Cellular signaling pathways of matrix metalloproteinase gene expression by Pseudomonas aeruginosa-infected human bronchial epithelial cells

Research Dissemination Reports - supported by funds (Research Fund for the Control of Infectious Diseases)published_or_final_versio

The mechanism and kinetics of methyl isobutyl ketone synthesis from acetone over ion-exchanged hydroxyapatite

The synthesis of methyl isobutyl ketone (MIBK) can be carried out by the condensation of acetone in the presence of hydrogen over a supported metal catalyst. Previous studies have shown that hydroxyapatite is an excellent catalyst for condensation reactions. The present investigation was undertaken in order to elucidate the reaction mechanism and site requirements for acetone coupling to MIBK over a physical mixture of hydroxyapatite and Pd/SiO2. The reaction is found to proceed by consecutive aldol addition to form diacetone alcohol (DAA), dehydration of DAA to mesityl oxide (MO), and hydrogenation of MO to MIBK. The products formed by feeding DAA and MO reveal that aldol addition of acetone is rapid and reversible, and that the subsequent dehydration of DAA is rate-limiting. Pyridine and CO2 titration show that aldol dehydration occurs over basic sites via an E1cB mechanism. A series of cation-substituted hydroxyapatite samples were prepared by ion-exchange to further investigate the role of acid-base strength on catalyst performance. Characterization of these samples by PXRD, BET, ICP-OES, XPS, CO2-TPD, and Raman spectroscopy demonstrated that the exchange procedure used does not affect the bulk properties of hydroxyapatite. DFT calculations reveal that in addition to affecting the Lewis acidity/basicity of the support, the size of the cation plays a significant role in the chemistry: cations that are too large (Ba2+) or too small (Mg2+) adversely affect reaction rates due to excessive stabilization of intermediate species. Strontium-exchanged hydroxyapatite was found to be the most active catalyst because it promoted α-hydrogen abstraction and C–O bond cleavage of DAA efficiently

Painting experiences

In a short paper of "seven or eight pages," what? One point generalized or a generalized development of my painting? The latter will serve better. Therefore, four things will become apparent: the experiences, a chronology, the vocabulary and some speculation. This means that events happened to me in time and appear here within my meanings. Each experience was arrived at as a discovery, however prefaced. This paper then may indicate an approach to painting and a few basic steps therein. If so, my personal achievement could be a social contribution. Hence, into the generalization

Effective data parallel computing on multicore processors

The rise of chip multiprocessing or the integration of multiple general purpose processing cores on a single chip (multicores), has impacted all computing platforms including high performance, servers, desktops, mobile, and embedded processors. Programmers can no longer expect continued increases in software performance without developing parallel, memory hierarchy friendly software that can effectively exploit the chip level multiprocessing paradigm of multicores. The goal of this dissertation is to demonstrate a design process for data parallel problems that starts with a sequential algorithm and ends with a high performance implementation on a multicore platform. Our design process combines theoretical algorithm analysis with practical optimization techniques. Our target multicores are quad-core processors from Intel and the eight-SPE IBM Cell B.E. Target applications include Matrix Multiplications (MM), Finite Difference Time Domain (FDTD), LU Decomposition (LUD), and Power Flow Solver based on Gauss-Seidel (PFS-GS) algorithms. These applications are popular computation methods in science and engineering problems and are characterized by unit-stride (MM, LUD, and PFS-GS) or 2-point stencil (FDTD) memory access pattern. The main contributions of this dissertation include a cache- and space-efficient algorithm model, integrated data pre-fetching and caching strategies, and in-core optimization techniques. Our multicore efficient implementations of the above described applications outperform nai¨ve parallel implementations by at least 2x and scales well with problem size and with the number of processing cores

Doxorubicin-induced cytotoxicity in rat myocardial H9c2 cells: the roles of reactive oxygen species and redox balance

