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.

Triarylborane conjugated dicyanovinyl chromophores: intriguing optical properties and colorimetric anion discrimination

Three new triarylborane conjugated dicyanovinyl chromophores (Mes(2)B-pi-donor-DCV); donor: N-methyldiphenylamine (1) and triphenylamine (2 and 3 with two BMes(2) substitutions]) of type A-D-A (acceptor-donor- acceptor) are reported. Compounds 1-3 exhibit intense charge transfer (CT) absorption bands in the visible region. These absorption peaks are combination CT bands of the amine donor to both the BMes(2) and DCV units. This inference was supported by theoretical studies. Compound 1 shows weak fluorescence compared to 2 and 3. The discrimination of fluoride and cyanide ions is essential in the case of triarylborane (TAB) based anion sensors as a similar response is given towards both the anions. Anion binding studies of 1, 2 and 3 showed that fluoride ions bind selectively to the boron centre and block the corresponding CT transition (donor to BMes(2)) leaving the other CT transition to be red shifted. On the other hand, cyanide ions bind with both the receptor sites and stop both the CT transition processes and hence a different colorimetric response was noted. The binding of F-/CN- induces colour changes in the visible region of the electronic spectra of 2 and 3, which allows for the naked-eye detection of F- and CN- ions. The anion binding mechanisms are established using NMR titration experiments.

Residue proximity information and protein model discrimination using saturation-suppressor mutagenesis

Identification of residue-residue contacts from primary sequence can be used to guide protein structure prediction. Using Escherichia coli CcdB as the test case, we describe an experimental method termed saturation-suppressor mutagenesis to acquire residue contact information. In this methodology, for each of five inactive CcdB mutants, exhaustive screens for suppressors were performed. Proximal suppressors were accurately discriminated from distal suppressors based on their phenotypes when present as single mutants. Experimentally identified putative proximal pairs formed spatial constraints to recover >98% of native-like models of CcdB from a decoy dataset. Suppressor methodology was also applied to the integral membrane protein, diacylglycerol kinase A where the structures determined by X-ray crystallography and NMR were significantly different. Suppressor as well as sequence co-variation data clearly point to the Xray structure being the functional one adopted in vivo. The methodology is applicable to any macromolecular system for which a convenient phenotypic assay exists.

Joan Robinson Was Almost Right: Output under Third-Degree Price Discrimination

In this paper, we show that in order for third-degree price discrimination to increase total output, the demands of the strong markets should be, as conjectured by Robinson (1933), more concave than the demands of the weak markets. By making the distinction between adjusted concavity of the inverse demand and adjusted concavity of the direct demand, we are able to state necessary conditions and sufficient conditions for third-degree price discrimination to increase total output.

Monopoly Price Discrimination and Demand Curvature

Published as an article in: American Economic Review, 2010, vol. 100, issue 4, pages 1601-15.

A Measure of Gender Wage Discrimination at Quantiles

Revised: 2006-05.-- Published as an article in: Journal of Population Economics, 2007, vol. 18, issue 1, pp. 165-179.

Monopoly price discrimination with constant elasticity demand

This paper presents new results on the welfare e¤ects of third-degree price discrimination under constant elasticity demand. We show that when both the share of the strong market under uniform pricing and the elasticity di¤erence between markets are high enough,then price discrimination not only can increase social welfare but also consumer surplus.

