Multifunctional nanocarriers encapsulating anti-Alzheimer drug for nasal delivery to central nervous system

Alzheimer's disease (AD) is a fatal neurodegenerative condition characterized clinically by progressive memory loss and irreversible cognitive deterioration. It has been shown that there is a progressive degeneration of the brain cholinergic neurons which leads to the appearance of cognitive symptoms of the disease. The aim of this work was the formulation of multifunctional nanocarriers for nasal administration of tacrine-HCl (THA). This route has many advantages; in particular is possible to convey the drug directly to the Central Nervous System, through the olfactory bulb. In particular, were prepared Albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin), and Multifunctional liposomes, prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol (Toc) and/or polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) (Ω3). Both nanosystems were characterized in terms of size, Zeta potential and encapsulation efficiency. Were also evaluated their functional properties such as mucoadhesion and permeability, using an ex-vivo assay based on nasal sheep mucosa. On Liposomes were also assessed drug neuronal uptake, cell toxicity, antioxidant and, cytoprotective activity in the human neuronal cell line SH-SY5Y and finally tocopherol trans-membrane diffusion. Both the nanocarriers produced presented excellent properties and a high potential as new systems for CNS-delivery of anti-Alzheimer drugs via the nasal route.

TV Signal Delivery to Cable Operators and DTH Platform Operators

The paper discusses new business models of transmission of television programs in the context of definitions of broadcasting and retransmission. Typically the whole process of supplying content to the end user has two stages: a media service provider supplies a signal assigned to a given TV channel to the cable operators and satellite DTH platform operators (dedicated transmission), and cable operators and satellite DTH platform operators transmit this signal to end users. In each stage the signals are encoded and are not available for the general public without the intervention of cable/platform operators. The services relating to the supply and transmission of the content are operated by different business entities: each earns money separately and each uses the content protected by copyright. We should determine how to define the actions of the entity supplying the signal with the TV program directly to the cable/digital platform operator and the actions of the entity providing the end user with the signal. The author criticizes the approach presented in the Chellomedia and Norma rulings, arguing that they lead to a significant level of legal uncertainty, and poses the basic questions concerning the notion of “public” in copyright.

Does low phosphorus supply limit seedling establishment and tree growth in groves of ectomycorrhizal trees in a central African rainforest?

In a forest grove at Korup dominated by the ectomycorrhizal species Microberlinia bisulcata, an experiment tested whether phosphorus (P) was a limiting nutrient. P-fertilization of seven subplots 1995-97 was compared with seven controls. It led to large increases in soil P concentrations. Trees were measured in 1995 and 2000. M. bisulcata and four other species were transplanted into the treatments, and a wild cohort of M. bisulcata seedlings was followed in both. Leaf litter fall from trees and seedlings were analysed for nutrients. Growth of trees was not affected by added P. Transplanted seedlings survived better in the controls than added-P subplots: they did not grow better with added-P.M. bisulcata wildlings survived slightly better in the added-P subplots in yr 1 but not later. Litter fall and transplanted survivors had much higher concentrations of P (not N) in the added-P than control subplots. Under current conditions, it appears that P does not limit growth of trees or hinder seedling establishment, especially of M. bisculcata, in these low-P grove soils.

Avoidable hospitalizations in Switzerland: a small area analysis on regional variation, density of physicians, hospital supply and rurality.

