Photophysics of a novel optical probe, 7-azaindole and an antiviral agent, hypericin

Transient absorption and fluorescence quantum yield measurements of indole, 7-azaindole, and their derivatives are performed in order to find out the differences and similarities between these molecules, which are the chromophoric moieties of the biological optical probes, tryptophan and 7-azatryptophan. Tryptophan, a nature amino acid, is widely used as an optical probe for studying protein-protein interaction. Recently, the non-natural amino acid, 7-azatryptophan, has been proposed to be an alternative to tryptophan, because of the intrinsical difficulties in using tryptophan. Pump-probe experiments show that in less than 1-ps after excitation of an indole or 7-azaindole molecule, a photo-electron is generated and well solvated, and this process is monophotonical. The electron yield is determined. Careful quantum yield measurements indicate that both indole and 7-azaindole emit with different quantum efficiencies for different excitation wavelengths. A quantitative analysis in combination with the electron yield and fluorescence quantum yield at different temperatures is provided in order to elucidate the earlier and later events after photo-excitation of indole and 7-azaindole molecules. Surprisingly, it is found that 7-azaindole has many great similarities to indole;The vibrationally cooled first singlet of 7-azaindole can execute a double-proton transfer process with the aid of a solvent or another solute molecule. A theory is derived to determine the mechanisms, namely, via step-wise or concerted process, of double-proton transfer reactions using the proton inventory technique;The absorption and fluorescence spectra of hypericin and its analog, mesonaphthobianthrone, are obtained in different solvents. In aprotic solvents mesonaphthobianthrone is non-fluorescent. In strong acids such as sulfuric or triflic acids, it becomes fluorescent. Its fluorescence spectrum is very similar to that of hypericin. We therefore conclude that the fluorescent species of hypericin has one or both of its carbonyl group protonated. The protonation equilibrium in both ground- and excited-state is discussed. Transient absorption measurements of hypericin with ~1-ps resolution indicate that upon optical excitation a new species is created that absorbs in the range of roughly 580-640 nm. This species exhibits a 6-12-ps decay, depending on the solvent. The stimulated emission signal, which is from the fluorescent state, grows in with a time constant of 6-12-ps. Based upon the identification of the fluorescent species as hypericin with one or both carbonyl groups protonated, this rise time is attributed to excited-state tautomerization. The role of solvents in excited-state proton transfer in hypericin is discussed

The effect of beta-blockers on mortality in patients with heart failure and atrial fibrillation: A meta-analysis of observational cohort and randomized controlled studies

Background: Beta-blockers (BB) are the cornerstone of therapy for heart failure (HF); however, theeffects of these drugs on the prognosis of patients with concomitant atrial fibrillation (AF) remaincontroversial. The objective of this meta-analysis was to evaluate the efficacy of BB on mortality in HFcoexisting with AF.Methods: A systematic search of PubMed, Embase and the Cochrane Library databases wasconducted. Observational cohort studies and randomized controlled trials reporting outcomes ofmortality or HF hospitalizations for patients with HF and AF, being assigned to BB treatment.A non-BB group was also included.Results: A total of 8 clinical studies (5 randomized controlled trials and 3 observational cohort studies)involving 34197 patients were included in the analysis. The pooled analysis demonstrated that BBtreatment was associated with a 22% reduction in relative risk of all-cause mortality in patients withHF and AF (RR: 0.78; 95% CI 0.71–0.86; p < 0.00001; I2 = 27%). The pooled analysis of 5 studiesreported the outcome of HF hospitalization (2774 patients) which showed that BB therapy was not associatedwith a reduction of HF hospitalizations (RR: 0.94; 95% CI 0.79–1.11; p = 0.46; I2 = 38%).Conclusions: Meta-analysis suggests the potential mortality benefit of BB in patients with HF and AF.It was concluded herein that it is premature to deny patients with AF and HF to receive BB therapyconsidering current evidence

Heteroepitaxial growth of ZnO branches selectively on TiO2 nanorod tips with improved light harvesting performance

