α-Methylene-β-Lactone Scaffold for Developing Chemical Probes at the Two Ends of the Selectivity Spectrum

The utilities of an α-methylene-β-lactone (MeLac) moiety as a warhead composed of multiple electrophilic sites are reported. We demonstrate that a MeLac-alkyne not only reacts with diverse proteins as a broadly reactive measurement probe, but also recruits reduced endogenous glutathione (GSH) to assemble a selective chemical probe of GSH-β-lactone (GSH-Lac)-alkyne in live cells. Tandem mass spectrometry reveals that MeLac reacts with nucleophilic cysteine, serine, lysine, threonine, and tyrosine residues, through either Michael or acyl addition. A peptide-centric proteomics platform demonstrates that the proteomic selectivity profiles of orlistat and parthenolide, which have distinct reactivities, are measurable by MeLac-alkyne as a high-coverage probe. The GSH-Lac-alkyne selectively probes the glutathione S-transferase P responsible for multidrug resistance. The assembly of the GSH-Lac probe exemplifies a modular and scalable route to develop selective probes with different recognizing moieties.     

The posthuman: AI,dronology, and “becoming alien”

AI & SOCIETY - This paper is addressed to recent theoretical discussions of the Anthropocene, in particular Bernard Stiegler’s Neganthropocene (Open Universities Press, 2018), which...     

Robust super-hydrophobic ceramic coating on alumina with water and dirt repelling properties

Artificial super-hydrophobic surfaces are required for various applications. The super-hydrophobic surfaces are usually made by applying a low surface-energy organic coating on a highly textured substrate. A major problem with the as-created surfaces is their poor durability. This problem is even severer for the surfaces created by applying the organic coating on inorganic substrates. The present study reports for the first time the all-inorganic super-hydrophobic surface created by modifying the inorganic substrates with polymer-derived inorganic coating. A polydimethylsiloxane (PDMS) film was applied to an alumina substrate having flower-like hierarchal micro-nano surface texture, and then subjected to pyrolysis at 400°C in a nonoxidizing atmosphere. As a result, a Si_xC_yO_z ceramic coating with low-surface energy methyl groups was formed on the alumina substrate. The as-modified alumina exhibited super-hydrophobicity with a water contact angle of 170° and a sliding angle of 5°. The super-hydrophobicity was well retained after abrasion with sandpaper and exposure to boiling water and acidic solution. The super-hydrophobic alumina demonstrated desired water repelling and self-cleaning function. The method explored in this study could also be used for super-hydrophobic surface modification of other inorganic materials such as glass and metals.     

Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC₅₀ value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC₅₀ value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.     

Rock brittleness indices and their applications to different fields of rock engineering:A review

Brittleness is an important parameter controlling the mechanical behavior and failure characteristics of rocks under loading and unloading conditions,such as fracability,cutability,drillability and rockburst proneness.As such,it is of high practical value to correctly evaluate rock brittleness.However,the definition and measurement method of rock brittleness have been very diverse and not yet been standardized.In this paper,the definitions of rock brittleness are firstly reviewed,and several representative definitions of rock brittleness are identified and briefly discussed.The development and role of rock brittleness in different fields of rock engineering are also studied.Eighty brittleness indices publicly available in rock mechanics literature are compiled,and the measurement method,applicability and limitations of some indices are discussed.The results show that(1)the large number of brittleness indices and brittleness definitions is attributed to the different foci on the rock behavior when it breaks;(2)indices developed in one field usually are not directly applicable to other fields;and(3)the term“brittleness”is sometimes misused,and many empirically-obtained brittleness indices,which lack theoretical basis,fail to truly reflect rock brittleness.On the basis of this review,three measurement methods are identified,i.e.(1)elastic deformation before fracture,(2)shape of post-peak stressestrain curves,and(3)methods based on fracture mechanics theory,which have the potential to be further refined and unified to become the standard measurement methods of rock brittleness.It is highly beneficial for the rock mechanics community to develop a robust definition of rock brittleness.This study will undoubtedly provide a comprehensive timely reference for selecting an appropriate brittleness index for their applications,and will also pave the way for the development of a standard definition and measurement method of rock brittleness in the long term.     

Constant hue bands in boundary colors discovered using a new appearance model

Boundary colors are observed when light from a scene is dispersed by a prism or diffraction grating. We discovered that patterns with repeating black and white stripes can produce repeating bands of boundary colors with two hues. These hues are virtually constant as measured by chromaticity or CIELAB. We found seven cases of this kind using a new appearance model for boundary colors. The model correctly predicts that green and magenta bands recur as stripe widths and dispersion strength vary. The first green/magenta case in the sequence traces out an accurate ellipse in XYZ color space. Green and magenta bands are prominent in supernumerary rainbows and interference rings, and we explain why that might be the case. The explanation is based on an interesting property of the visible spectrum. In addition to the green/magenta cases, the other cases are orange/cyan, yellowish‐green/purple, and yellow/violet. The success of the boundary color appearance model implies that bands are perceived as if the wavelength responses of the cones were essentially independent, which contradicts the actual behavior of cones. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 135–146, 2015