BACKGROUND Avoidable hospitalizations (AH) are hospital admissions for diseases and conditions that could have been prevented by appropriate ambulatory care. We examine regional variation of AH in Switzerland and the factors that determine AH. METHODS We used hospital service areas, and data from 2008-2010 hospital discharges in Switzerland to examine regional variation in AH. Age and sex standardized AH were the outcome variable, and year of admission, primary care physician density, medical specialist density, rurality, hospital bed density and type of hospital reimbursement system were explanatory variables in our multilevel poisson regression. RESULTS Regional differences in AH were as high as 12-fold. Poisson regression showed significant increase of all AH over time. There was a significantly lower rate of all AH in areas with more primary care physicians. Rates increased in areas with more specialists. Rates of all AH also increased where the proportion of residences in rural communities increased. Regional hospital capacity and type of hospital reimbursement did not have significant associations. Inconsistent patterns of significant determinants were found for disease specific analyses. CONCLUSION The identification of regions with high and low AH rates is a starting point for future studies on unwarranted medical procedures, and may help to reduce their incidence. AH have complex multifactorial origins and this study demonstrates that rurality and physician density are relevant determinants. The results are helpful to improve the performance of the outpatient sector with emphasis on local context. Rural and urban differences in health care delivery remain a cause of concern in Switzerland.

Limitation of seedling growth by potassium and magnesium supply for two ectomycorrhizal tree species of a Central African rain forest and its implication for their recruitment

In the ectomycorrhizal caesalpiniaceous groves of southern Korup National Park, the dominant tree species, Microberlinia bisulcata, displays very poor in situ recruitment compared with its codominant, Tetraberlinia bifoliolata. The reported ex situ experiment tested whether availabilities of soil potassium and magnesium play a role. Seedlings of the two species received applications of K and Mg fertilizer in potted native soil in a local shade house, and their responses in terms of growth and nutrient concentrations were recorded over 2 years. Amended soil concentrations were also determined. Microberlinia responded strongly and positively in its growth to Mg, but less to K; Tetraberlinia responded weakly to both. Added Mg led to strongly increased Mg concentration for Microberlinia while added K changed that concentration only slightly; Tetraberlinia strongly increased its concentration of K with added K, but only somewhat its Mg concentration with added Mg. Additions of Mg and K had small but important antagonistic effects. Microberlinia is Mg-demanding and apparently Mg-limited in Korup soil; Tetraberlinia, whilst K-demanding, appeared not to be K-limited (for growth). Added K enhanced plant P concentrations of both species. Extra applied Mg may also be alleviating soil aluminum toxicity, and hence improving growth indirectly and especially to the benefit of Microberlinia. Mg appears to be essential for Microberlinia seedling growth and its low soil availability in grove soils at Korup may be an important contributing factor to its poor recruitment. Microberlinia is highly shade-intolerant and strongly light-responding, whilst Tetraberlinia is more shade-tolerant and moderately light-responding, which affords an interesting contrast with respect to their differing responses to Mg supply. The study revealed novel aspects of functional traits and likely niche-partitioning among ectomycorrhizal caesalps in African rain forests. Identifying the direct and interacting indirect effects of essential elements on tropical tree seedling growth presents a considerable challenge due the complex nexus of causes involved.

Managing social policy under federalism: The challenges of hybrid funding and program delivery

This paper discusses generally the question of the level of government that should be used to administer different social policies. The chapter focuses on the Medicaid program, looking at recent state-level changes in health insurance for the poor and long-term care policy. Particular attention will be paid to the question of how states have used their new freedoms to outsource public insurance to the private sector and on the consequent differences in outcomes across states. Notably, this paper will be drawn from my forthcoming book “The American Myth of Markets in Social Policy” (Palgrave, MacMillan, November, 2015).

Parental Employment and Home Visiting Program Service Delivery

Home visiting programs, which provide in-home services to disadvantaged families with young children, rest on the assumption that poor parents can be reached at home. Increased levels of maternal employment raise questions about this assumption. In this study, longitudinal data collected for a home visiting program evaluation were analyzed to assess whether employment patterns of parents who receive home visiting services reflect employment patterns of other poor mothers between 1995 and 2000. The study also addresses the relationship between maternal employment and home visiting service intensity. To effectively reach home visiting participants, service providers may need to modify service delivery practices.

