Loops, Chains, Sheets, and Networks from Variable Coordination of Cu(hfac)(2) with a Flexibly Hinged Aminoxyl Radical Ligand

One pair of reactants, Cu(hfac)(2) = M and the hinge-flexible radical ligand 5-(3-N-tert-butyl-N-aminoxylphenyl)pyrimidine (3PPN = L), yields a diverse set of five coordination complexes: a cyclic loop M(2)L(1) dimer; a 1:1 cocrystal between an M(2)L(2) loop and an ML(2) fragment; a ID chain of M(2)L(2) loops linked by M; two 2D M(3)L(2) networks of (M-L)(n) chains crosslinked by M with different repeat length pitches; a 3D M(3)L(2) network of M(2)L(2) loops cross-linking (M-L)(n)-type chains with connectivity different from those in the 2D networks. Most of the higher dimensional complexes exhibit reversible, temperature-dependent spin-state conversion of high-temperature paramagnetic states to lower magnetic moment states having antiferromagnetic exchange within Cu-ON bonds upon cooling, with accompanying bond contraction. The 3D complex also exhibited antiferromagnetic exchange between Cu(II) ions linked in chains through pyrimidine rings.

Kraftutveckling för manuella trädfällningsredskap : Force development for manual tree felling tools

The objective with this study has been to build general models of the mechanics in tree felling with chain-saw and to compare felling torque for different tools. The theoretical models are completed and validated with a comparative study. The study includes a great number of felling tools of which some are used with different methods. Felling torque was measured using a naturally like measuring arrangement where a tree is cut at about 3.7 m height and then anchored with a dynamometer to a tree opposite to the felling direction. Notch and felling cut was made as ordinary with exception that the hinge was made extra thin to reduce bending resistance. The tree was consequently not felled during the trials and several combinations of felling tools and individuals could be used on the same tree.The results show big differences between tools, methods and persons. The differences were, however, not general, but could vary depending on conditions (first of all tree diameters). Tools and methods that push or pull on the stem are little affected by the size of the tree, while tools that press on the stump are very much dependent of a large stump-diameter. Hand force asserted on a simple pole is consequently a powerful tool on small trees. For trees of medium size there are several alternative methods with different sizes and brands of felling levers and wedges. Larger and more ungainly tools and methods like tree pusher, winch, etc. develop very high felling torque on all tree sizes. On large trees also the felling wedge and especially the use of several wedges together develop very high felling torque.

Generation of mutant leukaemia inhibitory factor (LIF)-IgG heavy chain fusion proteins as bivalent antagonists of LIF

Two leukaemia inhibitory factor (LIF) mutants, designated MH35-BD and LIF05, have been shown to have a capacity to inhibit the biological activities of not only human LIF (hLIF) but also other interleukin-6 (IL-6) subfamily cytokines such as human oncostatin M (hOSM). These cytokines share the same receptor complex in which the glycoprotein 130 (gp130) subunit is a common constituent. However, at low concentrations and in their monomeric forms, such molecules have a relatively short plasma half-life due to rapid clearance from the kidneys. Here, to prolong their serum half-lives, we have used a multi-step polymerase chain reaction (PCR) to fuse each of the LIF05 and MH35-BD cDNA fragments to a sequence encoding the Fc portion, and the hinge region, of the human immunoglobulin G (hIgG) heavy chain. The linking was achieved through an oligomer encoding a thrombin-sensitive peptide linker thus generating MH35-BD:Fc and LIF05:Fc, respectively. Both Fc fusion constructs were expressed in insect cell Sf21 and the proteins were purified by two successive affinity chromatography steps using nickel–nitrilotriacetic acid (Ni–NTA) agarose and protein A beads. The Ba/F3 cell-based proliferation assay was used to confirm that the proteins were biologically active. In addition, preliminary pharmacokinetics indicates that the Fc fusion constructs have a longer serum half-life compared to their non-fusion counterparts.

