Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Simultaneous two wavelength operation of an optically pumped HCOOH laser on orthogonally polarized modes

Simultaneous laser operation in orthogonally polarized EH₁₁ and TE₀₁ waveguide modes is reported for pairs of cascade lines from an optically pumped formic acid vapour laser incorporating a strip grating output coupler. Observations were made for the 394 μm/406 μm and 433 μm/446 μm cascade sequences, the resonator length being adjusted so that the laser was simultaneously resonant on a mode of the primary transition polarized perpendicular to the strips of the output coupler and the same transverse mode of the secondary transition polarized parallel to the coupler strips. Power measurements showed that for the laser configuration used in this study the power of the primary transition was increased only slightly when the cascade lines were simultaneously resonant, whereas the secondary line could only lase under these conditions.     

Mean stress dependence of the thermoelastic constant

The SPATE 8000 thermoelastic stress analyser has been used to demonstrate the mean stress dependence of the thermoelastic constant. This dependence has potential application in the measurement of residual stress provided the material has not yielded.     

Spectral sensing of foliar water conditions in two co-occurring conifer species: Pinus edulis and Juniperus monosperma

Many fundamental ecosystem properties and dynamics are determined by plant water stress, particularly in dryland ecosystems where water is usually limiting. Indeed, under severe drought, plant water stress and associated insect infestations can produce landscape-scale mortality. Despite the fundamental importance of plant water stress in determining properties and dynamics at ecosystem and landscape scales, approaches for remotely sensing plant water stress are largely lacking, particularly for conifers. We evaluated the remotely sensed detection of foliar drought stress in two conifer species, Pinus edulis and Juniperus monosperma, which are co-dominants of extensive-juniper woodlands in North America, the first of which experienced extensive mortality in association with a recent drought. Needle spectra were made on these species in the field using an integrating sphere and portable spectrometer. Two indices of foliar water condition, plant water content (% of dry mass) and plant water potential, were compared to five spectral analyses: continuum removal of the 970 and 1200 nm water absorption features, the Normalized Difference Water Index (NDWI), the Normalized Difference Vegetation Index (NDVI), and the red edge wavelength position. For P. edulis, plant water content was significantly correlated with four of the five indices: NDVI (R²=0.71) and NDWI (R²=0.68) which exhibited stronger relationships than 970 nm continuum removal (R²=0.57) or red edge position (R²=0.45). All five indices were significantly correlated with P. edulis water content when trees undergoing mortality were included in analyses (R²=0.60-0.93). Although the correlations were weaker than for plant water content, plant water potential was significantly correlated with NDWI (R²=0.49), 970 nm (R²=0.44), NDVI (R²=0.35), and red edge (R²=0.34); again all five indices had significant relationships when trees undergoing mortality were included (R²=0.51-0.86). The relationships were weaker for J. monosperma: water content was significantly related to 970 nm (R²=0.50) and 1200 nm (R²=0.37) continuums and NDVI (R²=0.33), while water potential was related only to 1200 nm (R²=0.40). Our results demonstrate a critical link between plant physiological characteristics tied to water stress and associated spectral signatures for two extensive co-occurring conifer species.     

