Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) phenotype and sphere-forming capacity

BACKGROUND Conventional chemotherapy in malignant pleural mesothelioma (MPM) has minimal impact on patient survival due to the supposed chemoresistance of cancer stem cells (CSCs). We sought to identify a sub-population of chemoresistant cells by using putative CSC markers, aldehyde dehydrogenase (ALDH) and CD44 in three MPM cell lines; H28, H2052 and Meso4. METHODS The Aldefluor assay was used to measure ALDH activity and sort ALDH(high) and ALDH(low) cells. Drug-resistance was evaluated by cell viability, anchorage-independent sphere formation, flow-cytometry and qRT-PCR analyses. RESULTS The ALDH(high) - and ALDH(low) -sorted fractions were able to demonstrate phenotypic heterogeneity and generate spheres, the latter being less efficient, and both showed an association with CD44. Cis- diamminedichloroplatinum (II) (cisplatin) treatment failed to reduce ALDH activity and conferred only a short-term inhibition of sphere generation in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Induction of drug sensitivity by an ALDH inhibitor, diethylaminobenzaldehyde (DEAB) resulted in significant reductions in cell viability but not a complete elimination of the sphere-forming cells, suggestive of the presence of a drug-resistant subpopulation. At the transcript level, the cisplatin + DEAB-resistant cells showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44 indicating the involvement of these markers in conferring chemoresistance in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. CONCLUSIONS Our study shows that ALDH(high) CD44(+) cells are implicated in conveying tolerance to cisplatin in the three MPM cell lines. The combined use of CD44 and ALDH widens the window for identification and targeting of a drug-resistant population which may improve the current treatment modalities in mesothelioma.

Functionalization of PAMAM dendrimers with nitronyl nitroxide radicals as models for the outer-sphere relaxation in dentritic potential MRI contrast agents

PAMAM dendrimers functionalized with nitronyl nitroxide radicals were characterized. Quantitative determination of substitution with radicals was performed using EPR and electrochemical methods. The study of the 1H NMR relaxation of the surrounding water showed how the outer-sphere contribution to the relaxivity may be limited by the presence of the dendrimer core.

European Public Sphere

Political communication scholars have investigated whether a public sphere emerges that adapts to the new supra- and intergovernmental European reality in the course of European Union integration. Such European public sphere(s) might link EU politics to citizens. The entry discusses not only how such Europeanized public sphere might affect the quality of democracy as well as the political process but also what a European public sphere could look like and how we might measure it. Our empirical knowledge on the existence or nonexistence of a European Public Sphere is summarized in five theses. The article concludes with future paths for research.

Neutron spectrometry using artificial neural networks for a bonner sphere spectrometer with 3He detector

Neutron spectra unfolding and dose equivalent calculation are complicated tasks in radiation protection, are highly dependent of the neutron energy, and a precise knowledge on neutron spectrometry is essential for all dosimetry-related studies as well as many nuclear physics experiments. In previous works have been reported neutron spectrometry and dosimetry results, by using the ANN technology as alternative solution, starting from the count rates of a Bonner spheres system with a LiI(Eu) thermal neutrons detector, 7 polyethylene spheres and the UTA4 response matrix with 31 energy bins. In this work, an ANN was designed and optimized by using the RDANN methodology for the Bonner spheres system used at CIEMAT Spain, which is composed of a He neutron detector, 12 moderator spheres and a response matrix for 72 energy bins. For the ANN design process a neutrons spectra catalogue compiled by the IAEA was used. From this compilation, the neutrons spectra were converted from lethargy to energy spectra. Then, the resulting energy ?uence spectra were re-binned by using the MCNP code to the corresponding energy bins of the He response matrix before mentioned. With the response matrix and the re-binned spectra the counts rate of the Bonner spheres system were calculated and the resulting re-binned neutrons spectra and calculated counts rate were used as the ANN training data set.

A theory of electron collection by a grid sphere

Use of a spherical grid as electron collector at the anodic end of a tether, as recently proposed, is considered. The standard analysis of space-charge limited current to a solid sphere (with neither magnetic nor plasma-motion effects), which has been shown to best fit TSS1R in-orbit results at very high bias, is used to determine effects from grid transparency on current collected; the analysis is first reformulated in the formalism recently introduced in the two-dimensional analysis of bare-tethers. A discussion of the electric potential created by a spherical grid in vacuum is then carried out; it is shown that each grid-wire collects current well below its maximum OML current, the effective grid transparency being close to its optical value. Formulae for the current to a spherical grid, showing the effects of grid transparency, is determined. A fully consistent analysis of electric potential and electron density, outside and inside the grid, is completed.

Religion, Democracy and the Public Sphere

Throughout the development and maturation of the American democratic experience, religiously inspired conduct has contributed significantly to democratically progressive political concerns such as the abolition of slavery and campaigns for civil rights, but also the encouragement and perpetuation pf anti-democratic practices such as the institution of slavery and policies of racial segregation. It may be rarely admitted, but there is no essential conceptual affinity between conduct proper to democratic political association. It may, therefore, be useful in our own political circumstances to try to determine boundaries for conduct that expresses and satisfies compatibly both religious and democratic commitments. Perhaps most Americans do recognize – if not in their own cases, at least in reference to the beliefs and actions of others – that religiously inspired conduct is neither thereby justified morally or legally nor absolved from further critical appraisal. Certainly, the history of American legal practice shows that religious belief or inspiration does not serve as acceptable legal defense for conduct charged as criminal infraction. The U.S. Constitution contains only two references to religion: the non-establishment clause prohibits governmental institutionalization of religious beliefs or liberty rights – is limited in scope and application both by other constitutional rights of individuals and by constitutionally authorized powers of government. As the U.S.S.C. has repeatedly held, individual constitutional features must be understood in a manner that harmonizes all stated and implied constitutional features, not by unbridled abstractions of selected phrases. Under the American legal system, there is no absolute or unlimited right to free exercise of religion: not everything done publicly under religious inspiration is legally permissible; what is otherwise illegal conduct is not legalized by religious inspiration. In important respects, general features of the legal boundaries concerning religiously inspired conduct in public life are reasonably clear; nevertheless, broader issues concerning further moral or ethical constraints upon religiously inspired conduct remain unresolved and rarely addressed explicitly.

Advances in random matrix theory, zeta functions, and sphere packing

Over four hundred years ago, Sir Walter Raleigh asked his mathematical assistant to find formulas for the number of cannonballs in regularly stacked piles. These investigations aroused the curiosity of the astronomer Johannes Kepler and led to a problem that has gone centuries without a solution: why is the familiar cannonball stack the most efficient arrangement possible? Here we discuss the solution that Hales found in 1998. Almost every part of the 282-page proof relies on long computer verifications. Random matrix theory was developed by physicists to describe the spectra of complex nuclei. In particular, the statistical fluctuations of the eigenvalues (“the energy levels”) follow certain universal laws based on symmetry types. We describe these and then discuss the remarkable appearance of these laws for zeros of the Riemann zeta function (which is the generating function for prime numbers and is the last special function from the last century that is not understood today.) Explaining this phenomenon is a central problem. These topics are distinct, so we present them separately with their own introductory remarks.