Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Photonic ring resonator filters for astronomical OH suppression.

Ring resonators provide a means of filtering specific wavelengths from a waveguide, and optionally dropping the filtered wavelengths into a second waveguide. Both of these features are potentially useful for astronomical instruments. In this paper we focus on their use as notch filters to remove the signal from atmospheric OH emission lines from astronomical spectra. We derive the design requirements for ring resonators for OH suppression from theory and finite difference time domain simulations. We find that rings with small radii (< 10 µm) are required to provide an adequate free spectral range, leading to high index contrast materials such as Si and Si3N4. Critically coupled rings with high self-coupling coefficients should provide the necessary Q factors, suppression depth, and throughput for efficient OH suppression, but will require post-inscription tuning of the coupling and the resonant wavelengths. The overall prospects for the use of ring resonators in astronomical instruments is promising, provided efficient fibre-chip coupling can be achieved.

Constitutive differences between natural and artificial container mosquito habitats: vector communities, resources, microorganisms, and habitat parameters.

Aquatic containers, including tree holes and vehicle tires, harbor a diverse assemblage of mosquitoes capable of vectoring important diseases. Many studies have examined containers as a mosquito breeding site, although no data exist that have simultaneously compared mosquito communities between tree holes and tires, and few have quantified differences in environmental factors or food resources that may be important for explaining population or community differences. At two times (early and late summer 2009) we sampled two tire and two tree hole sites in south-central Mississippi, and for each container we enumerated mosquito larvae and measured several environmental parameters (canopy cover, water volume, and detritus), and biomass and productivity of fungi and bacteria, and species richness and abundance of protozoans. Tree holes held less water but were more shaded compared with tires; however, after correcting for volume differences, tree holes contained more detritus and were higher in some microorganism measures (protozoan richness, bacterial productivity in the water column). Based on community dissimilarity analysis of mosquitoes, strong differences existed between container types and sampling period; Aedes albopictus (Skuse) and Culex quinquefasciatus (Say) were dominant in tires, whereas Ae. triseriatus (Say) and Orthopodomyia signifera (Coquillett) were dominant in tree holes. This study also reports the use of tires by the invasive mosquito Cx. coronator (Dyar and Knab). Tree holes supported a higher density of larvae but fewer species than tires, though there was variation across time. Our work illustrates that detrital inputs and some microorganisms differ in fundamental ways between tires and tree holes, and because of compositional differences in mosquito communities, these small aquatic habitats cannot be considered to be homogeneous mosquito habitats.

New anti-infective coatings of medical implants.

Implantable devices are highly susceptible to infection and are therefore a major risk in surgery. The present work presents a novel strategy to prevent the formation of a biofilm on polytetrafluoroethylene (PTFE) grafts. PTFE grafts were coated with gentamicin and teicoplanin incorporated into different lipid-like carriers under aseptic conditions in a dipping process. Poly-d,l-lactic acid, tocopherol acetate, the diglyceride Softisan 649, and the triglyceride Dynasan 118 were used as drug carriers. The drug release kinetics, anti-infective characteristics, biocompatibility, and hemocompatibility of the coatings developed were studied. All coatings showed an initial drug burst, followed by a low continuous drug release over 96 h. The dimension of release kinetics depended on the carrier used. All coated prostheses reduced bacterial growth drastically over 24 h, even below pathologically relevant concentrations. Different cytotoxic levels could be observed, revealing tocopherol acetate as the most promising biocompatible carrier. A possible reason for the highly cytotoxic effect of Softisan 649 could be assessed by demonstrating incorporated lipids in the cell soma with Oil Red O staining. Tromboelastography studies, enzyme-linked immunosorbent assays, and an amidolytic substrate assay could confirm the hemocompatibility of individual coatings. The development of the biodegradable drug delivery systems described here and in vitro studies of those systems highlight the most important requirements for effective as well as compatible anti-infective coatings of PTFE grafts. Through continuous local release, high drug levels can be produced at only the targeted area and physiological bacterial proliferation can be completely inhibited, while biocompatibility as well as hemocompatibility can be ensured.

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector.

