Fundamentos constructivos de las fortificaciones fronterizas entre las coronas de Castilla y Aragón de los siglos XII al XV en la actual provincia de Soria

La tesis doctoral desarrolla una investigación original, dentro del marco disciplinario de la historia de la construcción, sobre los fundamentos constructivos de las fortificaciones bajomedievales fronterizas entre las Coronas de Castilla y Aragón en la actual provincia de Soria. En el título de la tesis ya queda expresado el objeto fundamental y fundacional, así como el ámbito temporal —desde la reconquista del oriente soriano por parte de Alfonso I el Batallador a principios del siglo XII hasta la unificación de las coronas hispánicas en el siglo XV bajo el común mandato de los Reyes Católicos— y la extensión territorial que delimita la investigación: aquéllas comarcas castellanas lindantes con Aragón pertenecientes a la actual provincia de Soria. Durante este período bajomedieval se produjeron una serie de enfrentamientos fronterizos que obligó a fortificar la frontera y las vías de comunicación entre ambas coronas. La falta de estudios de conjunto de estas fortificaciones entendiéndolas como participantes en un sistema fortificado ha constituido la justificación de la investigación, que se realiza en varios niveles de análisis: territorial, histórico, arquitectónico, poliorcético y constructivo. Así mismo, se ha detectado cierta falta de rigor acompañada de inexactitudes en las consideraciones constructivas publicadas sobre algunas de las fortificaciones del ámbito de estudio, lo que ha provocado errores en su datación al no más haber elementos de corte artístico o estilístico que marquen indudablemente la pertenencia a una época. En la tesis se ponen en duda las dataciones tradicionalmente aceptadas planteando la hipótesis que da pie a la investigación: ante la falta de elementos artísticos o estilísticos en unos sobrios edificios eminentemente funcionales es posible establecer con suficiente aproximación la fecha de construcción en base a criterios constructivos una vez formada una clasificación cronotipológica de cada técnica constructiva. La hipótesis, por lo tanto, plantea un objetivo principal —el estudio de la razón constructiva del sistema fortificado fronterizo— desarrollado en una serie de objetivos específicos cuya consecución programa los sucesivos niveles de análisis: - Conocer y detallar los elementos históricos que originaron los enfrentamientos entre las Coronas de Castilla y Aragón y su desarrollo mediante herramientas historiográficas y analizar las características naturales del territorio en litigio mediante instrumentos cartográficos. - Conocer y analizar los tipos arquitectónicos y las tradiciones constructivas empleadas en las construcciones castrenses en el ámbito temporal en que se enmarca la investigación. - Localizar, documentar y seleccionar para su análisis las fortalezas y construcciones militares erigidas durante dichas luchas fronterizas en la actual provincia de Soria a través del trabajo de campo y métodos cartográficos y bibliográficos. - Realizar un estudio general sobre el sistema fortificado a escala territorial - Investigar la tipología arquitectónica, poliorcética y constructiva del conjunto de estas fortificaciones bajomedievales fronterizas. - Analizar los fundamentos constructivos de los casos de estudio seleccionados entre estas construcciones y caracterizarlas en cuanto al material, elementos, sistemas y procesos constructivos. - Ordenar la información histórica dispersa y corregir errores para hacer una base sobre la que establecer un discurso histórico de cada caso de estudio. - Comparar y relacionar las técnicas constructivas empleadas en estas fortalezas con los utilizados en el mismo ámbito temporal. - Difundir para su debate los resultados de la investigación por los foros científicos habituales. El método empleado combina los trabajos de gabinete con una intensa labor de campo, en la que se han documentado cincuenta fortificaciones y se han redactado sus correspondientes fichas de toma de datos. La recopilación de datos se ha incluido en una base de datos que incluye aspectos generales, tipológicos, constructivos y bibliográficos básicos del conjunto, a modo de inventario, de fortificaciones de la provincia. Las fortificaciones seleccionadas se agrupan según una clasificación tipológica y constructiva que marca las líneas de estudio posteriores. Se desarrolla un capítulo de antecedentes en el que se estudia la historia de la construcción fortificada medieval tanto en Europa como en España analizando la evolución de los tipos arquitectónicos y las múltiples influencias culturales que surcaron el Mediterráneo desde el Oriente cruzado e islámico al Poniente donde se desarrollaba la empresa reconquistadora que mantuvo en estado de guerra continuo a la Península Ibérica durante ochocientos años. El análisis del territorio como contenedor del hecho fortificado revela que hay una relación íntima entre la ubicación de las fortificaciones y las formas naturales que definen las vías de comunicación entre los valles del Duero, del Ebro y del Tajo. En efecto, el ámbito de estudio ha supuesto desde la Antigüedad un territorio de paso fundamental en la articulación de las comunicaciones en la Península Ibérica. Este carácter de paso más que de frontera explica las inquietudes y la preocupación por su control tanto por Roma como