The Role of the Rho-Associated Coiled-Coil Containing Kinase (ROCK) in Cytokine-Induced Chemokine Responses in Intestinal Epithelial Cells

Inflammatory Bowel Disease (IBD) affects over 1 million Americans and can cause severe tissue damage and even death. TNF-α is a pro-inflammatory cytokine that is elevated in IBD and plays a central role in inflammation. Previous results in our laboratory showed that another cytokine, IL-1β, induces chemokine expression in intestinal epithelial cells (IEC), which is mediated by Rho-associated kinase (ROCK). Because ROCK may be an important mediator of inflammation, we extended our investigations to examine the role of ROCK in TNF-α-stimulated chemokine responses in IEC. Inhibiting ROCK with the Y-27632 compound resulted in a significant, but incomplete, suppression of TNF-α-induced CXCL8 expression in Caco-2 cells, indicating that ROCK is required for optimal CXCL8 production in IEC. ROCK inhibition also blocked TNF-α-stimulated JNK phosphorylation in Caco-2 cells but did not affect NF-κB activation, suggesting an explanation for the partial suppression of CXCL8, as CXCL8 is under the control of both NF-κB and the JNK-activated AP-1 transcription factor. Unlike CXCL8, the production of TNF-α-induced CCL2 and CCL20 expression was enhanced by ROCK inhibition in Caco-2 cells, indicating that ROCK activity had a suppressive effect on these responses. Further experiments showed that the ROCK-dependent suppression was likely mediated by ERK since the MEK/ERK inhibitor, PD98059, had the same enhancement effect as the ROCK inhibitor on TNF-α-induced CCL2 secretion. These results suggest that ROCK plays a complex role in chemokine production in IEC. Furthermore, since ROCK appears to control the expression of several pro-inflammatory mediators, ROCK may be a promising therapeutic target for IBD

Passive Wireless SAW Sensors for IVHM

NASA aeronautical programs require integrated vehicle health monitoring (IVHM) to ensure the safety of the crew and the vehicles. Future IVHM sensors need to be small, light weight, inexpensive, and wireless. Surface acoustic wave (SAW) technology meets all of these constraints. In addition it operates in harsh environments and over wide temperature ranges, and it is inherently radiation hardened. This paper presents a survey of research opportunities for universities and industry to develop new sensors that address anticipated IVHM needs for aerospace vehicles. Potential applications of passive wireless SAW sensors from ground testing to high altitude aircraft operations are presented, along with some of the challenges and issues of the technology

Many-body effects in 16O(e,e'p)

Effects of nucleon-nucleon correlations on exclusive $(e,e'p)$ reactions on closed-shell nuclei leading to single-hole states are studied using $^{16}O(e,e'p)^{15}N$ ($6.32$ MeV, $3/2^-$) as an example. The quasi-hole wave function, calculated from the overlap of translationally invariant many-body variational wave functions containing realistic spatial, spin and isospin correlations, seems to describe the initial state of the struck proton accurately inside the nucleus, however it is too large at the surface. The effect of short-range correlations on the final state is found to be largely cancelled by the increase in the transparency for the struck proton. It is estimated that the values of the spectroscopic factors obtained with the DWIA may increase by a few percent due to correlation effects in the final state.Comment: 21 Pages, PHY-7849-TH-9

Improvements in ENDF/B-VI iron and possible impacts on pressure vessel surveillance dosimetry

The ENDF/B-VI cross-section evaluations for the four iron isotopes are summarized, emphasizing the major improvements over ENDF/B-V. The evaluations were mostly based on a preliminary file generated in 1986 for natural iron that has been used for re-calculating several neutron-transport experiments, of all which showed improved agreement. These re-analyses, including those for pressure-vessel surveillance dosimetry, are also discussed. 20 refs., 3 figs

New mechanism for the production of the extremely fast light particles in heavy-ion collisions in the Fermi energy domain

Employing a four-body classical model, various mechanisms responsible for the production of fast light particles in heavy ion collisions at low and intermediate energies have been studied. It has been shown that at energies lower than 50 A MeV, light particles of velocities of more than two times higher than the projectile velocities are produced due to the acceleration of the target light-particles by the mean field of the incident nucleus. It has also been shown that precision experimental reaction research in normal and inverse kinematics is likely to provide vital information about which mechanism is dominant in the production of fast light particles.Comment: 4 pages, 3 figures, LaTeX, to be published in Proceedings of VII International School-Seminar on Heavy Ion Physics, May 27 - June 1, 2002, Dubna, Russi

A Microscopic T-Violating Optical Potential: Implications for Neutron-Transmission Experiments

We derive a T-violating P-conserving optical potential for neutron-nucleus scattering, starting from a uniquely determined two-body $\rho$-exchange interaction with the same symmetry. We then obtain limits on the T-violating $\rho$-nucleon coupling $\overline{g}_{\rho}$ from neutron-transmission experiments in $^{165}$Ho. The limits may soon compete with those from measurements of atomic electric-dipole moments.Comment: 8 pages, 2 uuencoded figures in separate files (replaces version sent earlier in the day with figures attached), in RevTeX 3, submitted to PR

A full quantal theory of one-neutron halo breakup reactions

We present a theory of one-neutron halo breakup reactions within the framework of post-form distorted wave Born approximation wherein pure Coulomb, pure nuclear and their interference terms are treated consistently in a single setup. This formalism is used to study the breakup of one-neutron halo nucleus 11Be on several targets of different masses. We investigate the role played by the pure Coulomb, pure nuclear and the Coulomb-nuclear interference terms by calculating several reaction observables. The Coulomb-nuclear interference terms are found to be important for more exclusive observables.Comment: 22 pages latex, 9 figures, submitted to Phy. Rev.

