This study examines sequence divergence in three spacer regions of the ribosomal DNA (rDNA) cistron, to test the hypothesis of unequal mutation rates. Portions of two transcribed spacers (ITS-1 and ...5′ ETS) and the non-transcribed spacer (NTS) or intergenic spacer (IGS) formed the basis of comparative analyses. Sequence divergence was measured both within an individual lake trout (
Salvelinus namaycush) and among several related salmonid species (lake trout; brook trout,
Salvelinus fontinalis; Arctic char,
Salvelinus alpinus; Atlantic salmon,
Salmo salar; and brown trout,
Salmo trutta). Despite major differences in the length of the rDNA cistron within individual lake trout, minimal sequence difference was detected among cistrons. Interspecies comparisons found that molecular variation in the rDNA spacers did not conform to the predicted pattern of evolution (ITS spacers<ETS spacers<IGS). Specifically, the IGS contains a region that appears to be as highly, or more conserved than the ITS-1.
This Letter reports the first measurement of the ^{235}U νover ¯_{e} energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MW_{th} ...highly enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) νover ¯_{e}-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to ^{235}U. Despite broad agreement, comparison of the Huber ^{235}U model to the measured spectrum produces a χ^{2}/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured ^{235}U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the νover ¯_{e} energy region of 5-7 MeV.
Glucose and amino acids are key nutrients supporting cell growth. Amino acids are imported as monomers, but an alternative route induced by oncogenic KRAS involves uptake of extracellular proteins ...via macropinocytosis and subsequent lysosomal degradation of these proteins as a source of amino acids. In this study, we examined the metabolism of pancreatic ductal adenocarcinoma (PDAC), a poorly vascularized lethal KRAS-driven malignancy. Metabolomic comparisons of human PDAC and benign adjacent tissue revealed that tumor tissue was low in glucose, upper glycolytic intermediates, creatine phosphate, and the amino acids glutamine and serine, two major metabolic substrates. Surprisingly, PDAC accumulated essential amino acids. Such accumulation could arise from extracellular proteins being degraded through macropinocytosis in quantities necessary to meet glutamine requirements, which in turn produces excess of most other amino acids. Consistent with this hypothesis, active macropinocytosis is observed in primary human PDAC specimens. Moreover, in the presence of physiologic albumin, we found that cultured murine PDAC cells grow indefinitely in media lacking single essential amino acids and replicate once in the absence of free amino acids. Growth under these conditions was characterized by simultaneous glutamine depletion and essential amino acid accumulation. Overall, our findings argue that the scavenging of extracellular proteins is an important mode of nutrient uptake in PDAC.
The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with ...obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4 and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.
We wished to determine the role of hypoxic chemosensitivity in high-altitude pulmonary edema (HAPE) by studying persons when ill and upon recovery. We studied seven males with HAPE and seventeen ...controls at 4,400 m on Mt. McKinley. We measured ventilatory responses to both O2 breathing and progressive poikilocapnic hypoxia. Hypoxic ventilatory response (HVR) was described by the slope relating minute ventilation to percent arterial O2 saturation (delta VE/delta SaO2%). HAPE subjects were quite hypoxemic (SaO2% 59 +/- 6 vs. 85 +/- 1, P less than 0.01) and showed a high-frequency, low-tidal-volume pattern of breathing. O2 decreased ventilation in controls (-20%, P less than 0.01) but not in HAPE subjects. The HAPE group had low HVR values (0.15 +/- 0.07 vs. 0.54 +/- 0.08, P less than 0.01), although six controls had values in the same range. The three HAPE subjects with the lowest HVR values were the most hypoxemic and had a paradoxical increase in ventilation when breathing O2. We conclude that a low HVR plays a permissive rather than causative role in the pathogenesis of HAPE and that the combination of extreme hypoxemia and low HVR may result in hypoxic depression of ventilation.
