716 research outputs found
New developments in canine hepatozoonosis in North America: a review
Canine hepatozoonosis is caused by Hepatozoon canis and Hepatozoon americanum, apicomplexan parasites transmitted to dogs by ingestion of infectious stages. Although the two agents are phylogenetically related, specific aspects, including characteristics of clinical disease and the natural history of the parasites themselves, differ between the two species. Until recently, H. canis infections had not been clearly documented in North America, and autochthonous infection with H. americanum has yet to be reported outside of the southern United States. However, recent reports demonstrate H. canis is present in areas of North America where its vector tick, Rhipicephalus sanguineus, has long been endemic, and that the range of H. americanum is likely expanding along with that of its vector tick, Amblyomma maculatum; co-infections with the two organisms have also been identified. Significant intraspecific variation has been reported in the 18S rRNA gene sequence of both Hepatozoon spp.-infecting dogs, suggesting that each species may represent a complex of related genogroups rather than well-defined species. Transmission of H. americanum to dogs via ingestion of cystozoites in muscle of infected vertebrates was recently demonstrated, supporting the concept of predation as a means of natural transmission. Although several exciting advances have occurred in recent years, much remains to be learned about patterns of infection and the nature of clinical disease caused by the agents of canine hepatozoonosis in North America
Anisotropic optical properties of single-crystal GdBa2Cu3O7-delta
The optical spectrum of reduced-T(c) GdBa2Cu3O7-delta has been measured for polarizations parallel and perpendicular to the ab plane. The sample was an oxygen-deficient single crystal with a large face containing the c axis. The polarized reflectance from this face was measured from 20-300 K in the spectral region from 30-3000 cm-1, with 300 K data to 30 000 cm-1. Kramers-Kronig analysis was used to determine the spectral dependence of the ab and the c components of the dielectric tensor. The optical properties are strongly anisotropic. The ab-plane response resembles that of other reduced-T(c) materials whereas the c axis, in contrast, shows only the presence of several phonons. There is a complete absence of charge carrier response along c above and below T(c). This observation allows us to set an upper limit to the free-carrier spectral weight for transport perpendicular to the CuO2 planes
Recommended from our members
The XMM-Newton Wide field survey in the COSMOS field: redshift evolution of AGN bias and subdominant role of mergers in triggering moderate luminosity AGN at redshift up to 2.2
We present a study of the redshift evolution of the projected correlation
function of 593 X-ray selected AGN with I_AB<23 and spectroscopic redshifts
z<4, extracted from the 0.5-2 keV X-ray mosaic of the 2.13 deg^2 XMM-COSMOS
survey. We introduce a method to estimate the average bias of the AGN sample
and the mass of AGN hosting halos, solving the sample variance using the halo
model and taking into account the growth of the structure over time. We find
evidence of a redshift evolution of the bias factor for the total population of
XMM-COSMOS AGN from b(z=0.92)=2.30 +/- 0.11 to b(z=1.94)=4.37 +/- 0.27 with an
average mass of the hosting DM halos logM [h^-1 M_sun] ~ 13.12 +/- 0.12 that
remains constant at all z < 2. Splitting our sample into broad optical lines
AGN (BL), AGN without broad optical lines (NL) and X-ray unobscured and
obscured AGN, we observe an increase of the bias with redshift in the range
z=0.7-2.25 and z=0.6-1.5 which corresponds to a constant halo mass logM [h^-1
M_sun] ~ 13.28 +/- 0.07 and logM [h^-1 M_sun] ~ 13.00 +/- 0.06 for BL /X-ray
unobscured AGN and NL/X-ray obscured AGN, respectively. The theoretical models
which assume a quasar phase triggered by major mergers can not reproduce the
high bias factors and DM halo masses found for X-ray selected BL AGN with L_BOL
~ 2e45 erg s^-1. Our work extends up to z ~ 2.2 the z <= 1 statement that, for
moderate luminosity X-ray selected BL AGN, the contribution from major mergers
is outnumbered by other processes, possibly secular such as tidal disruptions
or disk instabilities.Comment: 16 emulateapj pages, 18 figures and 3 tables. Accepted for the
publication in The Astrophysical Journa
Enantioselective metabolism of primaquine by human CYP2D6
