Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase

Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp- Phe-Gly motif of the activation loop, with some, including FGFR1 kinase, appearing refractory to this so called ‘DFG flip’. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the first time in a ‘DFG-out’ state. Here, we use conformationally-selective inhibitors as chemical probes for interrogation of the structural and dynamic features that appear to govern the DFG flip in FGFR1. Our detailed structural and biophysical insights identify contributions from altered dynamics in distal elements, including the ?H helix towards the outstanding stability of the DFG-out complex with the inhibitor ponatinib. We conclude that the ?C-?4 loop and ‘molecular brake’ regions together impose a high energy barrier for this conformational rearrangement, and that this may have significance for maintaining autoinhibition in the non-phosphorylated basal state of FGFR1

Measurements of atmospheric electricity aloft

Measurements of the electrical characteristics of the atmosphere above the surface have been made for over 200 years, from a variety of different platforms, including kites, balloons, rockets and aircraft. From these measurements, a great deal of information about the electrical characteristics of the atmosphere has been gained, assisting our understanding of the global atmospheric electric circuit, thunderstorm electrification and lightning generation mechanisms, discovery of transient luminous events above thunderstorms, and many other electrical phenomena. This paper surveys the history of atmospheric electrical measurements aloft, from the earliest manned balloon ascents to current day observations with free balloons and aircraft. Measurements of atmospheric electrical parameters in a range of meteorological conditions are described, including clear air conditions, polluted conditions, non-thunderstorm clouds, and thunderstorm clouds, spanning a range of atmospheric conditions, from fair weather, to the most electrically active

EVALUATION OF STUDENT`S OPINION ABOUT OSCE FOR GRADUATE NURSING STUDENT –SHENDI UNIVERSITY SUDAN2012

This study was done in Sudan, NaherElneel state, shendi town, at shendi university faculty of nursing during September 2011. Seventy three second-year nurses students were asked to complete a brief anonymous questionnaire regarding their opinion as a new trend clinical exam strategy. The questionnaire was administered to all students post OSCE exam and required approximately ten minutes to complete it.68% of student agree that OSCE had covered wide area of knowledge and practice rather than ordinary exam. Few students were considered that OSCE is stressful and relatively intimidating. Majority of the student recommended that increasing time per station. The study aim to evaluate the student opinion about OSCE for undergraduate nursing student, so as to test the validity and reliability of the exam among them. The study concluded that, most of the student agreed that OSCE is better method of clinical evaluation because the matter of bias is minimum and it`s less stressful as compare with the ordinary exam. Also they were agreed that OSCE allow chance of compensation for poor performance. The study recommended that, OSCE should be integrated within the curriculum in conjunction with other relevant evaluation methods