Context.
The narrow-line Seyfert 1 galaxy Mrk 335 was one of the X-ray brightest active galactic nuclei, but it has systematically faded since 2007.
Aims.
We report the discovery with
Swift
of a ...sequence of bright and rapid X-ray flare events that reveal the emergence of Mrk 335 from its ultra-deep multiyear low state.
Methods.
Results are based on our dedicated multiyear monitoring of Mrk 335 with
Swift
.
Results.
Unlike other bright active galactic nuclei, the optical–UV is generally not correlated with the X-rays in Mrk 335 on a timescale of days to months. This fact either implies the absence of a direct link between the two emission components; or else implies that the observed X-rays are significantly affected by (dust-free) absorption along our line of sight. The UV and optical, however, are closely correlated at the 99.99% confidence level. The UV is leading the optical by Δ
t
= 1.5 ± 1.5 d. The
Swift
X-ray spectrum shows strong deviations from a single power law in all brightness states of the outbursts, indicating that significant absorption or reprocessing is taking place. Mrk 335 displays a softer-when-brighter variability pattern at intermediate X-ray count rates, which has been seen in our
Swift
data since 2007 (based on a total of 590 observations). This pattern breaks down at the highest and lowest count rates.
Conclusions.
We interpret the 2020 brightening of Mrk 335 as a decrease in column density and covering factor of a partial-covering absorber along our line of sight in the form of a clumpy accretion-disk wind that reveals an increasing portion of the intrinsic emission of Mrk 335 from the disk and/or corona region, while the optical emission-line regions receive a less variable spectral energy distribution. This then also explains why Mrk 335 was never seen to change its optical Seyfert type (not “changing look”) despite its factor ∼50 X-ray variability with
Swift
.
As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). ...Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.
Background and Purpose
There is growing interest in expanding healthy eating interventions in the retail setting. The purpose of this study was to evaluate the implementation of a successful 2-for-1 ...price incentive for fruits and vegetables (F&V), including frozen and canned, that took place in partnership with a large chain grocery retailer in Maine. Intervention Approach. A randomized controlled trial (RCT) pilot study was conducted in 2015–2016, followed by a larger RCT in 2016–2017, to assess whether a supermarket double-dollar F&V incentive increased purchases of these items.
Evaluation Methods
A convergent, parallel mixed-methods design was used to examine barriers and facilitators to implementing the interventions, using six implementation outcomes: acceptability, adoption, appropriateness, feasibility, implementation fidelity, and perceived cost.
Results
The intervention was deemed highly acceptable, appropriate, and feasible by shoppers, retailers, and researchers. The F&V discount had a high rate of initial adoption. There was a moderate degree of fidelity, which improved over time based on lessons learned from the pilot and applied to the subsequent RCT. Specific costs associated with implementation from the research perspective are reported. Implications for Practice, Policy, and Research. Partnerships between academic researchers and retailers can be an effective model for improving healthful purchases among shoppers. These findings are relevant for investigators, public health advocates, and retailers interested in implementing similar grocery retail-based interventions.
Monomeric Cu(I) amido and thiolate complexes that are supported by the N-heterocyclic carbene ligand 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) catalyze the hydroamination and ...hydrothiolation of electron-deficient vinylarenes with reactivity patterns that are consistent with an intermolecular nucleophilic addition of the amido/thiolate ligand of (IPr)Cu(XR) (X = NH or S; R = Ph, CH2Ph) to free vinylarene.
The monomeric Cu(I) complexes (IPr)Cu(Z) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, Z = NHPh, OEt, or OPh) react with YH (Y = PhNH, PhCH2NH, EtO, or PhO) to catalytically add Y−H bonds ...across the CC bond of electron-deficient olefins to yield anti-Markovnikov organic products. Catalytic activity has been observed for olefins CH2C(H)(X) with X = CN, C(O)Me, or CO2Me as well as crotononitrile. Preliminary studies implicate an intermediate in which the C−Y bond forms through a nucleophilic addition pathway.
The monomeric copper(I) alkyl complexes (IPr)Cu(R) R = Me or Et; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene react with substrates that possess N−H, O−H, and acidic C−H bonds to form ...monomeric systems of the type (IPr)Cu(X) (X = anilido, phenoxide, ethoxide, phenylacetylide, or N-pyrrolyl) and methane or ethane. Solid-state X-ray crystal structures of the anilido, ethoxide, and phenoxide complexes confirm that they are monomeric systems. Experimental studies on the reaction of (IPr)Cu(Me) and aniline to produce (IPr)Cu(NHPh) suggest that a likely reaction pathway is coordination of aniline to Cu(I) followed by proton transfer to produce methane and the copper(I) anilido complex.
Monomeric copper(I) amido, alkoxide, and aryloxide complexes catalyze the addition of N−H and O−H bonds of amines and alcohols, respectively, to electron-deficient olefins. The ancillary ligands of ...the active catalysts include the N-heterocyclic carbene (NHC) ligands IPr, IMes, and SIPr {IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene} as well as the chelating bisphosphine ligand dtbpe {dtbpe = 1,2-bis(di-tert-butylphosphino)ethane}. For the hydroamination and hydroalkoxylation of olefins, both aromatic and alkyl substituents can be incorporated into the nucleophile, and both primary and secondary amines are reactive. Monosubstituted and disubstituted olefins have been demonstrated to undergo reaction. For the addition of aniline to acrylonitrile, kinetic studies suggest a pathway that is dependent on the concentration of amine, olefin, and catalyst as well as inversely proportional to the concentration of the product 3-anilinopropionitrile. At low concentrations, the addition of tert-butylisonitrile increases the rate of catalysis. The proposed mechanism involves N−C or O−C bond formation by an intermolecular nucleophilic addition of the amido, alkoxide, or aryloxide ligand to free olefin.
OBJECTIVES
To investigate the potential therapeutic benefits of the selective α1A/1l‐adrenoceptor partial agonist Ro 115–1240 in women with mild‐to‐moderate stress urinary incontinence (SUI).
...PATIENTS AND METHODS
Thirty‐seven women with mild‐to‐moderate SUI were enrolled in a randomized, placebo‐controlled crossover study. Patients received 1.5 mg Ro 115–1240 twice daily or matching placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI episodes, urge incontinence episodes and pads used. Sitting blood pressures and heart rate were recorded at each visit.
RESULTS
Ro 115–1240 was associated with a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs 6.0; P= 0.0079), a 28% relative improvement over placebo. There was also a significantly lower mean number of pads used and wet pads changed/week with Ro 115–1240 than with placebo (P = 0.0055 and 0.0066, respectively). The most frequently reported treatment‐emergent adverse events were scalp tingling, headache, chills, piloerection, and pruritus. Generally these events were transient and mild to moderate. There was a slightly lower mean sitting heart rate with Ro 115–1240 than with placebo, but no difference in mean systolic or diastolic blood pressure between treatments.
CONCLUSIONS
This study suggests that selective α1A/1l‐adrenoceptor partial agonists have the potential to improve the symptoms of SUI with little or no cardiovascular effect. These results are encouraging and a randomized controlled trial of Ro 115–1240 in a larger population with SUI is warranted to substantiate these findings.
PDF
