We develop a framework for joint constraints on the CO luminosity function based on power spectra (PS) and voxel intensity distributions (VID) and apply this to simulations of CO Mapping Array ...Pathfinder (COMAP), a CO intensity mapping experiment. This Bayesian framework is based on a Markov chain Monte Carlo (MCMC) sampler coupled to a Gaussian likelihood with a joint PS + VID covariance matrix computed from a large number of fiducial simulations and re-calibrated with a small number of simulations per MCMC step. The simulations are based on dark matter halos from fast peak patch simulations combined with the LCO(Mhalo) model of Li et al. We find that the relative power to constrain the CO luminosity function depends on the luminosity range of interest. In particular, the VID is more sensitive at large luminosities, while the PS and the VID are both competitive at small and intermediate luminosities. The joint analysis is superior to using either observable separately. When averaging over CO luminosities ranging between , and over 10 cosmological realizations of COMAP Phase 2, the uncertainties (in dex) are larger by 58% and 30% for the PS and VID, respectively, when compared to the joint analysis (PS + VID). This method is generally applicable to any other random field, with a complicated likelihood, as long a fast simulation procedure is available.
Abstract
Most large galaxies host supermassive black holes in their nuclei and are subject to mergers, which can produce a supermassive black hole binary (SMBHB), and hence periodic signatures due to ...orbital motion. We report unique periodic radio flux density variations in the blazar PKS 2131−021, which strongly suggest an SMBHB with an orbital separation of ∼0.001–0.01 pc. Our 45.1 yr radio light curve shows two epochs of strong sinusoidal variation with the same period and phase to within ≲2% and ∼10%, respectively, straddling a 20 yr period when this variation was absent. Our simulated light curves accurately reproduce the “red noise” of this object, and Lomb–Scargle, weighted wavelet
Z
-transform and least-squares sine-wave analyses demonstrate conclusively, at the 4.6
σ
significance level, that the periodicity in this object is not due to random fluctuations in flux density. The observed period translates to 2.082 ± 0.003 yr in the rest frame at the
z
= 1.285 redshift of PKS 2131−021. The periodic variation in PKS 2131−021 is remarkably sinusoidal. We present a model in which orbital motion, combined with the strong Doppler boosting of the approaching relativistic jet, produces a sine-wave modulation in the flux density that easily fits the observations. Given the rapidly developing field of gravitational-wave experiments with pulsar timing arrays, closer counterparts to PKS 2131−021 and searches using the techniques we have developed are strongly motivated. These results constitute a compelling demonstration that the phenomenology, not the theory, must provide the lead in this field.
Antifungal compounds exert their activity through a variety of mechanisms, some of which are poorly understood. Novel approaches to characterize the mechanism of action of antifungal agents will be ...of great use in the antifungal drug development process. The aim of the present study was to investigate the changes in the gene expression profile of Saccharomyces cerevisiae following exposure to representatives of the four currently available classes of antifungal agents used in the management of systemic fungal infections. Microarray analysis indicated differential expression of 0.8, 4.1, 3.0, and 2.6% of the genes represented on the Affymetrix S98 yeast gene array in response to ketoconazole, amphotericin B, caspofungin, and 5-fluorocytosine (5-FC), respectively. Quantitative real time reverse transcriptase-PCR was used to confirm the microarray analyses. Genes responsive to ketoconazole, caspofungin, and 5-FC were indicative of the drug-specific effects. Ketoconazole exposure primarily affected genes involved in ergosterol biosynthesis and sterol uptake; caspofungin exposure affected genes involved in cell wall integrity; and 5-FC affected genes involved in DNA and protein synthesis, DNA damage repair, and cell cycle control. In contrast, amphotericin B elicited changes in gene expression reflecting cell stress, membrane reconstruction, transport, phosphate uptake, and cell wall integrity. Genes with the greatest specificity for a particular drug were grouped together as drug-specific genes, whereas genes with a lack of drug specificity were also identified. Taken together, these data shed new light on the mechanisms of action of these classes of antifungal agents and demonstrate the potential utility of gene expression profiling in antifungal drug development.
Silylene insertion into allylic ethers occurs suprafacially to provide enantioenriched allylic silanes and disilanes. Silylene insertion to a variety of protected allylic alcohols utilizing silver- ...and copper-mediated conditions proved to be a general method for allylic silane formation. Allylic disilanes reacted similarly to allylic silanes, undergoing both annulation and allylation reactions.
The large-scale polarization explorer (LSPE) is a cosmology program for the measurement of large-scale curl-like features (B-modes) in the polarization of the cosmic microwave background. Its goal is ...to constrain the background of inflationary gravity waves traveling through the universe at the time of matter-radiation decoupling. The two instruments of LSPE are meant to synergically operate by covering a large portion of the northern microwave sky. LSPE/STRIP is a coherent array of receivers planned to be operated from the Teide Observatory in Tenerife, for the control and characterization of the low-frequency polarized signals of galactic origin; LSPE/SWIPE is a balloon-borne bolometric polarimeter based on 330 large throughput multi-moded detectors, designed to measure the CMB polarization at 150 GHz and to monitor the polarized emission by galactic dust above 200 GHz. The combined performance and the expected level of systematics mitigation will allow LSPE to constrain primordial B-modes down to a tensor/scalar ratio of
10
-
2
. We here report the status of the STRIP pre-commissioning phase and the progress in the characterization of the key subsystems of the SWIPE payload (namely the cryogenic polarization modulation unit and the multi-moded TES pixels) prior to receiver integration.
