All-solid-state VUV frequency comb at 160 nm using high-harmonic generation in nonlinear femtosecond enhancement cavity.

We realized a solid-state-based vacuum ultraviolet frequency comb by harmonics generation in an external enhancement cavity. Optical conversions were so far reported by only using gaseous media. We present a theory that allows the most suited solid generation medium to be selected for specific target harmonics by adapting the material's bandgap. We experimentally use a thin AlN film grown on a sapphire substrate to realize a compact frequency comb high-harmonic source in the Deep Ultraviolet (DUV) / Vacuum Ultraviolet (VUV) spectral range. By extending our earlier VUV source [Opt. Express26, 21900 (2018)] with the enhancement cavity, a sub-Watt level Ti:sapphire femtosecond frequency comb is enhanced to 24 W stored average power, its 3rd, 5th, and 7th harmonics are generated, and the targeted 5th harmonic's power at 160 nm increased by two orders of magnitude. The emerging nonlinear effects in the solid medium, together with suitable intra-cavity dispersion management, support optimal enhancement and stable locking. To demonstrate the realized frequency comb's spectroscopic ability, we report on the beat measurement between the 3rd harmonic beam and a 266 nm CW laser reaching about 1 MHz accuracy.

Evolution of resistance to single and combined floral phytochemicals by a bumble bee parasite.

Repeated exposure to inhibitory compounds can drive the evolution of resistance, which weakens chemical defence against antagonists. Floral phytochemicals in nectar and pollen have antimicrobial properties that can ameliorate infection in pollinators, but evolved resistance among parasites could diminish the medicinal efficacy of phytochemicals. However, multicompound blends, which occur in nectar and pollen, present simultaneous chemical challenges that may slow resistance evolution. We assessed evolution of resistance by the common bumble bee gut parasite Crithidia bombi to two floral phytochemicals, singly and combined, over 6 weeks (~100 generations) of chronic exposure. Resistance of C. bombi increased under single and combined phytochemical exposure, without any associated costs of reduced growth under phytochemical-free conditions. After 6 weeks' exposure, phytochemical concentrations that initially inhibited growth by > 50%, and exceeded concentrations in floral nectar, had minimal effects on evolved parasite lines. Unexpectedly, the phytochemical combination did not impede resistance evolution compared to single compounds. These results demonstrate that repeated phytochemical exposure, which could occur in homogeneous floral landscapes or with therapeutic phytochemical treatment of managed hives, can cause rapid evolution of resistance in pollinator parasites. We discuss possible explanations for submaximal phytochemical resistance in natural populations. Evolved resistance could diminish the antiparasitic value of phytochemical ingestion, weakening an important natural defence against infection.

The effect of mindfulness meditation on cough reflex sensitivity.

BACKGROUND: Chronic cough is common, and medical treatment can be ineffective. Mindfulness is a psychological intervention that aims to teach moment-to-moment non-judgemental awareness of thoughts, feelings and sensations. METHOD: 30 healthy subjects and 30 patients with chronic cough were studied in two sequential trials. For both studies, cough reflex sensitivity to citric acid (C5) was measured on two occasions, with urge to cough rated following each inhalation; between challenges subjects were randomised to (1) no intervention, (2) mindfulness or (3) no intervention but modified cough challenge (subjects suppress coughing). For the healthy volunteers, measures were 1 h apart and mindfulness was practised for 15 min. For the patients with chronic cough measures were 1 week apart and mindfulness was practised daily for 30 min. RESULTS: In healthy volunteers, median change (interquartile range (IQR)) in cough reflex sensitivity (logC5) for no intervention, mindfulness and suppression was +1.0 (0.0 to +1.3), +2.0 (+1.0 to +3.0) and +3.0 (+2.8 to +3.0) doubling concentrations (p = 0.003); there were significant reductions for both mindfulness (p = 0.043) and suppression (p = 0.002) over no intervention. In patients with cough, median change (IQR) in logC5 for no intervention, mindfulness training and voluntary suppression was 0.0 (-1.0 to +1.0), +1.0 (-0.3 to +1.0) and +1.0 (+1.0 to +2.0) doubling concentrations (p = 0.046); there was a significant reduction for suppression (p = 0.02) but not mindfulness (p = 0.35). Urge to cough did not change after mindfulness compared with control in either healthy subjects (p = 0.33) or those with chronic cough (p = 0.47). CONCLUSION: Compared with control, mindfulness decreased cough reflex sensitivity in healthy volunteers, but did not alter cough threshold in patients with chronic cough. Both groups were able to suppress cough responses to citric acid inhalation.

C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.

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.

Efficient coupling of ligand binding to channel opening by the binding domain of a modulatory (beta) subunit of the olfactory cyclic nucleotide-gated channel.

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.

Influenza-specific ELISA IgA and IgG predict severity of influenza disease in subjects prescreened with hemagglutination inhibition.

Four influenza A challenge studies were performed over a period of three years using the same dose of one virus pool. The first three studies were conducted two influenza seasons apart from the last study. In all four studies only subjects with screening hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8 in sera were accepted as study subjects. The rate of infection after influenza challenge was 96% (25 of 26) in the first three studies, and only 73% (8 of 11) in the last study (P less than 0.04). The rate of influenza illness in the first three studies was 62% (16 of 26), and only 9% (1 of 11) in the last study (all subjects: P = 0.003; infected subjects: P = 0.01). Even though screening HAI titers were comparable between groups, prechallenge serum influenza-specific IgG titers correlated inversely with respiratory symptoms (P = 0.04). Prechallenge nasal wash influenza-specific IgA titers were lower in subjects who developed influenza illness (P = 0.03). Prechallenge influenza-specific nasal wash ELISA-IgA titers and serum ELISA-IgG titers predicted influenza severity in patients prescreened by HAI during influenza challenge studies.

Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A.

The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind, placebo-controlled, randomized studies. In a study of 476 subjects aged 18 to 55 years, adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day (P less than 0.009). The influenza attack rate in this study was too low to assess efficacy. In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg, 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness (P less than 0.02, 66, 74 and 82% protection, respectively), and in suppressing viral replication (P = 0.02). There was no significant difference between amantadine groups in influenza illness or viral shedding. Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate (100 mg: 40% protection: P = 0.012; 200 mg: 32% protection: P = 0.045) whereas the 50 mg group did not (20% protection: P = 0.187). These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day.

Evaluation of techniques for assessing neurobehavioral development in children.

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.

The dose distribution close to an 192Ir wire source: EGS4 Monte Carlo calculations.

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.

The variation of radon exhalation rates from building surfaces of different ages.

Standardized activated charcoal canisters (according to the U.S. EPA) have been used to collect radon exhaled from concrete surfaces covered with thin plaster (categorically different from thick plaster) of 32 buildings of different ages (0.5-31 y) in Hong Kong. Concrete surfaces covered with thin plaster is the commonest wall configuration in Hong Kong. The canisters are analyzed using gamma spectroscopy to obtain the radon exhalation rates. The results show that the radon exhalation rate decreases with the building age.

The bioconcentration of 131I in fresh water fish.

The dynamic characteristics of the radionuclide concentration process in fresh water fish have been studied. The experimental data for the tilapias were fitted using a simple compartment model to get characteristic parameters such as concentration factors, elimination rate constants, and initial concentration rates, which are 3.08 Bq kg-1/Bq L-1, 0.00573 h-1, and 12.42 Bq kg-1 h-1, respectively. The relative concentrations of 131I in different parts, i.e., head, gills, flesh, bone and internal organs, of the tilapias are also determined, which are found to be 10.8, 15.4, 26.1, 11.0, and 37.0%, respectively. The effects of different factors on the transfer of radionuclides in fresh water fishes are also discussed. Experiments on the tilapias and the common carp show that the variation of concentration factors for different species may be significant even for the same radionuclide and the same ecological system. On the other hand, the variation in the concentration factors for the flesh of the tilapias is not significant for a certain range of 131I concentrations in the water.

A study of factors affecting indoor radon properties.

The factors affecting indoor radon properties in Hong Kong have been studied, including the radon concentration, the total potential alpha energy concentration of radon progeny, the equilibrium factor, and the fraction of unattached radon progeny. These factors fall into three categories, namely, (1) the building characteristics, including cooling method, age of the buildings, wall coverings and floor coverings; (2) the location of sites, including nearby environments, geological materials of the area, and the elevation of the sites; and (3) the meteorological parameters, including rainfall, relative humidity, pressure, temperature, and wind speeds. For category (1), only the ventilation is found to affect the indoor radon properties. For category (2), only the nearby environments have effects. For category (3), the rainfall and temperature are found to have significant effects.

A survey of radon and thoron progeny for dwellings in Hong Kong.

The potential alpha energy concentrations of radon and thoron progeny have been surveyed for dwellings in Hong Kong and the mean values are obtained as 3.58 and 2.29 mWL, respectively. The relative importance of the value for thoron is unexpectedly high, which is attributed to the high 232Th content of the building materials used in Hong Kong. It has also been found that the potential alpha energy concentration values for radon progeny changed dramatically with the season due to the different aerosol contents in the air in different seasons. The factors affecting the potential alpha energy concentration values have also been studied. These factors fall into three categories, namely (1) the building characteristics including age of the buildings, wall coverings and floor coverings; (2) the location of sites including nearby environments and the elevation of the sites; and (3) the meteorological parameters including wind speed, atmospheric pressure, air temperature and relative humidity. For categories (1) and (2), all factors seem to affect the potential alpha energy concentration values, although the effects may be different for radon and thoron progeny, which may be due to the very much different half lives of radon and thoron gas and to the different behavior of radon and thoron progeny in the attachment to aerosols. For category (3), only wind speed has been found to have effects.

Measurement of tracheobronchial dose from simultaneous exposure to environmental radon and thoron progeny.

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.

Radon properties in offices.

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.

Assessment of the transfer of 137Cs in three types of vegetables consumed in Hong Kong.

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.

A preliminary study on the radon concentrations in water in Hong Kong and the associated health effects.

Tap water, flushing water and drinking water including natural mineral water, artificial mineral water and distilled water have been investigated for their radon concentrations. It has been found that the radon concentration in natural mineral water samples is the highest and that in tap water is the second highest, while other categories have values very near to the detection limit. From these the corresponding annual effective doses for the stomach and the lung are determined. It is found that annual effective dose due to direct consumption of water (mineral and tap water) is far greater than that due to inhalation of radon emanated from tap water and flushing water. Moreover, it is also shown that the annual effective doses due to inhalation of radon emanated from tap water and flushing water is negligible when compared to the total annual effective dose for indoor radon in Hong Kong.

A survey of radon properties in underground shopping centers in Hong Kong.

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.

Bronchial Rn dose survey for residences.

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%).

A study of radioactivities in six types of fish consumed 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.