Spawning of yellowfin tuna and the discrimination of subpopulations

ENGLISH: The spawning of yellowfin tuna (Thunnus albacares) in the eastern Pacific Ocean was examined to ascertain the existence of separate subpopulations within this area. Investigations of biochemical genetics of yellowfin indicate that there are a number of genetically distinct groups in the eastern Pacific. In addition, yellowfin belong to two recruitment cohorts, X and Y, which are composed of a mixture of these genetically different groups. Spawning data were collected from 1956 through 1961 from the coastal fishing grounds, and from 1970 through 1973 from the offshore fishing areas. Temporal and spatial aspects of spawning of the fish of the two cohorts were analyzed to determine if yellowfin spawning behavior supports the existence of genetically separate subpopulations. Spawning condition was inferred from the maturity of the ovaries. It was found that the coastal fish of each cohort exhibit at least two spawning periods per year which vary in length and time of occurrence from year to year. Fish taken from the offshore fishing grounds did not exhibit this variable spawning pattern. Although samples were not available for all months, the data showed that each cohort has a spawning period of at least 7 months and may spawn year around. Samples from offshore areas also had much higher percentages of spawners than those from the coastal areas. Temporal differences in spawning are not maintaining the genetically separate groups found in the fishery, since fish of both recruitment cohorts spawn at the same time. Also, fish of both the X and Y cohorts spawned in all areas examined; however, these data are insufficient to determine whether spatial isolation of spawning groups is occurring within the areas. SPANISH: Se examinó el desove del atún aleta amarilla (Thunnus albacares) en el Océano Pacífico oriental para averiguar la existencia de subpoblaciones separadas en esta zona. La investigación genética bioquímica del aleta amarilla indica que existen varios grupos genéticamente distintos en el Pacífico oriental. Además, el aleta amarilla pertenece a dos cohortes de reclutamiento X e Y, formadas por una mezcla de estos grupos genéticamente diferentes. Los datos del desove fueron obtenidos de 1956 a 1961, en las regiones neríticas de pesca y desde 1970 a 1973, en las áreas oceánicas de pesca. Se analizaron los aspectos temporales y espaciales del desove de los peces de las dos cohortes, para determinar si el comportamiento reproductor del aleta amarilla, apoya la existencia de subpoblaciones genéticamente diferentes. Se derivó la condición del desove según la madurez de los ovarios. Se encontró que los peces costeros de cada cohorte exhibían por lo menos dos períodos anuales de desove que varían en duración y fecha de ocurrencia de un año a otro. Los peces capturados en las regiones oceánicas de pesca no exhibieron este patrón variable de desove. Aunque o se consiguieron muestras en todos los meses, los datos indican que cada cohorte tiene un período de desove por lo menos de 7 meses y puede que desoven durante todo el año. Las muestras de las regiones oceánicas tuvieron porcentajes mucho mayores de reproductores que los de las zonas neríticas. Las diferencias temporales en el desove no sirven para explicar la presencia de grupos genéticamente separados que se encuentran en la pesca, ya que los peces de ambas cohortes de reclutamiento desovan al mismo tiempo. Además, los peces de ambas cohortes (X e Y) desovan en todas las zonas examinadas; sin embargo, estos datos no son suficientes para determinar si el aislamiento de los grupos de desove ocurre en las zonas. (PDF contains 53 pages.)

Generation and discrimination of Greenberger-Horne-Zeilinger states using dipole-induced transparency in a cavity-waveguide system

We propose an efficient scheme to build an arbitrary multipartite Greenberger-Horne-Zeilinger state and discriminate all the universal Greenberger-Horne-Zeilinger states using parity measurement based on dipole-induced transparency in a cavity-waveguide system. A prominent advantage is that initial entangled states remain after nondetective identification and they can be used for successive tasks. We analyze the performance and possible errors of the required single-qubit rotations and emphasize that the scheme is reliable and can satisfy the current experimental technology.

On a fiber grating sensor system with the capacity of cross-sensitivity discrimination

A novel fiber Bragg grating (FBG) sensor system based on an interrogating technique by two parallel matched gratings was designed and theoretically discussed. With an interrogation grating playing the role of temperature compensation grating simultaneously, the wavelength drifts induced by temperature and strain were discriminated. Additionally, the expressions of temperature and strain were deduced for our solution, and dual-value problem and cross sensitivity were solved synchronously through data processing. The influence of the FBG's parameters on the dynamic range and precision was discussed. Besides, the change of environment temperature cannot influence the dynamic range of the sensor system through temperature tuning. The system proposed in this paper will be of great significance to accelerate the real engineering applications of FBG sensing techniques. (c) 2007 Elsevier GmbH. All rights reserved.

Osteometric analysis of the scapula and humerus of Rangifer tarandus and Cervus elaphus : A contribution to the discrimination of Late Pleistocene cervids

Fossil remains of reindeer (Rangifer tarandus) occurring outside their present range are an important indicator of formerly cold climatic conditions, but are easily confused with those of the red deer (Cervus elaphus). The locality of Kiputz IX has yielded one of the best-preserved Late Pleistocene reindeer populations of the southern Pyrenees, occurring in association with Bison priscus and the much more abundant Cervus elaphus. Fossil remains from this site are mostly complete and not affected by human intervention, thus creating the perfect conditions for reliable osteometric analyses. Here, we quantify diagnostic morphological features of the scapula and the humerus of Cervus elaphus and Rangifer tarandus to establish the potential of these bones to aid in interspecific discrimination. In the case of the scapula, the best species discriminator is the ratio of the minimum anteroposterior diameter of the scapular neck and the development of the articular process, while the breadth of the trochlea is the best discriminator in the case of the humerus.