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam.

AIMS AND METHODS: Alcohol withdrawal treatment efficacy of tiapride/carbamazepine (A) vs clomethiazole (B) vs diazepam (C) in non-intoxicated patients and vs tiapride/carbamazepine in intoxicated patients (D; breath alcohol concentration > or = 1 g/l) was tested (n = 127) in a controlled randomized open-label study. RESULTS: Efficacy and safety were not different between groups (total group: delirium, 3.9%; seizure, 0.8%), except for a lack of efficacy in 18% of intoxicated tiapride/carbamazepine patients. A change of medication in this group was necessary only when primarily intoxicated patients had reached the non-intoxicated range. CONCLUSIONS: Treatment with tiapride/carbamazepine in alcohol-intoxicated patients proved to be safe.

Influence of the dopamine D2 receptor (DRD2) exon 8 genotype on efficacy of tiapride and clinical outcome of alcohol withdrawal.

We tested the hypothesis that allelic variants of the human dopamine D2 receptor E8 genotype are associated with (i) dopamine D2 antagonist tiapride dose in treatment of alcohol withdrawal (n = 50) and (ii) with anxiety and depression in patients during alcoholism detoxification therapy (admission n = 87; discharge n = 50). DRD2 E8 A/A genotype was associated with increased dose of tiapride during a 9-day detoxification therapy and with increased anxiety and depression scores on admission and 2 weeks later. The findings suggest a pharmacogenetic influence of DRD2 E8 genotype on tiapride efficacy in alcohol withdrawal. In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the dopamine D2 agonist apomorphine; however, it is not clear whether both findings share the same biological basis. Earlier findings concerning association of DRD2 E8 A/A with increased anxiety and depression are replicated for the first time.

Osmoregulatory Responses of Fungi Inhabiting Standing Litter of the Freshwater Emergent Macrophyte Juncus effusus.

Standing litter of emergent macrophytes often forms a major portion of the detrital mass in wetland habitats. Microbial assemblages inhabiting this detritus must adapt physiologically to daily fluctuations in temperature and water availability. We examined the effects of various environmental conditions on the concentrations of osmoregulatory solutes (polyols and trehalose) and the respiratory activities of fungal assemblages inhabiting standing litter of the freshwater emergent macrophyte Juncus effusus. Under field conditions, the concentrations of osmolytes (polyols plus trehalose) in fungal decomposers were negatively correlated with plant litter water potentials (r = -0.75, P < 0.001) and rates of microbial respiration (r = -0.66, P < 0.001). The highest concentration of osmolytes (polyols plus trehalose) occurred in standing litter exposed to desiccating conditions (range from wet to dry, 0.06 to 0.68 mumol . mg of fungal biomass). Similar fluctuations in polyol and trehalose concentrations were observed in standing litter wetted and dried under laboratory conditions and for four predominant fungal decomposers of J. effusus grown individually on sterilized Juncus leaves. These studies suggest that fungal inhabitants associated with standing litter of emergent macrophytes can adjust their intracellular solute concentrations in response to daily fluctuations in water availability.

Effect of simulated American, Bulgarian, and Japanese human diets and of selenium supplementation on the incidence of virally induced mammary tumors in female mice.

In attempts to simulate the effects of diet on human breast cancer development groups of female C3H mice infected with mammary tumor virus (MMTV-) were maintained on diets formulated to resemble the typical American, Bulgarian, and Japanese human diets. The incidence of mammary tumors was the highest (84%) in group of mice receiving the simulated meat- and fat-rich American diet, which was also low in selenium (Se content: 0.15 ppm). The appearance of mammary tumors was delayed in the mice maintained on the simulated Bulgarian diet, and the final tumor incidence (27%) paralleled the correspondingly lower Bulgarian breast cancer incidence. The simulated Bulgarian diet contained more Se (0.25 ppm), and was lower in fat, meat, and sugar and higher in complex carbohydrates (cereals) than the simulated American diet. In the mice fed the simulated Japanese diet, the appearance of mammary tumors was also delayed, and the tumor incidence was diminished to 47%. In this diet, fish meal was a major source of Se, which is known to have low bioavailability. Additional supplementation of the Japanese-type diet with bioavailable Se (1 ppm) lowered the tumor incidence to 10%. Based on these studies, recommendations are made for breast cancer risk reduction by dietary means.