Polyhedral : recycling boundary ecologies

Foregrounding the extent to which 'place' remains resistant to the politics and poetics of 'network culture', this essay approaches place as a boundary ecology rather than as an instance of cultural invariance. It calls on readers to think about attempts to actively recycle cultural 'debris' or 'waste' through an ethics of passage instead of the kind of instrumentalist statics that prevents the development of an ontology of mobility. Con-tending that such a capacity to inhabit passage is compromised by the eschatological language used to communicate the implications of environmental disaster, as well as by languages of consultation that (con-ceptually) empty place of any creative power to incubate alternatives – events, modes of relation –, the essay stresses the mythopoetic techniques that produce places as knots or nodal points within a network of pas-sage. The designer's task is to create the hinge mechanisms that render such boundary ecologies inhabitable imaginatively, and by materialising the nexus between creativity and change to alter our position vis-a-vis our ethical responsibilities as citizens of a shared biosphere.

Dobras em bainha macroscopicas relacionadas ao cisalhamento ductil de baixo angulo da nappe Araxa-Canastra no sudoeste de Minas Gerais

In the Proterozoic fold-thrust belt of Southwestern Minas Gerais, sheath folds belonging to Araxa-Canastra Group were mapped. These structures are explained by a tangential shear related to nappe transport, which acted together with an additional transcurrent shear, driven by a lateral ramp. An interesting feature recognized in these sheath folds is the striking obliquity between the hinge line of the macro structure and the hinge lines of the parasitic folds in the sheath fold closure. -English summary

Dependência estrutural da capacidade de rotação plástic em vigas de concreto armado

Summary In this work the structural dependence of plastic rotation capacity in RC beams is evaluated using the Finite Element Method. The objective is to achieve a better understanding of the non-linear behavior of reinforced concrete members and perform extensive parameter studies, using a rational model developed by Bigaj [1] to analyze the phenomenon of plastic rotation capacity in reinforced concrete members. It is assumed that only bending failure is relevant due to sufficient member resistance against shear and torsion. The paper begins with the physical and theoretical background of the phenomenon of plastic hinge development in RC structures. Special emphasis is laid on the issue of structural dependence of deformation capacity of plastic hinges in RC members. Member size dependence and influence of properties of construction materials were emphasized as well. The essential components of the Bigajs model for calculating the plastic rotation capacity are discussed. The behaviour of the plastic hinge is analysed taking into account the strain localisation in the damage zones of the hinge region. The Fictitious Crack Model (FCM) and the Compressive Damage Zone Model (CDZ) are adopted in a Fracture Mechanics approach to model the behaviour of concrete in tension and compression, respectively. The approach is implemented in FEMOOP, a FEM in-house solver under development, and applied to evaluate ductility in 2D beams. The models were generated with GiD, a pre-processor and post-processor developed by CIMNE, and analyzed with the capabilities implemented in FEMOOP. © Universitat Politècnica de Catalunya, Barcelona, España 2010.

Caracterização geológica e estrutural da porção centro-norte do greenstone belt de Faina, Faina-GO

The area where the study was conducted is located in the central-western state of Goias. It geologically inserts the northern portion of the Greenstone Belt of Faina which belongs to the Archean terranes that fits in Brasília Fold Belt and Tocantins Structural Province. This region is known for its greenstone lode gold potential and it was heavily exploited by pioneers and prospectors, leaving many records for where they have been through. Preliminary work done by Orinoco Brasil Mineração in their required areas at the region showed that the environment is promising for gold mineralization and that the ore is controlled by structures. Therefore the objectives of this work were the geological and structural mapping in semi detail scale to improve geological, stratigraphic and structural controls present attributing possible ore understanding. With the development of the work there were recognized on the desktop three structural domains separated by a thrust fault. For each domain were discriminated the geological units ranging in gneisses, quartzites formed from coarse sediments arcoseanos, and schists. By mapping structures there were found five deformation phases, Dn-2, Dn-1, the Dn event that generated the main foliation (Sn) in high representation and two post-stages Dn with brittle late manifestations. The detail mapping of the Rattlesnake Gallery showed that the mineralized quartz vein is consistent with axial-plane foliation Sn-2 belonging to the oldest deformation Dn-2 phase and that the high grade is distributed in the hinge region folds of the same phase