Nd, Sr and Pb isotopic composition of eolian dust deposited in the central North Pacific

The silicate fractions of recent pelagic sediments in the central north Pacific Ocean are dominated by eolian dust derived from central Asia. An 11 Myr sedimentary record at ODP Sites 885/886 at 44.7°N, 168.3°W allows the evaluation of how such dust and its sources have changed in response to late Cenozoic climate and tectonics. The extracted eolian fraction contains variable amounts (>70%) of clay minerals with subordinate quartz and plagioclase. Uniform Nd isotopic compositions (epsilon-Nd =38.6 to 310.5) and Sm/Nd ratios (0.170-0.192) for most of the 11 Myr record demonstrate a well-mixed provenance in the basins north of the Tibetan Plateau and the Gobi Desert that was a source of dust long before the oldest preserved Asian loess formed. epsilon-Nd values of up to 36.5 for samples 62.9 Ma indicate <=35 wt% admixture of a young, Kamchatka-like volcanic arc component. The coherence of Pb and Nd in the erosional cycle allows us to constrain the Pb isotopic composition of Asian loess devoid of anthropogenic contamination to 206Pb/204Pb =18.97 +/- 0.06, 207Pb/204Pb =15.67 +/- 0.02, 208Pb/204Pb =39.19 +/- 0.11. 87Sr/86Sr (0.711-0.721) and Rb/Sr ratios (0.39-1.1) vary with dust mineralogy and provide an age indication of ~250 Ma. 40Ar/39Ar ages of six dust samples are uniform around 200 Ma and match the K-Ar ages of modern dust deposited on Hawaii. These data reflect the weighted age average of illite formation. Changes from illite- smectite with significant kaolinite to illite- and chlorite-rich, kaolinite-free assemblages since the late Pliocene document changes in the intensity of chemical weathering in the source region. Such weathering evidently did not disturb the K-Ar systematics, and only induced scatter in the Rb-Sr data. We propose that when smectite forms at the expense of illite, K and Ar are quantitatively lost from what becomes smectite, but are quantitatively retained in adjacent illite layers. 40Ar/39Ar age data, therefore, are insensitive to smectite formation during chemical weathering but date the diagenetic growth of illite, the major K-bearing phase in the dust. Over the past 12 Myr, the dust flux to the north Pacific increased by more than an order of magnitude, documenting a substantial drying of central Asia. This climatic change, however, did not alter the ultimate source of the dust, and neoformational products of chemical weathering always remained subordinate to assemblages reworked by mechanical erosion in dust deposited in eastern Asia and the Pacific Ocean.

Geochemistry of terrigenous material in deep-sea sediments of the equatorial Pacific

Biological productivity in the modern equatorial Pacific Ocean, a region with high nutrients and low chlorophyll, is currently limited by the micronutrient Fe. In order to test whether Fe was limiting in the past and to identify potential pathways of Fe delivery that could drive Fe fertilization (i.e., dust delivery from eolian inputs vs. Fe supplied by the Equatorial Undercurrent), we chemically isolated the terrigenous material from sediment along a cross-equatorial transect in the central equatorial Pacific at 140°W and at Ocean Drilling Program Site 850 in the eastern equatorial Pacific. We quantified the contribution from each potential Fe-bearing terrigenous source using a suite of chemical- and isotopic discrimination strategies as well as multivariate statistical techniques. We find that the distribution of the terrigenous sources (i.e., Asian loess, South American ash, Papua New Guinea, and ocean island basalt) varies through time, latitude, and climate. Regardless of which method is used to determine accumulation rate, there also is no relationship between flux of any particular Fe source and climate. Moreover, there is no connection between a particular Fe source or pathway (eolian vs. Undercurrent) to total productivity during the Last Glacial Maximum, Pleistocene glacial episodes, and the Miocene "Biogenic Bloom". This would suggest an alternative process, such as an interoceanic reorganization of nutrient inventories, may be responsible for past changes in total export in the open ocean, rather than simply Fe supply from dust and/or Equatorial Undercurrent processes. Additionally, perhaps a change in Fe source or flux is related to a change in a particular component of the total productivity (e.g., the production of organic matter, calcium carbonate, or biogenic opal).

