Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine

Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.     

Potential influence of microorganisms on the corrosion of carbon steel in the French high- and intermediate-level long-lived radioactive waste disposal context

In the context of the high-level radioactive waste disposal CIGEO, the corrosion rate due to microbially influenced corrosion (MIC) has to be evaluated. In France, it is envisaged to dispose of high- and intermediate-level long-lived radioactive waste at a depth of 500 m in a deep geological disposal, drilled in the Callovo-Oxfordian claystone (Cox) formation. To do so, a carbon steel casing will be inserted inside disposal cells, which are horizontal tunnels drilled in the Cox. A specific cement grout will be injected between the carbon steel casing and the claystone. A study was conducted to evaluate the possibility of MIC on carbon steel in the foreseeable high radioactive waste disposal. The corrosiveness of various environments was investigated at 50°C and 80°C with or without microorganisms enriched from samples of Andra's underground research laboratory. The monitoring of corrosion during the experiments was ensured using gravimetric method and real-time corrosion monitoring using sensors based on the measurements of the electrical resistance. The corrosion data were completed with microbiological analyses including cultural and molecular characterizations.     

Comparative analysis of formaldehyde and toluene sorption on indoor floorings and consequence on Indoor Air Quality

Indoor surfaces may be adsorptive sinks with the potential to change Indoor Air Quality. To estimate this effect, the sorption parameters of formaldehyde and toluene were assessed on five floorings by an experimental method using solid-phase microextraction in an airtight emission cell. Adsorption rate constants ranged from 0.003 to 0.075 m·h⁻¹, desorption rate constants from 0.019 to 0.51 h⁻¹, and the partition coefficient from 0.005 to 3.9 m, and these parameters vary greatly from one volatile organic compound/material couple to another indicating contrasted sorption behaviors. A rubber was identified as a sink of formaldehyde characterized by a very low desorption constant close to 0. For these sorbent floorings identified, the adsorption rates of formaldehyde are from 2 to 4 times higher than those of toluene. Two models were used to evaluate the sink effects of floorings on indoor pollutant concentrations in one room from different realistic conditions. The scenarios tested came to the conclusion that the formaldehyde sorption on one rubber (identified as a sink) has a maximum contribution from 15% to 21% for the conditions of low air exchange rate. For other floorings, the sorption has a minor contribution less than or equal to 5%, regardless of the air exchange rate.     

Effect of gums on viability and β‐galactosidase activity of Lactobacillus spp. in milk drink during refrigerated storage

The viability and β‐galactosidase activity of four Lactobacillus strains in milk drink containing gums during 28 days of refrigerated storage at 4 °C were assessed. The population of Lactobacillus rhamnosus GGB101 and Lactobacillus rhamnosus GGB103 were maintained, whereas the population of Lactobacillus reuteri DSM20016 and Lactobacillus reuteri SD2112 significantly decreased. The recommended level of 6 log CFU g^?1 was exceeded for all tested trains throughout storage. The highest viable number of Lactobacillus rhamnosus GGB103 (8.76 ± 0.03 log CFU mL^?1) was obtained in the product containing carrageenan–maltodextrin. The addition of guar–locust bean–carrageenan led to 20‐fold increase in the level of β‐galactosidase activity for L. rhamnosus GGB101 (1208 ± 2.12 Miller units mL^?1) compared to the control (61 ± 2.83 Miller units mL^?1). Our results suggested that gums could be added to milk to improve viability and enhance β‐galactosidase activity of Lactobacillus.     

Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers

Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge.     

Responses of practicing psychologists to a web site developed to promote empirically supported treatments.

Increased adoption of empirically supported treatments (ESTs) has been hindered in part by inadequate and inconvenient access to EST information and training. To improve diffusion of ESTs, the authors developed a Web application to provide practitioners with concise information by disorder on ESTs. The resulting site, therapyadvisor.com, was evaluated by 239 practicing psychologists to assess the usefulness of the site and explore possible interactions of EST attitudes on ratings of usefulness and impact. Two thirds of participants indicated using ESTs in practice, and limited time and resources were cited as primary barriers to EST adoption. The Web application was rated positively by most participants and was reported to increase awareness of and commitment to try ESTs among approximately 60% of participants. The results of this project support the feasibility of a Web application to increase diffusion and promote further adoption of ESTs. Technological and e-learning advances are promising directions for encouraging the adoption of ESTs specifically and evidence-based practice generally, particularly among busy practitioners who have inadequate time and resources for more traditional forms of dissemination and training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Absence makes the adaptations grow fonder: Proportion of time apart from partner, male sexual psychology, and sperm competition in humans (Homo sapiens).

Sperm competition occurs when the sperm of multiple males concurrently occupy the reproductive tract of a female and compete to fertilize an egg. We used a questionnaire to investigate psychological responses to the risk of sperm competition for 237 men in committed, sexual relationships. As predicted, a man who spends a greater (relative to a man who spends a lesser) proportion of time apart from his partner since the couple's last copulation reported (a) greater sexual interest in his partner, (b) greater distress in response to his partner's sexual rejection, and (c) greater sexual persistence in response to his partner's sexual rejection. All effects were independent of total time since the couple's last copulation and the man's relationship satisfaction. Discussion addresses limitations of the current research and situates the current results within the broader comparative literature on adaptation to sperm competition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The negated conditional: A litmus test for the suppositional conditional?

Under the suppositional account of conditionals, when people think about a conditional assertion, "if p then q," they engage in a mental simulation in which they imagine p holds and evaluate the probability that q holds under this supposition. One implication of this account is that belief in a conditional equates to conditional probability [P(q/p)]. In this paper, the authors examine a further implication of this analysis with respect to the wide-scope negation of conditional assertions, "it is not the case that if p then q." Under the suppositional account, nothing categorically follows from the negation of a conditional, other than a second conditional, "if p then not-q." In contrast, according to the mental model theory, a negated conditional is consistent only with the determinate state of affairs, p and not-q. In 4 experiments, the authors compare the contrasting predictions that arise from each of these accounts. The findings are consistent with the suppositional theory but are incongruent with the mental model theory of conditionals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling Temperature in Coupled Electrical and Thermal Simulations of the Electroconsolidation® Process

Electroconsolidation® is a process for densifying complex-shaped parts by using electrically conductive particulate solids as a pressure-transmitting medium. The part is immersed in a bed of the particulate medium contained in a die chamber. Sintering temperature is achieved by resistive heating of the medium while applying compaction pressure. The process is capable of ultrahigh temperatures and short cycle times and offers the potential for low processing costs.

Control of the process and selection of process conditions require knowledge of the temperatures within the die. Temperature gradients exist because of the high heating rate and because of variations of density and electrical resistivity of the medium due to the presence of the part. Direct measurement of temperature with thermocouples or other conventional means is impractical because of the high temperatures, high currents, and high pressures that are involved. Therefore, a computer model was developed to predict temperature as a function of time and applied voltage for any location in the die. The computer model is composed of three parts: a geometrical model to approximate the density and resistivity variations in the medium, a finite-element model to calculate the rate of resistive heating within each element, and a finite-difference model to calculate the temperature distribution based on solution of the heat-transfer equations. Predicted temperatures have been shown to be in excellent agreement with measurements, and numerical simulation provided encouraging consistency and reasonably accurate predictions of temperature profiles within the die. The model demonstrated the feasibility of a new process to achieve simultaneous application of pressure and heat to powder densification in Electroconsolidation.