BACKGROUND: Primaquine, currently the only approved drug for the treatment and radical cure of Plasmodium vivax malaria, is still used as a racemic mixture. Clinical use of primaquine has been limited due to haemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. Earlier studies have linked its therapeutic effects to CYP2D6-generated metabolites. The aim of the current study was to investigate the differential generation of the CYP2D6 metabolites by racemic primaquine and its individual enantiomers. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers were incubated with recombinant cytochrome-P450 supersomes containing CYP2D6 under optimized conditions. Metabolite identification and time-point quantitative analysis were performed using LC-MS/MS. UHPLC retention time, twin peaks with a mass difference of 6, MS-MS fragmentation pattern, and relative peak area with respect to parent compound were used for phenotyping and quantitative analysis of metabolites. RESULTS: The rate of metabolism of (+)-(S)-primaquine was significantly higher (50% depletion of 20 μM in 120 min) compared to (−)-(R)-primaquine (30% depletion) when incubated with CYP2D6. The estimated V(max) (μmol/min/mg) were 0.75, 0.98 and 0.42, with K(m) (μM) of 24.2, 33.1 and 21.6 for (±)-primaquine, (+)-primaquine and (−)-primaquine, respectively. Three stable mono-hydroxylated metabolites, namely, 2-, 3- and 4-hydroxyprimaquine (2-OH-PQ, 3-OH-PQ, and 4-OH-PQ), were identified and quantified. 2-OH-PQ was preferentially formed from (+)-primaquine in a ratio of 4:1 compared to (−)-primaquine. The racemic (±)-primaquine showed a pattern similar to the (−)-primaquine; 2-OH-PQ accounted for about 15–17% of total CYP2D6-mediated conversion of (+)-primaquine. In contrast, 4-OH-PQ was preferentially formed with (−)-primaquine (5:1), accounting for 22% of the total (−)-primaquine conversion. 3-OH-PQ was generated from both enantiomers and racemate. 5-hydroxyprimaquine was unstable. Its orthoquinone degradation product (twice as abundant in (+)-primaquine compared to (−)-primaquine) was identified and accounted for 18–20% of the CYP2D6-mediated conversion of (+)-primaquine. Other minor metabolites included dihydroxyprimaquine species, two quinone-imine products of dihydroxylated primaquine, and a primaquine terminal alcohol with variable generation from the individual enantiomers. CONCLUSION: The metabolism of primaquine by human CYP2D6 and the generation of its metabolites display enantio-selectivity regarding formation of hydroxylated product profiles. This may partly explain differential pharmacologic and toxicologic properties of primaquine enantiomers
Enantioselective metabolism of primaquine by human CYP2D6
BACKGROUND: Primaquine, currently the only approved drug for the treatment and radical cure of Plasmodium vivax malaria, is still used as a racemic mixture. Clinical use of primaquine has been limited due to haemolytic toxicity in individuals with genetic deficiency in glucose-6-phosphate dehydrogenase. Earlier studies have linked its therapeutic effects to CYP2D6-generated metabolites. The aim of the current study was to investigate the differential generation of the CYP2D6 metabolites by racemic primaquine and its individual enantiomers. METHODS: Stable isotope (13)C-labelled primaquine and its two enantiomers were incubated with recombinant cytochrome-P450 supersomes containing CYP2D6 under optimized conditions. Metabolite identification and time-point quantitative analysis were performed using LC-MS/MS. UHPLC retention time, twin peaks with a mass difference of 6, MS-MS fragmentation pattern, and relative peak area with respect to parent compound were used for phenotyping and quantitative analysis of metabolites. RESULTS: The rate of metabolism of (+)-(S)-primaquine was significantly higher (50% depletion of 20 μM in 120 min) compared to (−)-(R)-primaquine (30% depletion) when incubated with CYP2D6. The estimated V(max) (μmol/min/mg) were 0.75, 0.98 and 0.42, with K(m) (μM) of 24.2, 33.1 and 21.6 for (±)-primaquine, (+)-primaquine and (−)-primaquine, respectively. Three stable mono-hydroxylated metabolites, namely, 2-, 3- and 4-hydroxyprimaquine (2-OH-PQ, 3-OH-PQ, and 4-OH-PQ), were identified and quantified. 2-OH-PQ was preferentially formed from (+)-primaquine in a ratio of 4:1 compared to (−)-primaquine. The racemic (±)-primaquine showed a pattern similar to the (−)-primaquine; 2-OH-PQ accounted for about 15–17% of total CYP2D6-mediated conversion of (+)-primaquine. In contrast, 4-OH-PQ was preferentially formed with (−)-primaquine (5:1), accounting for 22% of the total (−)-primaquine conversion. 3-OH-PQ was generated from both enantiomers and racemate. 5-hydroxyprimaquine was unstable. Its orthoquinone degradation product (twice as abundant in (+)-primaquine compared to (−)-primaquine) was identified and accounted for 18–20% of the CYP2D6-mediated conversion of (+)-primaquine. Other minor metabolites included dihydroxyprimaquine species, two quinone-imine products of dihydroxylated primaquine, and a primaquine terminal alcohol with variable generation from the individual enantiomers. CONCLUSION: The metabolism of primaquine by human CYP2D6 and the generation of its metabolites display enantio-selectivity regarding formation of hydroxylated product profiles. This may partly explain differential pharmacologic and toxicologic properties of primaquine enantiomers
