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Using philanthropy to change your reputation is a practice ns old as America itself. Just ask George Peabody. Philanthropy may be a cornerstone of the fortress inhabited by America's ruling [...]

Diffusion of hydrogen (H2) is important to understand the leakage risk and transport behavior for H2geologic storage. We applied molecular dynamics simulations to investigate the influencing factors of H2diffusion in the slit pores of calcite, hematite, and quartz, owing to their abundance. It is revealed that the H2self-diffusion coefficient increases with the temperature, regardless of the type of pore minerals. The diffusion of H2in the 20 nm slit pores falls into the bulk diffusion regime when the pressure is 10 MPa. The self-diffusion of H2decreases with pressure in all three types of slit pores, following a power law model with the exponents ranging from −0.825 to −0.964. Furthermore, the impact of confinement on H2diffusion is more pronounced for the slit pores with stronger interactions with H2-like calcite. The role of surface roughness in H2diffusion depends on the slit aperture. The rough surface enhances H2diffusion in the larger slit pores due to the enlarged effective pore space, whereas it weakens H2diffusion in the small slit pores due to stronger adsorption. These findings will fill the knowledge gap on the coupling effect of different factors influencing H2diffusion.

Copyright of Changement is the property of Solutions by HANDELSBLATT MEDIA GROUP GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Suspended membranes of monatomic graphene exhibit great potential for applications in electronic and nanoelectromechanical devices. In this work, a “hot and dry” transfer process is demonstrated to address the fabrication and patterning challenges of large-area graphene membranes on top of closed, sealed cavities. Here, “hot” refers to the use of high temperature during transfer, promoting the adhesion. Additionally, “dry” refers to the absence of liquids when graphene and target substrate are brought into contact. The method leads to higher yields of intact suspended monolayer chemical vapor deposition (CVD) graphene and artificially stacked double-layer CVD graphene membranes than previously reported. The yield evaluation is performed using neural-network-based object detection in scanning electron microscopy (SEM) images, ascertaining high yields of intact membranes with large statistical accuracy. The suspended membranes are examined by Raman tomography and atomic force microscopy (AFM). The method is verified by applying the suspended graphene devices as piezoresistive pressure sensors. Our technology advances the application of suspended graphene membranes and can be extended to other two-dimensional materials.

In Drosophila testis, myosin VI plays a special role, distinct from its motor function, by anchoring components to the unusual actin-based structures (cones) that are required for spermatid individualization. For this, the two calmodulin (CaM) light-chain molecules of myosin VI are replaced by androcam (ACaM), a related protein with 67% identity to CaM. Although ACaM has a similar bi-lobed structure to CaM, with two EF hand-type Ca2+binding sites per lobe, only one functional Ca2+binding site operates in the amino-terminus. To understand this light chain substitution, we used hydrogen–deuterium exchange mass spectrometry (HDX-MS) to examine dynamic changes in ACaM and CaM upon Ca2+binding and interaction with the two CaM binding motifs of myosin VI (insert2 and IQ motif). HDX-MS reveals that binding of Ca2+to ACaM destabilizes its N-lobe but stabilizes the entire C-lobe, whereas for CaM, Ca2+binding induces a pattern of alternating stabilization/destabilization throughout. The conformation of this stable holo-C-lobe of ACaM seems to be a “prefigured” version of the conformation adopted by the holo-C-lobe of CaM for binding to insert2 and the IQ motif of myosin VI. Strikingly, the interaction of holo-ACaM with either peptide converts the holo-N-lobe to its Ca2+-free, more stable, form. Thus, ACaM in vivo should bind the myosin VI light chain sites in an apo-N-lobe/holo-C-lobe state that cannot fulfill the Ca2+-related functions of holo-CaM required for myosin VI motor assembly and activity. These findings indicate that inhibition of myosin VI motor activity is a precondition for transition to an anchoring function.

The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2.

Fracture flow is the fluid movement in a fracture or a fracture zone. Since fracture flow can induce long-duration (LD) microseismic events, classifying different types of microseismicity is crucial for reliable monitoring of subsurface fracture flow. We analyze hydraulic fracturing-induced microseismic data recorded by borehole geophones and find four types of microseismic events: two types of short-duration events and two types of LD events. Among the two types of LD events, one contains frequency-drop LD (FDLD) characteristics, and the other exhibits low-frequency LD (LFLD) characteristics. We employ an unsupervised machine-learning algorithm based on the U-Net convolutional network to classify microseismic events. Our study shows that LFLD events occur only during the proppant injection period of hydraulic fracturing and that the spatiotemporal distributions of the LFLD events gradually grow from the fracture stimulation wells outward with time. Also, the cumulative seismic moment of the LFLD events is proportional to the cumulative amount of injected proppant. These results can be used to optimize hydraulic fracturing parameters in unconventional reservoirs.

