In vitro augmentation of carcinoembryonic antigen expression in colorectal cancer cells

Introduction: Carcinoembryonic antigen (CEA) is an oncofoetal antigen heterogeneously expressed by colorectal cancer cells, which may provide a useful target for antibody guided tumour localisation and therapy. The efficacy of tumour localisation would be improved by increased, more homogeneous CEA expression. Colorectal cancer cell lines are known to show augmentation of CEA expression on exposure to various chemical agents or to changing physicochemical environments. Aim: The aim of this work was to find chemical or environmental factors which successfully induced increased CEA expression in 3 different colorectal cell lines, Lovo, Ht29 and Colo, which are respectively high, low and non-expressors of CEA. Studies of differentiation were also undertaken, by observing concomitant changes in cell proliferation and morphology. Methods: The three cell lines were cultured in medium containing differentiating agents (Butyric acid, gamma-Interferon and 5-Azacytidine and Theophylline), or a range of commonly used cytotoxic drugs at a set dose, or in conditions of altered environmental factors (pH, temperature, oxygen supply, radiation, and serum content of medium). According to the observed effects of these factors used singly, combinations of chemical and physicochemical factors were also tested for additive or synergistic reactions. The growth, differentiation characteristics and CEA expression parameters were measured by a combination of Electron Microscopy, Immunocytochemistry and Fluorescein Activated Cell Sorting. Membrane CEA expression and total CEA content were compared. In addition, the degree of release of CEA by the growing cells into their medium was measured by Radioimmunoassay. A limited investigation of the genetic events which accompanied observed differentiation and CEA expression was conducted by immunostaining for oncogene products known to be associated with proliferation, apoptosis or tumour progression, e.g.,p53, Bcl-2, K-ras, and c-myc. Results: The differentiating agents were found to induce different effects in the three cell lines, with only the Ht29 cells showing increased CEA levels with each agent. It was noted that CEA expression was seen to rise in the Colo cells with two agents, using the more sensitive FACS analysis (Wilcoxon Rank Sum test). 5-Fluorouracil, hypoxia, serum-depletion and radiation induced increased CEA in some cells and not in others; Chloroquine, Methotrexate and Taxol were universally successful CEA-inducers. Of the combinations. Butyric Acid plus Interferon was particularly effective, causing potentiated augmentation of CEA in Lovo and Ht29 cells. Increases in CEA were frequently accompanied by significant growth inhibition (T-test, Correlation co-efficients -0.4, -0.54 & -0.57 for Lovo, Ht29 and Colo respectively); but were not associated with significant increases in CEA release into the supernatant, as measured by Radio-immunoassay. Electron Microscopy studies showed mixed responses to the various agents, with signs both of cell damage and of improved differentiation. No striking changes in oncogene expression by Ht29 cells exposed to successful CEA-inducers were observed; very slight changes in Bcl-2 or c-myc with 3 of the agents were noted. Conclusions: Apparent non-CEA expressing cells may be induced to express CEA using various agents. Different colorectal cell lines respond to chemical and environmental changes to different extents, via different mechanisms. Potentially useful CEA-inducing agents include Butyric Acid, Interferon, Theophylline, 5-Azacytidine, Chloroquine, 5-Fluorouracil, Methotrexate and Taxol. The combination of Butyric Acid and Interferon is particularly powerful in CEA augmentation. Increases in CEA expression are often accompanied by decreases in cell proliferation, but not by increases in CEA release. Augmentation of CEA expression may be accompanied by morphological features of cell damage or of improved differentiation

Metamemory in a familiar place: the effects of environmental context on feeling of knowing

Feeling-of-knowing (FOK) judgments are judgments of future recognizability of currently inaccessible information. They are known to depend both on the access to partial information about a target of retrieval and on the familiarity of the cue that is used as a memory probe. In the present study we assessed whether FOK judgments could also be shaped by incidental environmental context in which these judgments are made. To this end, we investigated 2 phenomena previously documented in studies on recognition memory—a context familiarity effect and a context reinstatement effect—in the procedure used to investigate FOK judgments. In 2 experiments, we found that FOK judgments increase in the presence of a familiar environmental context. The results of both experiments further revealed still higher FOK judgments when made in the presence of environmental context matching the encoding context of both cue and its associated target. The effect of context familiarity on FOK judgment was paralleled by an effect on the latencies of an unsuccessful memory search, but the effect of context reinstatement was not. Importantly, the elevated feeling of knowing in reinstated and familiar contexts was not accompanied by an increase in the accuracy of those judgments. Together, these results demonstrate that metacognitive processes are shaped by the overall volume of memory information accessed at retrieval, independently of whether this memory information is related to a cue, a target, or a context in which remembering takes place

