Cell volume regulation by Amphiuma red blood cells. The role of Ca+2 as a modulator of alkali metal/H+ exchange.

In response to osmotic perturbation, the Amphiuma red blood cell regulates volume back to "normal" levels. After osmotic swelling, the cells lose K, Cl, and osmotically obliged H2O (regulatory volume decrease [RVD] ). After osmotic shrinkage, cell volume is regulated as a result of Na, Cl, and H2O uptake (regulatory volume increase [RVI] ). As previously shown (Cala, 1980 alpha), ion fluxes responsible for volume regulation are electroneutral, with alkali metal ions obligatorily counter-coupled to H, whereas net Cl flux is in exchange for HCO3. When they were exposed to the Ca ionophore A23187, Amphiuma red blood cells lost K, Cl, and H2O with kinetics (time course) similar to those observed during RVD. In contrast, when cells were osmotically swollen in Ca-free media, net K loss during RVD was inhibited by approximately 60%. A role for Ca in the activation of K/H exchange during RVD was suggested from these experiments, but interpretation was complicated by the fact that an increase in cellular Ca resulted in an increase in the membrane conductance to K (GK). To determine the relative contributions of conductive K flux and K/H exchange to total K flux, electrical studies were performed and the correspondence of net K flux to thermodynamic models for conductive vs. K/H exchange was evaluated. These studies led to the conclusion that although Ca activates both conductive and electroneutral K flux pathways, only the latter pathways contribute significantly to net K flux. On the basis of observations that A23187 did not activate K loss from cells during RVI (when the Na/H exchange was functioning) and that amiloride inhibited K/H exchange by swollen cells only when cells had previously been shrunk in the presence of amiloride, I concluded that Na/H and K/H exchange are mediated by the same membrane transport moiety

Relational Spacetime Ontology

In the aftermath of the rediscovery of Einstein’s hole argument by Earman and Norton (1987), we hear that the ontological relational/substantival debate over the status of spacetime seems to have reached stable grounds. Despite Einstein’s early intention to cast GR’s spacetime as a relational entity à la Leibniz-Mach, most philosophers of science feel comfortable with the now standard sophisticated substantivalist (SS) account of spacetime. Furthermore, most philosophers share the impression that although relational accounts of certain highly restricted models of GR are viable, at a deep down level, they require substantival spacetime structures. SS claims that although manifold spacetime points do not enjoy the sort of robust existence provided by primitive identity, it is still natural to be realistic about the existence of spacetime as an independent entity in its own right. It is argued that since the bare manifold lacks the basic spacetime structures –such as geometry and inertia- one should count as an independent spacetime the couple manifold +metric (M, g). The metric tensor field of GR encodes inertial and metrical structure so, in a way, it plays the explanatory role that Newtonian absolute space played in classical dynamics. In a nutshell, according to the SS account of spacetime, one should view the metric field of GR as the modern version of a realistically constructed spacetime since it has the properties –or contains the structures- that Newtonian space had. I will try to dismantle the widespread impression that a relational account of full GR is implausible. To do so, I will start by highlighting that when turning back to the original Leibniz-Newton dispute one sees that substantivalism turns out prima facie triumphant since Newton was able to successfully formulate dynamics. However, to give relationalism a fair chance, one can also put forward the following hypothetical questions: What if Leibniz –or some leibnizian- had had a good relational theory? What role would geometry play in this type of theory? Would it be natural to view geometry and inertia as intrinsic properties of substantival space –if not spacetime? Would it still seem natural to interpret the metric field of GR along substantival lines regardless of the fact that it also encodes important material properties such as energy-momentum? After bringing these questions out into the light I will cast some important doubts on the substantival (SS) interpretation of the metric field. Perhaps the metric turns out to be viewed as a relational matter field. Finally, to strengthen the relational account of spacetime I expect to remove the possible remaining interpretative tension by briefly discussing the relevance of two important facts: i) Dynamical variables are usually linked to material objects in physical theories. The metric field of GR is a dynamical object so, I claim, it should be viewed as a matter field. ii) Barbour and Bertotti (BB2, 1982) have provided and alternative formulation of classical dynamics. They provide a “genuinely relational interpretation of dynamics” (Pooley & Brown 2001). Geometry and inertia become –contra SS- relational structures in BB2

Activation of electroneutral K flux in Amphiuma red blood cells by N-ethylmaleimide. Distinction between K/H exchange and KCl cotransport.

