Rapid Phospho-Turnover by Receptor Tyrosine Kinases Impacts Downstream Signaling and Drug Binding

Epidermal growth factor receptors (ErbB1–4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100–1000 times in the course of a typical immediate-early response to ligand. Rapid phospho-turnover is also observed for EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic tail of active receptors and the downstream signaling kinases they control are highly dynamic and antagonized by potent phosphatases. We develop a kinetic scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho-turnover significantly impacts their mechanisms of action.National Institutes of Health (U.S.) (Grant GM68762)National Institutes of Health (U.S.) (Grant CA112967

Persistent detwinning of iron pnictides by small magnetic fields

Our comprehensive study on EuFe$_2$As$_2$ reveals a dramatic reduction of magnetic detwinning fields compared to other AFe$_2$As$_2$ (A = Ba, Sr, Ca) iron pnictides by indirect magneto-elastic coupling of the Eu$^{2+}$ ions. We find that only 0.1T are sufficient for persistent detwinning below the local Eu$^{2+}$ ordering; above $T_\text{Eu}$ = 19K, higher fields are necessary. Even after the field is switched off, a significant imbalance of twin domains remains constant up to the structural and electronic phase transition (190K). This persistent detwinning provides the unique possibility to study the low temperature electronic in-plane anisotropy of iron pnictides without applying any symmetrybreaking external force.Comment: accepted by Physical Review Letter

Is flow velocity a significant parameter in flood damage modelling?

Flow velocity is generally presumed to influence flood damage. However, this influence is hardly quantified and virtually no damage models take it into account. Therefore, the influences of flow velocity, water depth and combinations of these two impact parameters on various types of flood damage were investigated in five communities affected by the Elbe catchment flood in Germany in 2002. 2-D hydraulic models with high to medium spatial resolutions were used to calculate the impact parameters at the sites in which damage occurred. A significant influence of flow velocity on structural damage, particularly on roads, could be shown in contrast to a minor influence on monetary losses and business interruption. Forecasts of structural damage to road infrastructure should be based on flow velocity alone. The energy head is suggested as a suitable flood impact parameter for reliable forecasting of structural damage to residential buildings above a critical impact level of 2 m of energy head or water depth. However, general consideration of flow velocity in flood damage modelling, particularly for estimating monetary loss, cannot be recommended

Is flow velocity a significant parameter in flood damage modelling?

Flow velocity is generally presumed to influence flood damage. However, this influence is hardly quantified and virtually no damage models take it into account. Therefore, the influences of flow velocity, water depth and combinations of these two impact parameters on various types of flood damage were investigated in five communities affected by the Elbe catchment flood in Germany in 2002. 2-D hydraulic models with high to medium spatial resolutions were used to calculate the impact parameters at the sites in which damage occurred. A significant influence of flow velocity on structural damage, particularly on roads, could be shown in contrast to a minor influence on monetary losses and business interruption. Forecasts of structural damage to road infrastructure should be based on flow velocity alone. The energy head is suggested as a suitable flood impact parameter for reliable forecasting of structural damage to residential buildings above a critical impact level of 2m of energy head or water depth. However, general consideration of flow velocity in flood damage modelling, particularly for estimating monetary loss, cannot be recommended

Gewisse morphologische, physiognomische und antropologische Merkmale bei einwohnern eines jugoslawischen Küstengebiets