Irreversible protein footprinting is a mass spectrometry–based approach in which solvent-accessible sites of a protein are modified to assess high-order protein structure. Structural insights can be gained by determining the position and extents of modification. The usual approach to obtain the “footprint” is to analyze the protein through bottom-up LC-MS/MS. In this approach, the proteins are digested to yield a mixture of peptides that are then separated by LC before locating the modification sites by MS/MS. This process consumes substantial amounts of time and is difficult to accelerate for applications that require quick and high-throughput analysis. Here, we describe employing matrix-assisted laser desorption/ionization (MALDI) in-source decay (ISD) to analyze a footprinted small test protein (ubiquitin) via a top-down approach. Matrix-assisted laser desorption/ionization is easily adapted for high-throughput analysis, and top-down strategies can avoid lengthy proteolysis and LC separation. We optimized the method with model peptides and then demonstrated its feasibility on ubiquitin submitted to two types of footprinting. We found that MALDI ISD can produce a comprehensive set of fragment ions for small proteins, affording footprinting information in a fast manner and giving results that agree with the established methods, and serve as a rough measure of protein solvent accessibility. To assist in the implementation of the MALDI approach, we developed a method of processing top-down ISD data.

ROYAL PAINS HANDSOME PRINCE MEETS BEAUTIFUL NON-PRINCESS? NOT SO LONG AGO IT MIGHT HAVE BEEN THE END OF THE FAIRY TALE. WHY EUROPE'S ROYAL HOUSES FINALLY DECIDED TO LET LOVE [...]

Characterizing changes in the higher order structure (HOS) of monoclonal antibodies upon stressed conditions is critical to gaining a better understanding of the product and process. One single biophysical approach may not be best suited to assess HOS comprehensively; thus, the synergy from multiple, complementary approaches improves characterization accuracy and resolution. In this study, we employed two mass spectrometry (MS )-based footprinting techniques, namely, fast photochemical oxidation of proteins (FPOP)-MS and hydrogen–deuterium exchange (HDX)-MS, supported by dynamic light scattering (DLS), differential scanning calorimetry (DSC), circular dichroism (CD), and nuclear magnetic resonance (NMR) to study changes to the HOS of a mAb upon thermal stress. The biophysical techniques report a nuanced characterization of the HOS in which CD detects no changes to the secondary or tertiary structure, yet DLS measurements show an increase in the hydrodynamic radius. DSC indicates that the stability decreases, and chemical or conformational changes accumulate with incubation time according to NMR. Furthermore, whereas HDX-MS does not indicate HOS changes, FPOP-MS footprinting reveals conformational changes at residue resolution for some amino acids. The local phenomena observed with FPOP-MS indicate that several residues show various patterns of degradation during thermal stress: no change, an increase in solvent exposure, and a biphasic response to solvent exposure. All evidences show that FPOP-MS efficiently resolves subtle structural changes and novel degradation pathways upon thermal stress treatment at residue-level resolution.

G-quadruplexes are thought to play an important role in gene regulation and telomere maintenance, but developing probes for their presence and location is challenging due to their transitory and highly dynamic nature. The majority of probes for G-quadruplexes have relied on antibody or small-molecule binding agents, many of which can also alter the dynamics and relative populations of G-quadruplexes. Recently, it was discovered that ultraviolet B (UVB) irradiation of human telomeric DNA and various G-quadruplex forming sequences found in human promoters, as well as reverse Hoogsteen hairpins, produces a unique class of non-adjacent anticyclobutane pyrimidine dimers (CPDs). Therefore, one can envision using a pulse of UVB light to irreversibly trap these non-B DNA structures via antiCPD formation without perturbing their dynamics, after which the antiCPDs can be identified and mapped. As a first step toward this goal, we report radioactive post- and pre-labeling assays for the detection of non-adjacent CPDs and illustrate their use in detecting trans,antiT=(T) CPD formation in a human telomeric DNA sequence. Both assays make use of snake venom phosphodiesterase (SVP) to degrade the trans,antiT=(T) CPD-containing DNA to the tetranucleotide pTT=(pTT) corresponding to CPD formation between the underlined T′s of two separate dinucleotides while degrading the adjacent synTT CPDs to the trinucleotide pGT=T. In the post-labeling assay, calf intestinal phosphodiesterase is used to dephosphorylate the tetranucleotides, which are then rephosphorylated with kinase and [32P]-ATP to produce radiolabeled mono- and diphosphorylated tetranucleotides. The tetranucleotides are confirmed to be non-adjacent CPDs by 254 nm photoreversion to the dinucleotide p*TT. In the pre-labeling assay, radiolabeled phosphates are introduced into non-adjacent CPD-forming sites by ligation prior to irradiation, thereby eliminating the dephosphorylation and rephosphorylation steps. The assays are also demonstrated to detect the stereoisomeric cis,antiT=(T) CPD.

Protein footprinting mass spectrometry probes protein higher order structure and dynamics by labeling amino acid side-chains or backbone amides as a function of solvent accessibility. One category of footprinting uses residue-specific, irreversible covalent modifications, affording flexibility of sample processing for bottom-up analysis. Although several specific amino acid footprinting technologies are becoming established in structural proteomics, there remains a need to assess fundamental properties of new reagents before their application. Often, footprinting reagents are applied to complex or novel protein systems soon after their discovery and sometimes without a thorough investigation of potential downsides of the reagent. In this work, we assemble and test a validation workflow that utilizes cyclic peptides and a model protein to characterize benzoyl fluoride, a recently published, next-generation nucleophile footprinter. The workflow includes the characterization of potential side-chain reactive groups, reaction “quench” efficacies, reagent considerations and caveats (e.g., buffer pH), residue-specific kinetics compared to those of established reagents, and protein-wide characterization of modification sites with considerations for proteolysis. The proposed workflow serves as a starting point for improved footprinting reagent discovery, validation, and introduction, the aspects of which we recommend before applying to unknown protein systems.

Cohen and Levinthal (1990) conceptualize 'absorptive capacity' as a limit to the quantity of scientific or technological information that a firm can absorb or the rate at which this information [...]

In defiance of international law, nonlethal weapons inflict direct harm upon noncombatants. To permit their use, this paper considers three competing arguments. First, nonlethal weapons inflict no harm; second, nonlethal [...]

THE YOUNGER OF TWO DOORMEN, who looks to be about 25, Latino, and straight, recognizes the woman on the sidewalk instantly. 'Damn, she looks good,' he says to his colleague [...]

I DON'T HAVE PERMISSION TO BE ON BASE, and I'm nervous, because when I told veterans what I planned to do, they all gave me pretty much the same warning: [...]

Background. Step-up exercises often are suggested for strengthening the hip abductor muscles and improving balance in older adults. Little is known, however, about whether the forward or lateral version of these exercises is best for activating the hip abductor muscles. Objective. The purpose of this study was to examine the electromyographic (EMG) amplitude of the gluteus medius (GM) muscles bilaterally during forward and lateral step-up exercises. Design. The study design involved single-occasion repeated measures. Methods. Twenty-seven community-dwelling adults (7 men and 20 women) with a mean (SD) age of 79.4 (8.0) years performed forward and lateral step-up exercises while the surface EMG activity of the GM muscles was recorded bilaterally. Pressure switches and dual forceplates were used to identify the ascent and descent phases. Subjects were instructed to lead with the right lower extremity during ascent and the left lower extremity during descent. Differences in normalized root-mean-square EMG amplitudes with exercise direction (forward versus lateral) and phase (ascent versus descent) were examined by use of separate repeated-measures analyses of variance for the right and left lower extremities. The alpha level was set at .05. Results. Gluteus medius muscle EMG activity was significantly greater for lateral than for forward step-up exercises for the left lower extremity during the ascent phase and for both lower extremities during the descent phase. In addition, right GM muscle EMG activity was significantly greater during ascent than during descent for both exercise directions. Limitations. Study limitations include use of a convenience sample and collection of limited information about participants. Conclusions. Step-up exercises are effective in activating the GM muscle, with lateral step-up exercises requiring greater GM muscle activation than forward step-up exercises. Further study is needed to determine whether exercise programs for hip abductor muscle strengthening in older adults should preferentially include lateral over forward step-up exercises., Compared with younger adults, older adults have greater difficulty maintaining and recovering postural stability, particularly in the frontal plane. (l-3) One likely cause of this difficulty is weakness of the [...]

Protein footprinting is a mass spectrometry (MS)-based approach to measure protein conformational changes. One approach, specific amino acid labeling, imparts often an irreversible modification to protein side chains but requires careful selection of the reactive reagent and often time-consuming optimization of experimental parameters prior to submission to bottom-up MS analysis. In this work, we repurpose a hydrogen–deuterium exchange MS (HDX-MS) LEAP HDX system for automated specific amino acid footprinting MS, demonstrating its efficacy in reaction optimization and monitoring applicability to specific ligand binding systems. We screened reagent conditions for two model ligand-binding systems and demonstrate the method’s efficacy for measuring differences induced by ligand binding. Our proof-of-concept experiments provide a platform for rapidly screening specific amino acid reagents and reaction conditions for protein systems to be studied by footprinting.

'OH, wow!' roars Olafur Eliasson, getting slapped in the face with long, ropy splashes of water, as he clings to the railing of a tiny Grady-White fishing boat. Rain clouds [...]

'Martha did these gift baskets with, like, cookies and tea and stuff. And I said, 'Could you make up one for Valentine's Day for Andy?' 'She said, 'Who's Andy?' 'I [...]

Houston's Lakewood Church, converted from a sports stadium by theatrical designers to accommodate 10,000 worshippers and a TV audience of millions, presents a powerful spectacle of devotion. Appropriate positioning of the pulpit enables worshippers to see the minister and his TV image in one view, special camera angles show off the church's magnitude, a waterfall gives a sacred feel and a giant revolving globe denotes the universal reach of Christianity.

Dolly the sheep was born in 1997. As the first cloned mammal she opened up the prospect that it might one day be possible to clone humans. Now, human embryos […]

Growing number of resorts and attractions for tourists at Riviera Maya in Mexico due to its scenic beauty, is detailed.