ABSTRACT We apply a number of statistical and machine learning techniques to classify and rank gamma-ray sources from the Third Fermi Large Area Telescope Source Catalog (3FGL), according to their ...likelihood of falling into the two major classes of gamma-ray emitters: pulsars (PSR) or active galactic nuclei (AGNs). Using 1904 3FGL sources that have been identified/associated with AGNs (1738) and PSR (166), we train (using 70% of our sample) and test (using 30%) our algorithms and find that the best overall accuracy (>96%) is obtained with the Random Forest (RF) technique, while using a logistic regression (LR) algorithm results in only marginally lower accuracy. We apply the same techniques on a subsample of 142 known gamma-ray pulsars to classify them into two major subcategories: young (YNG) and millisecond pulsars (MSP). Once more, the RF algorithm has the best overall accuracy (∼90%), while a boosted LR analysis comes a close second. We apply our two best models (RF and LR) to the entire 3FGL catalog, providing predictions on the likely nature of unassociated sources, including the likely type of pulsar (YNG or MSP). We also use our predictions to shed light on the possible nature of some gamma-ray sources with known associations (e.g., binaries, supernova remnants/pulsar wind nebulae). Finally, we provide a list of plausible X-ray counterparts for some pulsar candidates, obtained using Swift, Chandra, and XMM. The results of our study will be of interest both for in-depth follow-up searches (e.g., pulsar) at various wavelengths and for broader population studies.
We create squeezed light by exploiting the quantum nature of the mechanical interaction between laser light and a membrane mechanical resonator embedded in an optical cavity. The radiation-pressure ...shot noise (fluctuating optical force from quantum laser amplitude noise) induces resonator motion well above that of thermally driven motion. This motion imprints a phase shift on the laser light, hence correlating the amplitude and phase noise, a consequence of which is optical squeezing. We experimentally demonstrate strong and continuous optomechanical squeezing of 1.7±0.2dB below the shot-noise level. The peak level of squeezing measured near the mechanical resonance is well described by a model whose parameters are independently calibrated and that includes thermal motion of the membrane with no other classical noise sources.
Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and ...safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis.
In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values.
A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval CI, -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group.
Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen China Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).
Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with ...chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis.
In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9.
During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period.
In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen China Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).
We study the mechanical quality factors of bilayer aluminum-silicon-nitride membranes. By coating ultrahigh-Q Si(3)N(4) membranes with a more lossy metal, we can precisely measure the effect of ...material loss on Q's of tensioned resonator modes over a large range of frequencies. We develop a theoretical model that interprets our results and predicts the damping can be reduced significantly by patterning the metal film. Using such patterning, we fabricate Al-Si(3)N(4) membranes with ultrahigh Q at room temperature. Our work elucidates the role of material loss in the Q of membrane resonators and informs the design of hybrid mechanical oscillators for optical-electrical-mechanical quantum interfaces.
The polarization dependence of the photoconductivity response at cyclotron-resonance harmonics in a nondegenerate two-dimensional (2D) electron system formed on the surface of liquid helium is ...studied using a setup in which a circular polarization of opposite directions can be produced. Contrary to the results of similar investigations reported for semiconductor 2D electron systems, for electrons on liquid helium, a strong dependence of the amplitude of magnetoconductivity oscillations on the direction of circular polarization is observed. This observation is in accordance with theoretical models based on photon-assisted scattering, and, therefore, it presents a principal argument in the dispute over the origin of microwave-induced conductivity oscillations.
AIM: The goal of this study was to investigate the synergic effects between magnolol and azoles, and the potential antifungal mechanisms. METHODS AND RESULTS: Microdilution checkerboard, time‐kill ...and agar diffusion assay were employed to evaluate the synergic effects between magnolol and fluconazole (FLC). Magnolol significantly decreased the efflux of rhodamine 123 (Rh123), leading to greater intracellular accumulation of Rh123 in Candida albicans cells. Compared to the Candida drug resistance (cdr) 2 or multidrug resistance (mdr) 1 deletion mutant, the growth of cdr1 strain was most sensitive to magnolol exposure. In the presence of magnolol, MDR1 overexpressing cells were sensitive to FLC, whereas CDR1 and CDR2 overexpressing cells displayed tolerance to FLC. Magnolol treatment correlated with up‐regulation of transporter and ergosterol biosynthesis pathway genes, analyzed by real‐time reverse transcription‐polymerase chain reaction. The ergosterol content of C. albicansSC5314 was significantly decreased after magnolol exposure. CONCLUSIONS: Magnolol synergizes with azoles for targeting of C. albicans by inducing a higher intracellular content of antifungals, by tapping into the competitive effect of ABC transporter Cdr1p substrates, and enhancing the effect by targeting of the ergosterol biosynthesis pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains.
PDF