Terrestrial organic matter in marine sediments of the Central Equatorial Atlantic

Terrestrial organic matter (OM) in pelagic sediments is discussed with regard to depositional processes and land-sea interactions in the modern and past glacial/interglacial Equatorial Atlantic. Special emphasis is placed on a critical evaluation of different analytical approaches (C/N, Rock-Eval Pyrolysis, stable carbon isotopes, palynology, organic petrology, and selected biomarkers) which are currently used for the qualitative and quantitative assessment of terrigenous organic carbon. If binary mixing equations are used to calculate terrestrial and marine proportions of organic carbon, we consider the definition of endmember values to be most critical since these values may be biased by a great number of independent controls. A combination of geochemical methods including optical studies (organic petrology and palynology) is therefore suggested to evaluate each individual proxy. Organic geochemical analyses performed on sediments from the modern and Late Quaternary Equatorial Atlantic evidence fluctuations in eolian supply of terrigenous OM related to changes in intensity of the trade winds. Quantification of this organic fraction leads to differing proportions depending on the approach applied, i.e. the organic carbon isotopic composition or maceral analyses. Modern distribution of terrigenous OM reveals a decrease in supply towards the basin contributing less than a fifth of the total OM in pelagic areas. Organic geochemical data indicate that sedimentation in the modern northeastern Brasil Basin is affected by lateral advection of reworked OM probably from southern source areas. Glacial/interglacial deposits from the pelagic Equatorial Atlantic (ODP Site 663), covering isotopic stages 12 and 11, reveal that deposition of terrigenous OM was higher under past glacial conditions, in correspondence to generally enhanced dust fluxes. Proportions of terrigenous OM, however, never exceed 50% of the total OM according to maceral analyses. Other estimates, recently proposed by Verardo and Ruddiman (1996), are considered to be too high probably for analytical reasons. Palynological records in the Equatorial Atlantic parallel dust records. Increased portions of grass pollen suggest the admixture of C4-plant material under modern and past glacial conditions. It is therefore assumed, as one possible interpetation, that C4-plant debris has an effect on sedimentary d13Corg and might explain differences between isotopic and microscopic quantitative estimates. Using the difference between these two records, we calculate that maximum supply of C4-material remains below 20% of the total OM for the deep modern and past glacial/interglacial Equatorial Atlantic.

(Appendix 1) Crustal helium-4 abundance and flux data for ODP Hole 130-806B

The mass accumulation rates (MARs) of aeolian dust in the ocean basins provide an important record of climate in the continental source regions of atmospheric dust and of the prevailing wind patterns responsible for dust transport in the geologic past. The incorporation of other terrigenous components such as volcanic ashes in seafloor sediments, however, often obscures the aeolian dust record. We describe a new approach which uses the delivery rate of crustal 4He to seafloor sediments as a proxy for the mass accumulation rate of old continental dust which is unaffected by the addition of other terrigenous components. We have determined the flux of crustal 4He delivered to the seafloor of the Ontong Java Plateau (OJP) in the western equatorial Pacific over the last 1.9 Myrs. Crustal 4He fluxes vary between 7.7 and 30 ncc/cm**2/kyr and show excellent correlation with global climate as recorded by oxygen isotopes, with high crustal 4He fluxes associated with glacial periods over the entire interval studied. Furthermore, the onset of strong 100 kyr glacial-interglacial climate cycling is clearly seen in the 4He flux record about 700 kyrs ago. These data record variations in the supply of Asian dust in response to climate driven changes in the aridity of the Asian dust sources, consistent with earlier work on Asian dust flux to the northern Pacific Ocean. However, in contrast to previous studies of sites in the central and eastern equatorial Pacific Ocean, there is no evidence that the Inter Tropical Convergence Zone (an effective rainfall barrier to the southward transport of northern hemisphere dust across the equator in the central and eastern Pacific) has influenced the delivery of Asian dust to the OJP. The most likely carrier phase for crustal helium in these sediments is zircon, which can reasonably account for all the 4He observed in the samples. As a first order estimate, these results suggest that the mass accumulation rate of Asian dust on the OJP over the last 1.9 Myrs varied from about 4 to 15 mg/ cm**2/kyr. In contrast, previous studies show that over the same interval the total MAR of terrigenous dust (i.e. Asian dust plus local volcanics) on OJP varied between about 34 and 90 mg/ cm**2/kyr.

