Photoionization Suppression by Continuum Coherence: Experiment and Theory

We present experimental and theoretical results of a detailed study of laser-induced continuum structures (LICS) in the photoionization continuum of helium out of the metastable state 2s $^1S_0$. The continuum dressing with a 1064 nm laser, couples the same region of the continuum to the {4s $^1S_0$} state. The experimental data, presented for a range of intensities, show pronounced ionization suppression (by as much as 70% with respect to the far-from-resonance value) as well as enhancement, in a Beutler-Fano resonance profile. This ionization suppression is a clear indication of population trapping mediated by coupling to a contiuum. We present experimental results demonstrating the effect of pulse delay upon the LICS, and for the behavior of LICS for both weak and strong probe pulses. Simulations based upon numerical solution of the Schr\"{o}dinger equation model the experimental results. The atomic parameters (Rabi frequencies and Stark shifts) are calculated using a simple model-potential method for the computation of the needed wavefunctions. The simulations of the LICS profiles are in excellent agreement with experiment. We also present an analytic formulation of pulsed LICS. We show that in the case of a probe pulse shorter than the dressing one the LICS profile is the convolution of the power spectra of the probe pulse with the usual Fano profile of stationary LICS. We discuss some consequences of deviation from steady-state theory.Comment: 29 pages, 17 figures, accepted to PR

Preparation of nondegenerate coherent superpositions in a three-state ladder system assisted by Stark Shifts

We propose a technique to prepare coherent superpositions of two nondegenerate quantum states in a three-state ladder system, driven by two simultaneous fields near resonance with an intermediate state. The technique, of potential application to enhancement of nonlinear processes, uses adiabatic passage assisted by dynamic Stark shifts induced by a third laser field. The method offers significant advantages over alternative techniques: (\i) it does not require laser pulses of specific shape and duration and (\ii) it requires less intense fields than schemes based on two-photon excitation with non-resonant intermediate states. We discuss possible experimental implementation for enhancement of frequency conversion in mercury atoms.Comment: 22 pages, 8 figures, 1 table, submitted to PHys. Rev.

Individual Differences in the Neural Signature of Subjective Value Among Older Adults

Some healthy older adults show departures from standard decision-making patterns exhibited by younger adults. We asked if such departures are uniform or if heterogeneous aging processes can designate which older adults show differing decision patterns. Thirty-three healthy older adults with varying decision-making patterns on a complex decision task (the Iowa Gambling Task) completed an intertemporal choice task while undergoing functional magnetic resonance imaging. We examined whether value representation in the canonical valuation network differed across older adults based on complex decision-making ability. Older adults with advantageous decision patterns showed increased activity in the valuation network, including the ventromedial prefrontal cortex (VMPFC) and striatum. In contrast, older adults with disadvantageous decision patterns showed reduced or absent activation in the VMPFC and striatum, and these older adults also showed greater blood oxygen level dependent signal temporal variability in the striatum. Our results suggest that a reduced representation of value in the brain, possibly driven by increased neural noise, relates to suboptimal decision-making in a subset of older adults, which could translate to poor decision-making in many aspects of life, including finance, health and long-term care. Understanding the connection between suboptimal decision-making and neural value signals is a step toward mitigating age-related decision-making impairments

Medical Imaging Decision And Support (MIDAS):Study protocol for a multi-centre cluster randomized trial evaluating the ESR iGuide

Objectives: Medical imaging plays an essential role in healthcare. As a diagnostic test, imaging is prone to substantial overuse and potential overdiagnosis, with dire consequences to patient outcomes and health care costs. Clinical decision support systems (CDSSs) were developed to guide referring physicians in making appropriate imaging decisions. This study will evaluate the effect of implementing a CDSS (ESR iGuide) with versus without active decision support in a physician order entry on the appropriate use of imaging tests and ordering behaviour. Methods: A protocol for a multi-center cluster-randomized trial with departments acting as clusters, combined with a before-after-revert design. Four university hospitals with eight participating departments each for a total of thirty-two clusters will be included in the study. All departments start in control condition with structured data entry of the clinical indication and tracking of the imaging exams requested. Initially, the CDSS is implemented and all physicians remain blinded to appropriateness scores based on the ESR imaging referral guidelines. After randomization, half of the clusters switch to the active intervention of decision support. Physicians in the active condition are made aware of the categorization of their requests as appropriate, under certain conditions appropriate, or inappropriate, and appropriate exams are suggested. Physicians may change their requests in response to feedback. In the revert condition, active decision support is removed to study the educational effect. Results/conclusions: The main outcome is the proportion of inappropriate diagnostic imaging exams requested per cluster. Secondary outcomes are the absolute number of imaging exams, radiation from diagnostic imaging, and medical costs. Trial registration number: Approval from the Medical Ethics Review Committee was obtained under protocol numbers 20–069 (Augsburg), B 238/21 (Kiel), 20–318 (Lübeck) and 2020–15,125 (Mainz). The trial is registered in the ClinicalTrials.gov</p