Doxorubicin (Dox) is one of the most potent anti-neoplastic agents approved by the Food and Drug Administration. Its efficacy, however, is limited due to its well-documented cardiotoxic side effect. Since the first observation of this dosage-dependent side effect, the mechanisms and events leading to cardiotoxicity following exposure to doxorubicin have received much attention. However, the exact pathogenesis of Dox-induced cardiotoxicity remains to be elucidated. Although increased production of reactive oxygen species (ROS) from the redox cycling of Dox has been recognized as the primary mechanism of Dox-induced cardiotoxicity, it must be noted that many of the studies supporting the oxidative stress-induced cardiotoxicity hypothesis were conducted with supraclinical drug concentrations. This study examined the effect of clinically-relevant concentrations of Dox on H9c2 rat cardiomyoblasts. Through MTT-reduction cell viability assay, it was determined that exposure of H9c2 cells to Dox concentrations above 0.5 µM for more than 12 hours resulted in significant reduction in cell viability. To verify the role of oxidative stress on the development of cytotoxicity, ROS levels after exposure to low concentrations of Dox (less than 2 µM) were measured. Quantitative measurements of both cellular and mitochondrial ROS levels revealed no significant changes to superoxide presence while exhibiting significant decrease in hydrogen peroxide presence. However, despite the decreased presence of two major types of ROS, the potency of antioxidant responses from the H9c2 cells were found to have significantly increased. Also, exposure to Dox at clinically relevant concentrations led to significant increase in the gene expressions of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1(ICAM-1), two key adhesion molecules that have been implicated in Dox-induced cardiotoxicity. These results suggest that lower concentrations of Dox can stimulate intracellular anti-oxidative response that may thwart intracellular ROS levels required for maintaining of proper cell functions, ultimately leading to redox imbalance and inflammation in cardiomyocytes. While attempting to further investigate into the specific mode of cell death induced by Dox treatment, it was found that the innate fluorescence of Dox may be potent enough to be recognized by various fluorescence-based detection methods. Dox was found to exhibit fluorescence spectra consisting of a maximum excitation wavelength of 493 nm and a maximum emission wavelength of 592 nm, which were similar to the fluorescence characteristics of common fluorescent markers such as FITC, PI, MitoSOX, and DCF-DA which are widely used to assess cell viability, as well as ROS production. Furthermore, nuclear accumulation of Dox was confirmed by fluorescence microscopy, and spectrofluorometric measurements which detected the cellular uptake of Dox. This suggests that the innate fluorescence of Dox can be a valid probe used for future investigations for the uptake, release and distribution of Dox both in vitro and in vivo. Altogether, this study demonstrated for the first time that exposure to Dox at clinically relevant plasma concentrations significantly decreased hydrogen peroxide levels below the basal levels in both intact H9c2 rat cardiomyocytes and in isolated mitochondria. Cells treated with Dox showed a significant increase in the expression of genes associated with anti-oxidative response and inflammation. Utilizing the intrinsic fluorescence of Dox, it was found that incubation of H9c2 cells with Dox resulted in time-dependent intracellular uptake of Dox. This study may contribute in advancing our understanding of mechanisms responsible for Dox-induced cardiotoxicity and thereby improving the efficacy of Dox, one of the most prominent components of many chemotherapy regimens

The Effects of Red Wine and Grape Juice Consumption in Overweight Individuals on Multiple Health Parameters

PURPOSE: To investigate the effects of muscadine red wine and grape juice on weight, body fat, lipids, inflammation, and antioxidant capacity in overweight individuals. METHODS: In a randomized crossover design, 19 subjects consumed 300 mL of wine (WG) or grape juice (JG) for two weeks and acutely upon returning to the lab. Blood was drawn at baseline, post two weeks, and acutely. The statistical design was a 2 (treatments) x 3 (times) repeated measures ANOVA. RESULTS: Overall weight gain occurred in both groups with treatment effect (P=0.044) and time effect (P=0.018). Significant weight gain was found in WG (P=0.027). Total fat mass percentage, C-reactive protein and lipids were not affected by red wine or grape juice consumption. Ferric reducing ability of plasma significantly increased after acute, but not chronic, consumption of red wine (P<0.001). Oxygen radical absorptive capacity of plasma did not change significantly for either treatment. CONCLUSION: Adding wine or grape juice to the diets of overweight sedentary individuals, with no other dietary alterations, resulted in significant weight gain. Acute consumption of red wine resulted in significant changes in antioxidant capacity which may confer potential benefits on health variables other than ones examined in the present study

