El Conde de Sex (The Earl of Essex) by Antonio Coello y Ochoa - translated and edited with an introduction

This dissertation is concerned with El Conde de Sex by the Spanish dramatist Antonio Coello y Ochoa, An edited text of the play, based on the first edition of 1638, is given alternately with an English prose translation. This is the first time the play has been translated. Explanatory notes on textual, historical, theatrical, and other matters are given in the Commentary. El Conde de Sex is of unusual interest in Anglo-Spanish literary relationships since it portrays Queen Elizabeth I and the Earl of Essex as central figures in a romantic drama. Considering that the play was written within fifty years of the Armada, they are treated with remarkable sympathy. The Introduction attempts a sketch of Coello's life and literary career. Not much is known about him, but Spanish sources have been investigated and early manuscripts of the play have been consulted. An examination of El Conde de Sex in the context of the drama of its time suggests that Coello was concerned primarily to create a theatrically convincing romantic drama rather than to give an accurate picture of life in the English court. No primary sources have been discovered

An item's status in semantic memory determines how it is recognized : dissociable patterns of brain activity observed for famous and unfamiliar faces

This work was supported by a grant from the Biotechnology and Biological Sciences Research Council, United Kingdom (BB/L023644/1).Are all faces recognized in the same way, or does previous experience with a face change how it is retrieved? Previous research using human scalp-recorded Event-Related Potentials (ERPs) demonstrates that recognition memory can produce dissociable brain signals under a variety of circumstances. While many studies have reported dissociations between the putative ‘dual processes’ of familiarity and recollection, a growing number of reports demonstrate that recollection itself may be fractionated into component processes. Many recognition memory studies using lexical materials as stimuli have reported a left parietal ERP old/new effect for recollection; however, when unfamiliar faces are recollected, an anterior effect can be observed. This paper addresses two separate hypotheses concerning the functional significance of the anterior old/new effect: perceptual retrieval and semantic status. The perceptual retrieval view is that the anterior effect reflects reinstatement of perceptual information bound up in an episodic representation, while the semantic status view is that information not represented in semantic memory pre-experimentally elicits the anterior effect instead of the left parietal effect. We tested these two competing accounts by investigating recognition memory for unfamiliar faces and famous faces in two separate experiments, in which same or different pictures of studied faces were presented as test items to permit brain activity associated with retrieving face and perceptual information to be examined independently. The difference in neural activity between same and different picture hits was operationalized as a pattern of activation associated with perceptual retrieval; while the contrast between different picture hits and correct rejection of new faces was assumed to reflect face retrieval. In Experiment 1, using unfamiliar faces, the anterior old/new effect (500–700 ms) was observed for face retrieval but not for perceptual retrieval, challenging the perceptual retrieval hypothesis. In Experiment 2, using famous faces, face retrieval was associated with a left parietal effect (500–700 ms), supporting the semantic representation hypothesis. A between-subjects analysis comparing scalp topography across the two experiments found that the anterior effect observed for unfamiliar faces is dissociable from the left parietal effect found for famous faces. This pattern of results supports the hypothesis thatPublisher PDFPeer reviewe

Finding largest small polygons with GloptiPoly

A small polygon is a convex polygon of unit diameter. We are interested in small polygons which have the largest area for a given number of vertices $n$. Many instances are already solved in the literature, namely for all odd $n$, and for $n=4, 6$ and 8. Thus, for even $n\geq 10$, instances of this problem remain open. Finding those largest small polygons can be formulated as nonconvex quadratic programming problems which can challenge state-of-the-art global optimization algorithms. We show that a recently developed technique for global polynomial optimization, based on a semidefinite programming approach to the generalized problem of moments and implemented in the public-domain Matlab package GloptiPoly, can successfully find largest small polygons for $n=10$ and $n=12$. Therefore this significantly improves existing results in the domain. When coupled with accurate convex conic solvers, GloptiPoly can provide numerical guarantees of global optimality, as well as rigorous guarantees relying on interval arithmetic

Mirror-Descent Methods in Mixed-Integer Convex Optimization

In this paper, we address the problem of minimizing a convex function f over a convex set, with the extra constraint that some variables must be integer. This problem, even when f is a piecewise linear function, is NP-hard. We study an algorithmic approach to this problem, postponing its hardness to the realization of an oracle. If this oracle can be realized in polynomial time, then the problem can be solved in polynomial time as well. For problems with two integer variables, we show that the oracle can be implemented efficiently, that is, in O(ln(B)) approximate minimizations of f over the continuous variables, where B is a known bound on the absolute value of the integer variables.Our algorithm can be adapted to find the second best point of a purely integer convex optimization problem in two dimensions, and more generally its k-th best point. This observation allows us to formulate a finite-time algorithm for mixed-integer convex optimization

The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis

Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2−/− mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis

A novel HIV vaccine adjuvanted by IC31 induces robust and persistent humoral and cellular immunity.

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses

Organ-specific alteration in caspase expression and STK3 proteolysis during the aging process

Caspases and their substrates are key mediators of apoptosis and strongly implicated in various physiological processes. As the serine/threonine kinase family is involved in apoptosis and serine/threonine kinase 3 (STK3) is a recently identified caspase-6 substrate, we assessed the expression and cleavage of STK3 in murine peripheral organs and brain regions during the aging process. We also assessed caspase-3, -6, -7, and -8 expression and activity in order to delineate potential mechanism(s) underlying the generation of the STK3 fragments observed and their relation to the apoptotic pathway. We demonstrate for the first time the cleavage of STK3 by caspase-7 and show that STK3 protein levels globally increase throughout the organism with age. In contrast, caspase-3, -6, -7, and -8 expression and activity vary significantly among the different organs analyzed suggesting differential effects of aging on the apoptotic mechanism and/or nonapoptotic functions of caspases throughout the organism. These results further our understanding of the role of caspases and their substrates in the normal aging process and highlight a potential role for STK3 in neurodegeneration

Cosmological Histories for the New Variables

Histories and measures for quantum cosmology are investigated through a quantization of the Bianchi IX cosmology using path integral techniques. The result, derived in the context of Ashtekar variables, is compared with earlier work. A non-trivial correction to the measure is found, which may dominate the classical potential for universes on the Planck scale.Comment: 14, CGPG-94/2-

Evolution of genomes, host shifts and the geographic spread of SARS-CoV and related coronaviruses

Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS-CoV. There are conflicting reports on the animal reservoir of SARS-CoV. Many of the groups that argue carnivores are the original reservoir of SARS-CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS-CoV. Recently, SARS-CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS-CoV. We evaluated the hypothesis that SARS-CoV isolated from Chiroptera are the original zoonotic source for SARS-CoV by sampling SARS-CoV and non-SARS-CoV from diverse hosts including Chiroptera, carnivores, artiodactyls and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS-CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS-CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS-CoV. There is evidence of subsequent exchange of SARS-CoV between humans and carnivores. In addition SARS-CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS-CoV isolates from Chiroptera are basal to the SARS-CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS-CoV, the structural biology of the spike protein of SARS-CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In SARS-CoV study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS-CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS-CoV.Fil: Janies, Daniel. Ohio State University; Estados UnidosFil: Habib, Farhat. Ohio State University; Estados UnidosFil: Alexandrov, Boyan. Ohio State University; Estados UnidosFil: Hill, Andrew. University of Colorado; Estados UnidosFil: Pol, Diego. Museo Paleontológico Egidio Feruglio; Argentina. Ohio State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin