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At least 1,081 records · Page 60

Molecular recognition requires dimerization of a VHH antibody

Camelid heavy-chain-only antibodies are a unique class of antibody that possesses only a single variable domain (termed VHH) for antigen recognition. Despite their apparent canonical mechanism of target recognition, where a single VHH domain binds a single target, an anti-caffeine VHH has been observed to possess 2:1 stoichiometry. Here, the structure of the anti-caffeine VHH/caffeine complex enabled the generation and biophysical analysis of variants that were used to better understand the role of VHH homodimerization in caffeine recognition. VHH interface mutants and caffeine analogs, which were examined to probe the mechanism of caffeine binding, suggested caffeine recognition is only possible with the VHH dimer species. Correspondingly, in the absence of caffeine, the anti-caffeine VHH was found to form a dimer with a dimerization constant comparable to that observed with VH:VL domains in conventional antibody systems, which was most stable near physiological temperature. While the VHH:VHH dimer structure (at 1.13 Å resolution) is reminiscent of conventional VH:VL heterodimers, the homodimeric VHH possesses a smaller angle of domain interaction, as well as a larger amount of apolar surface area burial. To test the general hypothesis that the short complementarity-determining region-3 (CDR3) may help drive VHH:VHH homodimerization, an anti-picloram VHH domain containing a short CDR3 was generated and characterized, which revealed it also existed as dimer species in solution. These results suggest homodimer-driven recognition may represent a more common method of VHH ligand recognition, opening opportunities for novel VHH homodimer affinity reagents and helping to guide their use in chemically induced dimerization applications.

60 APPLIED LIFE SCIENCES↗

Investigation of low-energy particle remnants in high-energy collisions at the LHC with a skipper-CCD detector

We deployed the Mobile Skipper Testing Apparatus ∼33 m away from the Compact Muon Solenoid collision point, the first skipper-CCD detector probing low-energy particles produced in high-energy collisions at the Large Hadron Collider. In this work, we search for beam-related events using data collected in 2024 during beam-on and beam-off periods. The dataset corresponds to integrated luminosities of 113.3 fb −1 and 1.54 nb −1 for the proton-proton and Pb-Pb collision periods, respectively. We report observed event rates in a model-independent framework across two ionization regions: ≤ 20⁢𝑒 − and > 20⁢𝑒 − . For the low-energy region, we perform a likelihood analysis to test the null hypothesis of no beam-correlated signal. We found no significant correlation during proton-proton and Pb-Pb collisions. For the high-energy region, we present the energy spectra for both collision periods and compare event rates for images with and without luminosity. We observe a slight increase in the event rate following the Pb-Pb collisions, coinciding with a rise in the single-electron rate, which will be investigated in future work. Using the low-energy proton-proton results, we place 95% confidence level constraints on the mass-millicharge parameter space of millicharged particles. Overall, the results in this work demonstrate the viability of skipper-CCD technology to explore new physics at high-energy colliders and motivate future searches with more massive detectors.

Cervantes-Vergara, Brenda A. [Fermi National Accel↗

Prescribed fire selects for a pyrophilous soil sub‐community in a northern California mixed conifer forest

Abstract Prescribed fire is a critical strategy for mitigating the effects of catastrophic wildfires. While the above‐ground response to fire has been well‐documented, fewer studies have addressed the effect of prescribed fire on soil microorganisms. To understand how soil microbial communities respond to prescribed fire, we sampled four plots at a high temporal resolution (two burned, two controls), for 17 months, in a mixed conifer forest in northern California, USA. Using amplicon sequencing, we found that prescribed fire significantly altered both fungal and bacterial community structure. We found that most differentially abundant fungal taxa had a positive fold‐change, while differentially abundant bacterial taxa generally had a negative fold‐change. We tested the null hypothesis that these communities assembled due to neutral processes (i.e., drift and/or dispersal), finding that >90% of taxa fit this neutral prediction. However, a dynamic sub‐community composed of burn‐associated indicator taxa that were positively differentially abundant was enriched for non‐neutral amplicon sequence variants, suggesting assembly via deterministic processes. In synthesizing these results, we identified 15 pyrophilous taxa with a significant and positive response to prescribed burns. Together, these results lay the foundation for building a process‐driven understanding of microbial community assembly in the context of the classical disturbance regime of fire.

Microbiology↗

De novo design of transmembrane β barrels

Transmembrane β-barrel proteins (TMBs) are of great interest for single-molecule analytical technologies because they can spontaneously fold and insert into membranes and form stable pores, but the range of pore properties that can be achieved by repurposing natural TMBs is limited. We leverage the power of de novo computational design coupled with a “hypothesis, design, and test” approach to determine TMB design principles, notably, the importance of negative design to slow β-sheet assembly. We design new eight-stranded TMBs, with no homology to known TMBs, that insert and fold reversibly into synthetic lipid membranes and have nuclear magnetic resonance and x-ray crystal structures very similar to the computational models. These advances should enable the custom design of pores for a wide range of applications.

Vorobieva, Anastassia A.↗

Structural and Dynamical Design Principles for Iron-Sulfur Clusters in Sequence Defined Polymers

This integrated synthetic and computational effort uses sequence defined polymers such as peptoids, and triazines, capable of mimicking a flexible protein environment to control the positioning of side chains around redox cofactors. This strategy will allow modulation of redox properties through both direct and indirect mechanisms. To this end the aim is defined to test the underlying hypothesis: that principles and critical functionalities governing the binding and tuning of naturally occurring electron carrier co-factors can be identified and used to predictably design and synthesize maquettes based on non-natural polymers resulting in new modular biomimetic scaffolds for Electron Transfer Materials. This will be achieved through design and synthesis of ligands that can stabilize iron-sulfur clusters and tune the redox potential based on sequence.

36 MATERIALS SCIENCE↗

The Quest for High-Temperature Superconductivity in Nickelates under Ambient Pressure

Recently, superconductivity with Tc ≈ 80 K was discovered in La3Ni2O7 under extreme hydrostatic pressure (>14 GPa). For practical applications, we needed to stabilize this state at ambient pressure. It was proposed that this could be accomplished by substituting La with Ba. To put this hypothesis to the test, we used the state-of-the-art atomic-layer-by-layer molecular beam epitaxy (ALL-MBE) technique to synthesize (La1−xBax)3Ni2O7 films, varying x and the distribution of La (lanthanum) and Ba (barium). Regrettably, none of the compositions we explored could be stabilized epitaxially; the targeted compounds decomposed immediately into a mixture of other phases. So, this path to high-temperature superconductivity in nickelates at ambient pressure does not seem promising.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

A Systems Biology Approach to Identify Essential Epigenetic Regulators for Specific Biological Processes in Plants

Upon sensing developmental or environmental cues, epigenetic regulators transform the chromatin landscape of a network of genes to modulate their expression and dictate adequate cellular and organismal responses. Knowledge of the specific biological processes and genomic loci controlled by each epigenetic regulator will greatly advance our understanding of epigenetic regulation in plants. To facilitate hypothesis generation and testing in this domain, we present EpiNet, an extensive gene regulatory network (GRN) featuring epigenetic regulators. EpiNet was enabled by (i) curated knowledge of epigenetic regulators involved in DNA methylation, histone modification, chromatin remodeling, and siRNA pathways; and (ii) a machine-learning network inference approach powered by a wealth of public transcriptome datasets. We applied GENIE3, a machine-learning network inference approach, to mine public Arabidopsis transcriptomes and construct tissue-specific GRNs with both epigenetic regulators and transcription factors as predictors. The resultant GRNs, named EpiNet, can now be intersected with individual transcriptomic studies on biological processes of interest to identify the most influential epigenetic regulators, as well as predicted gene targets of the epigenetic regulators. We demonstrate the validity of this approach using case studies of shoot and root apical meristem development.

root apical meristem↗

A method of computing periods of cyclic phenomena.

