Acute pneumonia in adults: a retrospective clinical study on the response to penicillin in Malawi

A retrospective study was carried out between]anuary 1990 to December 1992. One hundred and sixty patients were admitted with acute pneumonia to Trinity Hospital, a mission hospital in the South of Malawi, and the response to penicillin was evaluated. 31 % of the patients did not respond to penicillin and needed a broad spectrum antibiotic to be cured

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.

Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport. Milciclib blocks glucose consumption by targeting cyclin-dependent kinase 7 (CDK7) similar to other CDK7 inhibitors including THZ1 and LDC4297. Enhanced PIK3CA signaling leads to CDK7 phosphorylation, which promotes RNA Polymerase II phosphorylation and transcription. Milciclib, THZ1, and LDC4297 lead to a reduction in RNA Polymerase II phosphorylation on the SLC2A1 promoter. These data indicate that our high-throughput assay can identify compounds that regulate glucose consumption and that CDK7 is a key regulator of glucose consumption in cells with an activated PI3K pathway

Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems

Untersuchungen zum Einsatz von Flugzeug-InSAR in der Gebirgskartographie

The aim of this thesis is to determine to what extent aircraft-borne radar remote sensing can be used as the sole method for making recordings of the surface of the earth as a basis for compiling topographical and relief maps of mountainous areas. This is done using three test areas: the Edelsberg area in the Allgäu Alps and the Silvretta and Verwall Groups in the Central Alps. The basis for discussion is provided by examination of the interaction between the objects to be imaged and the radar signal, the sensor-specific characteristics thereby being taken into account. Following this some data processing and conditioning methods used for extracting information on the relief and surface coverage for preparation of cartographical products are presented. Analysis of the quality of the results shows that, measured against the requirements of mountain cartography, radar remote sensing is a practical and useful tool for making maps in Alpine regions. As the sole source of information, however, aircraft-borne radar remote sensing p roves to date to be inadequate for cartographical applications in high-mountain regions.Ziel der vorliegenden Arbeit ist, festzustellen, inwieweit die flugzeuggetragene Radarfernerkundung als alleinige Erfassungsmethode der Erdoberfläche zur Erstellung von topographischen und reliefbeschreibenden Karten in Gebirgslandschaften dienen kann. Dies wird anhand von drei Testgebieten, dem Edelsberggebiet in den Allgäuer Alpen sowie der Silvretta- und Verwallgrupe in den Zentralalpen, untersucht. Die Betrachtung der Interaktion zwischen den abzubildenden Objekten und dem Radar-Signal unter Berücksichtigung der sensorspezifischen Charakteristika bildet dabei die Diskussionsgrundlage. Im weiteren werden Methoden zur Datenprozessierung und -aufbereitung vorgestellt, die eine Informa-tionsextraktion bezüglich des Reliefs und der Oberflächenbedeckung für die Erstellung kartographischer Produkte ermöglichen. Die Qualitätsanalyse der Ergebnisse zeigt, dass die Radarfernerkundung, gemessen an den Anforderungen der Gebirgskartographie, ein sinnvolles und nutzbringendes Werkzeug für die Kartenerstellung in alpinen Regionen ist. Für kartographische Anwendungen in Hochgebirgsregionen erweist sich die flugzeuggetragene Radarfernerkundung als einzige Informationsquelle bislang allerdings als nicht ausreichend