44 research outputs found
Cross-Mixing Hybrid Beamformer for Wideband Apertures
Existing beamforming arrays suffer from the size and cost of the RF front-end and digital back-end components. In this paper, a novel hybrid beamforming configuration for wideband receivers is introduced. The design replaces phase shifters and local oscillators (LO) with cross mixing antenna elements to maximize diversity gain. In this paper, an analytical model of the cross mixing beamformer (CMB) is first presented. Simulations are carried out showing that a maximum diversity gain can be achieved with the CMB approach. Two prototypes were implemented using and element arrays and tested at 2.31 GHz. Measured results show that CMB achieves coherent signal combining and can preserve the phase delay information needed for hybrid beamforming setups
Sustained proliferation in cancer: mechanisms and novel therapeutic targets
Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression
Self-reported medication side effects in an older cohort living independently in the community - the Melbourne Longitudinal Study on Health Ageing (MELSHA) : cross-sectional analysis of prevalence and risk factors
Background Medication side effects are an important cause of morbidity, mortality and costs in older people. The aim of our study was to examine prevalence and risk factors for self-reported medication side effects in an older cohort living independently in the community.Methods The Melbourne Longitudinal Study on Healthy Ageing (MELSHA), collected information on those aged 65 years or older living independently in the community and commenced in 1994. Data on medication side effects was collected from the baseline cohort (n = 1000) in face-to-face baseline interviews in 1994 and analysed as cross-sectional data. Risk factors examined were: socio-demographics, health status and medical conditions; medication use and health service factors. Analysis included univariate logistic regression to estimate unadjusted risk and multivariate logistic regression analysis to assess confounding and estimate adjusted risk.Results Self-reported medication side effects were reported by approximately 6.7% (67/1000) of the entire baseline MELSHA cohort, and by 8.5% (65/761) of those on medication. Identified risk factors were increased education level, co-morbidities and health service factors including recency of visiting the pharmacist, attending younger doctors, and their doctor\u27s awareness of their medications. The greatest increase in risk for medication side effects was associated with liver problems and their doctor\u27s awareness of their medications. Aging and gender were not risk factors.Conclusion Prevalence of self-reported medication side effects was comparable with that reported in adults attending General Practices in a primary care setting in Australia. The prevalence and identified risk factors provide further insight and opportunity to develop strategies to address the problem of medication side effects in older people living independently in the community setting. <br /
Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?
Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed
Oxidation and Nitration of Tyrosine by Ozone and Nitrogen Dioxide: Reaction Mechanisms and Biological and Atmospheric Implications
The nitration of tyrosine by atmospheric
oxidants, O<sub>3</sub> and NO<sub>2</sub>, is an important cause
for the spread of allergenic
diseases. In the present study, the mechanism and pathways for the
reaction of tyrosine with the atmospheric oxidants O<sub>3</sub> and
NO<sub>2</sub> are studied using DFT-M06-2X, B3LYP, and B3LYP-D methods
with the 6-311+G(d,p) basis set. The energy barrier for the initial
oxidation reactions is also calculated at the CCSD(T)/6-31+G(d,p)
level of theory. The reaction is studied in gas, aqueous, and lipid
media. The initial oxidation of tyrosine by O<sub>3</sub> proceeds
by H atom abstraction and addition reactions and leads to the formation
of six different intermediates. The subsequent nitration reaction
is studied for all the intermediates, and the results show that the
nitration affects both the side chain and the aromatic ring of tyrosine.
The rate constant of the favorable oxidation and nitration reaction
is calculated using variational transition state theory over the temperature
range of 278–350 K. The spectral properties of the oxidation
and nitration products are calculated at the TD-M06-2X/6-311+G(d,p)
level of theory. The fate of the tyrosine radical intermediate is
studied by its reaction with glutathione antioxidant. This study provides
an enhanced understanding of the oxidation and nitration of tyrosine
by O<sub>3</sub> and NO<sub>2</sub> in the context of improving the
air quality and reducing the allergic diseases
Mechanism and Kinetics of the Atmospheric Oxidative Degradation of Dimethylphenol Isomers Initiated by OH Radical
Dimethylphenols are highly reactive
in the atmosphere, and their
oxidation plays a vital role in the autoignition and combustion processes.
The dominant oxidation process for dimethylphenols is by gas-phase
reaction with OH radical. In the present study, the reaction of OH
radical with dimethylphenol isomers is studied using density functional
theory methods, B3LYP, M06-2X, and MPW1K, and also at the MP2 level
of theory using 6-31G(d,p) and 6-31+G(d,p) basis sets. The activation
energy values have also been calculated using the CCSD(T) method with
6-31G(d,p) and 6-311+G(d,p) basis sets using the geometries optimized
at the M06-2X/6-31G(d,p) level of theory. The reactions subsequent
to the principal oxidation steps are studied, and the different reaction
pathways are modeled. The positions of the OH and CH<sub>3</sub> substituents
in the aromatic ring have a great influence on the reactivity of dimethylphenol
toward OH radical. Accordingly, the reaction is initiated in four
different ways: H-atom abstraction from the phenol group, H-atom abstraction
from a methyl group, H-atom abstraction from the aromatic ring by
OH radical, or electrophilic addition of OH radical to the aromatic
ring. Aromatic peroxy radicals arising from initial H-atom abstraction
and subsequent O<sub>2</sub> addition lead to the formation of hydroperoxide
adducts and alkoxy radicals. The O<sub>2</sub> additions to dimethylphenol–OH
adduct results in the formation of epoxide and bicyclic radicals.
