Measurement of the muon capture rate in hydrogen gas and determination of the proton's pseudoscalar coupling gP

The rate of nuclear muon capture by the proton has been measured using a new technique based on a time projection chamber operating in ultraclean, deuterium-depleted hydrogen gas, which is key to avoiding uncertainties from muonic molecule formation. The capture rate from the hyperfine singlet ground state of the microp atom was obtained from the difference between the micro(-) disappearance rate in hydrogen and the world average for the micro(+) decay rate, yielding Lambda(S)=725.0+/-17.4 s(-1), from which the induced pseudoscalar coupling of the nucleon, g(P)(q(2)=-0.88m(2)(micro))=7.3+/-1.1, is extracted.     

Reentrant orbital order and the true ground state of LaSr2Mn2O7

Contrary to conventional wisdom, our purified La 2-2x Sr 1+2x Mn2O7 crystals exhibit CE-type orbital and charge order as the low-temperature ground state for a hole doping level h=0.5. For small deviations from h=0.5, the high-temperature CE phase is replaced at low temperatures by an A-type antiferromagnet without coexistence. Larger deviations result in a lack of CE order at any temperature. Thus, small inhomogeneities in cation or oxygen composition could explain why others commonly see this reentrance with coexistence.     

Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents

We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (1) robust targeting of peptide N-termini and lysyl side chains, (2) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (3) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (4) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da, are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition, we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally, we provide exemplar data that extend the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers.

Mutant-Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug-Resistant Mutations

Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug-resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced. Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP-site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR.     

On‐Surface Synthesis and Characterization of Triply Fused Porphyrin–Graphene Nanoribbon Hybrids

On‐surface synthesis offers a versatile approach to prepare novel carbon‐based nanostructures that cannot be obtained by conventional solution chemistry. Graphene nanoribbons (GNRs) have potential for a variety of applications. A key issue for their application in molecular electronics is in the fine‐tuning of their electronic properties through structural modifications, such as heteroatom doping or the incorporation of non‐benzenoid rings. In this context, the covalent fusion of GNRs and porphyrins (Pors) is a highly appealing strategy. Herein we present the selective on‐surface synthesis of a Por–GNR hybrid, which consists of two Pors connected by a short GNR segment. The atomically precise structure of the Por–GNR hybrid has been characterized by bond‐resolved scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc‐AFM). The electronic properties have been investigated by scanning tunneling spectroscopy (STS), in combination with DFT calculations, which reveals a low electronic gap of 0.4 eV.     

Host–Guest Complexation of Amphiphilic Molecules at the Air–Water Interface Prevents Oxidation by Hydroxyl Radicals and Singlet Oxygen

The oxidation of antioxidants by oxidizers imposes great challenges to both living organisms and the food industry. Here we show that the host–guest complexation of the carefully designed, positively charged, amphiphilic guanidinocalix[5]arene pentadodecyl ether (GC5A‐12C) and negatively charged oleic acid (OA), a well‐known cell membrane antioxidant, prevents the oxidation of the complex monolayers at the air–water interface from two potent oxidizers hydroxyl radicals (OH) and singlet delta oxygen (SDO). OH is generated from the gas phase and attacks from the top of the monolayer, while SDO is generated inside the monolayer and attacks amphiphiles from a lateral direction. Field‐induced droplet ionization mass spectrometry results have demonstrated that the host–guest complexation achieves steric shielding and prevents both types of oxidation as a result of the tight and “sleeved in” physical arrangement, rather than the chemical reactivity, of the complexes.     

The Elusive Ketene (H2CCO) Channel in the Infrared Multiphoton Dissociation of Solid 1,3,5-Trinitro-1,3,5-Triazinane (RDX)

Understanding of the fundamental mechanisms involved in the decomposition of 1,3,5-trinitro-1,3,5-triazinane (RDX) still represents a major challenge for the energetic materials and physical (organic) chemistry communities mainly because multiple competing dissociation channels are likely involved and previous detection methods of the products are not isomer selective. In this study we exploited a microsecond pulsed infrared laser to decompose thin RDX films at 5 K under mild conditions to limit the fragmentation channels. The subliming decomposition products during the temperature programed desorption phase are detected using isomer selective single photoionization time-of-flight mass spectrometry (PI-ReTOF-MS). This technique enables us to assign a product signal at m/z=42 to ketene (H₂CCO), but not to diazomethane (H₂CNN; 42 amu) as speculated previously. Electronic structure calculations support our experimental observations and unravel the decomposition mechanisms of RDX leading eventually to the elusive ketene (H₂CCO) via an exotic, four-membered ring intermediate. This study highlights the necessity to exploit isomer-selective detection schemes to probe the true decomposition products of nitramine-based energetic materials.     

Effects of internals and distributors on the distribution and growth of bubbles in the conventional gas-solid fluidized bed

The effects of internals and gas distributors on the local dynamics of the bubbles in the conventional gas-solid fluidized bed were studied.Mesh-type internals with different opening areas(50%,70%and 90%)and different arrangements(two-layer and four-layer);and a sintered plate with a smaller pore size(1μm)and a perforated plate with a larger pore size as distributors were investigated.Differential pressure drops and local solids holdups were measured under various superficial gas velocities to compare the performances of the different types of internals and distributors.The instantaneous solids holdup signals from the optical fibre probe were used to further examine the local bubble dynamics in detail.Smaller bubbles were found,with the installation of internals or using the sintered plate,resulting in lower pressure drops and a higher bed expansion.Internals with reduced opening area or distributor with smaller pore size further leads to a higher changeover rate between the bubbles and dense phase,both axially and radially,and hence a better gas-solid contacting and an earlier transition to the turbulent flow regime of the bed.     

Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.