75 research outputs found
Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure
Objective: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. Methods: Retrospective analysis of patient records at the Department of Cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients [median (25th-75th percentile)] [age 65 (56-72) years; 79% males; LVEF 34 (31-37) %] were included. Patients underwent a symptomlimited, maximal CPET on a treadmill. During a median follow up of 8.6 ± 2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. Results: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrellâs C-statistic, but the optimal combination of EOV + VE/VCO2 slope + OUES + VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the Heart Failure Survival Score (AUC=0.70;
Extreme population inversion in the fragments formed by UV photoinduced S-H bond fission in 2-thiophenethiol
H atom loss following near ultraviolet photoexcitation of gas phase 2-thiophenethiol molecules has been studied experimentally, by photofragment translational spectroscopy (PTS) methods, and computationally, by ab initio electronic structure calculations. The long wavelength (277.5 ℠λphot â„ 240 nm) PTS data are consistent with SâH bond fission after population of the first 1ÏÏ* state. The partner thiophenethiyl (R) radicals are formed predominantly in their first excited Ă2AâČ state, but assignment of a weak signal attributable to H + R([X with combining tilde]2AâČâČ) products allows determination of the SâH bond strength, D0 = 27 800 ± 100 cmâ1 and the Ăâ[X with combining tilde] state splitting in the thiophenethiyl radical (ÎE = 3580 ± 100 cmâ1). The deduced population inversion between the Ă and [X with combining tilde] states of the radical reflects the non-planar ground state geometry (wherein the SâH bond is directed near orthogonal to the ring plane) which, post-photoexcitation, is unable to planarise sufficiently prior to bond fission. This dictates that the dissociating molecules follow the adiabatic fragmentation pathway to electronically excited radical products. Ï* â Ï absorption dominates at shorter excitation wavelengths. Coupling to the same 1ÏÏ* potential energy surface (PES) remains the dominant dissociation route, but a minor yield of H atoms attributable to a rival fragmentation pathway is identified. These products are deduced to arise via unimolecular decay following internal conversion to the ground (S0) state PES via a conical intersection accessed by intra-ring CâS bond extension. The measured translational energy disposal shows a more striking change once λphot †220 nm. Once again, however, the dominant decay pathway is deduced to be SâH bond fission following coupling to the 1ÏÏ* PES but, in this case, many of the evolving molecules are deduced to have sufficiently near-planar geometries to allow passage through the conical intersection at extended SâH bond lengths and dissociation to ground ([X with combining tilde]) state radical products. The present data provide no definitive evidence that complete ring opening can compete with fast SâH bond fission following near UV photoexcitation of 2-thiophenethiol
Electronic Relaxation Dynamics of UV-Photoexcited 2-AminopurineâThymine Base Pairs in Watson-Crick and Hoogsteen Conformations
The fluorescent analogue 2-aminopurine (2AP) of the canonical nucleobase adenine (6-aminopurine) base-pairs with thymine (T) without disrupting the helical structure of DNA. It therefore finds frequent use in molecular biology for probing DNA and RNA structures and conformational dynamics. However, detailed understanding of the processes responsible for fluorescence quenching remains largely elusive on a fundamental level. Although attempts have been made to ascribe decreased excited-state lifetimes to intrastrand charge-transfer and stacking interactions, possible influences from dynamic interstrand H-bonding have been widely ignored. Here, we investigate the electronic relaxation of UV-excited 2AP center dot T in Watson Crick (WC) and Hoogsteen (HS) conformations. Although the WC conformation features slowed-down, monomer-like electronic relaxation in tau similar to 1.6 ns toward ground-state recovery and triplet formation, the dynamics associated with 2AP center dot T in the HS motif exhibit faster deactivation in tau similar to 70 ps. As recent research has revealed abundant transient interstrand H-bonding in the Hoogsteen motif for duplex DNA, the established model for dynamic fluorescence quenching may need to be revised in the light of our results. The underlying supramolecular photophysical mechanisms are discussed in terms of a proposed excited-state double-proton transfer as an efficient deactivation channel for recovery of the HS species in the electronic ground state
Synthesis of Black Phosphorene Quantum Dots from Red Phosphorus
