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.     

Detection of four species of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from roe deer (Capreolus capreolus) in The Netherlands

Epiglottic disruption is an uncommon injury usually associated with significant supraglottic trauma. This injury may be overlooked because of the difficulty in examining the larynx or other associated severe injuries. We present two cases of clinically unsuspected epiglottic disruption that were first seen on MR images of the neck.     

National survey of mammographic facilities in 1985, 1988, and 1992

PURPOSE: To determine trends in mammography in the United States. MATERIALS AND METHODS: A sample of mammographic facilities was selected for each year of the Nationwide Evaluation of X-ray Trends. The same protocol was followed for the 1985, 1988, and 1992 surveys. Data were collected with use of the same imaging phantom for all three surveys and also with a different phantom in the 1988 and 1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be in compliance with the Health Care Financing Administration (HCFA) mammography requirements, 42% were accredited by the American College of Radiology (ACR), and 23% did not hold credentials from either the HCFA or the ACR. Since 1985, there has been a 34% improvement in acceptable phantom image quality score and a 20% decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today is essentially a screen-film technique. Mammographic phantom image quality has improved considerably. The overall mean glandular dose has decreased primarily because of the elimination of xeroradiography.     

Continuous measurement of cardiac output by the Fick principle in infants and children: comparison with the thermodilution method

OBJECTIVE: To compare a system that continuously monitors cardiac output by the Fick principle with measurements by the thermodilution technique in pediatric patients. DESIGN: Prospective direct comparison of the above two techniques. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: 25 infants and children, aged 1 week to 17 years (median 10 months), who had undergone open heart surgery were studied. Only patients without an endotracheal tube leak and without a residual shunt were included. METHODS: The system based on the Fick principle uses measurements of oxygen consumption taken by a metabolic monitor and of arterial and mixed venous oxygen saturation taken by pulse- and fiberoptic oximetry to calculate cardiac output every 20s. INTERVENTIONS: In every patient one pair of measurements was taken. Continuous Fick and thermodilution cardiac output measurements were performed simultaneously, with the examiners remaining ignorant of the results of the other method. RESULTS: Cardiac output measurements ranged from 0.21 to 4.55 l/min. A good correlation coefficient was found: r2 = 0.98; P < 0.001; SEE = 0.41 l/min. The bias is absolute values and in percent of average cardiac output was - 0.05 l/min or - 4.4% with a precision of 0.32 l/min or 21.3% at 2 SD, respectively. The difference was most marked in a neonate with low cardiac output. CONCLUSION: Continuous measurement of cardiac output by the Fick principle offers a convenient method for the hemodynamic monitoring of unstable infants and children.     

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.     

Pigeon perception and discrimination of rapidly changing texture stimuli

The perception and discrimination of rapidly changing texture stimuli by pigeons was examined in a target localization task. Five experienced pigeons were rewarded for finding and pecking at a randomly placed odd target block of small repeated elements embedded in a larger rectangular array of contrasting distractor elements. On dynamic color test trials, the color of the target, distractor, or both of these regions changed at rates of 100, 250, 500, or 1000 ms per frame. The number of colors appearing within such trials also varied. Pigeons performed well above chance in all test conditions, with target-associated changes producing the best discrimination. The results suggest: (a) global relational information can exclusively guide target localization behavior, (b) pigeons can perceptually group and segregate colored textured differences quite rapidly (< or = 100 ms), and (c) pigeons may possess automatic search control processes that can be captured by stimulus-driven changes in the display.     

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.