Selenium in the blood of Japanese and American women with and without breast cancer and fibrocystic disease.

Selenium concentrations in whole blood of Japanese and American women with and without breast cancer and benign fibrocystic breast disease were determined. The observed blood Se levels of healthy Japanese women (0.286 +/- 0.021 micrograms/ml) were similar to previously reported values for healthy Japanese adults. The Japanese patients with benign breast disease and with breast cancer exhibited blood selenium concentrations of 0.200 +/- 0.045 and 0.195 +/- 0.057 micrograms/ml, respectively. The mean blood Se concentration of Japanese breast cancer patients with recurrence was 0.188 +/- 0.061 micrograms/ml. The mean blood Se concentrations of healthy American women from San Diego, Calif., were 0.191 +/- 0.023 micrograms/ml; of women with benign fibrocystic disease, 0.142 +/- 0.010 micrograms/ml; and of breast cancer patients, 0.167 +/- 0.032 micrograms/ml. The higher blood Se concentrations of Japanese healthy subjects as compared to healthy Americans can be attributed to differences in the dietary Se intakes; low blood Se concentration may be indicative of increased breast cancer risk.

Chemotherapy and trace element levels in blood and tissue of rats implanted with prostate tumor cells.

Male Copenhagen rats with transplanted prostatic adeno-carcinoma were treated with different polyamine synthesis inhibitors, such as methylglyoxal-bis-guanylhydrazone (MGBG), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) combined with 9-ß-D-arabin-ofuranosyl-adenine (ARA-A), α-difluoromethyl-ornithine (DFMO), and some of their combinations. Levels of the essential trace elements-copper, zinc, magnesium, iron, selenium, and manganese -have been determined in blood, tumor, kidney, and liver of these animals and are discussed in terms of efficiency of the treatment. MGBG had the strongest effect on trace element levels in tissues of treated animals. MGBG combined with DFMO exhibited the highest antitumor activity of all treatment protocols. Selenium given as selenite with drinking water was used as an adjuvant with the most toxic combination, (ARA-A/EHNA, MGBG). Selenite reduced the toxicity of these therapeutic agents.

Reduction of gastric acid secretion. The efficacy of pre-anaesthetic oral cimetidine in children.

Cimetidine 10 mg/kg orally was given at varying times from 60 to 240 minutes pre-operatively to 100 healthy children between the ages of 6 months and 14 years. Cimetidine proved to be most effective when given between 120 and 180 minutes before the induction of anaesthesia. All patients in this group had a gastric pH of more than 2.5 and the mean volume aspirated was also significantly lower than that in the control group. The average peak blood concentration after 10 mg/kg oral cimetidine in four healthy children was 3.25 micrograms/ml (range 1.20-4.80) and occurred 75 minutes after administration (range 60-120 minutes). In these patients the mean (SD) half-life of cimetidine was 138 (18) minutes. The reduction of gastric juice volume and acidity produced by 10 mg/kg oral cimetidine given 120-180 minutes prior to induction of anaesthesia has important clinical implications.

Dietary antioxidants and the biochemical response to oxidant inhalation : III. Selenium influence on mouse lung response and tolerance to ozone.