PLICATULOSTREA, A NEW GENUS OF PLICATULIDAE (BIVALVIA: PECTINOIDEA) FROM THAILAND

Plicatulostrea onca, a new genus and species of Plicatulidae, is described based on shell and anatomy. The samples were collected under intertidal rocks at Kungkrabaen Bay, Thailand. Plicatulostrea differs from other plicatulids mainly in lacking undulations or shell sculpture, by long projections of the hinge teeth of the right valve and extreme body compression. Plicatulostrea onca has a radially arranged spots at the shell surface and typical plicatulid anatomy, differing mainly by the richness of papillae on the mantle edge and by invasion of the gonad along the mantle lobes. Some comments on the anatomy of the family are also provided.

Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis

Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG(1) was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG(3) was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC- and isothermal titration calorimetry-based assays followed by Hill plots, revealed non-Michaelis-Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG(1) cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin-dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance.

Solution structure and interaction of cupiennin 1a, a spider venom peptide, with phospholipid bilayers

The solution structure of cupiennin 1a, a 35 residue, basic antibacterial peptide isolated from the venom of the spider Cupiennius salei, has been determined by nuclear magnetic resonance (NMR) spectroscopy. The peptide was found to adopt a helix−hinge−helix structure in a membrane mimicking solvent. The hinge may play a role in allowing the amphipathic N-terminal helix and polar C-terminal helix to orient independently upon membrane binding, in order to achieve maximal antibacterial efficacy. Solid-state 31P and 2H NMR was used to further study the effects of cupiennin 1a on the dynamic properties of lipid membranes, using zwitterionic chain deuterated dimyristoylphosphatidylcholine (d54-DMPC) and anionic dimyristoylphosphatidylglycerol (DMPG) multilamellar vesicles. In d54-DMPC alone, cupiennin 1a caused a decrease in the 31P chemical shift anisotropy, indicating some interaction with the lipid head groups, and a decrease in order over the entire acyl chain. In contrast, for the mixed (d54-DMPC/DMPG) lipid system cupiennin 1a appeared to induce lateral separation of the two lipids as evidenced by the 31P spectra, in which the peptide preferentially interacted with DMPG. Little effect was observed on the deuterated acyl chain order parameters in the d54-DMPC/DMPG model membranes. Furthermore, 31P NMR relaxation measurements confirmed a differential effect on the lipid motions depending upon the membrane composition. Therefore, subtle differences are likely in the mechanism by which cupiennin 1a causes membrane lysis in either prokaryotic or eukaryotic cells, and may explain the specific spectrum of activity.

Biochemical characterization of PICK1, a PKC binding protein

Protein kinase C (PKC) is a family of serine-threonine kinases that are activated by a wide variety of hormones, neurotransmitters and growth factors. A single cell type contains multiple isoforms that are translocated to distinct and different subcellular sites upon mitogenic stimulus. Many different cellular responses are attributed to PKC activity though relatively few substrates or binding proteins have been definitively characterized. We used the hinge and catalytic domain of PKC$\alpha$ (PKC7) in a yeast two-hybrid screen to clone proteins that interact with C-kinase (PICKs). One protein which we have termed PICK1 may be involved in PKC$\alpha$-specific function at the level of the nuclear membrane after activation. Binding of PICK1 to PKC$\alpha$ has been shown to be isoform specific as it does not bind to PKC$\beta$II or PKC$\alpha$ in the yeast two-hybrid system. PICK1 mRNA expression level is highest in testis and brain with lower levels of expression in skeletal muscle, heart, kidney, lung and liver. PICK1 protein contains five PKC consensus phosphorylation sites and serves as an in vitro substrate for PKC. The PICK1 protein also contains a P-Loop motif that has been shown to bind ATP or GTP in the Ras family of oncoproteins as well as the G-Protein family. Proteins which bind ATP or GTP using this motif all have some sort of catalytic function although none has been identified for PICK1 as yet. PICK1 contains a DHR/GLGF motif at the N-terminus of the protein. The DHR/GLGF motif is contained in a number of recently described proteins and has been shown to mediate protein-protein interactions at the level of membranes and cytoskeleton. When both PKC$\alpha$ and PICK1 are co-expressed in Cos1 cells the two proteins co-localize to the perinucleus in immunoflouresence studies and co-immunoprecipitate. The binding site for PKC7 has been localized to amino acids 1-358 on PICK1 which contains the DHR/GLGF motif. Binding of PICK1 to PKC$\alpha$ requires the hinge and C-terminal domains of PKC$\alpha$. In vitro, PICK1 binds to PKC$\alpha$ and inhibits its activity as assayed by myelin basic protein phosphorylation. PICK1 also binds to TIS21, a primary response gene that is expressed in response to phorbol ester and growth factor treatment. The Caenorhabditis elegans homologue of PICK1 has been cloned and sequenced revealing a high degree of conservation in the DHR/GLGF motif. A more C-terminal region also shows a high degree of conservation, and the C. elegans PICK1 homologue binds to PKC7 suggesting a conservation of function. Taken together these results suggest that PICK1 may be involved in a PKC$\alpha$-specific function at the level of the nuclear membrane. ^

La imagen de país en cuatro escritores argentinos contemporáneos: L. Lugones, J. L. Borges, J. Cortázar y T.E. Martínez

El propósito del trabajo no deja de ser ambicioso: tratar de recorrer casi un siglo (1910-2002) de un país controvertido, de una historia compleja expresada a través de algunos textos de sus exponentes más representativos. El planteo es sencillo: a comienzos de siglo, en el contexto modernista, Lugones propone una visión altamente positiva, de alabanza y de grandeza. Borges reconoce algunos desaciertos pero pervive fervientemente en él el orgullo de ser argentino y de ser el descendiente de quienes forjaron la patria. En nuestro esquema, este autor constituye el gozne entre la imagen inicial de principios de siglo y la que sobrevendrá después, en la segunda mitad y fines del siglo XX. En efecto, Cortázar y Tomás Eloy Martínez abandonan la mirada positiva y se inscriben en la crítica afanosa, en la desesperanza y el profundo dolor de pertenecer a un país que parece eyectarlos, rechazarlos, enviándolos al extranjero, donde estos escritores producirán lo mejor de su obra. Los textos elegidos son también un pretexto para reflexionar sobre nuestra identidad y nuestra literatura.

Las casualidades controladas : la primera visibilidad del cambio del paradigma moderno