Removing krypton from xenon by cryogenic distillation to the ppq level
The XENON1T experiment aims for the direct detection of dark matter in a
cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired
sensitivity, the background induced by radioactive decays inside the detector
has to be sufficiently low. One major contributor is the -emitter
Kr which is an intrinsic contamination of the xenon. For the XENON1T
experiment a concentration of natural krypton in xenon Kr/Xe < 200
ppq (parts per quadrillion, 1 ppq = 10 mol/mol) is required. In this
work, the design of a novel cryogenic distillation column using the common
McCabe-Thiele approach is described. The system demonstrated a krypton
reduction factor of 6.410 with thermodynamic stability at process
speeds above 3 kg/h. The resulting concentration of Kr/Xe < 26 ppq
is the lowest ever achieved, almost one order of magnitude below the
requirements for XENON1T and even sufficient for future dark matter experiments
using liquid xenon, such as XENONnT and DARWIN
Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment
The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410
has been developed by Hamamatsu for dark matter direct detection experiments
using liquid xenon as the target material. We present the results from the
joint effort between the XENON collaboration and the Hamamatsu company to
produce a highly radio-pure photosensor (version R11410-21) for the XENON1T
dark matter experiment. After introducing the photosensor and its components,
we show the methods and results of the radioactive contamination measurements
of the individual materials employed in the photomultiplier production. We then
discuss the adopted strategies to reduce the radioactivity of the various PMT
versions. Finally, we detail the results from screening 216 tubes with
ultra-low background germanium detectors, as well as their implications for the
expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure
Gas Accretion and Star Formation Rates
Cosmological numerical simulations of galaxy evolution show that accretion of
metal-poor gas from the cosmic web drives the star formation in galaxy disks.
Unfortunately, the observational support for this theoretical prediction is
still indirect, and modeling and analysis are required to identify hints as
actual signs of star-formation feeding from metal-poor gas accretion. Thus, a
meticulous interpretation of the observations is crucial, and this
observational review begins with a simple theoretical description of the
physical process and the key ingredients it involves, including the properties
of the accreted gas and of the star-formation that it induces. A number of
observations pointing out the connection between metal-poor gas accretion and
star-formation are analyzed, specifically, the short gas consumption time-scale
compared to the age of the stellar populations, the fundamental metallicity
relationship, the relationship between disk morphology and gas metallicity, the
existence of metallicity drops in starbursts of star-forming galaxies, the
so-called G dwarf problem, the existence of a minimum metallicity for the
star-forming gas in the local universe, the origin of the alpha-enhanced gas
forming stars in the local universe, the metallicity of the quiescent BCDs, and
the direct measurements of gas accretion onto galaxies. A final section
discusses intrinsic difficulties to obtain direct observational evidence, and
points out alternative observational pathways to further consolidate the
current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics
and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by
Springe
Search for Two-Neutrino Double Electron Capture of Xe with XENON100
Two-neutrino double electron capture is a rare nuclear decay where two
electrons are simultaneously captured from the atomic shell. For Xe
this process has not yet been observed and its detection would provide a new
reference for nuclear matrix element calculations. We have conducted a search
for two-neutrino double electron capture from the K-shell of Xe using
7636 kgd of data from the XENON100 dark matter detector. Using a
Bayesian analysis we observed no significant excess above background, leading
to a lower 90 % credibility limit on the half-life
yr. We also evaluated the sensitivity of the XENON1T experiment, which is
currently being commissioned, and find a sensitivity of
yr after an exposure of 2 tyr.Comment: 6 pages, 4 figure
- …