We fed female strain A/St mice selenium (Se) test diets containing either no Se (-Se) or 1 ppm Se (+Se) for 11 wk. Both diets contained 55 ppm vitamin E. We then exposed three groups of mice from each dietary regimen to either 0.8 ppm (1568 µg/m(3)) O3 (low-level) continuously for 5 d, 10.0 ppm (19,600 µg/m(3)) O3 (high-level) for 12 h, or filtered room air, where the latter served as a control for both O3 exposures. After O3 exposures we analyzed the lungs for various physical and biochemical parameters, and compared the results to those obtained from the air controls. The results showed that the difference in dietary Se intake produced an eightfold difference in Se content and a three-fold difference in glutathione peroxidase (GP) activity in the lung, but few changes in other lung parameters. With low-level O3 exposure, NADPH production increased significantly in +Se mice, but did not change in -Se mice. With high-level O3 exposure we observed comparable effects for both dietary regimens, including animal mortality, which was 24% for -Se and 14% for +Se mice. Thus, it seems that diminished GP activity resulting from Se deficiency and the ensuing lack of increase in NADPH production were poorly correlated with mouse tolerance to O3. The lung Se content increased in both dietary regimens after O3 exposure, but the increase was greater after high-level O3 exposure. This suggests a "mobilization" of Se to the lung under O3 stress. It is possible that such a mobilization contributes to the lung reserve of antioxidants, and hence the comparable mortality in both dietary Se regimens.

Dietary antioxidants and the biochemical response to oxidant inhalation. II. Influence of dietary selenium on the biochemical effects of ozone exposure in mouse lung.

We examined the influence of dietary selenium (Se) on the pulmonary biochemical response to ozone (O3) exposure. For 11 weeks, weanling female strain A/St mice were fed a test diet containing Se either at 0 ppm (-Se) or 1 ppm (+Se). Each diet contained 55 ppm vitamin E (vit E). Mice from each dietary group were exposed to 0.8 +/- 0.05 ppm (1568 +/- 98 micrograms/m3) O3 continuously for 5 days. After O3 exposure, they were killed along with a matched number of unexposed controls, and their lungs were analyzed for various biochemical parameters. The Se contents of lung tissue and whole blood were determined, and the levels were seven- to eightfold higher in +Se mice than in -Se mice, reflecting the Se intake of the animals. In unexposed control mice, Se deficiency caused a decline in glutathione peroxidase (GP) activity relative to +Se group. After O3 exposure, the GP activity in the -Se group was associated with a lack of stimulation of glutathione reductase (GR) activity and the pentose phosphate cycle (PPC) as assessed by measuring glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities. In contrast, the +Se group after O3 exposure exhibited increases in all four enzyme activities. Other parameters, e.g., lung weight, total lung protein, DNA and nonprotein sulfhydryl contents, and O2 consumption, were not affected by dietary Se in the presence or absence of O3 exposure. The data indicate that dietary Se alters the GP activity, which in turn influences the GR and PPC activities in the lung evidently through a reduced demand for NADPH. The level of vit E in the lung was found to be twofold higher in the -Se group than in the +Se group, suggesting a compensatory relationship between Se and vit E in the lung. With O3 exposure, both Se and vit E contents further increased in the lungs of each dietary group. It is plausible that Se and vit E under oxidant stress are "mobilized" to the lung from other body sites.

Dissolution half-times of nickel compounds in water, rat serum, and renal cytosol.

Seventeen nickel compounds were incubated in water, rat serum, and rat renal cytosol for 72 hr at 37 degrees C. Concentrations of dissolved nickel were analyzed by electrothermal atomic absorption spectrophotometry, and dissolution half-times (T50) were computed by the Weibull equation. Eleven of the nickel compounds (Ni, beta NiS, amorphous NiS, alpha Ni3S2, NiSe, Ni3Se2, NiTe, NiAs, Ni11As8, Ni5As2, and NiFeS4) dissolved more rapidly in serum or cytosol than in water. Four of the compounds (NiO, NiSb, NiFe alloy, and NiTiO3) had no detectable dissolution in any of the media (i.e., T50 greater than 11 yr). One compound (NiAsS) had approximately equal T50 values in the three media; the T50 value of one compound (NiS2) could not be determined in serum or cytosol owing to precipitation. T50 value of 34 and 21 days for dissolution of alpha Ni3S2 in serum and cytosol, respectively, agree closely with the excretion half-time of 24 days derived from previously reported data for excretion of 63Ni in urine and feces of rats after intramuscular injection of alpha 63Ni3S2. These findings suggest that in vitro dissolution half-times of nickel compounds may be used to predict their in vivo excretion half-times, since the dissolution process is rate-limiting to their metabolism and excretion.