Use of an analysis of Expected Mean Square Deviations to search for periodicities in an observational data sample is described. The statistic for testing the null hypothesis of nonperiodicity is derived from a partitioning of the total sum of squared deviations from the mean. Unlike most existing methods, the present one does not require equally spaced observations. No assumptions are made concerning the statistical nature of spacing intervals. The method is illustrated by numerical examples.

Jurkevich, I.↗

Two stochastic models useful in petroleum exploration

A model of the petroleum exploration process that tests empirically the hypothesis that at an early stage in the exploration of a basin, the process behaves like sampling without replacement is proposed along with a model of the spatial distribution of petroleum reserviors that conforms to observed facts. In developing the model of discovery, the following topics are discussed: probabilitistic proportionality, likelihood function, and maximum likelihood estimation. In addition, the spatial model is described, which is defined as a stochastic process generating values of a sequence or random variables in a way that simulates the frequency distribution of areal extent, the geographic location, and shape of oil deposits

Kaufman, G. M.↗

On the presence of phyllosilicate minerals in the interstellar grains

The composition of the interstellar silicate dust is investigated. Condensation or alteration of silicate grains at temperatures of a few hundred degrees, in the presence of H2O, would result in hydrous or phyllosilicates, the silicate type most abundant in the type I carbonaceous chondrites. Infrared spectra of small particles (about 0.1 microns) of the high temperature condensates, olivine and pyroxene, at 300 K and 4 K do not give a good match to the interstellar absorption band near 9.8 microns. Laboratory spectra of several phyllosilicates give better agreement as does the spectrum of a carbonaceous chondrite. We propose that the silicates in the interstellar grains are predominantly phyllosilicates and suggest additional spectral tests for this hypothesis.

Zaikowski, A.↗

Thermal interaction of the core and the mantle and long-term behavior of the geomagnetic field

The effects of temperature changes at the earth's core-mantle boundary on the velocity field of the core are analyzed. It is assumed that the geomagnetic field is maintained by thermal convection in the outer core. A model for the thermal interaction of the core and the mantle is presented which is consistent with current views on the presence of heat sources in the core and the properties of the lower mantle. Significant long-term variations in the frequency of geomagnetic reversals may be the result of fluctuating temperatures at the core-mantle boundary, caused by intermittent convection in the lower mantle. The thermal structure of the lower mantle region D double prime, extending from 2700 to 2900 km in depth, constitutes an important test of this hypothesis and offers a means of deciding whether the geomagnetic dynamo is thermally driven.

Jones, G. M.↗

Propeller tip vortex - A possible contributor to aircraft cabin noise

Wind tunnel model tests support the hypothesis that a propeller tip vortex may subject a downstream wing surface to greater excitation than would be experienced by the aircraft fuselage side wall exposed to propeller-generated noise, ultimately transmitting this structural response to incident dynamic pressure to the cabin interior. Even if structure-borne excitations are less efficient than airborne excitations in the creation of cabin noise, the higher level of the former could still govern cabin noise levels.

Miller, B. A.↗

Large-scale magnetic fields in spiral galaxies

The optical polarization vectors which measurements have shown to be parallel to the pronounced dark lanes of such galaxies as NGC 5128 and 4590 are interpreted as the consequence of a large scale, systematic field parallel to the dark lane that leads to the alignment of the grains. It is suggested that such polarization may also be produced by scattering off grains concentrated in the dark lane. It is recommended that there be further observational tests of the hypothesis that the observed polarization indicates the magnetic field in the galaxy.

