83 research outputs found
Phase-Resolved Rydberg Atom Field Sensing using Quantum Interferometry
Although Rydberg atom-based electric field sensing provides key advantages
over traditional antenna-based detection, it remains limited by the need for a
local oscillator (LO) for low-field and phase resolved detection. In this work,
we demonstrate that closed-loop quantum interferometric schemes can be used to
generate a system-internal reference that can directly replace an external LO
for Rydberg field sensing. We reveal that this quantum-interferometrically
defined internal reference phase and frequency can be used analogously to a
traditional LO for atom-based down-mixing to an intermediate frequency for
lock-in phase detection. We demonstrate that this LO-equivalent functionality
provides analogous benefits to an LO, including full 360 phase
resolution as well as improved sensitivity. The general applicability of this
approach is confirmed by demodulating a four phase-state signal broadcast on
the atoms. Our approach opens up new sensing schemes and provides a clear path
towards all-optical Rydberg atom sensing implementations
A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor
The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the
`Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic
neurotransmission, and whose other members include receptors for glycine,
gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a
three dimensional structure of the nAChR in its closed state. However, the
exact nature and location of the channel gate remains uncertain. Although the
transmembrane pore is constricted close to its center, it is not completely
occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A.
Model calculations suggest that such a constriction may form a hydrophobic
gate, preventing movement of ions through a channel. We present a detailed and
quantitative simulation study of the hydrophobic gating model of the nicotinic
receptor, in order to fully evaluate this hypothesis. We demonstrate that the
hydrophobic constriction of the nAChR pore indeed forms a closed gate.
Potential of mean force (PMF) calculations reveal that the constriction
presents a barrier of height ca. 10 kT to the permeation of sodium ions,
placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A
radius hydrophobic pore can form a functional barrier to the permeation of a 1
A radius Na+ ion. Using a united atom force field for the protein instead of an
all atom one retains the qualitative features but results in differing
conductances, showing that the PMF is sensitive to the detailed molecular
interactions.Comment: Accepted by Physical Biology; includes a supplement and a
supplementary mpeg movie can be found at
http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp
Ultrafast nano-focusing with full optical waveform control
The spatial confinement and temporal control of an optical excitation on
nanometer length scales and femtosecond time scales has been a long-standing
challenge in optics. It would provide spectroscopic access to the elementary
optical excitations in matter on their natural length and time scales and
enable applications from ultrafast nano-opto-electronics to single molecule
quantum coherent control. Previous approaches have largely focused on using
surface plasmon polariton (SPP) resonant nanostructures or SPP waveguides to
generate nanometer localized excitations. However, these implementations
generally suffer from mode mismatch between the far-field propagating light and
the near-field confinement. In addition, the spatial localization in itself may
depend on the spectral phase and amplitude of the driving laser pulse thus
limiting the degrees of freedom available to independently control the
nano-optical waveform. Here we utilize femtosecond broadband SPP coupling, by
laterally chirped fan gratings, onto the shaft of a monolithic noble metal tip,
leading to adiabatic SPP compression and localization at the tip apex. In
combination with spectral pulse shaping with feedback on the intrinsic
nonlinear response of the tip apex, we demonstrate the continuous micro- to
nano-scale self-similar mode matched transformation of the propagating
femtosecond SPP field into a 20 nm spatially and 16 fs temporally confined
light pulse at the tip apex. Furthermore, with the essentially wavelength and
phase independent 3D focusing mechanism we show the generation of arbitrary
optical waveforms nanofocused at the tip. This unique femtosecond nano-torch
with high nano-scale power delivery in free space and full spectral and
temporal control opens the door for the extension of the powerful nonlinear and
ultrafast vibrational and electronic spectroscopies to the nanoscale.Comment: Contains manuscript with 4 figures as well as supplementary material
with 2 figure
The impact of gender and parenthood on physicians' careers - professional and personal situation seven years after graduation
