Biomedical subjects
Publications and source records attributed to E C Young.
We report a giant bowing of the spin-orbit splitting energy Delta0 in the dilute GaAs1-xBix alloy for Bi concentrations ranging from 0% to 1.8%. This is the first observation of a large relativistic correction to the host electronic band structure induced by just a few percent of isoelectronic doping in a semiconductor material. It opens up the possibility of tailoring the spin-orbit splitting in semiconductors for spintronic applications.
The bronchial dosimeter for Rn progeny proposed by Yu and Guan in 1998 was employed to survey the bronchial dose from Rn progeny in 30 residences in Hong Kong. An average bronchial deposition fraction of Rn progeny was obtained as 0.0334, which gave an average dose conversion factor (DCF) of 8.5 mSv WLM-1. The mean values of potential alpha energy concentration (PAEC) deposited in the tracheobronchial region (PAECT-B), total PAEC in air (PAECT), annual effective dose (E), concentration of Rn gas (RC) and annual dose conversion factor (ADCF) for all the residential sites combined were 0.11 +/- 0.05, 3.1 +/- 1.4 mWL, 1.2 +/- 0.5 mSv yr-1, 23 +/- 10 Bq m-3 and 0.055 +/- 0.020 (mSv yr-1 per Bqm-3), respectively, with air-conditioned sites (AC sites) and non-AC sites having significantly different mean ADCF values. The indoor relative humidity affected PAECT and RC with high confidence levels (> 95%).
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CNG channels in vivo are heteromers of homologous alpha and beta subunits that each contain a six-transmembrane segment domain and a COOH-terminal cytoplasmic cyclic nucleotide binding domain (BD). In heterologous expression systems, heteromeric alphabeta channels activate with greater sensitivity to ligand than do homomeric alpha channels; however, ligand-gating of channels containing only beta subunit BDs has never been studied because beta subunits cannot form functional homomeric CNG channels. To characterize directly the contribution of the beta subunit BD to ligand-gating, we constructed a chimeric subunit, X-beta, whose BD sequence was that of the beta subunit CNG5 from rat, but whose sequence outside the BD was derived from alpha subunits. For comparison, we constructed another chimera, X-alpha, whose sequence outside the BD was identical to that of X-beta, but whose BD sequence was that of the alpha subunit CNG2 from catfish. When expressed in Xenopus oocytes, X-beta and X-alpha each formed functional homomeric channels activated by both cAMP and cGMP. This is the first demonstration that the beta subunit BD can couple ligand binding to activation in the absence of alpha subunit BD residues. Notably, both agonists activate X-beta more effectively than X-alpha (higher opening efficacy and lower K(1/2)). The BD is believed to comprise two functionally distinct subdomains: (1) the roll subdomain (beta-roll and flanking A- and B-helices) and (2) the C-helix subdomain. Opening efficacy was previously believed to be controlled primarily by the C-helix, but when we made additional chimeras by exchanging the subdomains between X-beta and X-alpha, we found that both subdomains contain significant determinants of efficacy and agonist selectivity. In particular, only channels containing the roll subdomain of the beta subunit had high efficacy. Thermodynamic linkage analysis shows that interaction between the two subdomains accounts for a significant portion of their contribution to activation energetics.
A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.
Cyclic nucleotide-gated channels are composed of a core transmembrane domain, structurally homologous to the voltage-gated K+ channels, and a cytoplasmic ligand-binding domain. These two modules are joined by approximately 90 conserved amino acids, the C-linker, whose precise role in the mechanism of channel activation by cyclic nucleotides is poorly understood. We examined cyclic nucleotide-gated channels from bovine photoreceptors and Caenorhabditis elegans sensory neurons that show marked differences in cyclic nucleotide efficacy and sensitivity. By constructing chimeras from these two channels, we identified a region of 30 amino acids in the C-linker (the L2 region) as an important determinant of activation properties. An increase in both the efficacy of gating and apparent affinity for cGMP and cAMP can be conferred onto the photoreceptor channel by the replacement of its L2 region with that of the C. elegans channel. Three residues within this region largely account for this effect. Despite the profound effect of the C-linker region on ligand gating, the identity of the C-linker does not affect the spontaneous, ligand-independent open probability. Based on a cyclic allosteric model of activation, we propose that the C-linker couples the opening reaction in the transmembrane core region to the enhancement of the affinity of the open channel for agonist, which underlies ligand gating.
