A study of the impact of the Ceramic Materials Research program at the University of Washington Final report, 15 Jun. 1968 - 15 Sep. 1969

Impact of Ceramic Materials Research Program at University of Washingto

Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct

Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir

The RootScope: A Simple High-Throughput Screening System For Quantitating Gene Expression Dynamics In Plant Roots

Background: High temperature stress responses are vital for plant survival. The mechanisms that plants use to sense high temperatures are only partially understood and involve multiple sensing and signaling pathways. Here we describe the development of the RootScope, an automated microscopy system for quantitating heat shock responses in plant roots.Results: The promoter of Hsp17.6 was used to build a Hsp17.6(p):GFP transcriptional reporter that is induced by heat shock in Arabidopsis. An automated fluorescence microscopy system which enables multiple roots to be imaged in rapid succession was used to quantitate Hsp17.6p: GFP response dynamics. Hsp17.6(p):GFP signal increased with temperature increases from 28 degrees C to 37 degrees C. At 40 degrees C the kinetics and localization of the response are markedly different from those at 37 degrees C. This suggests that different mechanisms mediate heat shock responses above and below 37 degrees C. Finally, we demonstrate that Hsp17.6(p):GFP expression exhibits wave like dynamics in growing roots.Conclusions: The RootScope system is a simple and powerful platform for investigating the heat shock response in plants

Fluorescence assisted capillary electrophoresis of glycans enabled by the negatively charged auxochromes in 1-Aminopyrenes

A compact and negatively charged acceptor group, N-(cyanamino)sulfonyl, is introduced for dye design and its influence on the absorption and emission spectra of the “push–pull” chromophores is demonstrated with 1,3,6-tris[(cyanamino)sulfonyl]-8-aminopyrene. The new sulfonamides, including O-phosphorylated (3-hydroxyazetidine)-N-sulfonyl, are negatively charged electron acceptors and auxochromes. 1-Aminopyrenes decorated with the new sulfonamides have three or six negative charges (pH ≥8), low m/z ratios, high mobilities in an electric field, and yellow to orange emission. We labeled maltodextrin oligomers by reductive amination, separated the products by electrophoresis, and demonstrated their high brightness in a commercial DNA analyzer and the distribution of the emission signal among the detection channels

Inflight Pharmacokinetic and Pharmacodynamic Responses to Medications Commonly Used in Spaceflight

Researchers do not know if medications act the same in the spaceflight environment as they do on Earth. Aspects of the spaceflight environment (low gravity, radiation exposure, closed environment, stress) have been shown to alter human physiology. Some of these physiological changes could be expected to alter either pharmacokinetics (PK, how the body absorbs, distributes, metabolizes and excretes administered medications) or pharmacodynamics (PD, receptors or signaling systems that are the targets of medication action). Anecdotal data has suggested that, at least for certain medications or indications, inflight medication efficacy is poor. In order to prepare for exploration missions where speedy evacuation to Earth may not be a possibility, the likelihood of unexpected medication action must be determined

Evidence that Amphotericin B Mediates Reactivation of Latent Epstein-Barr Virus in Hodgkin's Lymphoma Allowing Cytotoxicity by Acyclovir

This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy. A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir. Remission evidence was seen within days of starting these. A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given. Experimental work is required to confirm or refute this possibility. If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others

A Joint Venture of Ab Initio Molecular Dynamics, Coupled Cluster Electronic Structure Methods, and Liquid-State Theory to Compute Accurate Isotropic Hyperfine Constants of Nitroxide Probes in Water

The isotropic hyperfine coupling constant (HFCC, Aiso) of a pH-sensitive spin probe in a solution, HMI (2,2,3,4,5,5-hexamethylimidazolidin-1-oxyl, C9H19N2O) in water, is computed using an ensemble of state-of-the-art computational techniques and is gauged against X-band continuous wave electron paramagnetic resonance (EPR) measurement spectra at room temperature. Fundamentally, the investigation aims to delineate the cutting edge of current first-principles-based calculations of EPR parameters in aqueous solutions based on using rigorous statistical mechanics combined with correlated electronic structure techniques. In particular, the impact of solvation is described by exploiting fully atomistic, RISM integral equation, and implicit solvation approaches as offered by ab initio molecular dynamics (AIMD) of the periodic bulk solution (using the spin-polarized revPBE0-D3 hybrid functional), embedded cluster reference interaction site model integral equation theory (EC-RISM), and polarizable continuum embedding (using CPCM) of microsolvated complexes, respectively. HFCCs are obtained from efficient coupled cluster calculations (using open-shell DLPNO-CCSD theory) as well as from hybrid density functional theory (using revPBE0-D3). Re-solvation of “vertically desolvated” spin probe configuration snapshots by EC-RISM embedding is shown to provide significantly improved results compared to CPCM since only the former captures the inherent structural heterogeneity of the solvent close to the spin probe. The average values of the Aiso parameter obtained based on configurational statistics using explicit water within AIMD and from EC-RISM solvation are found to be satisfactorily close. Using either such explicit or RISM solvation in conjunction with DLPNO-CCSD calculations of the HFCCs provides an average Aiso parameter for HMI in aqueous solution at 300 K and 1 bar that is in good agreement with the experimentally determined one. The developed computational strategy is general in the sense that it can be readily applied to other spin probes of similar molecular complexity, to aqueous solutions beyond ambient conditions, as well as to other solvents in the longer run

Shot-noise spectroscopy of energy-resolved ballistic currents

We investigate the shot noise of nonequilibrium carriers injected into a ballistic conductor and interacting via long-range Coulomb forces. Coulomb interactions are shown to act as an energy analyzer of the profile of injected electrons by means of the fluctuations of the potential barrier at the emitter contact. We show that the details in the energy profile can be extracted from shot-noise measurements in the Coulomb interaction regime, but cannot be obtained from time-averaged quantities or shot-noise measurements in the absence of interactions.Comment: 7 pages, 4 figure