310 research outputs found
Spatially strongly confined atomic excitation via two dimensional stimulated Raman adiabatic passage
We consider a method of sub-wavelength superlocalization and patterning of
atomic matter waves via a two dimensional stimulated Raman adiabatic passage
(2D STIRAP) process. An atom initially prepared in its ground level interacts
with an optical vortex pump beam and a traveling wave Stokes laser beam. The
beams are sent in a counter-intuitive temporal sequence, in which the Stokes
pulse precedes the pump pulse. The atoms interacting with both the traveling
wave and the vortex beam are transferred to a final state through the 2D
STIRAP, while those located at the core of the vortex beam remain in the
initial state, creating a super-narrow nanometer scale atomic spot. Numerical
simulations of the Gross-Pitaevskii equation show that using such a method one
can create 2D bright and dark solitonic structures in trapped Bose-Einstein
condensates (BECs). The method allows one to circumvent the restriction set by
the diffraction limit inherent to conventional methods for formation of
localized solitons, with a full control over the position and size of nanometer
resolution defects
Theory of bright-state stimulated Raman adiabatic passage
We describe analytically and numerically the process of population transfer
by stimulated Raman adiabatic passage through a bright state when the pulses
propagate in a medium. Limitations of the adiabaticity are analyzed and
interpreted in terms of reshaping of the pulses. We find parameters for the
pulses for which the population transfer is nearly complete over long
distances.Comment: 9 pages, 9 figure
The [Het-s] Prion, an Amyloid Fold as a Cell Death Activation Trigger
International audienc
Recycling bins, garbage cans or think tanks? Three myths regarding policy analysis institutes
The phrase 'think tank' has become ubiquitous – overworked and underspecified – in the political lexicon. It is entrenched in scholarly discussions of public policy as well as in the 'policy wonk' of journalists, lobbyists and spin-doctors. This does not mean that there is an agreed definition of think tank or consensual understanding of their roles and functions. Nevertheless, the majority of organizations with this label undertake policy research of some kind. The idea of think tanks as a research communication 'bridge' presupposes that there are discernible boundaries between (social) science and policy. This paper will investigate some of these boundaries. The frontiers are not only organizational and legal; they also exist in how the 'public interest' is conceived by these bodies and their financiers. Moreover, the social interactions and exchanges involved in 'bridging', themselves muddy the conception of 'boundary', allowing for analysis to go beyond the dualism imposed in seeing science on one side of the bridge, and the state on the other, to address the complex relations between experts and public policy
Hsp90 depletion goes wild
Hsp90 reveals phenotypic variation in the laboratory, but is Hsp90 depletion important in the wild? Recent work from Chen and Wagner in BMC Evolutionary Biology has discovered a naturally occurring Drosophila allele that downregulates Hsp90, creating sensitivity to cryptic genetic variation. Laboratory studies suggest that the exact magnitude of Hsp90 downregulation is important. Extreme Hsp90 depletion might reactivate transposable elements and/or induce aneuploidy, in addition to revealing cryptic genetic variation
Fitness Landscape Transformation through a Single Amino Acid Change in the Rho Terminator
Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (rho*) in the global transcriptional terminator Rho of Escherichia coli. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in rho* versus rhoWT backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population
Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. Methods: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. Findings: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. Interpretation: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. Funding: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF
Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction
To define the mechanisms by which hPrP90-231 induces cell death, we analyzed its interaction with living cells and monitored its intracellular fate. Treatment of SH-SY5Y cells with fluorescein-5-isothiocyanate (FITC)-conjugated hPrP90-231 caused the accumulation of cytosolic aggregates of the prion protein fragment that increased in number and size in a time-dependent manner. The formation of large intracellular hPrP90-231 aggregates correlated with the activation of apoptosis. hPrP90-231 aggregates occurred within lysotracker-positive vesicles and induced the formation of activated cathepsin D (CD), indicating that hPrP90-231 is partitioned into the endosomal–lysosomal system structures, activating the proteolytic machinery. Remarkably, the inhibition of CD activity significantly reduced hPrP-90-231-dependent apoptosis. Internalized hPrP90-231 forms detergent-insoluble and SDS-stable aggregates, displaying partial resistance to proteolysis. By confocal microscopy analysis of lucifer yellow (LY) intracellular partition, we show that hPrP90-231 accumulation induces lysosome destabilization and loss of lysosomal membrane impermeability. In fact, although control cells evidenced a vesicular pattern of LY fluorescence (index of healthy lysosomes), hPrP90-231-treated cells showed diffuse cytosolic fluorescence, indicating LY diffusion through damaged lysosomes. In conclusion, these data indicate that exogenously added hPrP90-231 forms intralysosomal deposits having features of insoluble, protease-resistant aggregates and could trigger a lysosome-mediated apoptosis by inducing lysosome membrane permeabilization, followed by the release of hydrolytic enzymes
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