Phosphorene quantum dots (PQDs) are most commonly derived from high-cost black phosphorus, while previous syntheses from the low-cost red phosphorus (Pred) allotrope are highly oxidised. Herein, we present an intrinsically scalable method to producing high quality PQDs, by first ball-milling Pred to create nanocrystalline Pblack and subsequent reductive etching using lithium electride solvated in liquid ammonia. The resultant ~25 nm PQDs are crystalline with low oxygen content, and spontaneously soluble as individualized monolayers in tertiary amide solvents, as directly imaged by liquid-phase transmission electron microscopy. This new method presents a scalable route to producing quantities of high quality PQDs for academic and industrial applications
Contrasting ring-opening propensities in UV-excited α-pyrone and coumarin
Ring-opening quantum yields following UV-photoexcitation of coumarin and α-pyrone are influenced by the dynamics through, rather than just the geometries of, conical intersections.</p
Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci
ABSTRACT Antimicrobial resistance in Staphylococcus aureus presents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at the oriT region of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by the full 665-residue NES protein in vitro . Second, pSK156 and pCA347 are nonconjugative Staphylococcus aureus plasmids that contain sequences similar to the oriT region of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate the oriT sequences of these nonconjugative plasmids in vitro . Although pSK41 could mobilize a coresident plasmid harboring its cognate oriT , it was unable to mobilize plasmids containing the pSK156 and pCA347 variant oriT mimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-like oriT . These data indicate that the conjugative relaxase in trans mechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids. IMPORTANCE Understanding the mechanism of antimicrobial resistance transfer in bacteria such as Staphylococcus aureus is an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of the Staphylococcus aureus multiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variant oriT -like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase in trans mechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution
N-Heteroacenes as an Organic Gain Medium for Room-Temperature Masers
The development of future quantum devices such as the maser, i.e., the microwave analog of the laser, could be well-served by the exploration of chemically tunable organic materials. Current iterations of room-temperature organic solid-state masers are composed of an inert host material that is doped with a spin-active molecule. In this work, we systematically modulated the structure of three nitrogen-substituted tetracene derivatives to augment their photoexcited spin dynamics and then evaluated their potential as novel maser gain media by optical, computational, and electronic paramagnetic resonance (EPR) spectroscopy. To facilitate these investigations, we adopted an organic glass former, 1,3,5-tri(1-naphthyl)benzene to act as a universal host. These chemical modifications impacted the rates of intersystem crossing, triplet spin polarization, triplet decay, and spinâlattice relaxation, leading to significant consequences on the conditions required to surpass the maser threshold
Jahn-Teller effects in initial and final states: high-resolution X-ray absorption, photoelectron and Auger spectroscopy of allene
Carbon K-edge resonant Auger spectra of gas-phase allene following excitation of the pre-edge 1s â Ï* transitions are presented and analysed with the support of EOM-CCSD/cc-pVTZ calculations. X-Ray absorption (XAS), X-ray photoelectron (XPS), valence band and non-resonant Auger spectra are also reanalysed with a series of computational approaches. The results presented demonstrate the importance of including nuclear ensemble effects for simulating X-ray observables and as an effective strategy for capturing Jahn-Teller effects in spectra
Ultraviolet photochemistry of ethane:implications for the atmospheric chemistry of the gas giants
Chemical processing in the stratospheres of the gas giants is driven by incident vacuum ultraviolet (VUV) light. Ethane is an important constituent in the atmospheres of the gas giants in our solar system. The present work describes translational spectroscopy studies of the VUV photochemistry of ethane using tuneable radiation in the wavelength range 112 †λ †126 nm from a free electron laser and event-triggered, fast-framing, multi-mass imaging detection methods. Contributions from at least five primary photofragmentation pathways yielding CH(2), CH(3) and/or H atom products are demonstrated and interpreted in terms of unimolecular decay following rapid non-adiabatic coupling to the ground state potential energy surface. These data serve to highlight parallels with methane photochemistry and limitations in contemporary models of the photoinduced stratospheric chemistry of the gas giants. The work identifies additional photochemical reactions that require incorporation into next generation extraterrestrial atmospheric chemistry models which should help rationalise hitherto unexplained aspects of the atmospheric ethane/acetylene ratios revealed by the CassiniâHuygens fly-by of Jupiter
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