por el califato cordobés como por los reinos cristianos medievales. El análisis de los elementos históricos se complementa con el estudio detallado de los enfrentamientos fronterizos entre Castilla y Aragón así como los aspectos sociales y políticos que provocaron la fortificación como sistema de definición de la frontera y de organización espacial, jurisdiccional, social y administrativa del territorio. La arquitectura fortificada es esencialmente funcional: su cometido es la defensa. En este sentido, tras un estudio morfológico de los castillos seleccionados se realiza un extenso análisis poliorcético de sus elementos, investigando su origen y aplicación para servir también de parámetros de datación. Siendo el objeto inaugural de la tesis el estudio de los fundamentos constructivos, se explican los distintos materiales de construcción empleados y se agrupan las fábricas de las fortificaciones seleccionadas en dos grandes grupos constructivos: las fábricas aparejadas y las fábricas encofradas. Se han destacado y estudiado la evolución histórica y la tipología y mensiología constructiva de tres técnicas destacadas: el uso del ladrillo, la tapia de cal y canto o mampostería encofrada y la tapia de tierra. Para el estudio de la componente histórica y de la dimensión constructiva de cada técnica ha sido necesario documentar numerosos casos tanto en el ámbito de estudio como en la Península Ibérica con el fin de establecer grupos cronotipológicos constructivos entre los que poder ubicar las fábricas de estas técnicas presentes en el ámbito de estudio. Se ha observado una evolución dimensional de las fábricas de tapia que es más evidente en las hispanomusulmanas al modularse en codos pero que también se advierte significativamente en las cristianas bajomedievales. De cada una de las técnicas analizadas se ha seleccionado un caso de estudio singular y representativo. El castillo de Arcos de Jalón es un ejemplo significativo del empleo de la fábrica mixta de mampostería con verdugadas de ladrillo, así como las murallas de la ciudad fortificada de Peñalcázar lo es de la fábrica de mampostería encofrada y el castillo de Serón de Nágima constituye un caso característico y principal de la utilización de la tapia de tierra en la arquitectura militar bajomedieval. Cada uno de estos tres casos de estudios se examina bajo los mismos cuatro niveles anteriormente mencionados: territorial, histórico, arquitectónico y defensivo y constructivo. El sistemático método de estudio ha facilitado el orden en la investigación y la obtención de unos resultados y conclusiones que verifican la hipótesis y cumplen los objetivos marcados al comienzo. Se ha revisado la datación en la construcción de las fortificaciones analizadas mediante el estudio cronotipológico de sus fábricas, pudiendo trasladarse el método a otros sistemas fortificados. La tesis abre, finalmente, dos vías principales de investigación encaminadas a completar el estudio del sistema fortificado fronterizo bajomedieval en la raya oriental soriana de Castilla: la caracterización y datación por métodos físico-químicos de las muestras de piezas de madera de construcción que se conservan embebidas en las fábricas y la búsqueda documental y archivística que pueda revelar nuevos datos respecto a la fundación, reparación, venta o cualquier aspecto económico, legislativo, organizativo o administrativo relativo a las fortificaciones en documentos coetáneos. ABSTRACT The doctoral thesis develops an original research, held in the field of the Construction History, about the constructive reason of the frontier fortifications in the Late Middle Age between the Crowns of Castile and Aragón in the actual province of Soria, Spain. In the title is expressed the main objective, and also the temporal scope —from the reconquest in the 12th Century by Alfonso the First of Aragón to the unification under the common kingdom of the Catholic Kings— and the territorial extension that the research delimits: those Castilian regions in the border with Aragón in the actual province of Soria. During this period, a series of border wars were been, and this is the reason for the fortification of the border line and the main roads between both Crowns. The lack of studies of these fortifications as participants in a fortified system is the justification of the research. There is several analysis levels: territorial, historical, architectonic, defensive and constructive. Likewise, there is a lack of strictness and inaccuracy in the constructive items in the publications about several fortifications of this study field. This aspect has caused mistakes in the dating because there is neither artistic nor stylistic elements which determines a epoch. The traditionally accepted datings are challenged. An hypothesis is formulated: in the absence of artistic or stylistic elements in a sober and functional buildings is possible to date the time of construction with sufficiently approximation based on construction criteria once formed a cronotypologic classification of each building technique. The hypothesis, therefore, propose a main aim: the study of the constructive reason of the fortified border system. This aim is developed in a series of specifically targets whose achievement programs the analysis levels: - To know and to detail the historical elements which started the wars between Castile and Aragon and its development