Long-range modulation of chain motions within the intrinsically disordered transactivation domain of tumor suppressor p53

The tumor suppressor p53 is a hub protein with a multitude of binding partners, many of which target its intrinsically disordered N-terminal domain, p53-TAD. Partners, such as the N-terminal domain of MDM2, induce formation of local structure and leave the remainder of the domain apparently disordered. We investigated segmental chain motions in p53-TAD using fluorescence quenching of an extrinsic label by tryptophan in combination with fluorescence correlation spectroscopy (PET-FCS). We studied the loop closure kinetics of four consecutive segments within p53-TAD and their response to protein binding and phosphorylation. The kinetics was multiexponential, showing that the conformational ensemble of the domain deviates from random coil, in agreement with previous findings from NMR spectroscopy. Phosphorylations or binding of MDM2 changed the pattern of intrachain kinetics. Unexpectedly, we found that upon binding and phosphorylation chain motions were altered not only within the targeted segments but also in remote regions. Long-range interactions can be induced in an intrinsically disordered domain by partner proteins that induce apparently only local structure or by post-translational modification.     

Spatiotemporal multiplexing and streaming of hologram data for full-color holographic video display

We propose a new approach to spatiotemporally multiplex sub-holograms and stream hologram data in parallel by using multiple spatial light modulators (SLMs) to increase the spatiotemporal resolution of holographic display system. With the proposed approach, we have achieved a spatiotemporal resolution of 4.5 × 10¹⁰ pixel/s, as compared with 1.89 × 10⁹ pixel/s of a single SLM. Each frame of computer-generated hologram video has a pixel count of 378 Mpixels and is divided into 288 sub-holograms, each of 1.31 Mpixels. During the playback of holographic video, these sub-holograms are spatiotemporally multiplexed and streamed in parallel to form the integrated hologram within 16.67 ms, which enables full-color holographic video display with a 10-in. diagonal at a hologram data frame rate of 60 frames per second (fps). New SLM devices with higher spatiotemporal resolution need to be developed in order to meet the data bandwidth requirement of about 10¹²–10¹⁴ pixel/s for future 3D holographic displays.     

Quantification of force abnormalities during passive andactive-assisted upper-limb reaching movements in post-stroke hemiparesis

We evaluated a method for measuring abnormal upper-limb motor performance in post-stroke hemiparetic subjects. A servomechanism (MIME) moved the forearm in simple planar trajectories, directly controlling hand position and forearm orientation. Design specifications are presented, along with system performance data during an initial test of 13 stroke subjects with a wide range of impairment levels. Performance of subjects was quantified by measuring the forces and torques between the paretic limb and the servomechanism as the subjects relaxed (passive), or attempted to generate force in the direction of movement (active). During passive movements, the more severely impaired subjects resisted movement, producing higher levels of negative work than less-impaired subjects and neurologically normal controls. During active movements, the more severely impaired subjects produced forces with larger directional errors, and were less efficient in producing work. These metrics had significant test-retest repeatability. These motor performance metrics can potentially detect smaller within-subject changes than motor function scales. This method could complement currently used measurement tools for the evaluation of subjects during recovery from stroke, or during therapeutic interventions.     

Picosecond OMVPE GaAs/SiO2photoconductive devices and applications in materials characterization

Preliminary experiments utilizing thin polycrystalline OMVPE GaAs/SiO2films have resulted in photoconductive detectors with sampling oscilloscope limited responses of 35 ps (FWHM), and signal levels exceeding 1.0 V into a 50 Ω load. To our knowledge these are the largest sampling oscilloscope limited responses ever reported for thin film polycrystalline semiconductor photodetectors. This photoconductor was then utilized as a pulsed electrical bias to neutralize the effects of dielectric relaxation evident in simple evaporated metal contacts on crystalline semiconductors. This approach was successfully taken with the more difficult case of low dark resistivity (3000 Ω . cm), low dislocation density (0-5 cm^-2) Si, which is expected to have a dielectric relaxation time in the picosecond time scale. This opens up the use of picosecond time resolved photoconductivity as a sensitive probe of dislocations present in OMVPE and MBE single crystal semiconductor films deposited on lattice mismatched substrates, without special metallization processing.     

Activating effects of unsaturated and cyclopropyl groups in gas phase pyrolysis of acetates. Paper XVIII

The activating effects of a number of unsaturated groups and a cyclopropyl group have been evaluated in a solvent free system by determining the absolute rate constants, and energies and entropies of activation in the vapor phase pyrolysis of secondary and tertiary esters of the type RC(R′CH₃) OAc where R′ = H or CH₃ and R = c-Pr, i-Pr, CH₃, CH₂?CH, CH₂?CHCH₂, C₆H₅; the cyclopropyl showed only a moderate activating effect. The results are in contrast to the very significant activating effect of a cyclopropyl group in solvolysis of cyclopropylcarbinyl derivatives. Apparently marked activation by this group occurs only when a highly developed positive center forms adjacent to it. The lack of marked activation by the cyclopropyl group supports a mechanism for ester pyrolysis which involves a modest, but detectable, charge separation in the transition state [2] but questions a mechanism in which an intimate ion-pair was proposed [3].     

Internal standard signal suppression by co-eluting analyte in isotope dilution LC-ESI-MS

The suppression of the internal standard by increasing concentrations of the co-eluting analyte in calibration series and plasma samples analysed by LC-ESI-MS was studied using the isotope dilution technique. A series of three analyte/deuterated analyte pairs including fexofenadine/d6-fexofenadine, dapsone/d4-dapsone and peudoephedrine/d3-ephedrine were investigated. Suppression of the internal standard signal was noticed in extracted plasma samples containing fexofenadine and d6-fexofenadine as internal standard, as well as in solvent based calibration solutions of the three pair of compounds noted above during LC-ESI-MS analysis at flow rates greater than 100 microL min(-1). This signal suppression effect was described by invoking Enke's model of electrospray ion generation. This model suggests that signal suppression can be ascribed to the competition between ionic species for charged surface sites present on the generated droplets during the electrospray process. The slopes of the calibration curves of the three analytes were close to unity (fexofenadien/d6-fexofenadine 0.964 +/- 0.008, pseudoephedrine/d3-ephedrine 1.02 +/- 0.080 and dapsone/d4-dapsone 0.905 +/- 0.048) as predicted by the model, indicating that quantitation should not be affected by the variation in the peak area of the internal standard.