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Karolin Franke, Melanie Kettering, Kathleen Lange, Werner A Kaiser, Ingrid Hilger Institute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology I, University Hospital Jena, Friedrich-Schiller Universität Jena, Jena, Germany Purpose: The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. Methods: BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 µg Fe/cm2) or mitomycin C (up to 1.5 µg/cm2, 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results: When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. Discussion: The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology. Keywords: magnetic nanoparticles, hyperthermia, chemotherapy, drugs, MDR, MRP, cancer, nanotechnology, iron oxide

Swelling characteristics of compacted bentonite when hydrated with a hypersaline pore fluid (332 g/L total dissolved solids; 6.6 mol/L ionic strength) are reported. The pore fluid mimics the multiple constituents and their concentrations found for the Cobourg limestone of the Michigan Basin and is dominated by sodium (25% mole fraction) with some potassium, calcium, and magnesium (10%, 5%, and 4% mole fractions). Measurements of swell pressure for two sodium bentonites when hydrated under conditions of zero volume increase are reported. Swell pressure reached a peak within 10-30 h from the onset of hydration, followed by a continual decrease over 1 year of testing from chemical interaction between the bentonite and pore fluid. After 1 year, the swell pressure of the MX-80 bentonite tested decreased by a factor of nine relative to the peak swell pressure with deionized water when the dry density was 1.6 Mg/[m.sup.3]. Swell pressures increased as dry density increased. However, chemical interactions appear to have more influence on swell pressure than density for the pore fluid examined as a swell pressure of just under 1200 kPa was measured for MX-80 after 1.8 years of hydration when compacted to the highest dry density of 1.8 Mg/[m.sup.3] examined. Key words: bentonite, swelling soil, MX-80, hypersaline pore fluid, chemical interaction. Les caracteristiques de gonflement de la bentonite compactee lorsqu'elle est hydratee avec un liquide poreux hypersalin (332 g/L de solides dissous totaux; 6,6 mol/L de force ionique) sont signalees. Le liquide interstitiel imite les multiples constituants et leurs concentrations trouves pour le calcaire de Cobourg du bassin du Michigan et est domine par le sodium (25% de la fraction molaire) avec un peu de potassium, de calcium et de magnesium (10, 5 et 4% des fractions molaires). Des mesures de la pression de gonflement pour deux bentonites sodiques sont rapportees lorsqu'elles sont hydratees dans des conditions d'augmentation de volume nulle. La pression de gonflement a atteint un pic dans les 10 a 30 h suivant le debut de l'hydratation, suivi d'une diminution continue pendant un an d'essais due a l'interaction chimique entre la bentonite et le liquide interstitiel. Apres un an, la pression de gonflement de la bentonite MX-80 testee a diminue par un facteur de neuf par rapport a la pression de gonflement maximale avec de l'eau deionisee lorsque la densite seche etait de 1,6 Mg/[m.sup.3]. La pression de la houle augmente a mesure que la densite seche augmente. Cependant, les interactions chimiques semblent avoir plus d'influence sur la pression de gonflement que sur la densite pour le liquide interstitiel examine, car une pression de gonflement d'un peu moins de 1200 kPa a ete mesuree pour le MX-80 apres 1,8 an d'hydratation lorsqu'il etait compacte a la plus haute densite seche de 1,8 Mg/[m.sup.3] examinee. [Traduit par la Redaction] Mots-cles: bentonite, gonflement du sol, MX-80, liquide poreux hypersalin, interaction chimique., Introduction Swelling characteristics are of interest for compacted bentonite used as the clay mineral component of barrier systems that are being contemplated, or proposed, for the management of nuclear wastes [...]

Objective: To (a) compare characteristics of patients who fall with those of patients who did not fall; and (b) characterise falls (time, injury severity and location) through three fall reporting methods (incident system reports, medical notes and clinician reports). Methods: A substudy design within a stepped‐wedge clinical trial was used: 3239 trial participants were recruited from two inpatient Geriatric Evaluation and Management Units and one general medicine ward in two Australian states. To compare the characteristics of patients who had fallen with those who had not, descriptive tests were used. To characterise falls through three reporting methods, bivariate logistic regressions were used. Results: Patients who had fallen were more likely than patients who had not fallen to be cognitively impaired (51% vs. 29%, p < 0.01), admitted with falls (38% vs. 28%, p = 0.01) and have poor health outcomes such as prolonged length of stay (24 [16–34] vs. 12 [8–19] days [IQR], p < 0.01) and less likely to be discharged directly to the community (62% vs. 47%, p < 0.01). Most falls were captured from medical notes (93%), with clinician (71%) and incident reports (68%) missing 21%–25% of falls. The proportion of injurious falls identified through incident reports was higher than medical records or clinician reports (40% vs. 34% vs. 37%). Conclusions: This study reaffirms the need to improve reporting falls in incident systems and at clinical handover to the team leader. Research should continue to use more than one method of identifying falls, but include data from medical records. Many falls cause injury, resulting in poor health outcomes. [ABSTRACT FROM AUTHOR]

Background: There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped cis and trans regulatory loci due to copy number change for essentially all genes using a human-hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs).Results: Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an Xist independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained trans ceQTLs with -log10P > 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements.Conclusion: Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome. © 2011 Wang et al; licensee BioMed Central Ltd.

We consider the simple linear Boolean model, a fundamental coverage process also known as the Markov/General/infinity queue. In the model, line segments of independent and identically distributed length are located at the points of a Poisson process. The segments may overlap, resulting in a pattern of "clumps"-regions of the line that are covered by one or more segments-alternating with uncovered regions or "spacings". Study and application of the model have been impeded by the difficulty of obtaining the distribution of clump length. We present explicit expressions for the clump length distribution and density functions. The expressions take the form of integral equations, and we develop a method of successive approximation to solve them numerically. Use of the fast Fourier transform greatly enhances the computational efficiency of the method. We further present inference procedures for the model using maximum likelihood techniques. Applications in engineering and biomedicine illustrate the methods.