Como no pocos proyectos, el origen de esta tesis es fruto de una casualidad. Hace unos años me topé en Londres, en la librería Walden Books del 38 de Harmood St., con una primera edición de la conocida monografía de Mies a cargo de Philip Johnson. El librito, en realidad catálogo de la exposición que en 1947 el MoMA de Nueva York dedicara a la obra de Mies Van der Rohe a los diez años del desembarco del arquitecto en Estados Unidos, tiene un tamaño de 10 x 7,5 pulgadas, es decir, la mitad del formato americano Crown (20x15 pulgadas), equivalente a 508 x 381 mm. Se imprimieron, en su primera tirada, editada por The Plantin Press, 12.000 ejemplares. Ese mismo año, con edición al cuidado de Reynal y Hitchcock, se publicaría la primera traducción al inglés de Cuando las catedrales eran blancas de Le Corbusier y una selección de poemas de Lorca, siete años después de su Poeta en Nueva York. En la monografía, en la página 109, aparece el conocido croquis de Mies Sketch for a glass house on a hillside. c. 1934, escasamente unas líneas, aunque precisas y llenas de matices, de la casa en una ladera que rápidamente nos remite a aquella primera propuesta de Saarinen para una casa en el aire, primero en 1941 en Pensilvania y después, en 1945, con Charles Eames, en Los Angeles, que nunca llegarían a construirse, sino en su aliteraciones posteriores realizadas por Harry Seidler (Julian Rose House, Wahroonga, Sydney, 1949), Philip Johnson (Leonhardt house, Long Island, Nueva York, 1956) o Craig Ellwood (Smith House, Crestwood Hills, 1958; Frank & Polly Pierson House, Malibú, 1962; Chamorro House, Hollywood Hills, 1963, o la serie Weekend House, con Gerald Horn, entre 1964 y 1970, hasta el magnífico Art Center College of Design de Pasadera, su puente habitado de 1977). El relato que da origen al texto discurre en un estricto período de tiempo, desde los primeros dibujos de la Case Study House nº8, dentro del programa promovido por John Entenza y su revista Arts & Architecture en California, realizados en el estudio de Saarinen en Bloomfield Hills, Michigan, hasta que el proyecto de la casa Eames finaliza cinco años después de acabar la obra en 1955, en la versión conocida, radicalmente distinta al proyecto original, cuando la pareja Charles y Ray Eames edita el corto House After Five Years of Living. La discusión original en torno a esta casita, o mejor, a las circunstancias, casualidades controladas, que rodean su construcción, se produce estrictamente cuando rastreamos aquellos invariantes que se mantienen en las dos versiones y las reconcilian. En este corto período de tiempo se producen en el proyecto una serie de decisiones que permiten descubrir, tanto en la forma como en el mismo proceso transformador del proyecto, en su obsesivo registro, en los nuevos referentes asumidos y propuestos, la primera visibilidad del cambio del paradigma moderno. Pero este momento germinal que cristaliza el paso a la postmodernidad no es inédito en la historia de la arquitectura americana. Así, el relato abre su ámbito temporal hasta un nuevo período de cincuenta años que arranca en 1893, año de la celebración en Chicago de la Exposición Internacional Colombina. En la White City de Hunt & McKim y del traidor Burham, Louis Sullivan construye su Golden Doorway en el pabellón de los Transportes. Aquella que visitará Adolf Loos antes de volver, renovado, a Viena; la misma que admirará André Bouillet, representante de la Union Centrale des Arts Decoratifs de Paris, y que deslumbrará en los museos de toda Europa, de París a Moscú en grandes fotografías y maquetas. Hasta que en Finlandia alguien muestra una de esas fotografías a un joven estudiante de diecinueve años en el Instituto Politécnico. Eliel Saarinen queda fascinado por la poderosa novedad de la imagen. Cuelga la fotografía frente a su tablero de dibujo, consciente de que la Golden Doorway, esa puerta de la aventura y la catarsis que Sullivan acuñaría como distintivo y que resolvería como único elemento complejo sus proyectos más maduros, desprovistos de todo ornamento; la misma que repetirían más tarde, con profundo reconocimiento, Ladovsky, Wright, Scarpa o Moneo, puerta dentro de puerta, fuelle y umbral, contenía, en sus propias palabras emocionadas, todo el futuro de la arquitectura. Desde ahí, pasando por el año 1910, momento de la huida de Wright a La Toscana y el descubrimiento de su arquitectura en Europa, entre otros por un joven Mies van der Rohe, meritorio en el estudio de Peter Behrens, a través del Wasmuth Portfolio; y así como algo después, en 1914, Schindler y en 1923 Neutra, harán el camino inverso, hasta que Mies les siga en 1937, animado por un Philip Johnson que había viajado a Europa en 1930, volviendo a 1945 y el inicio del programa Case Study House en California, hasta 1949, momento de la construcción de la CSH#8, y, por fin, al año 1955, after 5 years of living, en el que Julius Shulman fotografía la casa de Ray y Charles Eames en el prado de Chautauqua sobre las Pacific Palisades de Los Angeles, lanzando sus finas líneas amarillas hasta Alison y Peter Smithson y su tardomoderno heroico, hasta el primer Foster y su poético hightech y hasta el O-riginal Ghery, deconstruyendo el espacio esencial de su casa desde el espacio mismo, abiertas ya las puertas al nuevo siglo. Y en estos cambios de paradigma, desde el rígido eclecticismo de los estilos al lirismo moderno en el gozne secular y de ahí a la frivolidad, ligereza, exhibicionismo y oportunismo cultos del hecho postmoderno, hay algo que se mantiene invariante en los bandazos de la relación del hombre contemporáneo con su entorno. Como la escultura, que según Barnett Newman no es sino aquello contra lo que uno choca cuando retrocede para mirar un cuadro, en estos prístinos lugares, comunes y corrientes, recorrido, puerta, umbral, recinto y vacío, te topas con la arquitectura antes de darte cuenta de que es arquitectura. ABSTRACT As with many other projects, the origin of this doctoral thesis is the result of a chance. A few years ago I found in a bookstore in London, 38 Harmood st., Walden Books, a first edition of the well-known monograph about Mies by Philip Johnson. The tiny book, in fact a catalog of the exhibition that the MoMA of New York devoted to the work of Mies van der Rohe in 1947, ten years after his landing in the United States, has a size of 10 x 7.5 inches, that is, half of Crown American format (20 x 15 inches), equivalent to 508 x 381 mm. In the first printing, published by The Plantin Press, 12,000 copies were released. That same year, produced by Reynal and Hitchcock, both the first English translation of When the cathedrals were white by Le Corbusier and a selection of poems by Lorca were published, seven years after his Poet in New York. Inside the book, the famous drawing from Mies Sketch for a glass house on a hillside c. 1934 appears on page 109, barely a few lines, precise and nuanced though, the house on a hillside that quickly reminds us of the proposals of Eero Saarinen for a house in the air, first in 1941, in Pennsylvania, and later, in 1945, with Charles Eames, in Los Angeles, that would never be built, but in their later alliterations made by Harry Seidler (Julian Rose House, Wahroonga, Sydney, 1949), Philip Johnson (Leonhardt house, Long Island, New York, 1956) or Craig Ellwood (Smith House, Crestwood Hills, 1958; Frank Pierson & Polly House, Malibu, 1962, Chamorro House, Hollywood Hills, 1963, or the Weekend House series, with Gerald Horn, between 1964 and 1970, to the magnificent Art Center College of Design Pasadena, the inhabited bridge, in 1977). The story that gives rise to the text flows in a short amount of time, from the first drawings of the Case Study House No. 8, within the program promoted by John Entenza and his magazine Arts & Architecture in California, made in the study of Saarinen in Bloomfield Hills, Michigan, until the project of the Eames house is completed five years after finishing the construction in 1955, in the final version we know, radically different from the initial state, when the couple, Charles and Ray, published the film House after Five Years of Living. The original discussion around this house, or better, about the circumstances, controlled coincidences, regarding its construction, appears when one takes account of those that remain, the invariants, in the two versions, drawn and built, which precisely allow the reconciliation between both projects. In this short period of time a series of decisions made in the transformation process of the project reveal, in the obsessive record made by Charles Eames and in the new proposed references, the first visibility of the changing of the modern paradigm. But this germinal moment that crystallizes the transition to postmodernism is not unprecedented in the history of American architecture. So, the story opens its temporal scope to a fifty-year period that started in 1893, date of the celebration of the Chicago World´s Columbian Exposition. In the White City by Hunt & McKim and Burnham, the traitor, Louis Sullivan builds his Golden Doorway in the Transportation Building. That visited by a renovated Adolf Loos before his coming back to Vienna; the same that André Bouillet, Head of the Union Centrale des Arts Decoratifs in Paris, admired and dazzled in museums all over Europe, from Paris to Moscow, in large photographs and models. Until someone in Finland showed one of those photos to a young nineteen-years-old student at the Polytechnic Institute. Eliel Saarinen became fascinated by the powerful new image: he hanged the picture in front of his drawing board, aware that the Golden Doorway, that door of adventure and catharsis Sullivan coined as distinctive and as a single complex element which would solve their most mature projects, devoid of all ornament; the same that would repeat later, with deep appreciation, Ladovsky, Wright, Scarpa, or Moneo, a door inside a door, a threshold, a gap that contained, in its own moving words, the whole future of architecture. From there, through 1910, when Wright's flight to Tuscany allows Europe to discover his architecture, including a young Mies van der Rohe, meritorious in the studio of Peter Behrens, via the Wasmuth Portfolio; and as a little bit later, in 1914, Schindler and Neutra in 1923, made the travel in opposite direction, until Mies follows them in 1937, led by a Philip Johnson who had traveled to Europe in 1930, we return to 1945 and the beginning of the program Case Study House in California, and from 1949, when construction of the CSH # 8 begins, and finally, to 1955, after five years of living, when Julius Shulman photographs the inside of the house with Ray and Charles Eames, and all their belongins, at the Chautauqua meadows on Pacific Palisades in Los Angeles, launching its fine yellow lines to Alison and Peter Smithson and his heroic late modern, up to the first Foster and his poetic hightech and even the O-riginal Gehry, deconstructing the essential space of his home from the space itself, opening the doors to the new century. And these paradigm shifts, from the hard eclectic styles to modern secular lyricism in the hinge and then overcoming the cultured frivolity, lightness, exhibitionism, and opportunism of the postmodern skeptical focus, something remains intense, invariant in the lurching relationship of contemporary man and his environment. As the sculpture, which according to Barnett Newman is what you bump into when you back up to see a painting, in these pristine, ordinary places, promenade, door, threshold, enclosure and emptiness, you stumble upon the architecture even before realizing that it is architecture.

