LF State Research Articles

Prognosis of low-flow low-gradient aortic valve stenosis with atrial fibrillation

Abstract Background Patients with Low-flow low-gradient (LFLG) aortic valve stenosis (AS) have possibly poor prognosis. Recently, it was reported that the LFLG AS patients have similar outcomes compared to high-gradient (HG) patients but worse outcomes compared to the normal-flow low-gradient [NFLG: SVi≥35 ml/m2, mPG <40mmHg] subgroup. The main determinant of LF state in severe AS patients with preserved LVEF are male gender, heart rate, LV volume and atrial fibrillation (AF). However, the relationship between the comorbidity with AF in LFLG AS and the risk of heart failure (HF) remains unclear. Purpose We elucidated about the prognosis of LFLG AS with AF. Methods We included 225 consecutive patients with severe AS (SAS, iAVA<0.6 cm2/m2) from 2013 to 2020. Among these patients, high-gradient SAS [HG-SAS; mean pressure gradient (mPG) ≥40 mmHg, n=88] and LFLG AS [stroke volume index (SVi) ≤35 ml/m2, mPG <40 mmHg, n=82] patients was extracted and the baseline characteristics including the presence or absence of AF were evaluated. The primary endpoint was worsening HF that required unplanned hospitalization or readjustment of HF drug therapy. Results Among patients with HG SAS and LFLG AS, worsening HF was observed in 65 patients. LFLG AS patients exhibited a higher oral rate of renin-angiotensin-system inhibitors (p=0.02). In addition, SVi and E/e' was lower in LFLG AS patients compared with HG SAS [SVi; 29.4 (24.4–34.0) versus 37.7 (28.2–45.3), p<0.0001, E/E'; 16.0 (13.1–21.5) vs 20.9 (16.0–27.4), p=0.002]. There is no differences between 2 groups in AF prevalence. Furthermore, 2 groups were subdivided as follow; HG SAS with AF (n=25), HG SAS without AF (n=63), LFLG AS with AF (n=24), LFLG AS without AF (n=58). The Kaplan Meier curves demonstrated LFLG SAS with AF experienced higher rate of worsening HF compared with HG SAS without AF and equivalent rate of worsening HF compared with HG SAS with AF (log rank, p<0.001). In the Cox hazard analysis among the LFLG AS patients, LFLG AS with paroxysmal AF (pAF, n=12) instead of chronic AF (cAF, n=12) showed a higher risk for worsening HF compared with those without AF (HR 5.0; 95% CI, 1.8–14; p=0.0028, HR 1.9; 95% CI, 0.62–5.8; p=0.26, respectively). Conclusion LFLG AS with AF exhibited a poor prognosis for HF compared with HG SAS without AF and equivalent rate of worsening HF compared with HG SAS with AF. Furthermore, the presence of pAf was associated with an increased risk of HF in patients with LFLF AS. Thus, intervention including drugs and catheter ablation for pAF in LFLG AS patients could lead to prevent worsening clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Effects of herd fertility on the economics of sexed semen in a high-producing, pasture-based dairy production system

This study used a stochastic simulation model to estimate the potential economic benefit of using sexed semen in heifers only and in heifers and lactating cows in a high-producing, pasture-based system under 3 fertility scenarios. Three breeding strategies were modeled: (1) only heifers inseminated with sexed semen and cows inseminated with conventional unsexed semen (SSH); (2) both heifers and cows inseminated with sexed semen (SSHC); and (3) a reference scenario in which all females were inseminated with conventional, unsexed semen (CONV). Each scenario was evaluated under 3 herd fertility states: high (HF), medium (MF), and low (LF), which, under the reference scenario, corresponded to herd replacement rates of 21, 25, and 31%, respectively. The model estimated the economic profit, including the net present value of the genetic gain from selection intensity. The economic return from adoption of sexed semen strategies declined, with reduced levels of baseline herd fertility turning negative in the LF state. The mean (±SD) sexed semen advantage (SSA) per cow for HF-SSH, MF-SSH, and LF-SSH scenarios were €30.61 ± 8.98, €27.45 ± 7.19, and €14.69 ± 11.06, respectively. However, the SSA per cow for HF-SSHC, MF-SSHC, and LF-SSHC scenarios were €49.14 ± 15.43, €18.46 ± 30.08, and -€19.30 ± 57.11. The range in economic profit for SSA for SSH was most sensitive to calf prices in HF-SSH and the pregnancy rate of sexed semen as a percentage of conventional unsorted semen in MF-SSH and LF-SSH. The range in economic profit for SSA for SSHC scenarios was most sensitive to the pregnancy rate of sexed semen as a percentage of conventional unsorted semen in HF-SSHC, MF-SSHC, and LF-SSHC. This study highlights the effect of baseline herd fertility state on the financial advantage of adopting sexed semen in a pasture-based dairy production system.