Interaction of P-selectin with its glycoprotein ligand (P-selectin glycoprotein ligand type 1) mediates inflammatory processes that may also include vascular thrombosis. Platelet P-selectin ...expression is increased in patients with coronary heart disease, and its antagonism represents a potential future therapeutic target for the prevention and treatment of atherothrombosis.
To investigate the effects of the novel small molecule P-selectin antagonist PSI-697 on thrombus formation in humans.
In a double-blind randomized crossover study, thrombus formation was measured in 12 healthy volunteers, using the Badimon ex vivo perfusion chamber under conditions of low and high shear stress. Saline placebo, low-dose (2 m) and high-dose (20 m) PSI-697 and the glycoprotein IIb-IIIa receptor antagonist tirofiban (50 ng mL(-1)) were administered into the extracorporeal circuit prior to the perfusion chamber. As compared with saline placebo, blockade of platelet glycoprotein IIb-IIIa receptor with tirofiban produced 28% and 56% reductions in thrombus formation in the low-shear and high-shear chambers, respectively. PSI-697 caused a dose-dependent, but more modest, reduction in thrombus formation. Low-dose PSI-796 (2 m) reduced total thrombus area by 14% (P = 0.04) and 30% (P = 0.0002) in the low-shear and high-shear chambers, respectively. At the high dose (20 m), PSI-697 reduced total thrombus area by 18% (P = 0.0094) and 41% (P = 0.0008) in the low-shear and high-shear chambers, respectively.
P-selectin antagonism with PSI-697 reduces ex vivo thrombus formation in humans. These findings provide further evidence that P-selectin antagonism may be a potential target for the prevention and treatment of cardiovascular disease.
The Diabetes Control and Complications Trial (DCCT) demonstrated the benefits of intensive treatment of diabetes in reducing glycemic levels and slowing the progression of diabetic nephropathy. The ...DCCT cohort has been examined annually for another 8 years as part of the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. During the EDIC study, glycemic levels no longer differed substantially between the 2 original treatment groups.
To determine the long-term effects of intensive vs conventional diabetes treatment during the DCCT on kidney function during the EDIC study.
Observational study begun in 1993 (following DCCT closeout) in 28 medical centers in the United States and Canada. Participants were 1349 (of 1375) EDIC volunteers who had kidney evaluation at years 7 or 8.
Development of microalbuminuria, clinical-grade albuminuria, hypertension, or increase in serum creatinine level.
Results were analyzed by intention-to-treat analyses, comparing the 2 original DCCT treatment groups. New cases of microalbuminuria occurred during the EDIC study in 39 (6.8%) of the participants originally assigned to the intensive-treatment group vs 87 (15.8%) of those assigned to the conventional-treatment group, for a 59% (95% confidence interval CI, 39%-73%) reduction in odds, adjusted for baseline values, compared with a 59% (95% CI, 36%-74%) reduction at the end of the DCCT (P<.001 for both comparisons). New cases of clinical albuminuria occurred in 9 (1.4%) of the participants in the original intensive-treatment group vs 59 (9.4%) of those in the original conventional-treatment group, representing an 84% reduction in odds (95% CI, 67%-92%), compared with a reduction of 57% (95% CI, -1% to +81%) at the end of the DCCT. Fewer cases of hypertension (prevalence at year 8, 29.9% vs 40.3%; P<.001) developed in the original intensive-treatment group. Significantly fewer participants reached a serum creatinine level of 2 mg/dL or greater in the intensive-treatment vs the conventional-treatment group (5 vs 19, P =.004), but there were no differences in mean log clearance values. Although small numbers of patients required dialysis and/or transplantation, fewer patients experienced either of these outcomes in the intensive group (4 vs 7, P =.36).
The persistent beneficial effects on albumin excretion and the reduced incidence of hypertension 7 to 8 years after the end of the DCCT suggest that previous intensive treatment of diabetes with near-normal glycemia during the DCCT has an extended benefit in delaying progression of diabetic nephropathy.
Long-standing concern about the effects of type 1 diabetes on cognitive ability has increased with the use of therapies designed to bring glucose levels close to the nondiabetic range and the ...attendant increased risk of severe hypoglycemia.
A total of 1144 patients with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study were examined on entry to the DCCT (at mean age 27 years) and a mean of 18 years later with the same comprehensive battery of cognitive tests. Glycated hemoglobin levels were measured and the frequency of severe hypoglycemic events leading to coma or seizures was recorded during the follow-up period. We assessed the effects of original DCCT treatment-group assignment, mean glycated hemoglobin values, and frequency of hypoglycemic events on measures of cognitive ability, with adjustment for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss due to peripheral neuropathy, and (to control for the effects of practice) the number of cognitive tests taken in the interval since the start of the DCCT.
Forty percent of the cohort reported having had at least one hypoglycemic coma or seizure. Neither frequency of severe hypoglycemia nor previous treatment-group assignment was associated with decline in any cognitive domain. Higher glycated hemoglobin values were associated with moderate declines in motor speed (P=0.001) and psychomotor efficiency (P<0.001), but no other cognitive domain was affected.
No evidence of substantial long-term declines in cognitive function was found in a large group of patients with type 1 diabetes who were carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia. (ClinicalTrials.gov number, NCT00360893.)
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