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.     

Changing our view on design evaluation meetings methodology: a study of software technical review meetings

By contrast to design meetings, design evaluation meetings (DEMs) have generally been considered as situations in which, according to DEM methodologies, design activities are quite marginal. In a study of DEMs in software development, i.e. in technical review meetings following a particular review methodology, we showed: (i) the occurrence of design activities as part of an argumentation process; (ii) the relative importance of cognitive synchronisation as a prerequisite for evaluation; (iii) the important role played in evaluation by argumentation that makes explicit the underlying design rationale (DR). On the basis of our results, we discuss the potential for using DR methodologies in this kind of meetings.     

Einsatzmöglichkeiten neuronaler Netze in der Industrierobotik

Zusammenfassung Es werden die prinzipiellen Einsatzm?glichkeiten neuronaler Netwwerke zur Modellbildung, Steuerung und Regelung von Robotern sowie zur Unterstützung sensomotorischer Aktionen dargelegt. Einige ausgew?hlte neuronale Regelungskonzepte werden vorgestellt und auf ihre Stabilit?t, Robustheit, Genauigkeit sowie Echtzeitf?higkeit hin untersucht. Ferner wird gezeigt, wie sich neuronale Regelungskonzepte in industrielle Robotersteuerungen integrieren lassen.     

A histological study on polyactive® for the prevention of peridural adhesions after spinal surgery: an experimental study in dogs with a 3 months follow-up

In the present study the potential of Polyactive^® bilayer sheets in the prevention of scar tissue formation after spinal surgery was investigated. Eight adult beagle dogs underwent 3 laminectomies at three levels (L2, L4 and L6). According to a randomized implantation schedule a Polyactive^® sheet or autogenous fat graft was placed in the defect. The third site served as a control without implant. After 4 or 12 weeks (4 dogs per period) the dogs were sacrificed and histological sections were prepared. The Polyactive^® treated defects showed partial closure by newly formed bone. The Polyactive^® was encapsuled by a thin fibrous tissue layer. Ventral to the defect, dense fibrous tissue was present which was separated from the dura by the Polyactive^® sheet in all cases. In some cases fibrous tissue was present between the implant capsule and the dura. In the fat graft group there were no signs of closure of the defect but most sites showed fibrous tissue at the edges of the graft, which was in 4 sites continous with the dura mater. Fibrosis and degeneration of the fat grafts were seen. All control defects showed partial closure by newly formed bone, and ventral to the defect extensive fibrous tissue, which was in 50% continous with the dura mater. Other sections showed loose connective tissue in contact with the dura mater. It is concluded that Polyactive^® has a potential as a mechanical barrier in the prevention of adhesions between the dorsal spinal muscles and the dura mater.     

Low-temperature phase diagram of the heavy-fermion superconductor UPt3

The transition to the superconducting state of UPt₃ has been studied in specific-heat experiments on polycrystalline and single-crystalline samples in dependence of heat treatment, purity of starting materials and deviations from stoichiometry, as well as on substituted compounds. The concepts behind the splitting of the transition in two anomalies that are 60 mK apart are critically reviewed. The superconducting phase diagram in the B-T plane has been studied with the use of a sensitive dilatometric technique. The three superconducting phases meet at a tetracritical point and all four phase lines are of second order. From the length anomalies at the phase boundaries the pressure derivatives of the phase lines have been determined and the most stable phase under uniaxial pressure along the c-axis has been identified.     

Muscle mass and fat mass in relation to bone mineral density in very old men and women: the Framingham Heart Study

Aim of the study was investigate the cross-sectional relationship between body composition and bone mineral density (BMD) in very old men and women. The study sample consisted of 504 women and 285 men, aged 72-93 yr, participating in examination 22 (1992-1993) of the Framingham Heart Study. Total body BMD, regional BMD, and soft-tissue body composition was measured by dual-energy X-ray absorptiometry. Both muscle mass and percentage body fat were positively associated with total body BMD in women. After adjustment for age, physical activity, smoking status, estrogen use, and thiazide use, BMD increased with increasing tertile of muscle mass (p = 0.007) and with increasing tertile of percentage body fat (p = 0.0001) in women. In men muscle mass, not percentage body fat, was positively associated with BMD. After adjustment for potential confounders, BMD remained associated with muscle mass only (p = 0.02). These results were similar for leg BMD and arm BMD. The study suggests that the influence of muscle and fat mass on bone mineral density is different between very old men and women.     

Misleading the Colorado potato beetle with an odor blend

Walking tracks of Colorado potato beetles,Leptinotarsa decemlineata Say, were recorded on a locomotion-compensator in response to wind, odors of host plantsSolanum tuberosum L. and nonhost plantsLycopersicon hirsutum f.glabratum C.H. Mull, and to mixtures of these plant species. Host-plant odor induced positive anemotactic responses in starved females, whereas odor of the nonhostL. hirsutum was neither repellent nor attractive. The attractiveness of host-plant odor, however, was neutralized in the odor blend of plant species. Masking the attractive host-plant odor will hinder the beetle's searching for host-plant patches, and this principle may be exploited in pest control by mixed cropping.The locomotion-compensator was constructed with financial support from the Foundation for Fundamental Biological Research (BION), which is subsidized by the Netherlands Organization for the Advancement of Pure Research (ZWO), grant 14-02-02. The first author was supported by a grant from the French Ministry of Industry and Research.     

Olfactory coding in the perception of semiochemicals

Information processing in the olfactory pathway underlying the perception of semiochemicals by insects is discussed. Both the chemical message for mates and the message for food consist of blends of chemicals. Olfactory receptors in an insect species are tuned to the detection of those compounds which comprise such chemical messages for that species. The classification of receptors as specialists or generalists coincides with two concepts of information processing, i.e., labeled lines and across-fiber patterns, respectively. The olfactory code coming from antennal receptors inPieris brassicae larvae is a combination of labeled lines and across-fiber patterning. When antennae of adult Colorado potato beetles,Leptinotarsa decemlineata, are stimulated by binary mixtures of leaf odor components, the pattern of neural activities in the olfactory receptors shows some separation into two channels, quantitative versus qualitative detection. The separation is complete in the antennal lobe of this beetle.Presented at the Symposium on Insect Chemical Communications: Unifying Concepts. ACS 194th National Meeting, New Orleans, Louisiana, August 31, 1987.     

Coupling of reversed-phase liquid column chromatography and fourier transform infrared spectrometry using postcolumn on-line extraction and solvent elimination

An on-line postcolumn extraction module was used in conjunction with a solvent elimination interface for the semi-on-line coupling of reversed-phase liquid chromatography (RP-LC) and Fourier transform infrared spectrometry (FT-IR). The extraction module consisted of a phase segmentor, an extraction coil, and a phase separator. Dichloromethane was used as extraction solvent. The organic phase delivered by the separator was evaporated by a spray-jet assembly that simultaneously deposited the extracted analytes onto a zinc selenide window, which was subsequently analyzed by FT-IR microscopy. The method is evaluated by studying parameters such as postcolumn band broadening, phase separation efficiency, evaporation efficiency, extraction yield, eluent composition, and use of nonvolatile buffer salts. Good-quality spectra were obtained for test compounds (phenylureas and quinones), which were separated by RP-LC using a buffered eluent with high water content. Large-volume injections allowed FT-IR detection at the submicrogram per milliliter level.