International Practical Temperature Scale of 1948: Text Revision of 1960

The International Practical Temperature Scale of 1948 is a text revision of the International Temperature Scale of 1948, the numerical values of temperatures remaining the same. The adjective “Practical” was added to the name by the International Committee on Weights and Measures. The scale continues to be based upon six fixed and reproducible equilibrium temperatures to which values have been assigned, and upon the same interpolation formulas relating temperatures to the indications of specified measuring instruments. Some changes have been made in the text to make the scale more reproducible than its predecessor. The triple point of water, with the value 0.01 °C replaces the former ice point as a defining fixed point of the scale. It is also recommended that the zinc point, with the value 419.505 °C, be used instead of the sulfur point. The recommendations include new information that has become available since 1948.An internationally accepted scale on which temperatures can be measured conveniently and accurately is necessary for science and industry. As early as 1911 the directors of the national laboratories of Germany, Great Britain, and the United States agreed to undertake the unification of the temperature scales in use in their respective countries. A practical scale, named the International Temperature Scale, was finally agreed upon, was recommended to the Seventh General Conference on Weights and Measures by its International Committee on Weights and Measures, and was adopted in 1927.¹The General Conference on Weights and Measures is the official international body now representing 36 nations that subscribe to the Treaty of the Meter. The General Conference normally meets every six years, and at those times may adopt recommendations submitted by the International Committee. The International Committee is the executive body elected by the General Conference. It consists of 18 scientists, only one from any one nation, and it normally meets every two years. The International Committee now has six advisory committees of specialists most of whom represent large national laboratories. The Advisory Committee on Thermometry was authorized in 1933 and first met in 1939.In 1948 a revision of the International Temperature Scale was prepared by the Advisory Committee and proposed to the International Committee. The International Committee recommended this revision to the Ninth General Conference which adopted it.² At this time the General Conference also adopted the designation of degree Celsius in place of degree Centigrade or Centesimal.³ The revised scale was designed to conform as nearly as practicable to the thermodynamic scale as then known, while incorporating certain refinements, based on experience, to make the scale more uniform and reproducible than its predecessor. In the revision there were only three changes which affected values of temperatures on the scale. One was to increase the value assigned to the silver point by 0.3 degree, merely to make the scale more uniform. Another was to specify Planck’s radiation formula instead of Wien’s formula so the scale would be consistent with the thermodynamic scale above the gold point. The third was to increase the value for the second radiation constant to bring it nearer to the value derived from atomic constants.In 1954 the Advisory Committee proposed a resolution redefining the Kelvin thermodynamic scale by assigning a value to the triple point of water. This kind of definition was what Kelvin, in 1854, had said “must be adopted ultimately.” This resolution was recommended by the International Committee and adopted by the Tenth General Conference.⁴ As soon as this resolution had been adopted it was pointed out that it would be necessary to revise the introduction of the text of the International Temperature Scale of 1948 to conform with the action just taken.In preparing a tentative proposal for a new text of the introduction it soon became evident that the other three parts of the text would also profit by a revision. For example, the triple point of water could now be made one of the defining fixed points of the scale and thus become the one defining fixed point common to both the international and the Kelvin scales. The Recommendations could include new information that had become available since 1948. At the higher temperatures some new determinations of differences between the international and thermodynamic scales could be included. The values reported for these differences, however, were still not certain enough to warrant a change of the scale itself. The new text, therefore, does not change the value of any temperature on the 1948 scale by as much as the experimental error of measurement.In 1958 the tenative proposal was discussed in detail at sessions of the Advisory Committee in June, and many suggested changes were agreed upon. It was proposed to the International Committee in October. Minor corrections were made during the next two years, and in 1960 the International Committee gave the scale its new name. The International Committee recommended this text revision to the Eleventh General Conference and it was adopted in October 1960.A translation of the official text ⁵ follows.     

Catalytic Properties of the Antibody H11

The catalytic activity of the antibody H11 is shown to reside chiefly in its ability to hydrolyze 1-acetoxybutadiene to crotonaldehyde and to promote the cycloaddition of the intermediate enol with N-alkylmaleimides. This conclusion is based upon the demonstration that the enol tautomerizes too rapidly in solution to be a competent intermediate and that under the reaction conditions for H11, no cycloaddition occurs with crotonaldehyde and N-ethylmaleimide. As a first step towards a structural understanding of the chemistry of H11, chemical modification experiments have shown that reactions of acidic amino acids, tyrosine, lysine, and histidine, but not arginine, inhibit the reactions mediated by H11.     

Predicting VHF/UHF electromagnetic noise from corona on power-lineconductors

A method for predicting VHF/UHF noise generated by corona on power-line conductors in steady rain has been developed. The corona sources are modeled as electric dipoles which are randomly distributed along the conductors and driven by impulsive currents. Each source induces currents on the conductors which in turn radiate as traveling-wave antennas. The receiving antenna then responds to the incoherent superposition of the fields from each source. The final formula is a function of the power-line parameters and receiving system characteristics. The most significant result is that the received noise is a strong function of the receiving antenna orientation. The noise is minimized for antennas directed at the line while it is maximized for antennas directed down the line at an angle dependent on the other problem parameters. Lower-frequency (i.e. 75 MHz) results are in good agreement with experiment