The rate constants for the most favorable reaction pathways are calculated
using canonical variational transition state theory with small curvature
tunneling corrections. This study provides thermochemical and kinetic
data for the oxidation of dimethylphenol in the atmosphere and demonstrates
the mechanism for the conversion of peroxy radical into aldehydes,
hydroperoxides, epoxides, and bicyclic radicals, and their lifetimes
in the atmosphere
Atmospheric Oxidation Mechanism and Kinetics of Hydrofluoroethers, CH<sub>3</sub>OCF<sub>3</sub>, CH<sub>3</sub>OCHF<sub>2</sub>, and CHF<sub>2</sub>OCH<sub>2</sub>CF<sub>3</sub>, by OH Radical: A Theoretical Study
In the present work,
the reaction mechanism of two <i>segregated</i> hydrofluoroethers
(HFEs), CH<sub>3</sub>OCF<sub>3</sub> (HFE-143a)
and CH<sub>3</sub>OCHF<sub>2</sub> (HFE-152a), and a <i>nonsegregated</i> HFE, CHF<sub>2</sub>OCH<sub>2</sub>CF<sub>3</sub> (HFE-245fa2),
with OH radical is studied using electronic structure calculations.
The initial reaction between HFE and OH radical is studied by considering
two (three for CHF<sub>2</sub>OCH<sub>2</sub>CF<sub>3</sub>) pathways,
H-atom abstraction and C–O bond breaking, OH addition reaction
and C–C bond breaking, and OH addition reaction, which leads
to the formation of alkyl radical intermediate. The dominant atmospheric
fate of initially formed alkyl radical intermediate is its reaction
with O<sub>2</sub>. The peroxy radicals thus formed exit through the
reaction with HO<sub>2</sub> radical and NO radical resulting in the
formation of products, carbonyl fluoride (COF<sub>2</sub>), trifluoromethylformate,
trifluoro(hydroperoxymethoxy)methane, difluoro(hydroperoxy methoxy)methane,
difluoromethylformate, 2-(difluoromethoxy)-1,1,1-trifluoro-2-hydroperoxyethane,
and difluoromethyl ester. The rate constant is calculated for the
initial H-atom abstraction reaction using canonical variational transition
state theory with small curvature tunnelling corrections over the
temperature range 272–350 K. The atmospheric lifetime and global
warming potential of HFEs are obtained from the calculated reaction
potential energy surface and rate constant. The results are discussed
with respect to the atmospheric implications of CH<sub>3</sub>OCF<sub>3</sub> (HFE-143a), CH<sub>3</sub>OCHF<sub>2</sub> (HFE-152a), and
CHF<sub>2</sub>OCH<sub>2</sub>CF<sub>3</sub> (HFE-245fa2)
Effects of Aging on mRNA Profiles for Drug-Metabolizing Enzymes and Transporters in Livers of Male and Female Mice
Direct Dynamics Simulation of the Thermal <sup>3</sup>CH<sub>2</sub> + <sup>3</sup>O<sub>2</sub> Reaction. Rate Constant and Product Branching Ratios
The
reaction of <sup>3</sup>CH<sub>2</sub> with <sup>3</sup>O<sub>2</sub> is of fundamental importance in combustion, and the reaction
is complex as a result of multiple extremely exothermic product channels.
In the present study, direct dynamics simulations were performed to
study the reaction on both the singlet and triplet potential energy
surfaces (PESs). The simulations were performed at the UM06/6-311++G(d,p)
level of theory. Trajectories were calculated at a temperature of
300 K, and all reactive trajectories proceeded through the carbonyl
oxide Criegee intermediate, CH<sub>2</sub>OO, on both the singlet
and triplet PESs. The triplet surface leads to only one product channel,
H<sub>2</sub>CO + O(<sup>3</sup>P), while the singlet surface leads
to eight product channels with their relative importance as CO + H<sub>2</sub>O > CO + OH + H ∼ H<sub>2</sub>CO + O(<sup>1</sup>D)
> HCO + OH ∼ CO<sub>2</sub> + H<sub>2</sub> ∼ CO
+ H<sub>2</sub> + O(<sup>1</sup>D) > CO<sub>2</sub> + H + H >
HCO + O(<sup>1</sup>D) + H. The reaction on the singlet PES is barrierless,
consistent
with experiment, and the total rate constant on the singlet surface
is (0.93 ± 0.22) × 10<sup>–12</sup> cm<sup>3</sup> molecule<sup>–1</sup> s<sup>–1</sup> in comparison
to the recommended experimental rate constant of 3.3 × 10<sup>–12</sup> cm<sup>3</sup> molecule<sup>–1</sup> s<sup>–1</sup>. The simulation product yields for the singlet PES
are compared with experiment, and the most significant differences
are for H, CO<sub>2</sub>, and H<sub>2</sub>O. The reaction on the
triplet surface is also barrierless, inconsistent with experiment.
A discussion is given of the need for future calculations to address
(1) the barrier on the triplet PES for <sup>3</sup>CH<sub>2</sub> + <sup>3</sup>O<sub>2</sub> → <sup>3</sup>CH<sub>2</sub>OO, (2) the
temperature dependence of the <sup>3</sup>CH<sub>2</sub> + <sup>3</sup>O<sub>2</sub> reaction rate constant and product branching ratios,
and (3) the possible non-RRKM dynamics of the <sup>1</sup>CH<sub>2</sub>OO Criegee intermediate