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

A method for probing the mutational landscape of amyloid structure

Motivation: Proteins of all kinds can self-assemble into highly ordered β-sheet aggregates known as amyloid fibrils, important both biologically and clinically. However, the specific molecular structure of a fibril can vary dramatically depending on sequence and environmental conditions, and mutations can drastically alter amyloid function and pathogenicity. Experimental structure determination has proven extremely difficult with only a handful of NMR-based models proposed, suggesting a need for computational methods. Results: We present AmyloidMutants, a statistical mechanics approach for de novo prediction and analysis of wild-type and mutant amyloid structures. Based on the premise of protein mutational landscapes, AmyloidMutants energetically quantifies the effects of sequence mutation on fibril conformation and stability. Tested on non-mutant, full-length amyloid structures with known chemical shift data, AmyloidMutants offers roughly 2-fold improvement in prediction accuracy over existing tools. Moreover, AmyloidMutants is the only method to predict complete super-secondary structures, enabling accurate discrimination of topologically dissimilar amyloid conformations that correspond to the same sequence locations. Applied to mutant prediction, AmyloidMutants identifies a global conformational switch between Aβ and its highly-toxic ‘Iowa’ mutant in agreement with a recent experimental model based on partial chemical shift data. Predictions on mutant, yeast-toxic strains of HET-s suggest similar alternate folds. When applied to HET-s and a HET-s mutant with core asparagines replaced by glutamines (both highly amyloidogenic chemically similar residues abundant in many amyloids), AmyloidMutants surprisingly predicts a greatly reduced capacity of the glutamine mutant to form amyloid. We confirm this finding by conducting mutagenesis experiments.National Institutes of Health (U.S.) (grant 1R01GM081871)National Institutes of Health (U.S.) (grant GM25874

Roadmap on STIRAP applications

STIRAP (stimulated Raman adiabatic passage) is a powerful laser-based method, usually involving two photons, for efficient and selective transfer of populations between quantum states. A particularly interesting feature is the fact that the coupling between the initial and the final quantum states is via an intermediate state, even though the lifetime of the latter can be much shorter than the interaction time with the laser radiation. Nevertheless, spontaneous emission from the intermediate state is prevented by quantum interference. Maintaining the coherence between the initial and final state throughout the transfer process is crucial. STIRAP was initially developed with applications in chemical dynamics in mind. That is why the original paper of 1990 was published in The Journal of Chemical Physics. However, from about the year 2000, the unique capabilities of STIRAP and its robustness with respect to small variations in some experimental parameters stimulated many researchers to apply the scheme to a variety of other fields of physics. The successes of these efforts are documented in this collection of articles. In Part A the experimental success of STIRAP in manipulating or controlling molecules, photons, ions or even quantum systems in a solid-state environment is documented. After a brief introduction to the basic physics of STIRAP, the central role of the method in the formation of ultracold molecules is discussed, followed by a presentation of how precision experiments (measurement of the upper limit of the electric dipole moment of the electron or detecting the consequences of parity violation in chiral molecules) or chemical dynamics studies at ultralow temperatures benefit from STIRAP. Next comes the STIRAP-based control of photons in cavities followed by a group of three contributions which highlight the potential of the STIRAP concept in classical physics by presenting data on the transfer of waves (photonic, magnonic and phononic) between respective waveguides. The works on ions or ion strings discuss options for applications, e.g. in quantum information. Finally, the success of STIRAP in the controlled manipulation of quantum states in solid-state systems, which are usually hostile towards coherent processes, is presented, dealing with data storage in rare-earth ion doped crystals and in nitrogen vacancy (NV) centers or even in superconducting quantum circuits. The works on ions and those involving solid-state systems emphasize the relevance of the results for quantum information protocols. Part B deals with theoretical work, including further concepts relevant to quantum information or invoking STIRAP for the manipulation of matter waves. The subsequent articles discuss the experiments underway to demonstrate the potential of STIRAP for populating otherwise inaccessible high-lying Rydberg states of molecules, or controlling and cooling the translational motion of particles in a molecular beam or the polarization of angular-momentum states. The series of articles concludes with a more speculative application of STIRAP in nuclear physics, which, if suitable radiation fields become available, could lead to spectacular results

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

The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy

BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope

Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3

The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria