The deep mycoses in HIV infection

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.).

Road to 1966 : caminos hacia "complejidad y contradicción en la arquitectura", en la cultura arquitectónica de la segunda posguerra en EE.UU

Complejidad y contradicción en la arquitectura ha resultado ser una de las referencias capitales más aludidas, citadas y reproducidas de la literatura arquitectónica de los tiempos recientes. No en vano, en la introducción de la propia obra, Vincent Scully afirmó que «probablemente es el texto más importante sobre arquitectura desde ‘Vers une Architecture’, escrito por Le Corbusier en 1923». Sin embargo, sus fuentes parece que están inexploradas o, al menos, no examinadas. Por ello, Road to 1966 se plantea como un trabajo de investigación con tres objetivos de partida fundamentales: (1) el interés en estudiar el debate arquitectónico candente, creado con las fricciones surgidas entre los protagonistas de unos años que cambiaron el estado de lo que se consideraba una obra legítima en arquitectura; (2) se pretende ampliar la cronología del desarrollo intelectual de un texto, el de Venturi, que marcó la segunda mitad del siglo xx, de manera retroactiva hasta los años de la II Guerra Mundial, cuando parece que empezaban a ser coherentes y reconocibles unas nuevas posiciones desde las que aproximarse a las cuestiones de la práctica, la teoría y la historia de la arquitectura; (3) poder ofrecer una nueva interpretación de dicho texto de Venturi, entendido no como el origen primigenio de parte de las grandes transformaciones de la arquitectura reciente (de los últimos cincuenta años), sino como el resultado necesario de esa cronología intelectual previa. La arquitectura norteamericana de estos años de posguerra ha resultado ser crucial en su posterior desarrollo, y, especialmente, en relación al libro de Venturi. De hecho, Scully en la introducción de la edición original de Complejidad y contradicción, señalaba que «el principal argumento del libro está expuesto a finales de los cincuenta». Que la arquitectura del siglo xx tiene en la Norteamérica de los años sesenta -cuando se consolida la figura de Venturi- uno de sus capítulos más decisivos, frecuentemente asumido como el paso siguiente a la importada modernidad heroica europea, hoy parece no ser discutido por casi nadie. Ahora bien: ¿qué ocurre con los años intermedios? ¿Qué acontece entre el final de la II Guerra Mundial y esos años sesenta? La posible carencia de una postura dominante y clara quizás haya sumido esta etapa en un cierto olvido o descuido por parte de historiadores y críticos. Así, este trabajo se estructura alrededor del papel que ocupa el texto venturiano, sin ser éste su único protagonista. Tomado más bien como excusa, la tesis va profundizando de manera deductiva en el conjunto de circunstancias que pudieron llevar a su autor hacia las conclusiones que desarrolló, detectando los ambientes biográficos y formativos, pensamientos compartidos e influencias epistemológicas y profesionales mutuas, que justificarían una novedosa interpretación de dicho texto como el corolario necesario de un panorama de crisis y cambios - éste sí protagonista en este trabajo-, al contrario de cómo habitualmente se ha venido entendiendo dicha obra. La investigación se centra predominantemente en el rastreo de las fuentes citadas por el propio Venturi en su libro, así como de los textos de mayor difusión (generalmente revistas profesionales no exclusivamente académicas, además de libros, catálogos de exposiciones, actas de simposios…), y no tanto en las obras construidas o proyectadas; sí, quizás, en los términos en los que dichas obras fueron publicadas, comentadas o reseñadas. Así, se ha adoptado una aproximación concebida sub specie bibliotecae, donde se han aplicado unos métodos de trabajo caracterizados por su componente cronológica, y, después, analítico-comparativa: dicho de otro modo, un método historiográfico-periodístico capaz de relacionar las historias o cursos de ciertas ideas o nociones, dentro de un contexto general más amplio en sus derivadas arquitectónicas, estéticas, socio-generacionales, culturales, filosóficas, científicas, políticas, literarias… Con ello, se pretende establecer una relectura del primer libro de Venturi y sus años de gestación desde unas nuevas concepciones, más modernas que postmodern(ist)as, proponiendo una posible evolución en la arquitectura más reciente cuyas raíces, a fin de cuentas, tendrían su origen en la Norteamérica de 1946 a 1966. ABSTRACT Complexity and Contradiction in Architecture has proved to be one of the capital, alluded references cited and reproduced in the architectural literature of the recent times. Not surprisingly, in the Introduction to the book, Vincent Scully wrote that "yet it is probably the most important writing on the making of architecture since Le Corbusier´s ‘Vers une Architecture’, of 1923". However, its sources seem to be unexplored or at least not examined. Therefore, Road to 1966 is presented as a research with three fundamental starting objectives: (1) first, the interest in studying the burning architectural debate, created within the arising frictions among the protagonists of the years that changed the status of what was considered a legitimate work in architecture; (2) second, it seeks to extend the chronology of the intellectual background of the book written by Venturi, which marked the second half of the twentieth century, in a retroactive manner to the years of the World War II, when it seems that some new positions from which to approach the issues of practice, theory and history of architecture began to be consistent and recognizable; (3) lastly, to offer a new interpretation of Venturi’s text, now understood not as the primal source of the great transformations of the recent architecture (of the last fifty years), but as the necessary result of that background intellectual chronology. The American architecture of these post-war years has proved to be crucial in its later stages, and especially in relation to the book of Robert Venturi. In fact, Scully in the Introduction to the first edition of Complexity and Contradiction, noted that "the major argument of this book was laid out in the late fifties". The fact that the architecture of the twentieth century –when the leading figure of Venturi was consolidated- has in the North America of the sixties one of its most decisive chapters, (often assumed as the next step to the imported European heroic modernism) today seems to be discussed by almost anyone. Now, what about the intervening years? What happens between the end of the World War II and the sixties? The potential lack of a clear dominant position of this stage may have plunged it into oblivion or oversight by historians and critics. Thus, this research is structured around the role that occupies Venturi’s work, whereas this is not its only subject. Rather taken as an excuse, the thesis deepens deductively in the set of circumstances that could lead its author to the conclusions he developed in 1966, detecting biographical and academic environments, shared thoughts and epistemological and mutual professional influences, that would justify a new interpretation of this book as a necessary corollary of an outlook of crisis and change (this major and center subject in this dissertation), contrary to what has been commonly understood upon this work. The research focuses predominantly on tracing the sources cited by Venturi himself in his book, as well as other texts of wider dissemination and outreach (usually professional journals not exclusively academic, as well as books, catalogs of exhibitions, symposia proceedings...), and not so much in the buildings or unbuilt projects; but also, perhaps, it is focused in the terms in which these works were published, commented or reviewed. Hence an approach conceived sub specie bibliotecae has been adopted, with working methods characterized by their chronological component, and then the analytical-comparative one: in other words, a historiographicaljournalistic method able to relate stories or courses of certain ideas or notions, within a broader general context in its architectural, aesthetic, sociological-generational, cultural, philosophical, scientific, political, literary... sides. This approach intends to establish a re-reading of Venturi’s first book and its years of gestation, from some new understandings, more modern than postmodern(ist), proposing a possible evolution of the latest architecture whose roots, after all, would have their origin in the North America of 1946-1966.

