259 research outputs found
Irreversible photon transfer in an ensemble of -type atoms and photon diode
We show that a pair of quantized cavity modes interacting with a spectrally
broadened ensemble of Lambda-type atoms is analogous to an ensemble of two
level systems coupled to a bosonic reservoir. This provides the possibility for
an irreversible photon transfer between photon modes. The density of states as
well as the quantum state of the reservoir can be engineered allowing the
observation of effects such as the quantum Zeno- and anti-Zeno effect, the
destructive interference of decay channels and the decay in a squeezed vacuum.
As a particular application we discuss a photon diode, i.e. a device which
directs a single photon from anyone of two input ports to a common output port.Comment: 5 pages, 2 figure
Fracture Propagation Driven by Fluid Outflow from a Low-permeability Aquifer
Deep saline aquifers are promising geological reservoirs for CO2
sequestration if they do not leak. The absence of leakage is provided by the
caprock integrity. However, CO2 injection operations may change the
geomechanical stresses and cause fracturing of the caprock. We present a model
for the propagation of a fracture in the caprock driven by the outflow of fluid
from a low-permeability aquifer. We show that to describe the fracture
propagation, it is necessary to solve the pressure diffusion problem in the
aquifer. We solve the problem numerically for the two-dimensional domain and
show that, after a relatively short time, the solution is close to that of
one-dimensional problem, which can be solved analytically. We use the relations
derived in the hydraulic fracture literature to relate the the width of the
fracture to its length and the flux into it, which allows us to obtain an
analytical expression for the fracture length as a function of time. Using
these results we predict the propagation of a hypothetical fracture at the In
Salah CO2 injection site to be as fast as a typical hydraulic fracture. We also
show that the hydrostatic and geostatic effects cause the increase of the
driving force for the fracture propagation and, therefore, our solution serves
as an estimate from below. Numerical estimates show that if a fracture appears,
it is likely that it will become a pathway for CO2 leakage.Comment: 21 page
Identification of diverse lipid-binding modes in the groove of zinc α2 glycoprotein reveals its functional versatility
ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16-BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16-BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related CD1-proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16-BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16-BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16-BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16-BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16-BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand
The solution structure of the heavy chain–only C5-Fc nanobody reveals exposed variable regions that are optimal for COVID-19 antigen interactions
Heavy chain–only antibodies can offer advantages of higher binding affinities, reduced sizes, and higher stabilities than conventional antibodies. To address the challenge of SARS-CoV-2 coronavirus, a llama-derived single-domain nanobody C5 was developed previously that has high COVID-19 virus neutralization potency. The fusion protein C5-Fc comprises two C5 domains attached to a glycosylated Fc region of a human IgG1 antibody and shows therapeutic efficacy in vivo. Here, we have characterized the solution arrangement of the molecule. Two 1443 Da N-linked glycans seen in the mass spectra of C5-Fc were removed and the glycosylated and deglycosylated structures were evaluated. Reduction of C5-Fc with 2-mercaptoethylamine indicated three interchain Cys–Cys disulfide bridges within the hinge. The X-ray and neutron Guinier RG values, which provide information about structural elongation, were similar at 4.1 to 4.2 nm for glycosylated and deglycosylated C5-Fc. To explain these RG values, atomistic scattering modeling based on Monte Carlo simulations resulted in 72,737 and 56,749 physically realistic trial X-ray and neutron structures, respectively. From these, the top 100 best-fit X-ray and neutron models were identified as representative asymmetric solution structures, similar to that of human IgG1, with good R-factors below 2.00%. Both C5 domains were solvent exposed, consistent with the functional effectiveness of C5-Fc. Greater disorder occurred in the Fc region after deglycosylation. Our results clarify the importance of variable and exposed C5 conformations in the therapeutic function of C5-Fc, while the glycans in the Fc region are key for conformational stability in C5-Fc.</p
Metastable bound state of a pair of two-dimensional spatially separated electrons in anti-parallel magnetic fields
We propose a new mechanism for binding of two equally charged carriers in a
double-layer system subjected by a magnetic field of a special form. A field
configuration for which the magnetic fields in adjacent layers are equal in
magnitude and opposite in direction is considered. In such a field an
additional integral of motion - the momentum of the pair P arises. For the case
when in one layer the carrier is in the zero (n=0) Landau level while in the
other layer - in the first (n=1) Landau level the dependence of the energy of
the pair on its momentum E(P} is found. This dependence turns out to be
nonmonotonic one : a local maximum and a local minimum appears, indicating the
emergence of a metastable bound state of two carrier with the same sign of
electrical charge.Comment: 7 page
Biochemical characterization of thermostable cellulase enzyme from mesophilic strains of actinomycete
A few mesophilic strains of actinomycete were used for detection, extraction and characterization of cellulase enzymes. These strains responded to produce all the three components of cellulase complex (endoglucanase, exoglucanase and â-glucosidase) in balanced quantities. Cellulase activity was determined on solid medium supplemented with 1% carboxy methyl cellulose (CMC). Production of cellulase was detected by the formation of clear or transparent zone around colonies. The greater size of transparent zone has been found proportional to the higher capabilities of the strains for enzymes. The extraction of cellulase enzyme was done in liquid basal medium. The assay of cellulase was observed by measuring the release of reducing sugar (RS) by DNS method. All the three components of cellulase viz. endoglucanase, exoglucanase and â -glucosidase were assayed in terms of CMCase, FPase and cellobiase, respectively and expressed in International units (IU). These strains were further tested for their ability to produce cellulase complex enzyme by growing on a defined substrates as well as on delignified cellulosics. The optimization for â-glucosidase enzyme was carried out by studying the various parameters viz. effect of pH, incubation period and nitrogen sources.Key words: Cellulase, actinomycete, optimization, reducing sugar, carboxy methyl cellulose
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Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.
BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD
The solution structure of the human IgG2 subclass is distinct from those for human IgG1 and IgG4 providing an explanation for their discrete functions
Human IgG2 antibody displays distinct therapeutically-useful properties compared with the IgG1, IgG3 and IgG4 antibody subclasses. IgG2 is the second most abundant IgG subclass, being able to bind human FcγRII/FcγRIII, but not to FcγRI or complement C1q. Structural information on IgG2 is limited by the absence of a full-length crystal structure for this. To this end, we determined the solution structure of human myeloma IgG2 by atomistic X-ray and neutron scattering modelling. Analytical ultracentrifugation disclosed that IgG2 is monomeric with a sedimentation coefficient s020,w of 7.2 S. IgG2 dimer formation was ≤ 5% and independent of the buffer conditions. Small-angle X-ray scattering in a range of NaCl concentrations and in light and heavy water revealed that the X-ray radius of gyration Rg is 5.2-5.4 nm, after allowing for radiation damage at higher concentrations, and that the neutron Rg value of 5.0 nm remained unchanged in all conditions. The X-ray and neutron distance distribution curves P(r) revealed two peaks, M1 and M2, that were unchanged in different buffers. The creation of ˃123,000 physically-realistic atomistic models by Monte Carlo simulations for joint X-ray and neutron-scattering curve fits, constrained by the requirement of correct disulfide bridges in the hinge, resulted in the determination of symmetric Y-shaped IgG2 structures. These molecular structures were distinct from those for asymmetric IgG1 and asymmetric and symmetric IgG4, and were attributable to the four hinge disulfides. Our IgG2 structures rationalize the existence of the human IgG1, IgG2, and IgG4 subclasses, and explain the receptor binding functions of IgG2
Adsorption-Induced Deformation in Nanopores: Unexpected Results Obtained by Molecular Simulations
International audienceThe adsorption of a fluid in a nanoporous material induces deformations of the solid. The saturating regime, where the solid is filled with liquid, generally exhibits a linear relationship between the liquid pressure and the solid strain. This provides an experimental way to measure the elastic moduli of the solid walls. For large pores, the strain is determined by the pressure of the liquid saturating the pores and the mechanical properties of the porous solid. What happens at the nanometric scale, where liquid/matrix interfacial effects dominate? We have performed molecular simulations of a simple Lennard-Jones fluid confined between deformable nanoplatelets. The simulations provide the deformation of the nanopore as a function of the liquid pressure, in a way similar to what is done experimentally. The results show unexpected interface effects, which could be relevant to experimental data analysis
Effect of rate of pyrolysis on the textural properties of naturally-templated porous carbons from alginic acid
AbstractThe effect of pyrolysis rate on the properties of alginic acid-derived carbonaceous materials, termed Starbon®, was investigated. Thermal Gravimetry-IR was used to prepare porous carbons up to 800°C at several rates and highlighted increased CO2 production at higher pyrolysis rates. N2 porosimetry of the resultant carbons shows how pyrolysis rate affects both the mesopore structure and thus surface area and surface energy. Surface capacity of these carbons was analysed by methylene blue dye adsorption. In general, as the rate of pyrolysis increased, the mesopore content and adsorbent capacity decreased. It is considered here that the rapid production of volatiles at these higher rates causes structural collapse of the non-templated pore network. The work here demonstrates that pyrolysis rate is a key variable which needs to be controlled to maximise the textural properties of Starbon® required for adsorption applications
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