TiO2(110)-(1 × 1) supported Cu particles: An FT-RAIRS investigation

The morphology of TiO₂(110)-(1 × 1) supported Cu particles has been investigated by Fourier Transform Reflection Absorption Infrared Spectroscopy (FT-RAIRS), employing adsorbed CO as a probe molecule sensitive to local surface structure. For Cu coverage (deposited at 300 K) less than 2.85 MLE nucleated Cu particles in the range 2 nm–4 nm are formed, as indicated by a final state shift in the core level Cu(2p_3/2) binding energy and by the existence of only transmission bands in the FT-RAIRS spectra for adsorbed CO. ν_S(CO) indicates that these small particles expose sites similar to those of the stepped Cu surfaces Cu(211), Cu(311), and Cu(755). At Cu coverages in the range of 6 MLE and above, corresponding to particle sizes above 4.6 nm, ν_S(CO) indicates the predominance of (110), (100) and (111) adsorption sites. Annealing the Cu layers to 650 K results in the slight growth of the particle sizes, and transformation of the CO adsorption sites corresponding to the close packed facets. The transformation of the local dielectric from that of titania to that dominated by the Cu particle is shown to take place between 3.7 and 4.2 nm, and this change is also to a smaller extent sensitive to the dispersion of the particles.     

Activation Energies Control the Macroscopic Properties of Physically Cross‐Linked Materials

Here we show the preparation of a series of water‐based physically cross‐linked polymeric materials utilizing cucurbit[8]uril (CB[8]) ternary complexes displaying a range of binding, and therefore cross‐linking, dynamics. We determined that the mechanical strength of these materials is correlated directly with a high energetic barrier for the dissociation of the CB[8] ternary complex cross‐links, whereas facile and rapid self‐healing requires a low energetic barrier to ternary complex association. The versatile CB[8] ternary complex has, therefore, proven to be a powerful asset for improving our understanding of challenging property–structure relationships in supramolecular systems and their associated influence on the bulk behavior of dynamically cross‐linked materials.     

Covalent inhibitors of human monoacylglycerol lipase: ligand-assisted characterization of the catalytic site by mass spectrometry and mutational analysis

The active site of recombinant hexa-histidine-tagged human monoacylglycerol lipase (hMGL) is characterized by mass spectrometry using the inhibitors 5-((biphenyl-4-yl)methyl)-N,N-dimethyl-2H-tetrazole-2-carboxamide (AM6701), and N-arachidonylmaleimide (NAM) as probes. Carbamylation of Ser(129) by AM6701 in the putative hMGL catalytic triad demonstrates this residue's essential role in catalysis. Partial NAM alkylation of hMGL cysteine residues 215 and/or 249 was sufficient to achieve approximately 80% enzyme inhibition. Although Cys(215) and/or Cys(249) mutations to alanine(s) did not affect hMGL hydrolytic activity as compared with nonmutated hMGL, the C215A displayed heightened NAM sensitivity, whereas the C249A evidenced reduced NAM sensitivity. These data conclusively demonstrate a sulfhydryl-based mechanism for NAM inhibition of hMGL in which Cys(249) is of paramount importance. Identification of amino acids critical to the catalytic activity and pharmacological modulation of hMGL informs the design of selective MGL inhibitors as potential drugs.     

Formal synthesis of Abyssomicin C

An alternative strategy towards Abyssomicin C (1) is described. The key ene-diene intermediate is synthesized via a Kishi type coupling of an E/Z mixture of triene-iodide 7 and a suitably functionalized derivative of 2,4-dimethylglutaric acid. A final in situ isomerization/intramolecular Diels-Alder cyclization resulted in the formation of the known intermediate 3 as a single isomer in high yield. Further heating of 3 using excess of iodine, afforded iodo-derivative 23, having the entire carbon skeleton of Abyssomicin D.     