A seeded heteroepitaxial growth of ZnO nanorods selectively on TiO2 nanorod tips was achieved by restricting crystal growth on highly hydrophobic TiO2 nanorod film surfaces. Intriguing light harvesting performance and efficient charge transport efficiency has been found, which suggest potential applications in photovoltaics and optoelectronics

Fast-HotStuff: A Fast and Resilient HotStuff Protocol

The HotStuff protocol is a breakthrough in Byzantine Fault Tolerant (BFT) consensus that enjoys both responsiveness and linear view change. It creatively adds an additional round to classic BFT protocols (like PBFT) using two rounds. This brings us to an interesting question: Is this additional round really necessary in practice? In this paper, we answer this question by designing a new two-round BFT protocol called Fast-HotStuff, which enjoys responsiveness and efficient view change that is comparable to linear view change in terms of performance. Compared to (three-round) HotStuff, Fast-HotStuff has lower latency and is more robust against performance attacks that HotStuff is susceptible to

Characterization of Cofactor-Induced Folding Mechanism of a Zinc Binding Peptide Using Computationally Designed Mutants

Metals are the most commonly encountered protein cofactors, and they play important structural and functional roles in biology. In many cases, metal binding provides a major driving force for a polypeptide chain to fold. While there are many studies on the structure, stability, and function of metal-binding proteins, there are few studies focusing on understanding the kinetic mechanism of metal-induced folding. Herein, the Zn(2+)-induced folding kinetics of a small zinc-binding protein are studied; the CH1(1) peptide is derived from the first cysteine/histidine-rich region (CH1 domain) of the protein interaction domains of the transcriptional coregulator CREB-binding protein. Computational design is used to introduce tryptophan and histidine mutations that are structurally consistent with CH1(1); these mutants are studied using stopped-flow tryptophan fluorescence experiments. The Zn(2+)-induced CH1(1) folding kinetics are consistent with two parallel pathways, where the initial binding of Zn(2+) occurs at two sites. However, the initially formed Zn(2+)-bound complexes can proceed either directly to the folded state where zinc adopts a tetrahedral coordination or to an off-pathway misligated intermediate. While elimination of those ligands responsible for misligation simplifies the folding kinetics, it also leads to a decrease in the zinc binding constant. Therefore, these results suggest why these nonnative zinc ligands in the CH1(1) motif are conserved in several distantly related organisms and why the requirement for function can lead to kinetic frustration in folding. In addition, the loop closure rate of the CH1(1) peptide is determined based on the proposed model and temperature-dependent kinetic measurements

Arbuscular Mycorrhizal Fungi Diversity and Contribution to Crop Growth in Agricultural Fields

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Crystal: Enhancing Blockchain Mining Transparency with Quorum Certificate

Researchers have discovered a series of theoretical attacks against Bitcoin's Nakamoto consensus; the most damaging ones are selfish mining, double-spending, and consistency delay attacks. These attacks have one common cause: block withholding. This paper proposes Crystal, which leverages quorum certificates to resist block withholding misbehavior. Crystal continuously elects committees from miners and requires each block to have a quorum certificate, i.e., a set of signatures issued by members of its committee. Consequently, an attacker has to publish its blocks to obtain quorum certificates, rendering block withholding impossible. To build Crystal, we design a novel two-round committee election in a Sybil-resistant, unpredictable and non-interactive way, and a reward mechanism to incentivize miners to follow the protocol. Our analysis and evaluations show that Crystal can significantly mitigate selfish mining and double-spending attacks. For example, in Bitcoin, an attacker with 30% of the total computation power will succeed in double-spending attacks with a probability of 15.6% to break the 6-confirmation rule; however, in Crystal, the success probability for the same attacker falls to 0.62%. We provide formal end-to-end safety proofs for Crystal, ensuring no unknown attacks will be introduced. To the best of our knowledge, Crystal is the first protocol that prevents selfish mining and double-spending attacks while providing safety proof.Comment: 17 pages, 9 figure