytokinesis with cytochalasin B. To obtain embryos with diploid sets of chromosomes, nuclei from each reconstructed embryo were transferred individually into separate enucleated fertilized one-cell embryos, thus doubling the number of identical embryos. This procedure produced a high frequency of development of reconstructed embryos to the blastocyst stage. Of 11 sets of identical embryos produced by serial nuclear transplantation, 83% developed into blastocysts, including three sets of identical septuplet blastocysts. After transfer to recipient mice, a total of 25 (57%) live young were obtained, which included one set of identical sextuplet and two sets of identical quadruplet mice.

Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: Reagents for tumor immunotherapy

Studies in melanoma patients have revealed that self proteins can function as targets for tumor-reactive cytotoxic T lymphocytes (CTL). One group of self proteins MAGE, BAGE, and GAGE are normally only expressed in testis and placenta, whilst another group of CTL recognized proteins are melanocyte-specific differentiation antigens. In this study we have investigated whether CTL can be raised against a ubiquitously expressed self protein, mdm-2, which is frequently overexpressed in tumors. The observation that T-cell tolerance is self major histocompatibility complex-restricted was exploited to generate CTL specific for an mdm-2 derived peptide presented by nonself major histocompatibility complex class I molecules. Thus, the allo-restricted T-cell repertoire of H-2d mice was used to isolate CTL specific for the mdm100 peptide presented by allogeneic H-2Kb class I molecules. In vitro, these CTL discriminated between transformed and normal cells, killing specifically Kb-positive melanoma and lymphoma tumors but not Kb-expressing dendritic cells. In vivo, the CTL showed antitumor activity and delayed the growth of melanoma as well as lymphoma tumors in H-2b recipient mice. These experiments show that it is possible to circumvent T-cell tolerance to ubiquitously expressed self antigens, and to target CTL responses against tumors expressing elevated levels of structurally unaltered proteins.

Murine hematopoietic reconstitution after tagging and selection of retrovirally transduced bone marrow cells

A major problem facing the effective treatment of patients with cancer is how to get the specific antitumor agent into every tumor cell. In this report we describe the use of a strategy that, by using retroviral vectors encoding a truncated human CD5 cDNA, allows the selection of only the infected cells, and we show the ability to obtain, before bone marrow transplantation, a population of 5-fluouraci-treated murine bone marrow cells that are 100% marked. This marked population of bone marrow cells is able to reconstitute the hematopoietic system in lethally irradiated mice, indicating that the surface marker lacks deleterious effects on the functionality of bone marrow cells. No gross abnormalities in hematopoiesis were detected in mice repopulated with CD5-expressing cells. Nevertheless, a significant proportion of the hematopoietic cells no longer expresses the surface marker CD5 in the 9-month-old recipient mice. This transcriptional inactivity of the proviral long terminal repeat (LTR) was accompanied by de novo methylation of the proviral sequences. Our results show that the use of the CD5 as a retrovirally encoded marker enables the rapid, efficient, and nontoxic selection in vitro of infected primary cells, which can entirely reconstitute the hematopoietic system in mice. These results should now greatly enhance the power of studies aimed at addressing questions such as generation of cancer-negative hematopoiesis.

Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow

The adhesive mechanisms allowing hematopoietic progenitor cells (HPC) homing to the bone marrow (BM) after BM transplantation are poorly understood. We investigated the role of endothelial selectins and vascular cell adhesion molecule-1 (VCAM-1) in this process. Lethally irradiated recipient mice deficient in both P-and E-selectins (P/E−/−), reconstituted with minimal numbers (≤5 × 104) of wild-type BM cells, poorly survived the procedure compared with wild-type recipients. Excess mortality in P/E−/− mice, after a lethal dose of irradiation, was likely caused by a defect of HPC homing. Indeed, we observed that the recruitment of HPC to the BM was reduced in P/E−/− animals, either splenectomized or spleen-intact. Homing into the BM of P/E−/− recipient mice was further compromised when a function-blocking VCAM-1 antibody was administered. Circulating HPC, 14 hr after transplantation, were greatly increased in P/E−/− mice treated with anti-VCAM-1 compared with P/E−/− mice treated with just IgG or wild-type mice treated with either anti-VCAM-1 or IgG. Our results indicate that endothelial selectins play an important role in HPC homing to the BM. Optimal recruitment of HPC after lethal doses of irradiation requires the combined action of both selectins and VCAM-1 expressed on endothelium of the BM.

Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter

Galactosialidosis (GS) is a human neurodegenerative disease caused by a deficiency of lysosomal protective protein/cathepsin A (PPCA). The GS mouse model resembles the severe human condition, resulting in nephropathy, ataxia, and premature death. To rescue the disease phenotype, GS mice were transplanted with bone marrow from transgenic mice overexpressing human PPCA specifically in monocytes/macrophages under the control of the colony stimulating factor-1 receptor promoter. Transgenic macrophages infiltrated and resided in all organs and expressed PPCA at high levels. Correction occurred in hematopoietic tissues and nonhematopoietic organs, including the central nervous system. PPCA-expressing perivascular and leptomeningeal macrophages were detected throughout the brain of recipient mice, although some neuronal cells, such as Purkinje cells, continued to show storage and died. GS mice crossed into the transgenic background reflected the outcome of bone marrow-transplanted mice, but the course of neuronal degeneration was delayed in this model. These studies present definite evidence that macrophages alone can provide a source of corrective enzyme for visceral organs and may be beneficial for neuronal correction if expression levels are sufficient.