Directed mutagenesis alters the stereochemistry of catalysis by isolated ketoreductase domains from the erythromycin polyketide synthase

The ketoreductase (KR) domains eryKR(1) and eryKR(2) from the erythromycin-producing polyketide synthase (PKS) reduce 3-ketoacyl-thioester intermediates with opposite stereospecificity. Modeling of eryKR(1) and eryKR(2) showed that conserved amino acids previously correlated with production of alternative alcohol configurations lie in the active site. eryKR(1) domains mutated at these positions showed an altered stereochemical outcome in reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester. The wild-type eryKR(1) domain exclusively gave the (2S, 3R)-3-hydroxy-2-methylpentanoic acid N-acetylcysteamine thioester, while the double mutant (F141W, P144G) gave only the (2S, 3S) isomer, a switch of the alcohol stereochemistry. Mutation of the eryKR(2) domain, in contrast, greatly increased the proportion of the wild-type (2R, 3S)-alcohol product. These data confirm the role of key residues in stereocontrol and suggest an additional way to make rational alterations in polyketide antibiotic structure.     

Numerical experiments on the efficiency of local grid refinement based on truncation error estimates

Local grid refinement aims to optimise the relationship between accuracy of the results and number of grid nodes. In the context of the finite volume method no single local refinement criterion has been globally established as optimum for the selection of the control volumes to subdivide, since it is not easy to associate the discretisation error with an easily computable quantity in each control volume. Often the grid refinement criterion is based on an estimate of the truncation error in each control volume, because the truncation error is a natural measure of the discrepancy between the algebraic finite-volume equations and the original differential equations. However, it is not a straightforward task to associate the truncation error with the optimum grid density because of the complexity of the relationship between truncation and discretisation errors. In the present work several criteria based on a truncation error estimate are tested and compared on a regularised lid-driven cavity case at various Reynolds numbers. It is shown that criteria where the truncation error is weighted by the volume of the grid cells perform better than using just the truncation error as the criterion. Also it is observed that the efficiency of local refinement increases with the Reynolds number. The truncation error is estimated by restricting the solution to a coarser grid and applying the coarse grid discrete operator. The complication that high truncation error develops at grid level interfaces is also investigated and several treatments are tested.     

Examining the Capacity of Text Mining and Software Metrics in Vulnerability Prediction

Software security is a very important aspect for software development organizations who wish to provide high-quality and dependable software to their consumers. A crucial part of software security is the early detection of software vulnerabilities. Vulnerability prediction is a mechanism that facilitates the identification (and, in turn, the mitigation) of vulnerabilities early enough during the software development cycle. The scientific community has recently focused a lot of attention on developing Deep Learning models using text mining techniques for predicting the existence of vulnerabilities in software components. However, there are also studies that examine whether the utilization of statically extracted software metrics can lead to adequate Vulnerability Prediction Models. In this paper, both software metrics- and text mining-based Vulnerability Prediction Models are constructed and compared. A combination of software metrics and text tokens using deep-learning models is examined as well in order to investigate if a combined model can lead to more accurate vulnerability prediction. For the purposes of the present study, a vulnerability dataset containing vulnerabilities from real-world software products is utilized and extended. The results of our analysis indicate that text mining-based models outperform software metrics-based models with respect to their F₂-score, whereas enriching the text mining-based models with software metrics was not found to provide any added value to their predictive performance.     

Schlenk's Legacy—Methyllithium Put under Close Scrutiny

Commercially available stock solutions of organolithium reagents are well-implemented tools in organic and organometallic chemistry. However, such solutions are inherently contaminated with lithium halide salts, which can complicate certain synthesis protocols and purification processes. Here, we report the isolation of chloride-free methyllithium employing K[N(SiMe₃)₂] as a halide-trapping reagent. The influence of distinct LiCl contaminations on the ⁷Li-NMR chemical shift is examined and their quantification demonstrated. The structural parameters of new chloride-free monomeric methyllithium complex [(Me₃TACN)LiCH₃], ligated by an azacrown ether, are assessed by comparison with a halide-contaminated variant and monomeric lithium chloride [(Me₃TACN)LiCl], further emphasizing the effect of halide impurities.