Molecular Electroporation and the Transduction of Oligoarginines

Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.Comment: 15 pages, 5 figure

Validation of the High Performance Conduction-Cooled Prototype LTS Pulse Coil for UPS-SMES

A conduction-cooled low temperature superconducting (LTS) pulse coil has been developed as a key technology for UPS-SMES. We have been developing a 1 MW, 1 s UPS-SMES for a protection from a momentary voltage drop and an instant power failure. A conduction-cooled LTS pulse coil has excellent characteristics, which are adequate for a short-time uninterruptible power supply (UPS). The LTS coil has better cost performance over the HTS coil at present and the conduction cooling has higher reliability and easier operation than the conventional cooling schemes such as pool boiling with liquid helium or forced flow of supercritical helium. To demonstrate the high performances of the LTS pulse coil, we have fabricated a prototype coil with stored energy of 100 kJ and have conducted cooling and excitation tests. The successful performance test results including current shut-off test with a time constant of 1.3 s and repeated excitation of a triangular waveform with high ramp rate are reporte

Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors

Background: Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [18F]fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods: Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region. Results: In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p < 0.0001). In the recurrent patient group, a TMR value of 1.37 (95% CI: 1.36-1.39) corresponded to a recurrence rate of 30%, the odds ratio was 5.18 (4.87-5.51), and the area under the curve (AUC) of the receiver operating characteristic curve was 0.613. In all 21 patients, a TMR value of 2.42 (2.36-2.49) corresponded to an estimated recurrence rate of 30%, and the AUC was only 0.591. Conclusions: The uptake of FMISO in the recurrent region was significantly higher than that in the non-recurrent region. However, the predictive value of FMISO-PET before IMRT is not sufficient for up-front dose escalation for the intra-tumoral high-uptake region of FMISO. Because of the higher mean TMR of the recurrence region, a new hypoxic imaging method is needed to improve the sensitivity and specificity for hypoxia

Thiol-Based Redox Switches in Eukaryotic Proteins

Abstract For many years, oxidative thiol modifications in cytosolic proteins were largely disregarded as in vitro artifacts, and considered unlikely to play significant roles within the reducing environment of the cell. Recent developments in in vivo thiol trapping technology combined with mass spectrometric analysis have now provided convincing evidence that thiol-based redox switches are used as molecular tools in many proteins to regulate their activity in response to reactive oxygen and nitrogen species. Reversible oxidative thiol modifications have been found to modulate the function of proteins involved in many different pathways, starting from gene transcription, translation and protein folding, to metabolism, signal transduction, and ultimately apoptosis. This review will focus on three well-characterized eukaryotic proteins that use thiol-based redox switches to influence gene transcription, metabolism, and signal transduction. The transcription factor Yap1p is a good illustration of how oxidative modifications affect the function of a protein without changing its activity. We use glyeraldehyde-3-phosphate dehydrogenase to demonstrate how thiol modification of an active site cysteine re-routes metabolic pathways and converts a metabolic enzyme into a pro-apoptotic factor. Finally, we introduce the redox-sensitive protein tyrosine phosphatase PTP1B to illustrate that reversibility is one of the fundamental aspects of redox-regulation. Antioxid. Redox Signal. 11, 997-1014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78110/1/ars.2008.2285.pd

Impact of the Wall Conditioning Program on Plasma Performance in NSTX

High performance operating regimes have been achieved on NSTX (National Spherical Torus Experiment) through impurity control and wall-conditioning techniques. These techniques include HeGDC-aided boronization using deuterated trimethylboron, inter-discharge HeGDC, 350 C PFC bake-out followed by D2 and HeGDC, and experiments to test fueling discharges with either a He-trimethylboron mixture or pure trimethylboron. The impact of this impurity and density control program on recent advances in NSTX plasma performance is discussed