A Digital, Constant-Frequency Pulsed Phase-Locked-Loop Instrument for Real-Time, Absolute Ultrasonic Phase Measurements

A digitally controlled instrument for conducting single-frequency and swept-frequency ultrasonic phase measurements has been developed based on a constant-frequency pulsed phase-locked-loop (CFPPLL) design. This instrument uses a pair of direct digital synthesizers to generate an ultrasonically transceived tone-burst and an internal reference wave for phase comparison. Real-time, constant-frequency phase tracking in an interrogated specimen is possible with a resolution of 0.000 38 rad (0.022), and swept-frequency phase measurements can be obtained. Using phase measurements, an absolute thickness in borosilicate glass is presented to show the instruments efficacy, and these results are compared to conventional ultrasonic pulse-echo time-of-flight (ToF) measurements. The newly developed instrument predicted the thickness with a mean error of 0.04 m and a standard deviation of error of 1.35 m. Additionally, the CFPPLL instrument shows a lower measured phase error in the absence of changing temperature and couplant thickness than high-resolution cross-correlation ToF measurements at a similar signal-to-noise ratio. By showing higher accuracy and precision than conventional pulse-echo ToF measurements and lower phase errors than cross-correlation ToF measurements, the new digitally controlled CFPPLL instrument provides high-resolution absolute ultrasonic velocity or path-length measurements in solids or liquids, as well as tracking of material property changes with high sensitivity. The ability to obtain absolute phase measurements allows for many new applications than possible with previous ultrasonic pulsed phase-locked loop instruments. In addition to improved resolution, swept-frequency phase measurements add useful capability in measuring properties of layered structures, such as bonded joints, or materials which exhibit non-linear frequency-dependent behavior, such as dispersive media

Nondestructive Evaluation of Adhesive Bonds via Ultrasonic Phase Measurements

The use of advanced composites utilizing adhesively bonded structures offers advantages in weight and cost for both the aerospace and automotive industries. Conventional nondestructive evaluation (NDE) has proved unable to reliably detect weak bonds or bond deterioration during service life conditions. A new nondestructive technique for quantitatively measuring adhesive bond strength is demonstrated. In this paper, an ultrasonic technique employing constant frequency pulsed phased-locked loop (CFPPLL) circuitry to monitor the phase response of a bonded structure from change in thermal stress is discussed. Theoretical research suggests that the thermal response of a bonded interface relates well with the quality of the adhesive bond. In particular, the effective stiffness of the adhesive-adherent interface may be extracted from the thermal phase response of the structure. The sensitivity of the CFPPLL instrument allows detection of bond pathologies that have been previously difficult-to-detect. Theoretical results with this ultrasonic technique on single epoxy lap joint (SLJ) specimens are presented and discussed. This technique has the potential to advance the use of adhesive bonds - and by association, advanced composite structures - by providing a reliable method to measure adhesive bond strength, thus permitting more complex, lightweight, and safe designs

Prospective assessment of CYP2D6 by genotyping, phenotyping and measurement of tamoxifen, PD 05-09 4-hydroxy-tamoxifen and endoxifen in breast cancer patients treated with tamoxifen.

Tamoxifen (tam) is a widely used endocrine therapy in the treatment of early and advanced stage breast cancer in women and men. It is a pro-drug having weak affinity with the estrogen receptor and needs to be converted to its main metabolite, endoxifen (endox), to have full anticancer activity. Cytochrome 2D6 (CYP2D6) plays a major role in the metabolism of tamoxifen to endoxifen. It is genetically highly polymorphic and its activity influences profoundly the synthesis of endoxifen and potentially the efficacy of tamoxifen treatment. Genotyping is currently the most widely used approach in studies and also in clinical practice to categorize patients as poor- (PM), intermediate- (IM), extensive- (EM) and ultra rapid-metabolizers (UM). Some clinicians already use genotyping in order to tailor the endocrine therapy of their patients. Owing to the large inter-individual variations in concentrations of the active moitey due to genetic and non-genetic influences renders the predictive value of the test uncertain for an individual patient. A significant number of patients classified as EM or IM by genotyping have indeed relatively low endoxifen levels similar to PMs1. This suggests that genotyping is probably not the opti ma l meth o d f or predi cti ng end oxif en l evels