Artificial Accelerators of the Molecular Chaperone Hsp90 Facilitate Rate‐Limiting Conformational Transitions

The molecular chaperone Hsp90 undergoes an ATP‐driven cycle of conformational changes in which large structural rearrangements precede ATP hydrolysis. Well‐established small‐molecule inhibitors of Hsp90 compete with ATP‐binding. We wondered whether compounds exist that can accelerate the conformational cycle. In a FRET‐based screen reporting on conformational rearrangements in Hsp90 we identified compounds. We elucidated their mode of action and showed that they can overcome the intrinsic inhibition in Hsp90 which prevents these rearrangements. The mode of action is similar to that of the co‐chaperone Aha1 which accelerates the Hsp90 ATPase. However, while the two identified compounds influence conformational changes, they target different aspects of the structural transitions. Also, the binding site determined by NMR spectroscopy is distinct. This study demonstrates that small molecules are capable of triggering specific rate‐limiting transitions in Hsp90 by mechanisms similar to those in protein cofactors.     

Exploring the performance of spatial stochastic simulation algorithms

Since the publication of Gillespie’s direct method, diverse methods have been developed to improve the performance of stochastic simulation methods and to enter the spatial realm. In this paper we discuss a spatial τ-leaping variant (Sτ) that extends the basic leap method. Sτ takes reaction and both outgoing and incoming diffusion events into account when calculating a leap candidate. A performance analysis shall reveal details on the achieved success in balancing speed and accuracy in comparison to other methods. However, performance analysis of spatial stochastic algorithms requires significant effort — it is crucial to choose suitable (benchmark) models and to carefully define model and simulation setups that take problem and simulation design spaces into account.     

Comparison of multi-echo spiral and echo planar imaging in functional MRI

Multi-echo spiral and echo-planar (EPI) imaging sequences were compared in functional imaging experiments at 3 Tesla. Both sequence types allow calculation of the effective transversal relaxation time T(2)* and the initial signal intensity I(0). These parameters can be used in evaluation of the functional signal with respect to inflow effects and other vascular sources. Prior to functional magnetic resonance imaging (fMRI) experiments T(2)* measurements in the human brain were performed with single- and multi-echo FLASH (fast low angle shot) and compared with EPI und spiral imaging sequences. These experiments resulted in T(2)* values ranging from 42.9 to 53.8 ms in a ROI including white and gray matter and CSF in a prefrontal brain region, and allowed validation of the quantitative results of the fast single-shot techniques. In functional experiments with motor stimulation mean absolute T(2)* increases during stimulation of 1.1 +/- 0.6 ms and 1.4 +/- 0.9 ms were found with multi-echo EPI and spiral imaging, respectively, averaged over the activated pixels. In addition, absolute T(2)* values and the size of activated areas obtained with both sequences are comparable. In these investigations spiral imaging allowed higher spatial resolution due to more efficient use of available gradient performance.     

Observation of doubly charged lead clusters below the critical size limit for Coulomb explosion of sphere configurations

Doubly charged lead clusters Pb₇²⁺, Pb₉²⁺, Pb₁₁²⁺ and Pb₁₃²⁺, far below the critical size for Coulomb explosion of par ticles with sphere like configurations (Pb₃₀) have been detected in time of flight mass spectra. Their existence can be explained by chain-like clusters.     

Biorthogonalentwicklungen analytischer Funktionen nach Eigenlösungen linearer Differentialgleichungen

Ohne Zusammenfassung     

Vergleichende Untersuchungen zur Genauigkeit photometrischer und chemischer Analysenverfahren

Zusammenfassung Wir haben in der vorstehenden Abhandlung zu zeigen versucht, in welcher Weise die Zuverlässigkeit photometrischer Meßeinrichtungen und Meßverfahren zu prüfen ist. Im vorliegenden Fall — beim lichtelektrischen Photometer ELKO II — hat die statistische Prüfung sämtlicher Arbeitsgänge ergeben, daß der Apparatefehler nicht größer ist als der zufällige Fehler bei klassischen chemischen Bestimmungsverfahren. Es ist demnach möglich, mit Hilfe photometrischer Messungen auch bei größeren Substanzmengen zu ebenso genauen und zuverlässigen Resultaten zu gelangen wie mit klassischen Verfahren. Statistisch überprüft und verglichen wurden beim Kupfer die photometrischen Bestimmungen mit Nitrilotriessigsäure und als Kupfersulfat     

Nuclear charge radii of 8,9Li determined by laser spectroscopy

The 2s-->3s transition of (6,7,8,9)Li was studied by high-resolution laser spectroscopy using two-photon Doppler-free excitation and resonance-ionization detection. Hyperfine structure splittings and isotope shifts were determined with precision at the 100 kHz level. Combined with recent theoretical work, the changes in the nuclear-charge radii of (8,9)Li were determined. These are now the lightest short-lived isotopes for which the charge radii have been measured. It is found that the charge radii monotonically decrease with increasing neutron number from 6Li to 9Li.