Rapid transition in the structure of a coral reef community: The effects of coral bleaching and physical disturbance

Coral reef communities are in a state of change throughout their geographical range. Factors contributing to this change include bleaching (the loss of algal symbionts), storm damage, disease, and increasing abundance of macroalgae. An additional factor for Caribbean reefs is the aftereffects of the epizootic that reduced the abundance of the herbivorous sea urchin, Diadema antillarum. Although coral reef communities have undergone phase shifts, there are few studies that document the details of such transitions. We report the results of a 40-month study that documents changes in a Caribbean reef community affected by bleaching, hurricane damage, and an increasing abundance of macroalgae. The study site was in a relatively pristine area of the reef surrounding the island of San Salvador in the Bahamas. Ten transects were sampled every 3–9 months from November 1994 to February 1998. During this period, the corals experienced a massive bleaching event resulting in a significant decline in coral abundance. Algae, especially macroalgae, increased in abundance until they effectively dominated the substrate. The direct impact of Hurricane Lili in October 1996 did not alter the developing community structure and may have facilitated increasing algal abundance. The results of this study document the rapid transition of this reef community from one in which corals and algae were codominant to a community dominated by macroalgae. The relatively brief time period required for this transition illustrates the dynamic nature of reef communities.

RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism

We have generated RANK (receptor activator of NF-κB) nullizygous mice to determine the molecular genetic interactions between osteoprotegerin, osteoprotegerin ligand, and RANK during bone resorption and remodeling processes. RANK−/− mice lack osteoclasts and have a profound defect in bone resorption and remodeling and in the development of the cartilaginous growth plates of endochondral bone. The osteopetrosis observed in these mice can be reversed by transplantation of bone marrow from rag1−/− (recombinase activating gene 1) mice, indicating that RANK−/− mice have an intrinsic defect in osteoclast function. Calciotropic hormones and proresorptive cytokines that are known to induce bone resorption in mice and human were administered to RANK−/− mice without inducing hypercalcemia, although tumor necrosis factor α treatment leads to the rare appearance of osteoclast-like cells near the site of injection. Osteoclastogenesis can be initiated in RANK−/− mice by transfer of the RANK cDNA back into hematopoietic precursors, suggesting a means to critically evaluate RANK structural features required for bone resorption. Together these data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.

