Water oxidation is an essential reaction of an artificial photosystem for solar fuel generation because it provides electrons needed to reduce carbon dioxide or protons to a fuel. Earth-abundant metal oxides are among the most attractive catalytic materials for this reaction because of their robustness and scalability, but their efficiency poses a challenge. Knowledge of catalytic surface intermediates gained by vibrational spectroscopy under reaction conditions plays a key role in uncovering kinetic bottlenecks and provides a basis for catalyst design improvements. Recent dynamic infrared and Raman studies reveal the molecular identity of transient surface intermediates of water oxidation on metal oxides. Combined with ultrafast infrared observations of how charges are delivered to active sites of the metal oxide catalyst and drive the multielectron reaction, spectroscopic advances are poised to play a key role in accelerating progress toward improved catalysts for artificial photosynthesis.

Using internal fiducial markers and electronic portal imaging (EPID) to realign patients has been shown to significantly reduce positioning uncertainties in prostate radiation treatment. This creates the possibility of decreasing the planning target volume (PTV) margin added on the clinical target volume (CTV), which in turn may allow for dose escalation. We compared the outcome of two plans: 70Gy/35fx, 10 mm PTV margin without patient realignment (Reference Plan) vs. 78Gy/39fx, 5 mm PTV margin with patient realignment (Escalated Plan). Four-field-oblique (gantry angles 35 degrees, 90 degrees, 270 degrees, 176 degrees, 325 degrees) beam arrangement was used. Monte Carlo code was used to simulate the daily organ motion. Dose to each organ was calculated. Tumour control probability (TCP) and the effective dose to critical organ (Deff) were calculated using the biologically normalized dose-volume histograms. By comparing the biological factors, we found that the prescription dose can be escalated to 78Gy/39fx with a 5 mm PTV margin when using internal fiducial markers and EPID. Based on the available dose-response data for intermediate risk prostate patients, this will result in a 20% increase of local control and significantly reduced rectal complications provided that less serial dose-volume behaviour of rectum is proven.

Background

Low-depth sequencing allows researchers to increase sample size at the expense of lower accuracy. To incorporate uncertainties while maintaining statistical power, we introduce MCPCA_PopGen to analyze population structure of low-depth sequencing data.

Results

The method optimizes the choice of nonlinear transformations of dosages to maximize the Ky Fan norm of the covariance matrix. The transformation incorporates the uncertainty in calling between heterozygotes and the common homozygotes for loci having a rare allele and is more linear when both variants are common.

Conclusions

We apply MCPCA_PopGen to samples from two indigenous Siberian populations and reveal hidden population structure accurately using only a single chromosome. The MCPCA_PopGen package is available on https://github.com/yiwenstat/MCPCA_PopGen .

Electrification of chemical reactions is crucial to fundamentally transform our society that is still heavily dependent on fossil resources and unsustainable practices. In addition, electrochemistry-based approaches offer a unique way of catalyzing reactions by the fast and continuous alteration of applied potentials, unlike traditional thermal processes. Here, we show how the continuous cyclic application of electrode potential allows Pt nanoparticles to electrooxidize biomass-derived polyols with turnover frequency improved by orders of magnitude compared with the usual rates at fixed potential conditions. Moreover, secondary alcohol oxidation is enhanced, with a ketoses-to-aldoses ratio increased up to sixfold. The idea has been translated into the construction of a symmetric single-compartment system in a two-electrode configuration. Its operation via voltage cycling demonstrates high-rate sorbitol electrolysis with the formation of H₂ as a desired coproduct at operating voltages below 1.4 V. The devised method presents a potential approach to using renewable electricity to drive chemical processes.

The ultrashort (10s of femtoseconds) X-ray pulses generated by X-ray free electron lasers enable the measurement of X-ray diffraction and spectroscopic data from radiation-sensitive metalloenzymes at room temperature while mostly avoiding the effects of radiation damage usually encountered when performing such experiments at synchrotron sources. Here we discuss an approach to measure both X-ray emission and X-ray crystallographic data at the same time from the same sample volume. The droplet-on-tape setup described allows for efficient sample use and the integration of different reaction triggering options in order to conduct time-resolved studies with limited sample amounts. The approach is illustrated by two examples, photosystem II that catalyzes the light-driven oxidation of water to oxygen, and isopenicillin N synthase, an enzyme that catalyzes the double ring cyclization of a tripeptide precursor into the β-lactam isopenicillin and can be activated by oxygen exposure. We describe the necessary steps to obtain microcrystals of both proteins as well as the operation procedure for the drop-on-tape setup and details of the data acquisition and processing involved in this experiment. At the end, we present how the combination of time-resolved X-ray emission spectra and diffraction data can be used to improve the knowledge about the enzyme reaction mechanism.

Intermediate-conductance (K_Ca3.1) and small-conductance (K_Ca2) calcium-activated K⁺ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing K_Ca activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309), and 1-ethylbenzimidazolin-2-one (EBIO), activate both channel types with similar potencies. In a previous chemistry effort, we optimized the benzothiazole pharmacophore of SKA-31 toward K_Ca3.1 selectivity and identified 5-methylnaphtho[2,1-d]oxazol-2-amine (SKA-121), which exhibits 40-fold selectivity for K_Ca3.1 over K_Ca2.3. To understand why introduction of a single CH₃ group in five-position of the benzothiazole/oxazole system could achieve such a gain in selectivity for K_Ca3.1 over K_Ca2.3, we first localized the binding site of the benzothiazoles/oxazoles to the CaM-BD/CaM interface and then used computational modeling software to generate models of the K_Ca3.1 and K_Ca2.3 CaM-BD/CaM complexes with SKA-121. Based on a combination of mutagenesis and structural modeling, we suggest that all benzothiazole/oxazole-type K_Ca activators bind relatively "deep" in the CaM-BD/CaM interface and hydrogen bond with E54 on CaM. In K_Ca3.1, SKA-121 forms an additional hydrogen bond network with R362. In contrast, NS309 sits more "forward" and directly hydrogen bonds with R362 in K_Ca3.1. Mutating R362 to serine, the corresponding residue in K_Ca2.3 reduces the potency of SKA-121 by 7-fold, suggesting that R362 is responsible for the generally greater potency of K_Ca activators on K_Ca3.1. The increase in SKA-121's K_Ca3.1 selectivity compared with its parent, SKA-31, seems to be due to better overall shape complementarity and hydrophobic interactions with S372 and M368 on K_Ca3.1 and M72 on CaM at the K_Ca3.1-CaM-BD/CaM interface.

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and SKS-14 (7-fluoro-3-(hydroxyimino)indolin-2-one). A combination of x-ray crystallographic, computational and electrophysiological approaches was utilized to investigate the interactions between the positive modulators and their binding pocket. A strong trend exists between the interaction energy of the compounds within their binding site calculated from the crystal structures, and the potency of these compounds in potentiating the SK2 channel current determined by electrophysiological recordings. Our results further reveal that the difference in potency of the positive modulators in potentiating SK2 channel activity may be attributed primarily to specific electrostatic interactions between the modulators and their binding pocket.

By utilizing the interaction between inorganic species and organic surfactants, the ordered layered mesostructures were generated for the synthesis of the one-dimensional oxide nanomaterials. The oxide nanomaterial products which evolved from the above layered structures were demonstrated as ultrathin (less than 2 nm) one-dimensional structures with superior catalytic performance. The synthetic method based on layered structures can be extended to prepare other one-dimensional oxide nanomaterials with the same ultrathin structures.