The effect of a single administration of morphine sulfate (15 mg/kg, s.c. or 30 mg/kg, i.p., 30 min) on Ca2+-stimulated Mg2+-dependent ATPase activity was investigated in synaptosomal plasma ...membranes (SPM) prepared from rat cortex. Morphine produced a significant decrease in Ca2+,Mg2+-ATPase activity in synaptosomal fractions (SPM 1 + 2) known to contain a high density of opiate receptors and calmodulin-dependent Ca2+,Mg2+-ATPase. However, in another subpopulation (SPM 3) that contains fewer opiate receptors and less enzyme activity, no such decrease in the enzyme activity was observed after the opiate administration. The decrease in Ca2+,Mg2+-ATPase activity seen in SPM 1 + 2 was specifically antagonized by the opiate antagonist naloxone hydrochloride (2 mg/kg, s.c.) when given 15 min before morphine administration. Mg2+-ATPase was not altered either by morphine or by a naloxone-morphine combination. These findings give further evidence for the role of intracellular Ca2+ in mediating many of the acute effects of opiates.
A system was designed to allow the physiological monitoring of a fully mobile, unstressed baboon (Papio anubis) in a single animal cage for the purpose of measuring the changes occurring in a ...hyperbaric environment. It was required to operate for at least three months, both inside a pressure chamber and outside, and to measure the following parameters; electroencephalogram (EEG, three channels), electrooculogram (EOG), electromyelogram (EMG, two channels), electrocardiogram (ECG), arterial blood pressure, respiration and body temperature. Also in the system were catheters through which blood samples could be taken and intravenous drugs given. The overall system consisted of a harness and jacket, and umbilical and back pack, a combined electrical and fluid transmission swivel and a monitoring implant and catheters.
The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia ...(PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS (n=4), high-risk (HR)SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.
Abstract
We describe the algorithm used to select the emission line galaxy (ELG) sample at z ∼ 0.85 for the extended Baryon Oscillation Spectroscopic Survey of the Sloan Digital Sky Survey IV, using ...photometric data from the DECam Legacy Survey. Our selection is based on a selection box in the g − r versus r − z colour–colour space and a cut on the g-band magnitude, to favour galaxies in the desired redshift range with strong
${{\rm O}\,\small {II}}$
emission. It provides a target density of 200 deg−2 on the North Galactic Cap and of 240 deg−2 on the South Galactic Cap (SGC), where we use a larger selection box because of deeper imaging. We demonstrate that this selection passes the extended Baryon Oscillation Spectroscopic Survey requirements in terms of homogeneity. About 50 000 ELGs have been observed since the observations have started in 2016, September. These roughly match the expected redshift distribution, though the measured efficiency is slightly lower than expected. The efficiency can be increased by enlarging the redshift range and with incoming pipeline improvement. The cosmological forecast based on these first data predict
$\sigma _{D_V}/D_V = 0.023$
, in agreement with previous forecasts. Lastly, we present the stellar population properties of the ELG SGC sample. Once observations are completed, this sample will be suited to provide a cosmological analysis at z ∼ 0.85, and will pave the way for the next decade of massive spectroscopic cosmological surveys, which heavily rely on ELGs. The target catalogue over the SGC will be released along with DR14.
We have assessed the role of growth hormone-releasing hormone (GHRH) as a diagnostic test in 40 children and young adults with growth hormone deficiency (GHD), principally using the GHRH(1-29)NH2 ...analogue. Following 200 micrograms GHRH as an acute intravenous bolus, serum GH rose to normal or just subnormal levels in 13 out of 17 children with structural lesions, and in 8 of 14 patients with idiopathic GHD or panhypopituitarism. Of 9 children (mean age 12 years) with GHD following treatment with cranial irradiation for nonendocrine tumours, all responded acutely to GHRH. 12- and 24-hour infusions with GHRH(1-29)NH2, and 1- and 2-week treatments with twice-daily subcutaneous GHRH(1-29)NH2, showed persistent stimulation of GH release. It is concluded that many children with GHD of diverse aetiology will respond both acutely and chronically to treatment with GHRH.