High-density reflection spectroscopy: I. A case study of GX 339-4

We present a broad band spectral analysis of the black hole binary GX~339-4 with NuSTAR and Swift using high density reflection model. The observations were taken when the source was in low flux hard states (LF) during the outbursts in 2013 and 2015, and in a very high flux soft state (HF) in 2015. The high density reflection model can explain its LF spectra with no requirement for an additional low temperature thermal component. This model enables us to constrain the density in the disc surface of GX~339-4 in different flux states. The disc density in the LF state is $\log(n_{\rm e}/$ cm$^{-3})\approx21$, 100 times higher than the density in the HF state ($\log(n_{\rm e}/$ cm$^{-3})=18.93^{+0.12}_{-0.16}$). A close-to-solar iron abundance is obtained by modelling the LF and HF broad band spectra with variable density reflection model ($Z_{\rm Fe}=1.50^{+0.12}_{-0.04}Z_{\odot}$ and $Z_{\rm Fe}=1.05^{+0.17}_{-0.15}Z_{\odot}$ respectively).

Increasing energy flux to decrease the biological drive toward weight regain after weight loss – A proof-of-concept pilot study

Weight loss induces compensatory biological adjustments that increase hunger and decrease resting metabolic rate (RMR), which increase propensity for weight regain. In non-obese adults high levels of physical activity coupled with high energy intake (high energy flux) are associated with higher RMR and reduced hunger. We tested the possibility that a high flux state attenuates the increase in hunger and the decrease in RMR characteristic of diet-induced weight loss. Six obese adults [age (mean±SE)=42±12y; body mass index (BMI)=35.7±3.7kg/m2] underwent measures of RMR, the thermic effect of a meal (TEM), and fasting and postprandial measures of hunger and fullness as well as plasma glucose and insulin. Following weight loss, subjects completed two 5-day conditions of energy balance in random order-Low Flux (LF): sedentary with energy intake (EI)=RMR (kcal/d)×1.35; and High Flux (HF): net exercise energy cost of ∼500kcal/d and EI=RMR (kcal/d)×1.7. RMR was measured daily for each flux condition. The morning following each of the respective experimentally controlled HF and LF conditions (flux day 5), they underwent the same pre-weight loss tests and also reported their perceptions of hunger and fullness during the previous four days of HF and LF, respectively. Average daily RMR was higher during HF (1926±138kcal/day) compared to LF (1847±126kcal/day; P<0.05). Perceived hunger at the end of day was lower (p<0.03) and fullness throughout the day was higher (p<0.02) in HF compared to LF conditions. On day 5 of each flux condition, the thermic effect of a meal and circulating glucose and insulin after the meal did not differ between HF and LF. Following weight loss, compared to a sedentary LF state of energy balance, a short-term HF energy balance state is associated with higher RMR, lower perceived hunger, and greater perceived fullness, all of which could help attenuate the biologic drive to regain weight. Given the pilot nature of this study and the relatively short period of time spent in the high and low flux states, future research is needed to address this research question in a larger sample over a longer time period.

New Ru(II) complexes for dual photoreactivity: ligand exchange and (1)O2 generation.

Uncovering the factors that govern the electronic structure of Ru(II)-polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and (1)O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field ((3)LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer ((3)MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2](2+) (bpy = 2,2'-bipyridine; L = CH3CN or py). This suggests that population of the (3)LF state proceeds from the vibrationally excited (3)MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the (3)LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)](2+) complexes (tpy = 2,2':6',2″-terpyridine; NN = bpy, 6,6'-dimethyl-2,2'-bipyridine (Me2bpy), 2,2'-biquinoline (biq)) increases by 2-3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the (3)LF state within 3-7 ps when NN is bulky, and density functional theory calculations support stabilized (3)LF states. Dual activity via ligand dissociation and (1)O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2](2+) (dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) and [Ru(tpy)(Me2dppn)(py)](2+) (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine) introduces low-lying, long-lived dppn/Me2dppn (3)ππ* excited states that generate (1)O2. Similar to [Ru(bpy)2(CH3CN)2](2+), photodissociation of CH3CN occurs upon irradiation of [Ru(bpy)(dppn)(CH3CN)2](2+), although with lower efficiency because of the presence of the (3)ππ* state. The steric bulk in [Ru(tpy)(Me2dppn)(py)](2+) is critical in facilitating the photoinduced py dissociation, as the analogous complex [Ru(tpy)(dppn)(py)](2+) produces (1)O2 with near-unit efficiency. The ability to tune the relative energies of the excited states provides a means to design potentially more active drugs for photochemotherapy because the photorelease of drugs can be coupled to the therapeutic action of reactive oxygen species, effecting cell death via two different mechanisms. The lessons learned about tuning of the excited-state properties can be applied to the use of Ru(II)-polypyridyl compounds in a variety of applications, such as solar energy conversion, sensors and switches, and molecular machines.