A single molecule of the "two-headed" motor enzyme kinesin can move along a microtubule continuously for many enzymatic turnovers (processive movement), and the velocity produced by one kinesin molecule is the same as that produced by many kinesin molecules (high duty ratio). We studied the microtubule movement driven at 1 mM ATP by biotinated N-terminal fragments of Drosophila kinesin heavy chain attached to streptavidin-coated coverslips at various surface densities. K448-BIO has velocity at a high density of vmax = 750 nm s-1 and is dimeric (hence two-headed); K365-BIO (vmax = 200 nm s-1) and K340-BIO (vmax = 90 nm s-1) are monomeric. Escape of microtubules from the surface was prevented by methylcellulose so that continuous trajectories of microtubules not continuously attached to motor molecules could be recorded by video microscopy. The component of instantaneous velocity parallel to the microtubule axis (v) was analyzed in trajectories with a mean velocity 0.4-0.7 times vmax. In K448-BIO trajectories, the distribution of v was bimodal with peaks near 0 and 750 nm s-1. Temporal autocorrelation analysis of v detected lengthy episodes of high-velocity movement consistent with isolated processive microtubule runs driven at vmax by single K448-BIO dimers. K365-BIO and K340-BIO trajectories had unimodal distributions of v and autocorrelation times much shorter than those for K448-BIO. Therefore the monomeric motors have duty ratio < 55% (i.e., no forward movement is generated for at least 45% of the enzymatic cycle time) or processivity below the detection limit of approximately 300 turnovers even in methylcellulose. Continuous movement at maximal velocity thus requires more than one kinesin head.
A dynamic food chain model has been built for the modeling of the transfer of 137Cs in three types of vegetables consumed in Hong Kong, namely, white flowering cabbage (Brassica chinensis), head lettuce (Lactuca sativa) and celery (Apium graveolens). Some parameters have been estimated from the experimental data obtained in this work. The experimental data include the transfer factors of 137Cs from soil to the different vegetable species which are determined through high resolution gamma spectrometry, maximum crop biomasses for the vegetable species, the dry-to-fresh ratios for the vegetable species, the bulk density of soil layers and the average concentration of 137Cs in air. The derived parameters include the deposition rate and the root uptake rate, information for tillage, the logistic growth model and radionuclide concentrations in vegetables. The dynamic food chain model is solved by the Birchall-James algorithm to give the 137Cs concentration in subsurface soil, from the 0.1-25 cm soil layer, and the 137Cs concentration in harvested and unwashed vegetables. As validation of the model and parameters, the concentrations obtained experimentally and from the model are compared and are found to be in good agreement.
Standardized charcoal canisters with diameters of 4 inch, of a type recommended by the USEPA for passive measurement of radon gas concentrations, have been modified for active air sampling. Simultaneous measurement of the concentrations of radon (Rn) and thoron (Tn) in air can be obtained by counting the areas under gamma-ray peaks. Sample results obtained in a laboratory and in a residence with different conditions are also given. The largest uncertainties are about 2% and 3% for Rn and Tn respectively. The minimum detection limits are around 2.0 Bq/m3 for both gases. If only Rn concentration is required, the measurement time can be significantly shortened.
Although it is well-established that G protein-coupled receptor signaling systems can network with those of tyrosine kinase receptors by several mechanisms, the point(s) of convergence of the two pathways remains largely undelineated, particularly for opioids. Here we demonstrate that opioid agonists modulate the activity of the extracellular signal-regulated protein kinase (ERK) in African green monkey kidney COS-7 cells transiently cotransfected with mu-, delta-, or kappa-opioid receptors and ERK1- or ERK2-containing plasmids. Recombinant proteins in transfected cells were characterized by binding assay or immunoblotting. On treatment with corresponding mu- ([D-Ala2,Me-Phe4,Gly-ol5]enkephalin)-, delta- ([D-Pen2,D-Pen5]enkephalin)-, or kappa- (U69593)-selective opioid agonists, a dose-dependent, rapid stimulation of ERK1 and ERK2 activity was observed. This activation was inhibited by specific antagonists, suggesting the involvement of opioid receptors. Pretreatment of cells with pertussis toxin abolished ERK1 and ERK2 activation by agonists. Cotransfection of cells with dominant negative mutant N17-Ras or with a betagamma scavenger, CD8- beta-adrenergic receptor kinase-C, suppressed opioid stimulation of ERK1 and ERK2. When epidermal growth factor was used to activate ERK1, chronic (>2-h) opioid agonist treatment resulted in attenuation of the stimulation by the growth factor. This inhibition was blocked by the corresponding antagonists and CD8- beta-adrenergic receptor kinase-C cotransfection. These results suggest a mechanism involving Ras and betagamma subunits of Gi/o proteins in opioid agonist activation of ERK1 and ERK2, as well as opioid modulation of epidermal growth factor-induced ERK activity.