using historiographical tools, and to analyze the natural characteristic of the territory through cartographical tools. - To understand and to analyze the different architectural types and the building traditions employed in the military buildings in the time researched. - To locate, to document, and to select for their analysis the fortresses and military constructions erected during these border wars in the actual province of Soria through fieldwork and bibliographical and cartographical methods. - To conduct a general study on the fortified system in territorial scale. - To research the architectural, constructive and defensive typology of the system of these border late medieval fortifications. - To analyze the construction logic of the selected case studies and to characterize in the items of material, elements, systems and construction processes. - To sort scattered historical information and to correct mistakes to make a base by which to establish a historic speech of each case study. - To compare and to relate the construction techniques employed in these fortresses with those used in the same time range . - To spread for discussion the research results in the usual scientists forums. The method combines the destock work with an intense fieldwork. Fifty fortifications have been documented and it has written their corresponding data collection card. Data collection has been included in a database that includes general aspects, typological, constructive and basic bibliographical data, as an inventory of fortifications in the province. The selected fortifications are grouped according to a typological and constructive classification which lead the lines of the later study. There is a chapter for the antecedents in which the history of the medieval fortified construction in Europe and in Spain is studied by analyzing the evolution of architectural types and the many cultural influences along the opposite seasides of the Mediterranean Sea, from the Islamic and Crusader East to the Iberian Peninsula in where there were a long and continuous war during eight hundred years. The territory is analyzed as a container of fortifications. This analysis reveals that there is an intimate relationship between the location of the fortifications and the natural forms that define the communication roads between the Duero, Ebro and Tajo valleys. Indeed, the study area has been a cross-territory from ancient times more than a frontierterritory. This communication character explains the concerns about its control both by Rome and by the Muslims of Córdoba as medieval Christian kingdoms. The analysis of historical elements is supplemented by detailed study of border war between Castile and Aragon and the social and political issues that led to the fortification as border definition system and spatial, jurisdictional, social and administrative planning. The fortified architecture is essentially functional: it is responsible for defense. In this sense, after a morphological study of selected castles is performed an extensive analysis of its defensive elements, investigating its origin and application. This analisis serves for the definition of parameters for dating. The purpose of the thesis is the study of the constructive logic. First, various building materials are explained. Then, masonry is grouped into two major constructive groups: rigged masonry and formwork masonry. The historical evolution and the constructive typology and mensiology are studied for each one of the three main techniques: the use of brickwork, the mortar wall and rammed-earth. Many case studies have been documented along the Iberian Peninsula and also in the study area. As conclusion, there is a dimensional evolution of the rammed-earth walls. This evolution is more evident into the Muslim masonry than in the late medieval walls: the reason is the use of the cubit as module. From each of the techniques discussed, a singular and representative case of study has been selected. The castle of Arcos de Jalon is a significant example of mix masonry of stone and brick rows. The walled city of Peñalcázar is built with masonry formwork. Serón de Nágima castle, at last, is a typical and main case of the use of the rammedearth wall of late medieval military architecture. Each of these three case studies were examined under the same four analysis levels above mentioned: territorial, historical, architectural and defensive and constructive. The systematic method of study has facilitated the order in the research and the obtaining of results and conclusions that verify the hypotheses and achieve the research objectives. Dating of the fortifications construction has been revised by studying the cronotypological issues of its masonry. The method can be transferred to the study of other fortified systems. Finally, the thesis describes two main research new ways aimed at completing the study of the late medieval fortified border of Castile in the actual province of Soria. The first of them is the characterization and datig by physicochemical methods the sample pieces of wood construction preserved embedded in the masonry. The second research way is the investigation of the documents in archives that may reveal new information about the foundation, repair, sale or any aspect to economic, legal, organizational or administrative concerning fortifications in contemporary documents.

