The Python-based program Protex was initially developed for simulating proton transfers in a pure protic ionic liquid via polarizable molecular dynamics simulations. This method employs a single ...topology approach wherein deprotonated species retain a dummy atom, which is transformed into a real hydrogen atom during the protonation process. In this work, we extended Protex to include more intricate systems and to facilitate the simulation of the Grotthuss mechanism to enhance alignment with the empirical findings. The handling of proton transfer events within Protex was further refined for increased flexibility. In the original model, each deprotonated molecule contained a single dummy atom connected to the hydrogen acceptor atom. This model posed limitations for molecules with multiple atoms that could undergo protonation. To mitigate this issue, Protex was extended to execute a proton transfer when one of these potential atoms was within a suitable proximity for the transfer event. For the purpose of maintaining simplicity, Protex continues to utilize only a single dummy atom per deprotonated molecule. Another new feature pertains to the determination of the eligibility for a proton transfer event. A range of acceptable distances can now be defined within which the transfer probability is gradually turned off. These modifications allow for a more nuanced approach to simulating proton transfer events, offering greater accuracy and control of the modeling process.
The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an ...attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.
Shrubs in pastures are expected to adversely affect plant species diversity and community composition at various spatial scales. We recorded vegetation composition as well as light conditions and ...other environmental variables in 105 1 m
2
plots nested in 35 sampling sites in shrubby pastures in Romanian Banat. We used generalized linear models, generalized linear mixed-effects models, and linear regression to find determinants of species turnover and richness at patch and community level. We expected shrubs to negatively influence species richness on the patch level but to introduce spatial heterogeneity to the light availability resulting in a unimodal relationship of light availability with species richness on the community level. Species turnover was significantly influenced by light conditions, grazing variability, and distance between the plots. We found a unimodal relationship between light availability and species richness consistently across the two spatial scales in grazed sites. However, the same relationship changed its shape from linear to unimodal in non-grazed sites. Shrubs in pastures may not be considered as a threat to plant species diversity. Instead, they contribute significantly to plant species diversity and vegetation heterogeneity.
The need to determine the content of plutonium in Pu–Be neutron sources of Russian provenience arises from the administrative regulations applying to nuclear materials. The determination of a ...plutonium (all isotopes) amount was based on the measurement of an activity Pu-239. Gamma-ray spectrometry with semiconductor detector HPGe was applied. The determination of plutonium (all isotopes) amount was based on the measurement of Pu-239 activity by means of Gamma-ray spectrometry with semiconductor detector HPGe. Gamma lines of radionuclides Am-241, Pu-238, Pu-239 and Pu-241 were detected in spectra. Detection efficiencies were calculated by Monte Carlo method using MCNP4A code. Computations were done for several hypothetical plutonium amounts. Activities determined from peak areas of 129 and 413 keV photons emitted from Pu-239 were confronted. The right amount was established under the condition of equality of both activities.
A new large-volume metal reference standard has been developed. The intended use is for calibration of free-release radioactivity measurement systems and is made up of cast iron tubes placed inside a ...box of the size of a Euro-pallet (80 × 120 cm). The tubes contain certified activity concentrations of (60)Co (0.290 ± 0.006 Bq g(-1)) and (110m)Ag (3.05 ± 0.09 Bq g(-1)) (reference date: 30 September 2013). They were produced using centrifugal casting from a smelt into which (60)Co was first added and then one piece of neutron irradiated silver wire was progressively diluted. The iron castings were machined to the desirable dimensions. The final material consists of 12 iron tubes of 20 cm outer diameter, 17.6 cm inner diameter, 40 cm length/height and 245.9 kg total mass. This paper describes the reference standard and the process of determining the reference activity values.
The kaolinite/TiO₂ composite was prepared using thermal hydrolysis of kaolinite/titanyl sulphate suspension and characterized by XRFS, XRPD, SEM and N₂ physical adsorption. Its photocatalytic ...properties were evaluated by photocatalytic reduction of CO₂ by water and compared with commercial TiO₂ photocatalyst Degussa P25. Results showed that the yields of CO₂ photocatalytic reduction products methane and methanol were higher over a kaolinite/TiO₂ composite than over commercial TiO₂ (Degussa P25) in spite of smaller proportion of TiO₂ in the composite. Introducing of TiO₂ nanoparticles into the kaolinite structure caused a decrease of anatase crystallite size. Kaolinite can also change acidobasic properties of catalyst surface, inhibit the recombination of electron–hole pairs and prevent the formation of TiO₂ aggregates in suspension. These facts can contribute to the observed higher photocatalytic efficiency of kaolinite/TiO₂ compared to the commercial TiO₂ photocatalyst.
In the present study, the coupling of adsorption capacity and photocatalytic efficiency of two different industrially produced titania catalysts was investigated and compared. The azo dye Reactive ...Red 195 was selected as a model compound. The tested catalysts, PK-10 and PK-180, exhibited different adsorption capacities due to their significant difference in their specific surface, but both have proven to be effective photocatalysts for photodegradation of the studied dye. PK-10 exhibited strong adsorption of the studied dye due to its high specific surface area, while the second studied catalyst, PK-180, demonstrated negligible adsorption of Reactive Red 195. The effect of the pH, the concentration of the catalyst and the initial concentration of the dye appear to affect the photocatalytic rate. The effect of the presence of humic acids and inorganic ions was also examined, while the contribution of various reactive species was indirectly evaluated through the addition of various scavengers. To evaluate the extent of mineralisation of the studied dye, total organic carbon (TOC) measurements during the experiment were also conducted. Besides total colour removal, evident reduction of TOC was also achieved using both catalysts.
This paper addresses the measurement facilities for pre-selection of waste materials prior to measurement for repository acceptance or possible free release (segregation measurement system); and free ...release (free release measurement system), based on a single standardized concept characterized by unique, patented lead-free shielding.
The key objective is to improve the throughput, accuracy, reliability, modularity and mobility of segregation and free-release measurement. This will result in a more reliable decision-making with regard to the safe release and disposal of radioactive wastes into the environment and, resulting in positive economic outcomes.
The research was carried out within “Metrology for Decommissioning Nuclear Facilities” (MetroDecom) project.
•New-concept system for segregation and free release was developed.•Patented material with low natural radioactivity is used as lead-free shielding.•Accurate measurement is facilitated by new certified calibration/testing standards.•Precise measurements reduce the quantity of waste sent to repositories.
PDF