According to the theory and idea of Hopke et al., a bronchial dosimeter consisting of multiple metal screens has been developed to measure the deposition fractions of radon and thoron progeny in the nasal (N) and tracheobronchial (T-B) regions of the human respiratory tract and to give the dose conversion factors in the T-B region in units of mGy WLM(-1) and mSv y(-1) per Bq m(-3). Different air treatments have been performed in a closed laboratory, which include the use of air conditioning and the application of positive and negative ions for the investigation of the change of the dose conversion factors. At the same time, the radon and thoron gas concentrations have also been measured in the laboratory by active sampling using newly designed activated charcoal canisters connected in series with the bronchial dosimeter for the calculation of the resulted annual effective dose under different air treatments. It is observed that the calculated dose conversion factors derived from the bronchial dosimeter have large discrepancies with those computed using existing lung models. It has also been found that the application of negative ions cannot reduce the annual effective dose in the T-B region; the application of positive ions can lead to a reduction, but not as much as the use of air conditioning. The mitigation of radon effects by air conditioning demonstrated using the bronchial dosimeter is more prominent than that shown by using lung models.
The radon concentration (RC), total potential alpha energy concentration of radon decay products (PAEC), equilibrium factor (F), and the fraction of unattached radon decay products (fp) were measured for 94 offices in Hong Kong. The mean values for RC, PAEC, F, and fp were 51 Bq m(-3), 1.19x10(-7) J m(-3) (5.7 mWL), 0.43, and 0.13, respectively. The first three are much higher than the corresponding values for dwellings. The radon properties vary significantly for different sites. The time for measurements, cumulative time since the air conditioning system was turned on, and whether smoking is allowed in the office have been identified from the available data as possible factors affecting the radon characteristics in offices. The mean contribution of the lung exposure to the annual effective dose equivalent due to radon in offices has been calculated to be 0.35 mSv y(-1). Considering other sources of natural radiation, a rough estimate of the total annual equivalent dose of about 2.7 mSv for a person living in Hong Kong is obtained. Two simple methods are proposed to mitigate the radon hazard in offices: (1) the provision of smoke-free environments and (2) switching on the air conditioners earlier. The first method reduces the equivalent dose by about 0.13 mSv y(-1) while the second reduces by about 0.1 mSv y(-1), which can be regarded as significant.
A key goal in the study of the function of ATP-driven motor enzymes is to quantify the movement produced from consumption of one ATP molecule. Discrete displacements of the processive motor kinesin along a microtubule have been reported as 5 and/or 8 nm. However, analysis of nanometre-scale movements is hindered by superimposed brownian motion. Moreover, because kinesin is processive and turns over stochastically, some observed displacements must arise from summation of smaller movements that are too closely spaced in time to be resolved. To address both of these problems, we used light microscopy instrumentation with low positional drift (< 39 pms[-1]) to observe single molecules of a kinesin derivative moving slowly (approximately 2.5nm s[-1]) at very low (150nM) ATP concentration, so that ATP-induced displacements were widely spaced in time. This allowed increased time-averaging to suppress brownian noise (without application of external force), permitting objective measurement of the distribution of all observed displacement sizes. The distribution was analysed with a statistics-based method which explicitly takes into account the occurrence of unresolved movements, and determines both the underlying step size and the coupling of steps to ATP hydrolytic events. Our data support a fundamental enzymatic cycle for kinesin in which hydrolysis of a single ATP molecule is coupled to a step distance of the microtubule protofilament lattice spacing of 8.12 nm. Step distances other than 8nm are excluded, as is the coupling of each step to two or more consecutive ATP hydrolysis reactions with similar rates, or the coupling of two 8-nm steps to a single hydrolysis. The measured ratio of ATP consumption rate to stepping rate is invariant over a wide range of ATP concentration, suggesting that the 1 ATP to 8nm coupling inferred from behaviour at low ATP can be generalized to high ATP.