Induction of ovulation in rabbits by adding Lecirelin to the seminal dose: In vitro and in vivo effects of different excipients.

This study evaluates the effect of Lecirelin (Dalmarelin®, Fatro, Italy) diluted in different excipients (benzilic alcohol, benzoic acid and paraben) added to a seminal dose on LH concentrations, progesterone concentrations and ovarian status in rabbits. The in vitro effect on spermatozoa was also tested. A total of 100 multiparous female rabbits were divided into 5 groups, which at the moment of AI, received 0.2 mL (5 μg/dose) intramuscular (im) inoculation of Lecirelin (control) or the same Lecirelin dose administered intravaginally (iv) with the seminal dose alone (Lecirelin group) or with benzilic alcohol (Lecirelin BA group), benzoic acid (Lecirelin BAc group) or parabens (Lecirelin PA group) as an excipient. After 7 days, 10 rabbits per group were euthanized to analyze their ovarian status. In the control group, a high LH peak was detected 30 min post AI, while in the iv groups a slight increase in LH occurred after 120 min. The ovulation and fertility rate was similar in control and Lecirelin groups, while the lowest fertility rate was detected in the Lecirelin BA group. In a second experiment, the semen samples collected from male rabbits were diluted in TALP (control) or mixed with the 5 μg of Lecirelin solutions used in the first experiment. The highest percentage of capacitated sperm (68.3%) was recorded in the Lecirelin PA. The lowest percentages were observed in the Lecirelin BA and BAc groups. In conclusion, the iv administration of Lecirelin represents an alternative method for simplifying rabbit insemination procedures.

3-D modeling of perimeter recombination in GaAs diodes and its influence on concentrator solar cells

This paper describes a complete modelling of the perimeter recombination of GaAs diodes which solves most unknowns and suppresses the limitations of previous models. Because of the three dimensional nature of the implemented model, it is able to simulate real devices. GaAs diodes on two epiwafers with different base doping levels, sizes and geometries, namely square and circular are manufactured. The validation of the model is achieved by fitting the experimental measurements of the dark IV curve of the manufactured GaAs diodes. A comprehensive 3-D description of the occurring phenomena affecting the perimeter recombination is supplied with the help of the model. Finally, the model is applied to concentrator GaAs solar cells to assess the impact of their doping level, size and geometry on the perimeter recombination.

Identification of functional domains on human interleukin 10

Interleukin 10 (IL-10) is a recently described natural endogenous immunosuppressive cytokine that has been identified in human, murine, and other organisms. Human IL-10 (hIL-10) has high homology with murine IL-10 (mIL-10) as well as with an Epstein–Barr virus genome product BCRFI. This viral IL-10 (vIL-10) shares a number of activities with hIL-10. IL-10 significantly affects chemokine biology, because human IL-10 inhibits chemokine production and is a specific chemotactic factor for CD8+ T cells. It suppresses the ability of CD4+ T cells, but not CD8+ T cells, to migrate in response to IL-8. A nonapeptide (IT9302) with complete homology to a sequence of hIL-10 located in the C-terminal portion (residues 152–160) of the cytokine was found to possess activities that mimic some of those of hIL-10. These are: (i) inhibition of IL-1β-induced IL-8 production by peripheral blood mononuclear cell, (ii) inhibition of spontaneous IL-8 production by cultured human monocytes, (iii) induction of IL-1 receptor antagonistic protein production by human monocytes, (iv) induction of chemotactic migration of CD8+ human T lymphocytes in vitro, (v) desensitization of human CD8+ T cells resulting in an unresponsiveness toward rhIL-10-induced chemotaxis, (vi) suppression of the chemotactic response of CD4+ T human lymphocytes toward IL-8, (vii) induction of IL-4 production by cultured normal human CD4+ T cells, (viii) down-regulation of tumor necrosis factor-α production by CD8+ T cells, and (ix) inhibition of class II major histocompatibility complex antigen expression on IFN-γ-stimulated human monocytes. Another nonapeptide (IT9403) close to the NH2-terminal part of hIL-10 did not reveal cytokine synthesis inhibitory properties, but proved to be a regulator of mast cell proliferation. In conclusion, we have identified two functional domains of IL-10 exerting different IL-10 like activities, an observation that suggests that relatively small segments of these signal proteins are responsible for particular biological functions.

Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family

The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells—chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.

Identification of the coding region for a second poly(A) polymerase in Escherichia coli.