Autori su obavili analizu nalaza 498 ispitanika obaju spolova djece starosjedilaca (najmanje jedna generacija) u Solinu i Kaštelima. Ispitivanja su provedena kod djece stare 10—14 godina, s namjerom da se pridonese prikupljanju podataka nacionalnih obilježja. Ispitivanja su po karakteru sondažna. Problematika se je sastojala u tome da se utvrdi postoje li signifikantni nalazi i njihove međusobne korelacije. Ispitivanja su obavljena u području identične geografske širine, u kojoj je obavljao ispitivanja i Francuz Pont30, s namjerom da se ustanovi da li utvrđeni indeks odgovara onom spomenutog autora. Mjerenja, su izvedena standardnim instrumentarijem, a vršila ih je ekipa od triju članova, koautora ovog rada, koja je prethodno prošla blind test, konstruiran za ispitivanja te vrsti. Unošenje i obrada podataka učinjeno je na obrascima za ortodontske sistematske preglede (rubno bušene kartice br. 1226/038). Rezultati su komparirani s nalazima stranih autora. Utvrđeno je između ostalog da je SI i parametar Zy-Zy veći kod muških ispitanika. PŠ i SŠ su u cijelosti veće kod ispitanika bez anomalija. Usporedbene vrijednosti dobivenog indeksa za PŠ i SŠ vrlo su blizu mjerama po Pontu30, što potvrđuje pretpostavku, da se je radilo o ispitanicima sa širokim čeljustima. Statistička obrada vlastitih podataka prikazana je na tab. 1., dok ostale tablice prikazuju rezultate stranih autora. Tab. 2 i 4 sadrže i vlastite rezultate zbog preglednije komparacije. Autori se kritički osvrću na pomanjkanje standardne metodike u ispitivanjima te vrsti u nacionalnoj stomatološkoj literaturi Njemačke i Jugoslavije.The authors published an analysis of the findings in 498 test subjects of both sexes, children of the indigenes (at least one generation) of Solin and Kaštela. The testing was carried out in children aged between 10 to 14 for the purpose of contributing to the collection of data on national characteristics. The tests had a probing character and were meant to investigate the problem whether there existed any significant findings and to establish their mutual correlation. Testings were carried out in a region of identical geographical latitude to that in which the Frenchman Pont made his investigations (30). The aim was to establish whether the index obtained corresponded to that of the mentioned author. Measuring was carried out by means of standard instruments and a team consisting of three members, coauthors of this paper, was engaged in the task. The team had previously undergone the blind test for investigations of that kind. The elaboration and entry of data was made on forms for ortodontic systematic examinations (punch cards no. 1226/038). The results were compared1 to^ the findings of the foreign authors. It was ascertained that the width of the upper incisors and the distance Zy-Zy were higher in boys. Anterior and posterior widths of the upper dental arch were higher in subjects without malocclusions. The obtained values for both widths of the dental arch were very close to those of Pont, thus confirming the hypothesis that the test subjects had wide jaws. The statistical elaboration of our own data is shown in Table 1, while the other tables show the results of foreign authors. Table 2 and 4 contain also our own results for easier comparison. The authors point out at the lack of standard methods in investigations of that kind in the national German and Yugoslav dental literature.Die Autoren haben eine Befunderhebung bei 498 Kindern beiderlei Geschlechts von Alteingesessenen in Solin und Kaštela auf gewisse Merkmale, durchgeführt. Die Untersuchungen wurden an Kindern im Alter von 10 bis 14 Jahren gemacht, mit der Absicht Beiträge für nationale Merkmale zu sammeln. Es sollte festgestellt werden ob deutliche Befunde erhoben werden können, und ihre gegen seitigen Zusammenhänge geprüft werden. Die Untersuchungen wurden in Gebieten der gleichen geographischen Breite durchgeführt, in welchen auch der Franzose Pont seine Untersuchungen anstellte, mit der Absicht festzustellen ob der erhaltene Index dem Pontschen-Index gleich ist. Die Messungen wurden von den drei Koautoren dieser Arbeit mit standardisierten Methoden ausgeführt. Die Resultate wurden mit Befunden anderer Autoren verglichen. Unter Anderem wurde festgestellt, dass die Sl und der Parameter Zy-Zy bei männlichen Probanaen grösser ist. Die vordere und die hintere obere Zahn bogen breite ist im Ganzen grösser bei Untersuchten die keine Anomalien aufwiesen. Der Vergleichswert der erhaltenen Indexe für die angeführten Breiten sind den Pont - Werten sehr nahe, was die Vorraussetzung bestätigt, dass es sich um Probanden mit breiten Kiefern handelt. Die statistische Bearbeitung der eigenen Befunde ist auf Tabelle 1 dargestellt, während die übrigen Tabellen Resultate anderer Autoren zeigen. Die Tabellen 2 und 4 behalten auch eigene Resultate, wegen besserer Übersicht bei der Vergleichung. Die Autoren beanständen das Fehlen einer Standard- -Methode für Untersuchungen dieser Art in der nationalen stomatologischen Literatur Deutschlands und Jugoslawiens