This study describes five patients with slowly developing dysphagia secondary to oculopharyngeal muscular dystrophy (OPMD), a progressive neurological disorder characterized by gradual onset of dysphagia, ptosis, and facial and trunk limb weakness. OPMD is a genetic disorder that affects formerly healthy adults who typically begin to experience symptoms in the fourth or fifth decade of life. Despite the debilitating nature of the disease, it is common for affected individuals to live to old age. Because of the gradual progression of dysphagia, as well as the deterioration of articulation, resonance, and breath support, patients with OPMD may come to the attention of physicians, nurses, and speech pathologists before a diagnosis is made. We hope to heighten awareness of how these subjects developed strategies to cope with their swallowing problems without medical intervention until the disease was producing marked symptoms. Patients with suspected dysphagia should be questioned about overt problems with eating and swallowing, but also about their adaptations and compensatory strategies. A Clinical Interview Questionnaire is included that may yield additional information about hidden dysphagia.
The steep dose gradient around 192Ir brachytherapy wire implants is predicted by the EGS4 (PRESTA version) Monte Carlo simulation. When considering radiation absorbing regions close to the wire source, the accurate dose distribution cannot be calculated by the GE Target II Sun Sparc treatment-planning system. Experiments using GafChromic film have been performed to prove the validity of the EGS4 user code when calculating the dose close to the wire source in a low energy range.
A number of radon-related properties have been surveyed in underground shopping centers in Hong Kong. These parameters include the radon concentration, the total potential alpha energy concentration of radon progeny, the equilibrium factor and the unattached fraction of radon progeny. The mean values recorded for these were 29.2 +/- 7.8 Bq/m3, 3.60 +/- 1.53 mWL, 0.46 +/- 0.16 and 0.05 +/- 0.03, respectively. Based on these figures, we have calculated the average radon dose received by employees in an underground shopping center in Hong Kong to be 0.22 mSv/yr, which represents an approximate increase of 8% over the total dose of about 2.7 mSv/yr received by the average person in Hong Kong.
The contents of natural and artificial radionuclides in two types of fresh water fish and four types of marine fish commonly consumed by the Hong Kong population have been measured using HPGe gamma-ray spectrometry. The two types of fresh water fish are grey mullet (mugil cephalus) and grass carp (ctenopharyngodon idellus). The four types of marine fish are white pomfret (pampus argenteus), red bullseye (priacanthus macracanthus), golden thread (nemipterus) and ginkgo (gymnocranius griseus). All measurements of U and Th chain radionuclides in the samples have yielded values below MDA except for positive detection of 228Ra (assuming 228Ra to be in equilibrium with 228Ac) in grey mullet and bullseye perch. The 40K and 137Cs radionuclides were detectable in all samples, with values of 0.01-0.2 and 41.23-111.47 Bq/kg fresh respectively. The different levels of radioactivity in different species of fish is suggested to be due to differences in metabolism and feeding patterns. The radionuclide 60Co, the only other artificial radionuclide to be investigated herein, recorded values below MDA for most of the samples; observable values ranged from 0.01 to 0.04 Bq/kg fresh. Committed effective doses due to ingestion of radionuclides from fish have been estimated to be 1.2 (male) and 6.4 (female) microSv/yr for natural radionuclides; 0.027 (male) and 0.026 (female) microSv/yr for artificial radionuclides.
A Monte Carlo simulation using the PRESTA version of the EGS4 code has been employed as an investigative tool to calculate the absorbed dose in water close to 192Ir wire implants. It has been shown that a treatment planning system, such as GE Target II, using the Sievert integral and the Meisberger polynomial is only able to reproduce the Monte Carlo results at radial distance of 1 mm and farther away. The Sievert integral used with the Meisberger polynomial is proven to be in good agreement with the Monte Carlo generated data at distances between 1 mm and 1 cm.