Visible‐Light Photochromism of Triarylamine‐ or Ferrocene‐Bound Diethynylethenes that Switches Electronic Communication between Redox Sites and Luminescence

Redox-active ferrocene- and triarylamine-terminated diethynylethene derivatives have been synthesized and their photochromic properties and switching behavior based on through-bond electronic communication between the two redox sites, as well as their emissions, have been examined. Both bis(ferrocenylethynyl)ethene 1 and bis(triarylaminoethynyl)ethene 2 show visible-light photochromism induced by donor-acceptor charge-transfer (CT) transitions from the ferrocene or triarylamine to the diethynylethene moieties. The reversibility and quantum yields of the photochromism of 2 (Phi(E-->Z)=6.1 x 10(-2), Phi(Z-->E)=1.4 x 10(-2)) are far higher than those of 1 (Phi(E-->Z)=8.6 x 10(-6), Phi(Z-->E)=2.5 x 10(-6)). The higher efficiency in 2 may be attributed to the absence of the heavy atom effect and of a low-lying (3)LF state, which are characteristic of ferrocenyl compounds. This proposition is further supported by the fact that bis(ferrocenylbuta-1,3-diynyl)ethene 3, which, unlike 1, is free from steric interference between the two ferrocenyl groups in the Z form, does not show a significant improvement in its photoisomerization quantum yields (Phi(E-->Z)=6.2x10(-5), Phi(Z-->E)=3.4 x 10(-5)). The visible-light photochromism of 1 and 2 is accompanied by a switch in the strength of the electronic communication between the two redox sites in their mixed-valence states (DeltaE(0)' values are 70 and 48 mV for (E)-1 and (Z)-1, and 74 and 63 mV for (E)-2 and (Z)-2). In the case of 2, further evaluations were carried out through intervalence charge-transfer (IVCT) band analyses and DFT calculations. We have also demonstrated that steric repulsion between the methyl ester moieties in the Z form is implicated in the reduction in the through-bond electronic communication. Compound 2 exhibits photoluminescence, which is more efficient in the E form than in the Z form, whereas 1 and 3 show no photoluminescence.

Excited state properties of norbornadiene adducts of nickel(II), palladium(II) and platinum(II) bis-1,2-diphenyl-1,2-dithiolene complexes

The norbornadiene adducts of nickel(II) and palladium(II) bis-1,2-diphenyl-1,2-dithiolene complexes, M(S 2C 2Ph 2) 2×C 7H 8, are rather light sensitive. In solution they release the olefin with high quantum yields ( φ∼0.2). It is suggested that the reactive excited state is of the LF type. The liberation of the olefin is a consequence of the steric strain of the tetradentate ligand in the LF state which is distorted toward a tetrahedral coordination. On the contrary, the corresponding platinum complex Pt(S 2C 2Ph 2) 2×C 7H 8 is only slightly light sensitive ( φ∼0.02), but shows a room temperature luminescence ( λ max=520 nm; φ=4.5×10 −3) which originates from a IL/MLCT excited state.

Photoluminescence of dicyclopentadienylniobium(IV) complexes

The absorption spectra of the d 1 complexes (C 5H 5)Nb IVCl 2 and [(C 5H 5)Nb IV(2,2′-bipyridine)] 2+ show longest-wavelength absorptions at 340 and 350 nm, respectively, which are assigned to LMCT or, more likely, LF transitions. Both complexes are luminescent at 77 K with λ max≈600 nm. The emission is a spin-allowed process and may originate from the lowest LF state.