Exposure of Amphiuma red blood cells to millimolar concentrations of N-ethylmaleimide (NEM) resulted in net K loss. In order to determine whether net K loss was conductive or was by electroneutral K/H exchange or KCl cotransport, studies were performed evaluating K flux in terms of the thermodynamic forces to which K flux by the above pathways should couple. The direction and magnitude of the NEM-induced net K flux did not correspond with the direction and magnitude of the forces relevant to K conductance or electroneutral KCl cotransport. Both the magnitude and direction of the NEM-activated K flux responded to the driving force for K/H exchange. We therefore conclude that NEM-induced K loss, like that by osmotically swollen Amphiuma red blood cells, is by an electroneutral K/H exchanger. In addition to the above studies, we evaluated the kinetic behavior of the volume- and NEM-induced K/H exchange flux pathways in media where Cl was replaced by SCN, NO3, para-aminohippurate (PAH), or gluconate. The anion replacement studies did not permit a distinction between K/H exchange and KCl cotransport, since, depending upon the anion used as a Cl replacement, partial inhibition or stimulation of volume-activated K/H exchange fluxes was observed. In contrast, all anions used were stimulatory to the NEM-induced K loss. Since, on the basis of force-flow analysis, both volume-and NEM-induced K loss are K/H exchange, it was necessary to reevaluate assumptions (i.e., anions serve as substrates and therefore probe the translocation step) associated with the use of anion replacement as a means of flux route identification. When viewed together with the force-flow studies, the Cl replacement studies suggest that anion effects upon K/H exchange are indirect. The different anions appear to alter mechanisms that couple NEM exposure and cell swelling to the activation of K/H exchange, as opposed to exerting direct effects upon K and H translocation

pH regulatory Na/H exchange by Amphiuma red blood cells.

In Amphiuma red blood cells, the Na/H exchanger has been shown to play a central role in the regulation of cell volume following cell shrinkage (Cala, P. M. 1980. Journal of General Physiology. 76:683-708.) The present study was designed to evaluate the existence of pH regulatory Na/H exchange in the Amphiuma red blood cell. The data illustrate that when the intracellular pHi was decreased below the normal value of 7.00, Na/H exchange was activated in proportion to the degree of acidification. Once activated, net Na/H exchange flux persisted until normal intracellular pH (6.9-7.0) was restored, with a half time of approximately 5 min. These observations established a pHi set point of 7.00 for the pH-activated Na/H exchange of Amphiuma red blood cell. This is in contrast to the behavior of osmotically shrunken Amphiuma red blood cells in which no pHi set point could be demonstrated. That is, when activated by cell shrinkage the Na/H exchange mediated net Na flux persisted until normal volume was restored regardless of pHi. In contrast, when activated by cell acidification, the Na/H exchanger functioned until pHi was restored to normal and cell volume appeared to have no effect on pH-activated Na/H exchange. Studies evaluating the kinetic and inferentially, the molecular equivalence of the volume and pHi-induced Amphiuma erythrocyte Na/H exchanger(s), indicated that the apparent Na affinity of the pH activated cells is four times greater than that of shrunken cells. The apparent Vmax is also higher (two times) in the pH activated cells, suggesting the involvement of two distinct populations of the transporter in pH and volume regulation. However, when analyzed in terms of a bisubstrate model, the same data are consistent with the conclusion that both pH and volume regulatory functions are mediated by the same transport protein. Taken together, these data support the conclusion that volume and pH are regulated by the same effector (Na/H exchanger) under the control of as yet unidentified, distinct and cross inhibitory volume and pH sensing mechanisms

Multipoint rational approximants with preassigned poles

20 pages, no figures.-- MSC1991 codes: 41A21, 42C05, 30E10.MR#: MR1820073 (2002i:41021)Zbl#: Zbl 1160.41305Let $\mu$ be a finite positive Borel measure whose support $S(\mu)$ is a compact regular set contained in $\Bbb R$. For a function of Markov type $\hat\mu(z)=\int_{S(\mu)}d\mu(x)/(z-x)$, z\in\Bbb C\sbs S(\mu), we consider multipoint Padé-type approximants (MPTAs), where some poles are preassigned and interpolation is carried out along a table of points contained in \overline{\Bbb C}\sbs {\rm Co}(S(\mu)) which is symmetrical with respect to the real line. The main purpose of this paper is the study of the `exact rate of convergence' of the MPTAs to the function $\hat\mu$.Research by first author (F.C.) partially carried out at the Mathematics Department of Umeå University under Guest Scholarship from the Swedish Institute. Research by second author (G.L.L.) partially supported by Dirección General de Enseñanza Superior under grant PB 96-0120-CO3-01 and by INTAS under grant 93-0219 EXT.Publicad