The nuclear hormone receptor coactivator SRC-1 is a specific target of p300.

p300 and its family member, CREB-binding protein (CBP), function as key transcriptional coactivators by virtue of their interaction with the activated forms of certain transcription factors. In a search for additional cellular targets of p300/CBP, a protein-protein cloning strategy, surprisingly identified SRC-1, a coactivator involved in nuclear hormone receptor transcriptional activity, as a p300/CBP interactive protein. p300 and SRC-1 interact, specifically, in vitro and they also form complexes in vivo. Moreover, we show that SRC-1 encodes a new member of the basic helix-loop-helix-PAS domain family and that it physically interacts with the retinoic acid receptor in response to hormone binding. Together, these results implicate p300 as a component of the retinoic acid signaling pathway, operating, in part, through specific interaction with a nuclear hormone receptor coactivator, SRC-1.

G1 arrest and down-regulation of cyclin E/cyclin-dependent kinase 2 by the protein kinase inhibitor staurosporine are dependent on the retinoblastoma protein in the bladder carcinoma cell line 5637.

The protein kinase inhibitor staurosporine has been shown to induce G1 phase arrest in normal cells but not in most transformed cells. Staurosporine did not induce G1 phase arrest in the bladder carcinoma cell line 5637 that lacks a functional retinoblastoma protein (pRB-). However, when infected with a pRB-expressing retrovirus [Goodrich, D. W., Chen, Y., Scully, P. & Lee, W.-H. (1992) Cancer Res. 52, 1968-1973], these cells, now pRB+, were arrested by staurosporine in G1 phase. This arrest was accompanied by the accumulation of hypophosphorylated pRB. In both the pRB+ and pRB- cells, cyclin D1-associated kinase activities were reduced on staurosporine treatment. In contrast, cyclin-dependent kinase (CDK) 2 and cyclin E/CDK2 activities were inhibited only in pRB+ cells. Staurosporine treatment did not cause reductions in the protein levels of CDK4, cyclin D1, CDK2, or cyclin E. The CDK inhibitor proteins p21(Waf1/Cip1) and p27 (Kip1) levels increased in staurosporine-treated cells. Immunoprecipitation of CDK2, cyclin E, and p2l from staurosporine-treated pRB+ cells revealed a 2.5- to 3-fold higher ratio of p2l bound to CDK2 compared with staurosporine-treated pRB- cells. In pRB+ cells, p2l was preferentially associated with Thrl6O phosphorylated active CDK2. In pRB- cells, however, p2l was bound preferentially to the unphosphorylated, inactive form of CDK2 even though the phosphorylated form was abundant. This is the first evidence suggesting that G1 arrest by 4 nM staurosporine is dependent on a functional pRB protein. Cell cycle arrest at the pRB- dependent checkpoint may prevent activation of cyclin E/CDK2 by stabilizing its interaction with inhibitor proteins p2l and p27.

1912 University of Michigan Baseball Team

Top Row: Leo? Kenyon, student mngr. Earl Good, ? Warehin, Thomas Wheat, Roy Baribeau

3rd Row:Francis Scully, Donald Duncanson, captain Elmer D Mitchell, coach Branch Rickey, Cecil Corbin, Goodloe Rogers, Charles Hippler, ? Ward

2nd Row:Francis Scully, Donald Duncanson, captain Elmer D Mitchell, coach Branch Rickey, Cecil Corbin, Goodloe Rogers, Charles Hippler, ? Ward

Front Row: ? Creamer (mascot), Emery Munson

Stories by English authors.

The mystery of Sasassa Valley / by A. Conan Doyle -- Long odds / by H. Rider Haggard -- King Bemba's Point / by J. Landers -- Ghamba / by W. C. Scully -- Mary Musgrave / Anonymous -- Gregorio / by Percy Hemingway.

By Veldt and Kopje /

A novel.

The white hecatomb, and other stories /

The white hecatomb -- The vengeance of the Dogolwana -- Gquma, or, The white waif -- The tramp's tragedy -- The seed of the church -- Little Tobè -- The Imishologu -- The madness of Gweva -- The love charm -- Derelicts -- The return of Sobèdè -- The quick and the dead -- Aiala.

Memorials of the old Chicago library, formerly Young men's association, and of the advent of the new.

Mode of access: Internet.

A statement of the penal laws, which aggrieve the Catholics of Ireland: with commentaries. In two parts.

The table of contents of pt. 1 is for another edition, with xviii, xii, [13]-148 p.

1912 University of Michigan Baseball Team

Top Row: Ath. Dir. Phillip Bartelme, Perry Howard, Robert Snadjr, Miller Pontius Emery Monson, Roy Baribeau, coach Branch Rickey,

Middle Row: Francis Scully, Howard Smith, Goodloe Rogers, captain Elmer D. Mitchell, Joseph Bell, Cecil Corbin, student mngr Earl Good

Front Row: John Lavans, Edmund Blackmore, Donald Duncanson