Free-Flight Aerodynamic-Heating Data to Mach Number 10.4 for a Modified Von Karman Nose Shape

Aerodynamic-heating data have been obtained on a modified fineness-ratio-5.0 Von Karman nose shape at free-stream Mach numbers up to 10.4 with a rocket-propelled model. Transient skin temperatures were measured at one station, 26.6 inches behind the tip of a nose 31.6 inches long. A maximum skin temperature of 1,663 deg R was measured soon after the maximum Mach number was obtained. During the periods for which experimental Stanton numbers were presented, flow parameters just outside the boundary layer at the temperature measuring station varied as follows: the local Mach number varied in the range between 0.8 and 9.0 and the local Reynolds number varied in the range between 0.8 x 10(exp 6) and 35.5 x 10(exp 6). The ratio of skin temperature to local static temperature varied between 1.0 and 3.6. The experimental Stanton numbers agreed well with Van Driest's turbulent theory while the local Reynolds number was high - that is, while the local Reynolds number varied in a range above 6.8 x 10(exp 6). For local Reynolds numbers less than 3.5 x 10(exp 6) the experimental Stanton numbers were of the magnitude predicted by Van Driest's laminar theory. Transition from turbulent to laminar flow at the temperature measuring station, as indicated by the change in the magnitude of the Stanton number, occurred as the local Reynolds number decreased from 6.8 x 10(exp 6) to 3.5 x 10(exp 6) at essentially a constant local Mach number of about 9.0

A comparison between warm-water fish assemblages of Narragansett Bay and those of Long Island Sound waters

Fish species of warm-water origin appear in northeastern U.S. coastal waters in the late summer and remain until late fall when the temperate waters cool. The annual abundance and species composition of warm-water species is highly variable from year to year, and these variables may have effects on the trophic dynamics of this region. To understand this variability, records of warm-water fish occurrence were examined in two neighboring temperate areas, Narragansett Bay and Long Island Sound. The most abundant fish species were the same in both areas, and regional abundances peaked in both areas in the middle of September, four weeks after the maximum temperature in the middle of August. On average, abundance of warm-water species increased throughout the years sampled, although this increase can not be said to be exclusively related to temperature. Weekly mean temperatures between the two locations were highly correlated (r= 0.99;

The New Political Economy of EU State Aid Policy

Despite its importance and singularity, the EU’s state aid policy has attracted less scholarly attention than other elements of EU competition policy. Introducing the themes addressed by the special issue, this article briefly reviews the development of EU policy and highlights why the control of state aid matters. The Commission’s response to the current economic crisis notably in banking and the car industry is a key concern, but the interests of the special issue go far beyond. They include: the role of the European Commission in the development of EU policy, the politics of state aid, and a clash between models of capitalism. The special issue also examines the impact of EU policy. It investigates how EU state aid decisions affect not only industrial policy at the national level (and therefore at the EU level), but the welfare state and territorial relations within federal member states, the external implications of EU action and the strategies pursued by the Commission to limit any potential disadvantage to European firms, and the conflict between the EU’s expanding legal order and national

The Partonic Nature of Instantons

In both Yang-Mills theories and sigma models, instantons are endowed with degrees of freedom associated to their scale size and orientation. It has long been conjectured that these degrees of freedom have a dual interpretation as the positions of partonic constituents of the instanton. These conjectures are usually framed in d=3+1 and d=1+1 dimensions respectively where the partons are supposed to be responsible for confinement and other strong coupling phenomena. We revisit this partonic interpretation of instantons in the context of d=4+1 and d=2+1 dimensions. Here the instantons are particle-like solitons and the theories are non-renormalizable. We present an explicit and calculable model in d=2+1 dimensions where the single soliton in the CP^N sigma-model can be shown to be a multi-particle state whose partons are identified with the ultra-violet degrees of freedom which render the theory well-defined at high energies. We introduce a number of methods which reveal the partons inside the soliton, including deforming the sigma model and a dual version of the Bogomolnyi equations. We conjecture that partons inside Yang-Mills instantons hold the key to understanding the ultra-violet completion of five-dimensional gauge theories.Comment: 28 pages. v3: extra references and comments. Mathematica notebooks for the figures can be downloaded from http://www.damtp.cam.ac.uk/user/dt281/parton.htm

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Neutrino masses in the SU(5)xSU(5)' mirror symmetric model

Motivated by the atmospheric and solar neutrino anomalies, we study neutrino masses in a parity invariant SU(5)xSU(5)' grand unified model. Constraints from photon-mirror photon kinetic mixing are discussed.Comment: about 8 pages, minor change