The information sources of the first Spanish Newspapers (1618-1635): the construction of information credibility

Este trabajo analiza las fuentes de información utilizadas en un corpus numeroso de avisos recogidos en periódicos españoles impresos entre 1618 y 1635. El objetivo de partida es determinar cómo se construye, en términos tanto históricos como retóricos, la credibilidad informativa. Analizaremos la construcción retórica de la credibilidad en el texto mismo de los avisos, concretamente en las fuentes de información que estos declaran u ocultan; para comprobar si existe una intención deliberada de encubrir las fuentes de información, estudiaremos la frecuencia con que aparece la atribución on deep background. La aproximación metodológica que orienta este estudio es la que sostiene el Historical News Discourse, que aplica las conclusiones y métodos de análisis del Análisis Crítico del Discurso a los periódicos del pasado, y contextualiza y explica sus resultados en relación a los planteamientos de la Historia del Periodismo y de la Comunicación (Conboy, Brownlees, Broersma y otros). Defendemos en este trabajo que el análisis del discurso de los primeros impresos informativos resulta fundamental para conocer cómo se consolida en España la profesión periodística, gracias a una nueva forma de auctoritas basada en la competencia discursiva. El gacetero o periodista aparece como una nueva modalidad de escritor, cuya credibilidad y reputación dependen de su capacidad para acceder, organizar y declarar –de acuerdo a patrones retóricos reconocibles para sus lectores– las fuentes de información a las que tiene acceso.This paper analyses the information sources used in a large corpus of news items published in Spanish printed newspapers between 1618 and 1635. The initial aim is to determine how information credibility was constructed in both historical and rhetorical terms. To this end, the rhetorical construction of credibility in the news stories are analysed by focusing on the information sources that these reveal or conceal. And in order to determine whether or not these sources were deliberately concealed, the frequency with which ‘on deep background’ attribution appears is examined. The methodological approach on which this study is based is Historical News Discourse, which applies the conclusions and methods of critical discourse analysis to newspapers of the past, in addition to contextualising and explaining the results in terms of journalism history and communication approaches (Conboy, Brownlees and Broersma, among others). In this work, we contend that the discourse analysis of the first printed newspapers is essential for gaining further insights into how the journalistic profession consolidated its position in Spain thanks to a new form of auctoritas based on discourse competence. The gazetteer or journalist emerged as a new kind of writer, whose credibility and reputation depended on his ability to access, organise and reveal –according to rhetorical patterns recognisable to readers– the information sources available to him

Design and evaluation of a genomics variant analysis pipeline using GATK Spark tools

Scalable and efficient processing of genome sequence data, i.e. for variant discovery, is key to the mainstream adoption of High Throughput technology for disease prevention and for clinical use. Achieving scalability, however, requires a significant effort to enable the parallel execution of the analysis tools that make up the pipelines. This is facilitated by the new Spark versions of the well-known GATK toolkit, which offer a black-box approach by transparently exploiting the underlying Map Reduce architecture. In this paper we report on our experience implementing a standard variant discovery pipeline using GATK 4.0 with Docker-based deployment over a cluster. We provide a preliminary performance analysis, comparing the processing times and cost to those of the new Microsoft Genomics Services