We had earlier identified the pcnB locus as the gene for the major Escherichia coli poly(A) polymerase (PAP I). In this report, we describe the disruption and identification of a candidate gene for a second poly(A) polymerase (PAP II) by an experimental strategy which was based on the assumption that the viability of E. coli depends on the presence of either PAP I or PAP II. The coding region thus identified is the open reading frame f310, located at about 87 min on the E. coli chromosome. The following lines of evidence support f310 as the gene for PAP II: (i) the deduced peptide encoded by f310 has a molecular weight of 36,300, similar to the molecular weight of 35,000 estimated by gel filtration of PAP II; (ii) the deduced f310 product is a relatively hydrophobic polypeptide with a pI of 9.4, consistent with the properties of partially purified PAP II; (iii) overexpression of f310 leads to the formation of inclusion bodies whose solubilization and renaturation yields poly(A) polymerase activity that corresponds to a 35-kDa protein as shown by enzyme blotting; and (iv) expression of a f310 fusion construct with hexahistidine at the N-terminus of the coding region allowed purification of a poly(A) polymerase fraction whose major component is a 36-kDa protein. E. coli PAP II has no significant sequence homology either to PAP I or to the viral and eukaryotic poly(A) polymerases, suggesting that the bacterial poly(A) polymerases have evolved independently. An interesting feature of the PAP II sequence is the presence of sets of two paired cysteine and histidine residues that resemble the RNA binding motifs seen in some other proteins.

In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.

To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo. Washed platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the same baboons. Three-color whole blood flow cytometry was used to simultaneously (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2 fluorescence, and (iii) analyze platelet function with mAbs. Two hours after infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2-labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled platelets had become P-selectin-negative. Compared with platelets not activated with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P-selectin-negative platelets was similar 24 h after infusion and only slightly less 48 h after infusion. The loss of platelet surface P-selectin was fully accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets were still able to function in vivo, as determined by their (i) participation in platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platelet-derived microparticles. In summary, (i) circulating degranulated platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function; and (ii) we have developed novel three-color whole blood flow cytometric methods for tracking of platelets and measurement of platelet function in vivo.

DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2 proteins expressed in vivo.

E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at least five closely related genes, E2F-1 through -5. Here we report studies of DP-2, the second member of the DP family of genes. Our results indicate that (i) DP-2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2-related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2-related protein is a novel DP-2 isoform that results from alternative splicing. Thus, we conclude that DP-2 encodes a set of structurally, and perhaps functionally, distinct proteins in vivo.

G protein subunits and the stimulation of phospholipase C by Gs-and Gi-coupled receptors: Lack of receptor selectivity of Galpha(16) and evidence for a synergic interaction between Gbeta gamma and the alpha subunit of a receptor activated G protein.

Stimulatory guanine nucleotide binding protein (Gs)-coupled receptors activated by luteinizing hormone, vasopressin, and the catecholamine isoproterenol (luteinizing hormone receptor, type 2 vasopressin receptor, and types 1 and 2 beta-adrenergic receptors) and the Gi-coupled M2 muscarinic receptor (M2R) were expressed transiently in COS cells, alone and in combination with Gbeta gamma dimers, their corresponding Galphas (Galpha(s), or Galpha(i3)) and either Galpha(q) or Galpha(16). Phospholipase C (PLC) activity, assessed by inositol phosphate production from preincorporated myo[3H]inositol, was then determined to gain insight into differential coupling preferences among receptors and G proteins. The following were observed: (i) All receptors tested were able to stimulate PLC activity in response to agonist occupation. The effect of the M2R was pertussis toxin sensitive. (ii) While, as expected, expression of Galpha(q) facilitated an agonist-induced activation of PLC that varied widely from receptor to receptor (400% with type 2 vasopressin receptor and only 30% with M2R), expression of Galpha(16) facilitated about equally well the activation of PLC by any of the tested receptors and thus showed little if any discrimination for one receptor over another. (iii) Gbeta gamma elevated basal (agonist independent) PLC activity between 2- and 4-fold, confirming the proven ability of Gbeta gamma to stimulate PLCbeta. (iv) Activation of expressed receptors by their respective ligands in cells coexpressing excess Gbeta gamma elicited agonist stimulated PLC activities, which, in the case of the M2R, was not blocked by pertussis toxin (PTX), suggesting mediation by a PTX-insensitive PLC-stimulating Galpha subunit, presumably, but not necessarily, of the Gq family. (v) The effects of Gbeta gamma and the PTX-insensitive Galpha elicited by M2R were synergistic, suggesting the possibility that one or more forms of PLC are under conditional or dual regulation of G protein subunits such that stimulation by one sensitizes to the stimulation by the other.

Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel.

The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of the membrane but block neuronal Na+ channels only from the intracellular side. This difference in extracellular access to QX-314 is retained when rat brain rIIA Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are expressed transiently in tsA-201 cells. Amino acid residues in transmembrane segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have important effects on block by local anesthetic drugs. Although five amino acid residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these amino acid residues by site-directed mutagenesis showed that only conversion of Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of block by extracellular QX-314 and slow the escape of drug from closed channels after use-dependent block. Tetrodotoxin also reduced the rate of block by extracellular QX-314 and slowed escape of bound QX-314 via the extracellular pathway in rH1, indicating that QX-314 must move through the pore to escape. QX-314 binding was inhibited by mutation of Phe-1762 in the local anesthetic receptor site of rH1 to Ala whether the drug was applied extracellularly or intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha subunit that contains Phe-1762, whether it is applied from the extracellular or intracellular side of the membrane. Access to that site from the extracellular side of the pore is determined by the amino acid at position 1755 in the rH1 cardiac Na+ channel.

Aspectos de la poliédrica influencia de los clásicos: nuevas imágenes clave de la influencia de san Vicente Ferrer en Italia

Este artículo analiza la función de la figura de san Vicente Ferrer en la política de afianzamiento y expansión de la Corona de Aragón en la Italia de mediados del siglo XV y hasta el siglo XVIII. San Vicente Ferrer, clásico innegable de la cultura de la Corona de Aragón, ejerció una extraordinaria influencia en el pensamiento, la predicación y la ortodoxia católicas, así como también, en el tablero de ajedrez de la alta política de fines del siglo XIV y principios del XV. Su influencia fue prácticamente ubicua y omnímoda: predicaba a las masas de casi toda Europa occidental, enfervorizadas por sus dotes oratorias y su dominio de las artes de la predicación, al mismo tiempo que ejercía de consejero de máxima confianza de papas, reyes y gobernantes, escribía densos tratados de teología y filosofía moral, y obraba milagros (más de 900 registrados en su Causa de Canonización). Caló muy hondo, también después de su muerte y durante siglos, en toda Italia, que era el gran escenario de la política y de la cultura humanística y del Renacimiento. Ello se aprovechó por parte de la Corona de Aragón para su expansión en Italia, desde la conquista de Nápoles por Alfonso el Magnánimo. Todo ello se analiza en este estudio a partir de obras de arte (capillas, cuadros, retablos, frescos y mosaicos), nunca tenidas en cuenta en este sentido, pero que, como queda demostrado, son muestra y prueba de esa influencia tanto religiosa como también política de la “figura” de este santo valenciano. Se trata en definitiva del análisis de la poliédrica función de los clásicos.

Electrochemical behaviour of different redox probes on single wall carbon nanotube buckypaper-modified electrodes

In the present work, the electrochemical properties of single-walled carbon nanotube buckypapers (BPs) were examined in terms of carbon nanotubes nature and preparation conditions. The performance of the different free-standing single wall carbon nanotube sheets was evaluated via cyclic voltammetry of several redox probes in aqueous electrolyte. Significant differences are observed in the electron transfer kinetics of the buckypaper-modified electrodes for both the outer- and inner-sphere redox systems. These differences can be ascribed to the nature of the carbon nanotubes (nanotube diameter, chirality and aspect ratio), surface oxidation degree and type of functionalities. In the case of dopamine, ferrocene/ferrocenium, and quinone/hydroquinone redox systems the voltammetric response should be thought as a complex contribution of different tips and sidewall domains which act as mediators for the electron transfer between the adsorbate species and the molecules in solution. In the other redox systems only nanotube ends are active sites for the electron transfer. It is also interesting to point out that a higher electroactive surface area not always lead to an improvement in the electron transfer rate of various redox systems. In addition, the current densities produced by the redox reactions studied here are high enough to ensure a proper electrochemical signal, which enables the use of BPs in sensing devices.

[Admittatur of Ephraim Abbott (Harvard AB 1806)], 1802 September 24

Printed copy of an undated abstract of the laws and regulations with the admittatur of undergraduate Ephraim Abbott signed by President Joseph Willard on September 24, 1802.

[Admittatur of Thomas Wigglesworth], 1829 August 24

Printed copy of an undated abstract of laws and regulations with the admittatur of undergraduate Thomas Wigglesworth signed by President Josiah Quincy on August 24, 1829.