Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1 beta in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n = 27) and GBM (n = 28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.7% and p < 0.0001. The high abundance of C-reactive protein (CRP) in GBM sera was confirmed in 264 independent samples. High levels of CRP protein was seen in GBM but without a change in transcript levels suggesting a non-tumoral origin. Glioma-secreted Interleukin 6 (IL6) was found to induce hepatocytes to secrete CRP, involving JAK-STAT pathway. The culture supernatant from CRP-treated microglial cells induced endothelial cell survival under nutrient-deprivation condition involving CRP-Fc gamma RIII signaling cascade. Transcript profiling of CRP-treated microglial cells identified Interleukin 1 beta (IL1 beta) present in the microglial secretome as the key mediator of CRP-induced endothelial cell survival. IL1 beta neutralization by antibody-binding or siRNA-mediated silencing in microglial cells reduced the ability of the supernatant from CRP-treated microglial cells to induce endothelial cell survival. Thus our study identifies a serum based three-marker panel for GBM diagnosis and provides leads for developing targeted therapies. Biological significance A complex antibody microarray based serum marker profiling identified a three-marker panel - LYAM1, BHE40 and CRP as an accurate discriminator of glioblastoma sera from that of healthy individuals. CRP protein is seen in high levels without a concomitant increase of CRP transcripts in glioblastoma. Glioma-secreted IL6 induced hepatocytes to produce CRP in a JAK-STAT signaling dependent manner. CRP induced microglial cells to release IL1 beta which in turn promoted endothelial cell survival. This study, besides defining a serum panel for glioblastoma discrimination, identified IL1 beta as a potential candidate for developing targeted therapy. (C) 2015 Elsevier B.V. All rights reserved.

Divining for meaning and searching for a female literary identity in Alice Munros Lives of girls and women and Margaret Laurences The diviners

Esta dissertação tem por objetivo investigar como Alice Munro e Margaret Laurence se apropriam de gêneros canônicos, especificamente do Bildungsroman e do Künstlerroman, para subvertê-los e representar versões diferentes do sujeito feminino através de romances de cunho autobiográfico escritos por mulheres. A investigação é focada em dois romances: Lives of Girls and Women (1971), escrito por Alice Munro, e The Diviners (1974), escrito por Margaret Laurence. No romance de Alice Munro, as estratégias de apagamento das fronteiras entre gêneros, a ideia de que perspectivas de realidade mudam de acordo com a experiência e a memória de cada indivíduo, como também a ênfase no desenvolvimento da protagonista enquanto pessoa e escritora, são assuntos amplamente discutidos. No romance de Margaret Laurence, a ênfase no aspecto subjetivo da memória, a desconstrução de estereótipos de gênero e a renegociação da representação do sujeito feminino para o alcance de uma identidade feminina autônoma na vida e na arte são os principais assuntos investigados. Em vista disso, esta dissertação visa mostrar como a representação da identidade feminina é redefinida por duas escritoras canadenses que se apropriaram de discursos dominantes para subvertê-los e, então, reescreverem suas histórias

Pacific Salmon, Oncorhynchus spp., and the Definition of "Species" Under the Endangered Species Act

For purposes ofthe Endangered Species Act (ESA), a "species" is defined to include "any distinct population segment of any species of vertebrate fish or wildlife which interbreeds when mature. "Federal agencies charged with carrying out the provisions of the ESA have struggled for over a decade to develop a consistent approach for interpreting the term "distinct population segment." This paper outlines such an approach and explains in some detail how it can be applied to ESA evaluations of anadromous Pacific salmonids. The following definition is proposed: A population (or group of populations) will be considered "distinct" (and hence a "species ")for purposes of the ESA if it represents an evolutionarily significant unit (ESU) of the biological species. A population must satisfy two criteria to be considered an ESU: 1) It must be substantially reproductively isolated from other conspecific population units, and 2) It must represent an important component in the evolutionary legacy of the species. Isolation does not have to be absolute, but it must be strong enough to permit evolutionarily important differences to accrue in different population units. The second criterion would be met if the population contributes substantially to the ecological/genetic diversity of the species as a whole. Insights into the extent of reproductive isolation can be provided by movements of tagged fish, natural recolonization rates observed in other populations, measurements of genetic differences between populations, and evaluations of the efficacy of natural barriers. Each of these methods has its limitations. Identification of physical barriers to genetic exchange can help define the geographic extent of distinct populations, but reliance on physical features alone can be misleading in the absence of supporting biological information. Physical tags provide information about the movements of individual fish but not the genetic consequences of migration. Furthermore, measurements ofc urrent straying or recolonization rates provide no direct information about the magnitude or consistency of such rates in the past. In this respect, data from protein electrophoresis or DNA analyses can be very useful because they reflect levels of gene flow that have occurred over evolutionary time scales. The best strategy is to use all available lines of evidence for or against reproductive isolation, recognizing the limitations of each and taking advantage of the often complementary nature of the different types of information. If available evidence indicates significant reproductive isolation, the next step is to determine whether the population in question is of substantial ecological/genetic importance to the species as a whole. In other words, if the population became extinct, would this event represent a significant loss to the ecological/genetic diversity of thes pecies? In making this determination, the following questions are relevant: 1) Is the population genetically distinct from other conspecific populations? 2) Does the population occupy unusual or distinctive habitat? 3) Does the population show evidence of unusual or distinctive adaptation to its environment? Several types of information are useful in addressing these questions. Again, the strengths and limitations of each should be kept in mind in making the evaluation. Phenotypic/life-history traits such as size, fecundity, and age and time of spawning may reflect local adaptations of evolutionary importance, but interpretation of these traits is complicated by their sensitivity to environmental conditions. Data from protein electrophoresis or DNA analyses provide valuable insight into theprocessofgenetic differentiation among populations but little direct information regarding the extent of adaptive genetic differences. Habitat differences suggest the possibility for local adaptations but do not prove that such adaptations exist. The framework suggested here provides a focal point for accomplishing the majorgoal of the Act-to conserve the genetic diversity of species and the ecosystems they inhabit. At the same time, it allows discretion in the listing of populations by requiring that they represent units of real evolutionary significance to the species. Further, this framework provides a means of addressing several issues of particular concern for Pacific salmon, including anadromous/nonanadromous population segments, differences in run-timing, groups of populations, introduced populations, and the role of hatchery fish.

