Determination of Ras-GTP and Ras-GDP in patients with acute myelogenous leukemia (AML), myeloproliferative syndrome (MPS), juvenile myelomonocytic leukemia (JMML), acute lymphocytic leukemia (ALL), and malignant lymphoma: assessment of mutational and indirect activation

The 21-kD protein Ras of the low-molecular-weight GTP-binding (LMWG) family plays an important role in transduction of extracellular signals. Ras functions as a ‘molecular switch’ in transduction of signals from the membrane receptors of many growth factors, cytokines, and other second messengers to the cell nucleus. Numerous studies have shown that in multiple malignant tumors and hematopoietic malignancies, faulty signal transduction via the Ras pathway plays a key role in tumorigenesis. In this work, a non-radioactive assay was used to quantify Ras activity in hematologic malignancies. Ras activation was measured in six different cell lines and 24 patient samples, and sequence analysis of N- and K-ras was performed. The 24 patient samples comprised of seven acute myelogenous leukemia (AML) samples, five acute lymphocytic leukemia (ALL) samples, four myeloproliferative disease (MPD) samples, four lymphoma samples, four juvenile myelomonocytic leukemia (JMML) samples, and WBC from a healthy donor. The purpose of this study was to compare Ras activity determined by percentage of Ras-GTP with the mutational status of the Ras gene in the hematopoietic cells of the patients. Mutation analysis revealed ras mutations in two of the seven AML samples, one in codon 12 and one in codon 61; ras mutations were also found in two of the four JMML samples, and in one of the four lymphoma samples (codon 12). We found a mean Ras activation of 23.1% in cell lines with known constitutively activating ras mutations, which was significantly different from cell lines with ras wildtype sequence (Ras activation of 4.8%). Two of the five activating ras mutations in the patient samples correlated with increased Ras activation. In the other three samples, Ras was probably activated through “upstream” or “downstream” mechanisms

Actually, What Does “Ontology” Mean?

This article is a fictitious, moderated dialogue between an information scientist, a philosopher, and a psychologist. They explore the term “ontology” from the point of view of their own discipline, with the object of learning from each other. The target audience of this article are laypersons with respect to the specific disciplines – but who have a scientific background.The authors work in the fields of computer science, knowledge engineering, electrical engineering, mathematics, neurobiology, philosophy, and psychology.</p

Slowing and cooling molecules and neutral atoms by time-varying electric field gradients

A method of slowing, accelerating, cooling, and bunching molecules and neutral atoms using time-varying electric field gradients is demonstrated with cesium atoms in a fountain. The effects are measured and found to be in agreement with calculation. Time-varying electric field gradient slowing and cooling is applicable to atoms that have large dipole polarizabilities, including atoms that are not amenable to laser slowing and cooling, to Rydberg atoms, and to molecules, especially polar molecules with large electric dipole moments. The possible applications of this method include slowing and cooling thermal beams of atoms and molecules, launching cold atoms from a trap into a fountain, and measuring atomic dipole polarizabilities.Comment: 13 pages, 10 figures. Scheduled for publication in Nov. 1 Phys. Rev.

Infektionsmedizinische und chirurgische Herausforderungen durch Carbapenem-resistente bakterielle Erreger bei der Versorgung Kriegsverletzter aus der Ukraine

Aufgrund von Hygienedefiziten und dem sehr breiten, kalkulierten Antibiotikaeinsatz bei zeit¬gleich offener Wundbehandlung in ukrainischen Militärkrankenhäusern ist das Risiko für schwerwiegende Wundinfektionen mit multiresis¬tenten Erregern (MRE) bei Übernahme ziviler Kriegsopfer hoch. Insofern kommt der Surveillance mit risikoadaptiertem Screening auf MRE, welches am Universitätsklinikum Leipzig seit 2012 durchgeführt wird, eine große Bedeutung zu. Es werden die Komplexität der Versorgung Kriegsverletzter aus der Ukraine sowie die damit einhergehenden Infektions- und Resistenzprobleme dargestellt und auf die Notwendigkeit eines interdisziplinären und -professionellen Managements hingewiesen.Peer Reviewe