Metal–CO photodissociation in transition metal complexes:: The role of ligand-field and charge-transfer excited states in the photochemical dissociation of metal–ligand bonds

The photodissociation of a CO ligand from a series of d 6 metal–carbonyl complexes, with various other substituents (Cl, α-diimine, H, Mn(CO) 5) is discussed. The considerations are based on calculations of potential energy curves, using a density functional method. Particular attention is given to the long-standing question of the possible role of charge-transfer excited states in the photodissociation. Such CT states exist at relatively high energy (ca. 4 eV) in an unsubstituted complex like Cr(CO) 6, but at much lower energy if α-diimine ligands are introduced. For Cr(CO) 6, it is argued that the classical interpretation of the Cr–CO photodissociation upon excitation into the weak intensity low energy band in the spectrum at ca. 4 eV, due to the occupation of a ligand-field excited state having to be revised: the lowest excited state, from which the photodissociation occurs, has a charge-transfer character at R e. The LF excited states are much higher in energy. They decrease in energy rapidly, however, upon Cr–CO bond lengthening, so the dissociation is due to an avoided crossing of the CT state with a LF state. This photodissociation mechanism does not depend on the nature of the lowest excited state and is shown to be operative in a variety of d 6 systems Mn(CO) 5L (L=H, Cl or Mn(CO) 5). This immediately explains the relatively high yield of CO dissociation upon low energy excitation in Mn 2(CO) 10 and MnCl(CO) 5, even though the excitation is to an Mn–L σ* LUMO orbital. Mn–L bond breaking has very different quantum yields in these compounds, which is also explained from the electronic structure. Finally, equatorial substitution with an α-diimine ligand with low-lying π* orbitals generates MnCl(CO) 3( α-diimine). The CT states in this case are so low that excitation does not provide enough energy for CO dissociation if the atomic configuration is kept fixed. Nevertheless, dissociation can occur by an altogether different mechanism that involves relaxation of the Cl from axial to equatorial position upon equatorial CO departure.

Synthesis and Photophysical Properties of Zeolite-Entrapped Bisterpyridine Ruthenium(II). Dramatic Consequences of Ligand-Field-State Destabilization

A bisterpyridine complex of ruthenium(II) (Ru(tpy)22+) has been prepared in zeolite Y supercages and investigated by electronic absorption, electronic emission, and resonance Raman spectroscopy. In free solution this complex is practically nonluminescent, having a very short excited-state lifetime (250 ps) at room temperature. However, entrapment within the zeolite supercage results in dramatic increases in emission intensity and excited-state lifetime (140 ns) at room temperature. The observed temperature dependence of the excited-state lifetime has been modeled by a kinetic equation with two thermal terms corresponding to the so-called fourth 3MLCT state and ligand-field state (LF), respectively. It is shown that the increased lifetime of the entrapped complex results from zeolite-induced destabilization of the LF state, a conclusion which is in agreement with results obtained for a number of other zeolite-entrapped ruthenium(II) polypyridine complexes.

Comparing the spectroscopic and electrochemical properties of ruthenium and osmium complexes of the tridentate polyazine ligands 2,2′:6′,2″-terpyridine and 2,3,5,6-tetrakis(2-pyridyl)pyrazine

A number of osmium and ruthenium complexes of the tridentate ligands 2,2′:6′,2″-terpyridine (tpy) and 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tpp) have been prepared and characterized by our laboratory. All these complexes possess metal based oxidations and ligand based reductions localized on each polyazine ligand. Polymetallic complexes bridged by the tpp ligand exhibit two sequential tpp based reductions prior to the reduction of other polyazine ligands in these complexes. The spectroscopy of these complexes is dominated by ligand based π-π ∗ transitions in the ultraviolet and MLCT (metal-to-ligand charge transfer) bands terminating on each polyzine ligand in the visible. For the complexes reported herein the lowest lying optical transitionis a M → BL CT band. For most of the complexes reported, occupation of this excited state gives rise to an observable emission at room temperature. For ruthenium complexes of these tridentate ligands, the presence of a low-lying LF state shortens the excited state lifetimes of these chromophores. This gives rise to ruthenium complexes that display shorter excited state lifetimes than the analogous osmium based systems. Incorporation of tpp based chromophores into polymetallic frameworks leads to the production of bimetallic species with long-lived excited states, ∼ 100 ns at room temperature. This makes these chromophores good candidates for the development of stereochemically defined supramolecular complexes. It is possible to measure an electrochemical HOMO-LUMO energy gap and a correlation between this electrochemically measured energy gap and the spectroscopic energy associated with this HOMO→LUMO transition are reported herein (HOMO== highest occupied molecular orbital, LUMO = lowest unoccupied molecular orbital).