BACKGROUND: The profile of the medical profession is changing in regard to feminization, attitudes towards the profession, and the lifestyle aspirations of young physicians. The issues addressed in this study are the careers of female and male physicians seven years after graduation and the impact of parenthood on career development. METHODS: Data reported originates from the fifth assessment (T5) of the prospective SwissMedCareer Study, beginning in 2001 (T1). At T5 in 2009, 579 residents (81.4% of the initial sample at T1) participated in the questionnaire survey. They were asked about occupational factors, career-related factors including specialty choice and workplace, work-life balance and life satisfaction. The impact of gender and parenthood on the continuous variables was investigated by means of multivariate and univariate analyses of variance; categorical variables were analyzed using Chi-square tests. RESULTS: Female physicians, especially those with children, have lower rates of employment and show lower values in terms of career success and career support experiences than male physicians. In addition, parenthood has a negative impact on these career factors. In terms of work-life balance aspired to, female doctors are less career-oriented and are more inclined to consider part-time work or to continue their professional career following a break to bring up a family. Parenthood means less career-orientation and more part-time orientation. As regards life satisfaction, females show higher levels of satisfaction overall, especially where friends, leisure activities, and income are concerned. Compared to their male colleagues, female physicians are less advanced in their specialty qualification, are less prone to choosing prestigious surgical fields, have a mentor less often, more often work at small hospitals or in private practice, aspire less often to senior hospital or academic positions and consider part-time work more often. Any negative impact on career path and advancement is exacerbated by parenthood, especially as far as women are concerned. CONCLUSION: The results of the present study reflect socially-rooted gender role stereotypes. Taking into account the feminization of medicine, special attention needs to be paid to female physicians, especially those with children. At an early stage of their career, they should be advised to be more proactive in seeking mentoring and career-planning opportunities. If gender equity in terms of career chances is to be achieved, special career-support measures will have to be provided, such as mentoring programs, role models, flexitime and flexible career structures
Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle
<p>Abstract</p> <p>Background</p> <p>The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle.</p> <p>Methods</p> <p>Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (−maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models.</p> <p>Results and discussion</p> <p>On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (−maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (−maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence.</p> <p>Conclusions</p> <p>For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (−maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions.</p
Discovering Conformational Sub-States Relevant to Protein Function
Background: Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these substates present significant challenges for their identification and characterization. Methods and Findings: To overcome these challenges we have developed a new computational technique, quasianharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions: Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. © 2011 Ramanathan et al
Adaptive tip-enhanced nano-spectroscopy
Tip-enhanced nano-spectroscopy, such as tip-enhanced photoluminescence (TEPL) and tip-enhanced Raman spectroscopy (TERS), generally suffers from inconsistent signal enhancement and difficulty in polarization-resolved measurement. To address this problem, we present adaptive tip-enhanced nano-spectroscopy optimizing the nano-optical vector-field at the tip apex. Specifically, we demonstrate dynamic wavefront shaping of the excitation field to effectively couple light to the tip and adaptively control for enhanced sensitivity and polarization-controlled TEPL and TERS. Employing a sequence feedback algorithm, we achieve similar to 4.4x10(4)-fold TEPL enhancement of a WSe2 monolayer which is >2x larger than the normal TEPL intensity without wavefront shaping. In addition, with dynamical near-field polarization control in TERS, we demonstrate the investigation of conformational heterogeneity of brilliant cresyl blue molecules and the controllable observation of IR-active modes due to a large gradient field effect. Adaptive tip-enhanced nano-spectroscopy thus provides for a systematic approach towards computational nanoscopy making optical nano-imaging more robust and widely deployable. Tip-enhanced nano-spectroscopy suffers from inconsistent signal and difficulty in polarization-resolved measurement. Here, the authors present adaptive tip-enhanced nano-spectroscopy, which enables the additional signal enhancement and near-field polarization control via dynamic wavefront shaping
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