Sustainable Tourism Planning in Small Towns

The Calgary Regional Partnership (CRP) and its Calgary Metropolitan Plan are strongly committed to strengthening local economies in the region. In the fall of 2014, the Town of Irricana expressed interest in being part of a pilot project proposed by CRP to strengthen sustainable tourism strategies and programs in small towns within the Calgary Region. The goal of sustainable tourism is to provide stable, ongoing economic and social benefits to the communities while protecting their natural resources. Since 2008, the Town of Irricana has pursued an economic growth strategy that honours the traditional values of a small town but also provides opportunities for development. The Town’s goals for growth are to (1) manage growth to maintain quality of life; (2) provide for economic growth and local business development, and (3) provide the necessary community services to area residents. Between May 2015 and April 2016, a Tourism Assessment Team (TAT) was engaged in a tourism assessment process in Irricana. The process was design to integrate the perspectives of local residents and businesses with the expert advice and support of resource individuals and organizations active in the regional and provincial tourism industry. Intended to assess the Town’s potential for tourism and its associated benefits, the assessment process included a variety of activities, including but not limited to community meetings, awareness campaigns, workshops, both resident and visitor surveys, as well as the creation of an attractions and facilities inventory list and a community asset map. Thanks to the work of the Tourism Assessment Team along with the CRP facilitator and members of the Resource Group (group of experts) the Town of Irricana is well positioned to execute tangible actions in support of a sustainable tourism plan that will have ongoing economic and social benefits to the community. “We are one step closer to achieving our Vision, to increase tourism that celebrates who we are and enhances our Town through community engagement, increased economic opportunities and promotion.

Il progetto \ue8 stato selezionato in Israele PARCO DELLA MEMORIA. Ancora un successo per gli architetti Lucentini e Cal\ue0, autori del lavoro su \uabPizzolungo\ubb.

Continuano a mietere successi i due architetti siciliani Giovanni Lucentini e Marcello Cal\ue0, dei quali ci siamo occupati su queste stesse pagine la scorsa primavera a proposito del progetto gi\ue0 in fase di cantiere per il parco della memoria di Pizzolungo. Dopo avere vinto il concorso a gennaio, il progetto (al quale hanno partecipatio anche i consulenti Lucia Gitto, paesaggista, e Marcello Ziino, architetto) si \ue8 aggiudicato un World Architecture Community Award ad aprile ed \ue8 stato selezionato, il 23 luglio scorso, dopo una partecipazione ad un bando internazionale dal sito www.bezalel-architecture.com sito ufficiale del dipartimento di architettura (accademia) di Gerusalemme Bezalel considerato la pi\uf9 importante istituzione universitaria culturale israeliana. Il bando di Bezalel prevedeva la selezione di progetti che avevano come tema il reale in Architettura. L'idea dei promotori \ue8 \uabche oggi esista un Architettura del Reale come gi\ue0 da loro studiato ed analizzato nell'arte Ebraica e che tale architettura abbia ormai una portata globale. L'architettura del reale, " secondo il loro giudizio" , per la capacit\ue0 di cogliere i cambiamenti repentini politici e sociali nel mondo oggi permette di dare risposte immediate e qualificanti alle necessit\ue0 che si stanno andando a determinare con i cambiamenti dei sistemi mondiali\ubb. \uabOggi - secondo quanto rilevato in un articolo del gruppo Lg=mC sul numero trimestrale della rivista www.bezalelarchitecture.org sito ufficiale dell'accademia (Universit\ue0) Bezalel di Gerusalemme - il progetto \ue8 una finestra sul mare con un giardino di piante spontanee e l'ombra di un vecchio albero di ulivo. Il giardino \ue8 delimitato da un muro di pietra con gabbioni in metallo contenenti terreno che definiscono la frontiera con un piano inclinato che da chi viene dal mare \ue8 visto come un fronte che si estende tra la terra e il mare, che guarda il cielo e che riprende la sagoma spigolosa delle montagne\ubb. Marcello Cal\ue0 \ue8 nato a San Cataldo (Cl) il 23 giugno del 1979. Le vicende della sua adolescenza ruotano tutte intorno alla musica che coltiva con passione frequentando il Conservatorio di musica in chitarra classica e si dedica anche alla fotografia. Si \ue8 laureato a Palermo dove si laurea con lode nel 2007 con una tesi sull'architettura per la musica. Giovanni Lucentini \ue8 nato a Castelvetrano (Tp) il 7 giugno del 1967. E' approdato agli studi universitari in architettura laureandosi a Palermo nel 1997. Nel 2004 ha vinto il concorso internazionale del Waterfront di Palermo, progetto dove fondamentali sono state le scelte progettuali anche di natura socio-economiche e di pianificazione urbana che risulteranno vincenti e che gli valgono un incarico di consulenza e una partecipazione alla biennale sezione Palermo-Porto