Effects of long term exposure to beer on the genesis and development of spontaneous mammary adenocarcinoma and prolactin levels in female virgin C3H/St mice.

The exposure of female inbred virgin C3H/St mice infected with the Bittner particle to a commercial brand of beer increases body weight but has no significant effects on survival, the incidence of spontaneous mammary adenocarcinoma, tumor latency, or growth even on continuous administration of beer in place of drinking water over the entire postweaning lifespan of the animals. Prolactin excretion in young beer-group mice was slightly elevated but not significantly different from the prolactin levels observed in normally maintained control animals.

Phagocytosis of particulate nickel compounds by rat peritoneal macrophages in vitro.

Phagocytic indices of 17 nickel compounds were measured in vitro in monolayer cultures of rat peritoneal macrophages. The macrophages were exposed for 1 h at 37 degrees C to particles (1.5 micrometer median diameter) of the nickel compounds, at concentrations of 10 microgram/ml of medium (2 microgram/cm2 of monolayer). Phagocytic induces (i.e., the percentages of macrophages with one or more engulfed particles) ranged from 69% (NiO) to 3% (amorphous NiS). In order to decreasing phagocytic indices, the 17 nickel compounds were ranked as follows: NiO greater than Ni4FeS4 greater than NiTiO3 greater than NiSe greater than alpha Ni3S2 greater than Ni greater than Ni5As2 greater than NiS2 greater than NiFe alloy greater than NiSb greater than Ni11As8 greater Ni3-Se2 greater than beta NiS greater than NiTe greater than NiAs greater than NiAsS greater than amorphous NiS. Rank-correlation (P less than 0.03) was observed between the phagocytic indices of the nickel compounds and their dissolution half-times in rat serum. Nickel subsulfide, alpha Ni3S2, was a notable exception to the general concordance between phagocytic indices and dissolution half-times: alpha Ni3S2 was avidly phagocytized by macrophages, yet it had one or the shortest dissolution half-times. Preliminary results of carcinogenesis tests of 14 of the nickel compounds do not indicate significant rank-correlation between the phagocytic indices of the nickel compounds and the sarcoma incidences at 1 yr after i.m. administration of the compounds to rats.

Effects of dietary selenium and of lead on the genesis of spontaneous mammary tumors in mice.

Selenium added to the diet significantly lowers the incidence of spontaneous mammary adenocarcinoma in female inbred C3H/St mice infected with the Bittner Milk Factor. Lead, 5 ppm, added to the drinking water in the form of the acetate, diminishes the uptake of selenium and reduces its anticarcinogenic effects, causing mammary tumors to appear with the same high incidence as in Se-unsupplemented controls. At higher lead concentrations in the drinking water (25 ppm), the overall tumor incidence is lowered, but tumor growth is significantly accelerated and the survival of tumor-bearing mice is shortened. Under the conditions of administration chosen, lead acts as a selenium antagonist and lowers the concentrations of selenium in liver, kidney, and spleen. The deposition of selenium, copper, and arsenic in bone is increased as compared to lead-unexposed controls.

Effects of temporary selenium supplementation on the genesis of spontaneous mammary tumors in inbred female C3H/St mice.

Female inbred C3H/St mice infected with the Bittner Milk Particle, develop mammary adenocarcinoma with 27% incidence if maintained on a Torula Yeast diet supplemented with 1 ppm of selenium (organically bound, in yeast). Animals switched from the 1 ppm Se diet to a diet containing only 0.15 ppm Se after reaching the age of 13.8 months develop mammary tumors rapidly during their remaining lifespan, the overall tumor incidence reaches 69%, not statistically different from the 77% incidence of tumors observed in animals maintained on the 0.15 ppm Se diet over their entire post-weaning life span. Conversely, animals changed from the 0.15 ppm Se diet to that containing 1.0 ppm Se at the age of 13.8 months develop mammary tumors with a total incidence of only 46%, significantly lower (P < 0.05) than in the 0.15 ppm Se control group. This study demonstrates that dietary selenium prevents and retards tumor development only as long as it is supplied in adequate amounts, consistent with its role as a non-accumulative trace nutrient.