Natural production of Tuber aestivum in central Spain: Pinus spp. versus Quercus spp. brûles

Aim of study: Tuber aestivum is the most widespread edible truffle, with increasing commercial interest. This species can produce carpophores with conifer hosts, in contrast with the inability of Pinus spp. to induce fruiting in other truffle species such as Tuber melanosporum. Therefore the objective is to compare the characteristics and carpophore production of T. aestivum brûlés associated with Pinus spp. versus Quercus spp. Area of study: We studied the natural habitats of T. aestivum in the Alto Tajo Nature Reserve in central Spain. Material and methods: During 5 years, we monitored the production of carpophores and brûlé size of 145 T. aestivum brûlés associated with Pinus nigra subsp. salzmanni and P. sylvestris and Quercus ilex subsp. ballota and Q. faginea hosts. Statistical treatment was performed using the Statistica Program v. 6. Main results: The size of brûlés associated with Pinus was significantly smaller than that of brûlés associated with Quercus. However, carpophore production per brûlé, and especially for brûlés of similar size, was greater when the host plant was a pine. After accounting for brûlé size, the production of brûlés associated with Pinus spp. was 2.23 (95% CI, between 1.35 and 3.69) and 1.61 (95% CI, between 1.02 and 2.54) times greater than the production of brûlés associated with Quercus faginea and Q. ilex subsp. ballota, respectively. Research highlights: The considerable ability of Pinus nigra subsp. salzmanni and P. sylvestris to form effective brûlés and to produce carpophores of Tuber aestivum in natural conditions was clearly demonstrated, and suggest that those species can be of use in the culture of T. aestivum.

Espacios máximos con recursos mínimos : edificio Central Lechera CLESA, Alejandro de la Sota