Investigation on relationship between charge transfer position and dielectric definition of average energy gap in Eu3+-doped compounds

The dielectric definition of average energy gap E-g of the chemical bond has been calculated quantitatively in Eu3+-doped 30 lanthanide compounds based on the dielectric theory of chemical bond for complex structure crystals. The relationship between the experimental charge transfer (CT) energy of Eu3+ and the corresponding average energy gap E-g has been studied. The results show that the CT energy increases linearly with increasing of the average energy gap E-g. The linear model is obtained. It allows us to predict the CT position of Eu3+-doped lanthanide compounds with knowledge of the crystal structure and index of refraction. Applied to the Ca4GdO(BO3)(3):Eu and Li2Lu5O4(BO3)(3):Eu crystals, the predicted results of CT energies are in good agreement with the experimental values, and it can be concluded that the lowest CT energy in Li2Lu5O4(BO3)(3):Eu originates from the site of Lu1.

The Definition and Implementation of a Computer Programming Language Based on Constraints

The constraint paradigm is a model of computation in which values are deduced whenever possible, under the limitation that deductions be local in a certain sense. One may visualize a constraint 'program' as a network of devices connected by wires. Data values may flow along the wires, and computation is performed by the devices. A device computes using only locally available information (with a few exceptions), and places newly derived values on other, locally attached wires. In this way computed values are propagated. An advantage of the constraint paradigm (not unique to it) is that a single relationship can be used in more than one direction. The connections to a device are not labelled as inputs and outputs; a device will compute with whatever values are available, and produce as many new values as it can. General theorem provers are capable of such behavior, but tend to suffer from combinatorial explosion; it is not usually useful to derive all the possible consequences of a set of hypotheses. The constraint paradigm places a certain kind of limitation on the deduction process. The limitations imposed by the constraint paradigm are not the only one possible. It is argued, however, that they are restrictive enough to forestall combinatorial explosion in many interesting computational situations, yet permissive enough to allow useful computations in practical situations. Moreover, the paradigm is intuitive: It is easy to visualize the computational effects of these particular limitations, and the paradigm is a natural way of expressing programs for certain applications, in particular relationships arising in computer-aided design. A number of implementations of constraint-based programming languages are presented. A progression of ever more powerful languages is described, complete implementations are presented and design difficulties and alternatives are discussed. The goal approached, though not quite reached, is a complete programming system which will implicitly support the constraint paradigm to the same extent that LISP, say, supports automatic storage management.

Littered with meaning: The problem of sign pollution in postmodern, post-structuralist, and ecocritical thought

Slocombe, W. (2005). Littered with meaning: The problem of sign pollution in postmodern, post-structuralist, and ecocritical thought. Textual Practice. 19 (4), 493-508. RAE2008

Religious memory as a conveyor of authoritative tradition: The necessary and essential component in a definition of religion

In a landmark book published in 2000, the sociologist Danièle Hervieu-Léger defined religion as a chain of memory, by which she meant that within religious communities remembered traditions are transmitted with an overpowering authority from generation to generation. After analysing Hervieu-Léger’s sociological approach as overcoming the dichotomy between substantive and functional definitions, this article compares a ritual honouring the ancestors in which a medium becomes possessed by the senior elder’s ancestor spirit among the Shona of Zimbabwe with a cleansing ritual performed by a Celtic shaman in New Hampshire, USA. In both instances, despite different social and historical contexts, appeals are made to an authoritative tradition to legitimize the rituals performed. This lends support to the claim that the authoritative transmission of a remembered tradition, by exercising an overwhelming power over communities, even if the memory of such a tradition is merely postulated, identifies the necessary and essential component for any activity to be labelled “religious”.