Jura, M.↗

X-rays from radio pulsars - The detection of PSR 1055-52

The short-period pulsar PSR 1055-52 has been detected as a soft X-ray source in the course of an Einstein Observatory survey of radio pulsars. Its X-ray to radio luminosity ratio is about 10,000, although the X-rays are not modulated at the neutron star's rotation frequency. High spatial resolution observations suggest that a significant fraction of the emission comes from an extended region surrounding the pulsar. Several possible scenarios for the origin of both point and extended X-ray emission from isolated neutron stars are investigated: radiation from the hot stellar surface, from hot polar caps, and from an optically thick atmosphere, as well as from a circumstellar nebula emitting thermal bremsstrahlung or synchrotron radiation. It is concluded that the spatial, spectral, and temporal characteristics of this source are most consistent with a model in which relativistic particles generated by the pulsar are radiating synchrotron X-rays in the surrounding magnetic field; i.e., that PSR 1055 is embedded in a mini-Crab nebula. Observational tests of this hypothesis are suggested, and the implications of this result for pulsar evolution are briefly discussed.

Cheng, A. F.↗

Mass loss rates and anisotropies in the outflows from late-type stars

It has been found that late-type giants and supergiants are losing large amounts of mass. However, it is still not known why these stars lose mass. In connection with the aim to understand this process, it is attempted to establish more accurate mass loss rates in order to consider in detail a popular model for mass loss, taking into account the hypothesis that radiation pressure on grains is important or even controls the mass outflows. This hypothesis can be tested by comparing measurements of the flux from the star, the mass loss rate, and the outflow velocity of the material. The largest uncertainty is related to the mass loss rate. Most models for interpreting the observations of these stars have been for spherically symmetric envelopes. However, highly anisotropic outflows have been observed. It is, therefore, one of the purposes of this investigation to study the importance of the anisotropy in the physical characteristics of the outflow. It is found that anisotropy does not greatly alter the important basic photochemical processes, and that radiation pressure on grains can be important.

Jura, M.↗

Flexure of the continental lithosphere beneath Apennine and Carpathian foredeep basins

The preservation of foredeep basins after an associated mountain belt has been greatly reduced by erosion suggests that an additional load must act on the subducted slab's lithosphere independently of topography. This hypothesis is presently tested for the case of young orogenic belts, through the construction of transects through the Apennine and outer Carpathian thrust belts of the Mediterranean region. A simple elastic model is used to show that the topographic loads present along the transects are not sufficient to cause the observed plate deflection, suggesting that an additional load or downward force is acting on the plate to generate the plate deflection observed. It is proposed that this extra load is due either to the negative buoyancy contrast between the subducted slab and the asthenosphere, or to the crustal structure's modification by backarc rifling in the hinterland.

Royden, L.↗

Cosmic-ray antiprotons as a probe of a photino-dominated universe

Observational tests of the hypothesis that the universe is flat and dominated by dark matter in the form of massive photinos include the production of significant fluxes of cosmic rays and gamma rays in our galactic halo. Specification of the cosmological photino density and the masses of scalar quarks and leptons determines the present annihilation rate. The predicted number of low-energy cosmic-ray antiprotons is comparable to the observed flux.

Silk, J.↗

A preliminary study of a cryogenic equivalence principle experiment on Shuttle

The Weak Equivalence Principle is the hypothesis that all test bodies fall with the same acceleration in the same gravitational field. The current limit on violations of the Weak Equivalence Principle, measured by the ratio of the difference in acceleration of two test masses to their average acceleration, is about 3 parts in one-hundred billion. It is anticipated that this can be improved in a shuttle experiment to a part in one quadrillion. Topics covered include: (1) studies of the shuttle environment, including interference with the experiment, interfacing to the experiment, and possible alternatives; (2) numerical simulations of the proposed experiment, including analytic solutions for special cases of the mass motion and preliminary estimates of sensitivity and time required; (3) error analysis of several noise sources such as thermal distortion, gas and radiation pressure effects, and mechanical distortion; and (4) development and performance tests of a laboratory version of the instrument.

Everitt, C. W. F.↗