La tesis aborda el estudio de la Central lechera CLESA, uno de los edificios industriales de Alejandro de la Sota más significativos de la década de los años cincuenta en España. Las centrales lecheras fueron abordadas por Sota en distintas ocasiones entre 1955 y 1969, siendo CLESA la única de todas ellas que llega a construirse. Se trata de uno de los exponentes más brillantes de la arquitectura moderna industrial española de la posguerra, incluido en "La arquitectura de la industria, REGISTRO DOCOMOMO IBÉRICO”1 entre la veintena de edificios seleccionados de la arquitectura madrileña de este periodo. Plantea una solución singular para alcanzar la diafanidad exigida en la implantación del proceso de producción. La estructura de las naves se realiza con hormigón pretensado, siendo uno de los pioneros en la utilización de esta técnica. La hipótesis de partida considera la realidad del proyecto construido como respuesta desde la arquitectura a un programa industrial resuelto con sencillez, que partiendo de una economía de recursos que le es inherente, consigue desde la coherencia del planteamiento, soluciones donde la complejidad espacial constituye una respuesta eficaz y del máximo interés. Los objetivos de esta tesis son contribuir a un conocimiento riguroso del edificio, que permita descubrir la particularidad de su entramado espacial y el interés de las soluciones adoptadas en su configuración final, en aras de contrastar su calidad arquitectónica. El edificio de la Central Lechera CLESA, si bien es un edificio muy conocido, lo es de una manera superficial. Aparece en numerosas publicaciones, en muchas ocasiones formando parte de un relato extenso de la obra de su autor. El libro monográfico publicado en 2007 por la Fundación Alejandro de la Sota, cuya edición está a cargo de Teresa Couceiro, es la única publicación específica sobre él. Tras una breve introducción, en la que se destaca la intensa dedicación de Sota a esta obra, reúne una colección de planos, fotografías y croquis, junto a la memoria del proyecto. Ofrece una visión fragmentada, que permite vislumbrar el interés de esta obra, pero no facilita comprenderla en su integridad. Es importante destacar la publicación de CLESA en el libro editado por Pronaos (1989), que incluye una selección, realizada por el autor, de plantas, alzados y secciones que corresponden al proyecto construido junto a fotografías de la obra terminada, además de un breve texto tan conciso como esclarecedor. Sobre Alejandro de la Sota se han escrito, tesis doctorales, numerosos artículos, varios libros así como realizado exposiciones que recogen su obra global, reflejados en este documento en las consiguientes bibliografías específicas. Cabe destacar la exposición realizada en la sede del COAM en 2014, con ocasión de su centenario, que el edificio CLESA protagoniza en cierto modo, por su riesgo de desaparición.2 La tesis se estructura en cuatro capítulos: descripción, análisis, síntesis y conclusiones. El primer capítulo contempla la descripción del edificio objeto de la tesis, con una introducción que nos sitúa en el contexto histórico, económico, cultural y social en el que se desarrolla el encargo, proyecto y obra de la central lechera. La descripción propiamente dicha del conjunto industrial, partiendo del encargo de la central lechera al autor del proyecto, pasando por el anteproyecto, el proyecto visado y llegando a la obra realizada. Se compara el proyecto visado, la obra terminada y la CLESA publicada, así como el devenir del edificio. La segunda parte corresponde al análisis, en primer lugar desde el programa como planteamiento general, estudiando las circulaciones, relaciones espaciales, geométricas, esqueléticas, geográficas -parte a parte- que integran el conjunto de la central. La estructura, introducción explicativa de las soluciones adoptadas por Alejandro de la Sota; análisis del sistema esquelético del edificio por partes, operaciones geométricas y espaciales. Construcción, análisis de la materialización de la obra, sistemas constructivos empleados en cerramientos, cubiertas, lucernarios; de lo general a lo particular, estudiando los sistemas. Finalmente a través de la pequeña escala se compendian elementos singulares que forman parte de sistemas complejos, como las múltiples escaleras, barandillas, carpinterías, miradores. Se recapitula en una síntesis que configura un todo con la suma de las partes, mediante la utilización de recursos de enlace de esa arquitectura aditiva, como es el módulo, los recorridos y los enlaces visuales. El capítulo final de Conclusiones contrasta la hipótesis de partida de la tesis en cuanto a una arquitectura de espacios máximos con recursos mínimos. Recoge también diversas reflexiones como la dialéctica entre el espacio fragmentado y el espacio único; crecimiento expansivo o inclusivo; imagen singular y representación; escala doméstica y escala industrial; renuncias estructurales o limitaciones de medios. Quizás, el mayor interés de esta tesis reside los dibujos realizados en axonométrica del complejo CLESA, que han permitido restituir y reconstruir idealmente la fábrica al inicio de su actividad. Teniendo en cuenta su posible desaparición total o parcial, esta restitución cobra relevancia como testimonio de lo que fue. ABSTRACT The thesis deals with the study of CLESA's Dairy Plant, one of the most significant industrial buildings of the Decade of the fifties in Spain, by Alejandro de la Sota. The Dairies were addressed by Sota at various occasions between 1955 and 1969, being the CLESA plant the only one that is has been built. This is one of the most brilliant exponents of