Dramatic Increase of 3MLCT State Lifetimes of a Ruthenium(II) Polypyridine Complex upon Entrapment within Y-Zeolite Supercages

A bis-heteroleptic, tris-ligated polypyridine complex of ruthenium(II) (Ru(bpy){sub 2}(daf){sup 2+}) has been prepared in zeolite Y supercages and investigated by electronic absorption, electronic emission, and resonance Raman spectroscopy. While liquid solutions of this complex exhibit very weak luminescence with excited-state lifetime shorter than 10 ns at room temperature, entrapment in zeolite supercage results in dramatic increases in emission intensity and lifetime (302 ns at room temperature), providing access to practically important potential photoredox reactivity of the complex. The observed temperature dependence of the excited-state lifetime has been modeled by a kinetic equation with two thermal terms corresponding to the so-called fourth {sup 3}MLCT state and ligand field state (LF), respectively. It is shown that the increased lifetime of the entrapped complex results from zeolite-induced destabilization of the LF state, a conclusion which is in agreement with results obtained for a number of other zeolite-entrapped Ru(II) polypyridine complexes.

Contrasting photosubstitution reactions of diazanorbornene-chromium and -tungsten pentacarbonyls

Electronic excitation causes efficient labilization of both the azo and carbonyl ligands in Cr(CO) 5(diazanorbornene) via an excited LF state. On the contrary the corresponding tungsten complex undergoes only inefficient azo labilization via a MLCT state. Azo labilization is also promoted by electron-transfer sensitization.

Photochemistry of Biologically Important Transition Metal Complexes. II. Carbonylpiperidinetetraphenylporphine Complexes of Iron(II) and Ruthenium(II)

AbstractCarbonylpiperidinetetraphenylporphineiron(II) and dipiperidinetetraphenylporphineiron(II) do not emit the characteristic porphyrin phosphorescence. It is suggested that the porphyrin singlets initially excited undergo an efficient radiationless transition to an excited state which lies below the lowest porphyrin triplet. It is concluded that this lower excited state initiates the release of coordinated CO which has been observed for a variety of biologically important carbonylporphyrins of iron(II). It is assumed that the reactive state is either an excited CT or, more likely, a LF state. If iron(II) is replaced by the homologous ruthenium(II) the lowest LF excited state lies apparently at higher energies than the lowest porphyrin triplet due to the larger LF splitting of the heavier ruthenium. Hence carbonylpiperidinetetra‐phenylporphineruthenium(II) dissolved in piperidine shows the typical porphyrin phosphorescence, but undergoes also a simultaneous photosubstitution of CO by piperidine with low efficiency. Quantum yields of CO release and relative emission intensities were determined at two irradiating wavelengths (412 and 530 nm) and at two temperatures (25 °C and 80 °C). The results led to the suggestion that the reactive LF state can be populated from the lower porphyrin triplet by thermal activation. In addition to this thermally activated photolysis a temperature independent contribution seems to be important at higher excitation energies. It is assumed that the deactivation cascade starting from higher excited singlets of the porphyrin ligand includes the population of the reactive LF state before the lowest porphyrin triplet is reached. It is also possible that it is not a LF state but a low‐lying CT state which is responsible for the photoreactivity.

Photochemistry of Biologically Important Transition Metal Complexes. I. Cyanocobalamin and Related Corrin Complexes of Rhodium(III)

AbstractThe quantum yield of the well known photoaquation of cyanocobalamin (vitamin B12) was determined (ϕ ˜ 10−4) and was found to be independent of the irradiating wavelength. In addition cyanocobalamin did not show the characteristic corrin phosphorescence. In agreement with an earlier suggestion it is concluded that the excitation energy initially absorbed by the corrin ligand is rapidly transferred to a reactive excited LF state which lies below the lowest corrin triplet. This conclusion is supported by the behavior of corrin complexes of Rh(III). Contrary to cyanocobalamin the complex dicyanorhodium(III)‐corrin did not undergo a photoaquation but has been shown to emit a strong corrin phosphorescence. These observations are consistent with the assumption that the lowest excited LF state lies now well above the lowest corrin triplet. If both axial cyanide ligands which have a strong field are replaced by the weak‐field ligand chloride the energy of the lowest excited LF state should drop considerably. The behavior of dichlororhodium(III)‐corrin indicates that the lowest corrin triplet lies only slightly below the lowest excited LF state which is responsible for the photoreactivity. The reactive LF state may be populated from the lowest corrin triplet by thermal activation. At 77 K dichlororhodium(III)‐corrin showed a strong corrin phosphorescence. At room temperature this emission was essentially quenched and the complex underwent a photoaquation.