We present a novel approach for the search of dark matter in the DarkSide-50 experiment, relying on Bayesian Networks. This method incorporates the detector response model into the likelihood ...function, explicitly maintaining the connection with the quantity of interest. No assumptions about the linearity of the problem or the shape of the probability distribution functions are required, and there is no need to morph signal and background spectra as a function of nuisance parameters. By expressing the problem in terms of Bayesian Networks, we have developed an inference algorithm based on a Markov Chain Monte Carlo to calculate the posterior probability. A clever description of the detector response model in terms of parametric matrices allows us to study the impact of systematic variations of any parameter on the final results. Our approach not only provides the desired information on the parameter of interest, but also potential constraints on the response model. Our results are consistent with recent published analyses and further refine the parameters of the detector response model.
The DarkSide experiment aims to perform a background-free direct search for dark matter with a dual-phase argon TPC. The current phase of the experiment, DarkSide-50, is acquiring data at Laboratori ...Nazionali del Gran Sasso and produced the most sensitive limit on the WIMP-nucleon cross section ever obtained with a liquid argon target (2.0 × 10-44 cm2 for a WIMP mass of 100 GeV/c2). The future phase of the experiment will be a 20 t fiducial mass detector, designed to reach a sensitivity of ~1 × 10-47 cm2 (at 1 TeV/c2 WIMP mass) with a background-free exposure of 100 ty. Here, this work contains a discussion of the current status of the DarkSide-50 WIMP search and of the results which are more relevant for the construction of the future detector.
To evaluate the appropriate duration for conducting ocular biocompatibility studies with an intraocular lens (IOL) in the pseudophakic rabbit model.
Alcon Laboratories, Inc., Fort Worth, Texas, USA.
...A single-piece biconvex poly(methyl methacrylate) (PMMA) IOL was implanted in the capsular bag of 18 eyes of New Zealand white rabbits; 8 eyes received sham surgeries. Rabbits were monitored clinically and then sacrificed 6 or 12 months after surgery for histopathological examination of ocular tissues.
Biomicroscopic examination revealed mild ocular changes in all surgical eyes during the first 3 months postoperatively. After that, there was a high incidence of posterior synechias, flare, and posterior capsule opacification (PCO) in eyes with PMMA IOLs. Posterior synechias and flare scores remained mild to moderate throughout the study, whereas PCO severity increased over time. Similar findings were observed in sham eyes. In addition, several eyes with PMMA IOLs developed IOL dislocation, hyphema, iris bombe, and a fibrous membrane covering the IOL. No discernible differences in biomicroscopic scores were observed in eyes at 6 or 12 months. Intraocular pressures and morphology of the corneal endothelium were normal in both groups. Results from histopathological analysis of the ocular tissues were consistent with observations from the biomicroscopic examinations.
The results suggest that IOL implantation studies in the pseudophakic rabbit eye should be conducted for 3 or fewer months. Regulatory guidelines requiring longer ocular implantation studies should be revised to reflect the inherently rapid and extensive ocular response in the rabbit model.
Finding unequivocal evidence of dark matter interactions in a particle detector is a major objective of physics research. Liquid argon time projection chambers offer a path to probe Weakly ...Interacting Massive Particles scattering cross sections on nucleus down to the so-called neutrino floor, in a mass range from few GeV's to hundredths of TeV's. Based on the successful operation of the DarkSide-50 detector at LNGS, a new and more sensitive experiment, DarkSide-20k, has been designed and is now under construction. A thorough understanding of the DarkSide-50 detector response and, therefore, of all kind of observed events, is essential for an optimal design of the new experiment. In this paper, we report on a particular set of events, which were not used for dark matter searches. Namely, standard two-pulse scintillation-ionization signals accompanied by a small amplitude third pulse, originating from single or few electrons, in a time window of less than a maximum drift time. We compare our findings to those of a recent paper of the LUX Collaboration (D.S.Akerib et al. Phys.Rev.D 102, 092004). Indeed, both experiments observe events related to photoionization of the cathode. From the measured rate of these events, we estimate for the first time the quantum efficiency of the tetraphenyl butadiene deposited on the DarkSide-50 cathode at wavelengths around 128 nm, in liquid argon. Also, both experiments observe events likely related to photoionization of impurities in the liquid. The probability of photoelectron emission per unit length turns out to be one order of magnitude smaller in DarkSide-50 than in LUX. This result, together with the much larger measured electron lifetime, coherently hints toward a lower concentration of contaminants in DarkSide-50 than in LUX.
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