Zeolite-Catalyzed Isobutene Amination: Mechanism and Kinetics

Amination of isobutene with NH was investigated over Brønsted acidic zeolites at 1 atm and 453-483 K. To compare catalytic activities over different zeolites, the measured reaction rates are normalized by the number of active sites determined by tert-butylamine temperature-programmed desorption (TPD). Small- A nd medium-pore zeolites with one-dimensional channels exhibit low activity because of pore blockage by adsorbed tert-butylammonium ions. However, turnover frequencies and activation energies are not sensitive to framework identity, as long as the active site is accessible to isobutene and tert-butylamine. Kinetic measurements and FTIR spectroscopy reveal that the Brønsted acid sites in MFI are covered predominantly with tert-butylammonium ions under reaction conditions. The desorption of tert-butylamine is assisted by the concurrent adsorption of isobutene. DFT simulations show that at very low tert-butylamine partial pressures, for example, at the inlet to the reactor, tert-butylamine desorption is rate-limiting. However, at sufficiently high tert-butylamine partial pressures (>0.03 kPa), protonation of isobutene to the corresponding carbenium ion limits the rate of amination.

Evidence of Airborne Transmission of the Severe Acute Respiratory Syndrome Virus

BACKGROUND: There is uncertainty about the mode of transmission of the severe acute respiratory syndrome (SARS) virus. We analyzed the temporal and spatial distributions of cases in a large community outbreak of SARS in Hong Kong and examined the correlation of these data with the three-dimensional spread of a virus-laden aerosol plume that was modeled using studies of airflow dynamics. METHODS: We determined the distribution of the initial 187 cases of SARS in the Amoy Gardens housing complex in 2003 according to the date of onset and location of residence. We then studied the association between the location (building, floor, and direction the apartment unit faced) and the probability of infection using logistic regression. The spread of the airborne, virus-laden aerosols generated by the index patient was modeled with the use of airflow-dynamics studies, including studies performed with the use of computational fluid-dynamics and multizone modeling. RESULTS: The curves of the epidemic suggested a common source of the outbreak. All but 5 patients lived in seven buildings (A to G), and the index patient and more than half the other patients with SARS (99 patients) lived in building E. Residents of the floors at the middle and upper levels in building E were at a significantly higher risk than residents on lower floors; this finding is consistent with a rising plume of contaminated warm air in the air shaft generated from a middle-level apartment unit. The risks for the different units matched the virus concentrations predicted with the use of multizone modeling. The distribution of risk in buildings B, C, and D corresponded well with the three-dimensional spread of virus-laden aerosols predicted with the use of computational fluid-dynamics modeling. CONCLUSIONS: Airborne spread of the virus appears to explain this large community outbreak of SARS, and future efforts at prevention and control must take into consideration the potential for airborne spread of this virus. Copyright © 2004 Massachusetts Medical Society.published_or_final_versio

Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle

Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested—arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V))—arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca(2+) measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K(+) without concomitant increase in intracellular Ca(2+) elevation, suggesting that, rather than direct Ca(2+) elevation, Ca(2+) sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these in vitro results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels

Design and development of a low-cost mask-type eye tracker to collect quality fixation measurements in the sport domain

The aim of the study was to build a low-cost mask-type eye tracker with accuracy and precision levels similar to those reported for commercial eye tracking devices. To this end, head-mounted hardware was designed and developed, while open-source software was modified for digital image capture, manipulation, and fixation analysis. An image recognition application was also included with different lighting scenarios. Moreover, parallax and viewing perspective errors were controlled to ensure the quality of data collection. The device was wireless and lightweight (99 g) to allow for natural movement and avoid participant discomfort. After calibration of a 9-target monocular grid, spatial accuracy and precision of the eye tracker was evaluated by 30 participants, at four different lighting setups, both before and after a climbing task. Validity tests showed high levels of accuracy in all conditions as evidenced by a systematic error for a 13-target grid of <0.5°. The reliability tests also showed consistent measurements with no differences in accuracy recorded between participants, lighting conditions, and visual behaviors for the pre- versus post-climbing task. These results suggest that the present eye tracker reports spatial accuracy similar to other commercial systems with levels of high quality. Altogether, this innovative user interface is suitable for research purposes and/or performance analysis in physical activity and sport-related activities. Also, features of this mask-type eye tracking system make it a suitable perceptual user interface to investigate human–computer interactions in a large number of other research fields including psychology, education, marketing, transportation, and medicine