Nucleolar Localization Elements of Xenopus laevis U3 Small Nucleolar RNA

The Nucleolar Localization Elements (NoLEs) of Xenopus laevis U3 small nucleolar RNA (snoRNA) have been defined. Fluorescein-labeled wild-type U3 snoRNA injected into Xenopus oocyte nuclei localized specifically to nucleoli as shown by fluorescence microscopy. Injection of mutated U3 snoRNA revealed that the 5′ region containing Boxes A and A′, known to be important for rRNA processing, is not essential for nucleolar localization. Nucleolar localization of U3 snoRNA was independent of the presence and nature of the 5′ cap and the terminal stem. In contrast, Boxes C and D, common to the Box C/D snoRNA family, are critical elements for U3 localization. Mutation of the hinge region, Box B, or Box C′ led to reduced U3 nucleolar localization. Results of competition experiments suggested that Boxes C and D act in a cooperative manner. It is proposed that Box B facilitates U3 snoRNA nucleolar localization by the primary NoLEs (Boxes C and D), with the hinge region of U3 subsequently base pairing to the external transcribed spacer of pre-rRNA, thus positioning U3 snoRNA for its roles in rRNA processing.

Molecular determinants of tissue selectivity in estrogen receptor modulators

Interaction of the estrogen receptor/ligand complex with a DNA estrogen response element is known to regulate gene transcription. In turn, specific conformations of the receptor-ligand complex have been postulated to influence unique subsets of estrogen-responsive genes resulting in differential modulation and, ultimately, tissue-selective outcomes. The estrogen receptor ligands raloxifene and tamoxifen have demonstrated such tissue-specific estrogen agonist/antagonist effects. Both agents antagonize the effects of estrogen on mammary tissue while mimicking the actions of estrogen on bone. However, tamoxifen induces significant stimulation of uterine tissue whereas raloxifene does not. We postulate that structural differences between raloxifene and tamoxifen may influence the conformations of their respective receptor/ligand complexes, thereby affecting which estrogen-responsive genes are modulated in various tissues. These structural differences are 4-fold: (A) the presence of phenolic hydroxyls, (B) different substituents on the basic amine, (C) incorporation of the stilbene moiety into a cyclic benzothiophene framework, and (D) the imposition of a carbonyl “hinge” between the basic amine-containing side chain and the olefin. A series of raloxifene analogs that separately exemplify each of these differences have been prepared and evaluated in a series of in vitro and in vivo assays. This strategy has resulted in the development of a pharmacophore model that attributes the differences in effects on the uterus between raloxifene and tamoxifen to a low-energy conformational preference imparting an orthogonal orientation of the basic side chain with respect to the stilbene plane. This three-dimensional array is dictated by a single carbon atom in the hinge region of raloxifene. These data indicate that differences in tissue selective actions among benzothiophene and triarylethylene estrogen receptor modulators can be ascribed to discrete ligand conformations.