Spanish industrial post-war modern architecture, included in "The architecture industry, IBERIAN DOCOMOMO RECORD"3 between the score of selected buildings of Madrid architecture of this period. It poses a singular solution to achieve the openness of the space required in the implementation of the manufacturing process. The structure of the nave is done with prestressed concrete, being one of the pioneers in the use of this technique. The initial hypothesis considers the reality of the project built from the architecture in response to an industrial program solved with simplicity, that from a resource economy that is inherent, gets from the consistency of the approach, solutions where the space complexity is an effective response of great interest. The objectives of this thesis are to contribute to a rigorous knowledge of the building, which allows to discover the particularity of its space lattice and the interest of the solutions adopted in its final configuration, in order to contrast its architectural quality. The building of the Central Lechera CLESA, despite it is a well known building, is in a superficial way. It appears in several publications, often as part of an extensive account of the work of its author. The monograph published in 2007 by the Foundation Alejandro de la Sota, whose edition is run by Teresa Couceiro, is the only specific publication about it. After a brief introduction, in which Sota's intense dedication to this work stands out, it brings together a collection of drawings, photographs and sketches, along with the project report. It offers a fragmented view, which enable to glimpse the interest of this work, but not helps to understand it in full. It is important to highlight the publication of CLESA in the book edited by Pronaos (1989), which includes a selection made by the author of plants, elevations and sections corresponding to the project built, next to photographs of the finished construction, in addition to a brief text as concise as enlightening. About Alejandro de la Sota have been written doctoral thesis, numerous articles, several books as well as held exhibitions collecting his global work, which have been reflected in this document in the resulting specific bibliographies. It should be noted the exhibition in COAM headquarters in 2014, on the occasion of its Centennial, where the building CLESA has a leading role, in a certain way, because of its risk of disappearance.4 The thesis is structured in four chapters: description, analysis, synthesis, and conclusions. The first chapter provides the description of the building object of this thesis. Includes an introduction that puts us in the historic, economic, cultural and social context in which it is developed the commission, the project and construction of the dairy building. The description itself of the industrial complex, starts with the order of the dairy to the author of the project, moves through the draft, the visa project and reaches the completion of the work. The visa project, CLESA's finished and published work, as well as the future of the building is compared. The second part corresponds to the analysis, first from the program as a general approach, studying the circulations, geometric, spatial, skeletal, geographical relations - bit by bit - comprising the manufacturing plant ("la central"). The structure, explanatory introduction of the solutions adopted by Alejandro de la Sota; analysis of the skeletal system of the building by parts, geometric and spatial operations. Construction, analysis of the realization of the work, constructive systems used in the building enclosures, roofs, skylights; from the general to the particular and studying the systems. Finally through small scale unique elements that are part of complex systems, such as multiple stairs, railings, carpentry, viewpoints are summarized. It is recapitulated in a synthesis which forms a whole with the sum of the parts, using linking resources that belongs to the additive architecture, such as the module, tours and visual links The final chapter of Conclusions contrast the hypothesis of the thesis regarding the maximum space architecture with minimal resources. It also includes various reflections as the dialectic between the fragmented space and the single space; expansive or inclusive growth; unique image and representation; domestic and industrial scale; structural abandonment or limitation of means. Perhaps the greatest interest of this thesis lies in the axonometric drawings made of the CLESA complex, which ideally have allowed to restore and rebuild the factory back to the beginning of its activity. Considering its potential full or partial disappearance, such recovery becomes relevant as a testimonial evidence of what it was.

Pacific Coast of Mexico, Central America, and the Region Around the Galapagos Islands Showing Route of the Steamer Albatross, 1891 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Explorations of the U. S. Fish Commission steamer Albatross : Lieut. Comdr. Z. L. Tanner U.S.N. Comdg. : Februrary to April 1891. It was printed for the Museum of Comparative Zoology, Harvard University in 1892. Scale [ca. 1:7,500,000]. Covers the Pacific Coast of Mexico, Central America, and the region around the Galapagos Islands. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Mercator' projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, human settlements, shoreline features, bays, harbors, islands, and more. Relief shown by soundings and bathymetric isolines and tints. Shows the route of the Agassiz-Albatross Cruise 1891. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.