We present a detailed investigation of the variability of 428 C IV and 235 Si IV broad absorption line (BAL) troughs identified in multi-epoch observations of 291 quasars by the Sloan Digital Sky ...Survey-I/II/III. These observations primarily sample rest-frame timescales of 1-3.7 yr over which significant rearrangement of the BAL wind is expected. We derive a number of observational results on, e.g., the frequency of BAL variability, the velocity range over which BAL variability occurs, the primary observed form of BAL-trough variability, the dependence of BAL variability upon timescale, the frequency of BAL strengthening versus weakening, correlations between BAL variability and BAL-trough profiles, relations between C IV and Si IV BAL variability, coordinated multi-trough variability, and BAL variations as a function of quasar properties. We assess implications of these observational results for quasar winds. Our results support models where most BAL absorption is formed within an order-of-magnitude of the wind-launching radius, although a significant minority of BAL troughs may arise on larger scales. We estimate an average lifetime for a BAL trough along our line-of-sight of a few thousand years. BAL disappearance and emergence events appear to be extremes of general BAL variability, rather than being qualitatively distinct phenomena. We derive the parameters of a random-walk model for BAL EW variability, finding that this model can acceptably describe some key aspects of EW variability. The coordinated trough variability of BAL quasars with multiple troughs suggests that changes in "shielding gas" may play a significant role in driving general BAL variability.
Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG-6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies, from ...accreting stellar-mass black holes and even from accreting neutron stars. The iron K line is prominent in the reflection spectrum created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion of the line makes it sensitive to the strong gravity and spin of the black hole. The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
We study the modelling of the halo occupation distribution (HOD) for the eBOSS DR16 emission line galaxies (ELGs). Motivated by previous theoretical and observational studies, we consider ...different physical effects that can change how ELGs populate haloes. We explore the shape of the average HOD, the fraction of satellite galaxies, their probability distribution function (PDF), and their density and velocity profiles. Our baseline HOD shape was fitted to a semi-analytical model of galaxy formation and evolution, with a decaying occupation of central ELGs at high halo masses. We consider Poisson and sub/super-Poissonian PDFs for satellite assignment. We model both Navarro–Frenk–White and particle profiles for satellite positions, also allowing for decreased concentrations. We model velocities with the virial theorem and particle velocity distributions. Additionally, we introduce a velocity bias and a net infall velocity. We study how these choices impact the clustering statistics while keeping the number density and bias fixed to that from eBOSS ELGs. The projected correlation function, wp, captures most of the effects from the PDF and satellites profile. The quadrupole, ξ2, captures most of the effects coming from the velocity profile. We find that the impact of the mean HOD shape is subdominant relative to the rest of choices. We fit the clustering of the eBOSS DR16 ELG data under different combinations of the above assumptions. The catalogues presented here have been analysed in companion papers, showing that eBOSS RSD+BAO measurements are insensitive to the details of galaxy physics considered here. These catalogues are made publicly available.
A V617F mutation in the Janus kinase 2 gene (
JAK2
) occurs in most patients with polycythemia vera and in many with essential thrombocythemia or idiopathic myelofibrosis. The mutation causes ...unregulated signaling by the cytoplasmic tyrosine kinase of the JAK2 protein. The authors describe new mutations in exon 12 of
JAK2
in patients with polycythemia vera or idiopathic erythrocytosis who do not have the V617F mutation. The exon 12 mutations, which also induce unregulated signaling by JAK2, appear to define a distinctive myeloproliferative syndrome.
The authors describe new mutations in exon 12 of
JAK2
in patients with polycythemia vera or idiopathic erythrocytosis who do not have the V617F mutation.
The myeloproliferative disorders comprise a spectrum of chronic hematologic diseases that are likely to arise from a mutant multipotent hematopoietic stem cell.
1
,
2
The V617F somatic mutation in the Janus kinase (JAK) 2 gene (
JAK2
), which causes the substitution of phenylalanine for valine at position 617, has recently been found in the majority of patients with polycythemia vera and in many with essential thrombocythemia or idiopathic myelofibrosis.
3
–
7
This gene encodes a cytoplasmic tyrosine kinase. The mutation, which occurs in the JAK homology 2 (JH2) negative regulatory domain, increases JAK2 kinase activity and causes cytokine-independent growth of cell . . .
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