We propose a discrete transition-based reweighting analysis method (dTRAM) for analyzing configuration-space-discretized simulation trajectories produced at different thermodynamic states ...(temperatures, Hamiltonians, etc.) dTRAM provides maximum-likelihood estimates of stationary quantities (probabilities, free energies, expectation values) at any thermodynamic state. In contrast to the weighted histogram analysis method (WHAM), dTRAM does not require data to be sampled from global equilibrium, and can thus produce superior estimates for enhanced sampling data such as parallel/simulated tempering, replica exchange, umbrella sampling, or metadynamics. In addition, dTRAM provides optimal estimates of Markov state models (MSMs) from the discretized state-space trajectories at all thermodynamic states. Under suitable conditions, these MSMs can be used to calculate kinetic quantities (e.g., rates, timescales). In the limit of a single thermodynamic state, dTRAM estimates a maximum likelihood reversible MSM, while in the limit of uncorrelated sampling data, dTRAM is identical to WHAM. dTRAM is thus a generalization to both estimators.
Variational Approach to Molecular Kinetics Nüske, Feliks; Keller, Bettina G; Pérez-Hernández, Guillermo ...
Journal of chemical theory and computation,
04/2014, Letnik:
10, Številka:
4
Journal Article
Recenzirano
The eigenvalues and eigenvectors of the molecular dynamics propagator (or transfer operator) contain the essential information about the molecular thermodynamics and kinetics. This includes the ...stationary distribution, the metastable states, and state-to-state transition rates. Here, we present a variational approach for computing these dominant eigenvalues and eigenvectors. This approach is analogous to the variational approach used for computing stationary states in quantum mechanics. A corresponding method of linear variation is formulated. It is shown that the matrices needed for the linear variation method are correlation matrices that can be estimated from simple MD simulations for a given basis set. The method proposed here is thus to first define a basis set able to capture the relevant conformational transitions, then compute the respective correlation matrices, and then to compute their dominant eigenvalues and eigenvectors, thus obtaining the key ingredients of the slow kinetics.
Abstract Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach ...for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t -tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning.
Abstract
The inner ∼200 pc region of the Galaxy contains a 4 million M
⊙
supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic-ray energy densities ...that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation-driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total-intensity and spectral-index mosaics of the region from 20 pointings (144 hr on-target in total), covering 6.5 square degrees with an angular resolution of 4″ at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT’s high sensitivity, exceptional
u
,
v
-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new nonthermal filament complexes, and enhanced views of the Radio Arc bubble, Sagittarius A, and Sagittarius B regions. This project is a South African Radio Astronomy Observatory public legacy survey, and the image products are made available with this article.
Purpose Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related ...quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL— Quality of Life in Neurological Disorders and PROMIS— Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. Methods New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. Results Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between NeuroQoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. Conclusions HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.
Purpose Huntington disease (HD) is an incurable terminal disease. Thus, end of life (EOL) concerns are common in these individuals. A quantitative measure of EOL concerns in HD would enable a better ...understanding of how these concerns impact health-related quality of life. Therefore, we developed new measures of EOL for use in HD. Methods An EOL item pool of 45 items was field tested in 507 individuals with prodromal or manifest HD. Exploratory and confirmatory factor analyses (EFA and CFA, respectively) were conducted to establish unidimensional item pools. Item response theory (IRT) and differential item functioning analyses were applied to the identified unidimensional item pools to select the final items. Results EFA and CFA supported two separate unidimensional sets of items: Concern with Death and Dying (16 items), and Meaning and Purpose (14 items). IRT and DIF supported the retention of 12 Concern with Death and Dying items and 4 Meaning and Purpose items. IRT data supported the development of both a computer adaptive test (CAT) and a 6-item, static short form for Concern with Death and Dying. Conclusion The HDQLIFE Concern with Death and Dying CAT and corresponding 6-item short form, and the 4-item calibrated HDQLIFE Meaning and Purpose scale demonstrate excellent psychometric properties. These new measures have the potential to provide clinically meaningful information about end-of-life preferences and concerns to clinicians and researchers working with individuals with HD. In addition, these measures may also be relevant and useful for other terminal conditions.
Break junctions provide tip-shaped contact electrodes that are fundamental components of nano and molecular electronics. However, the fabrication of break junctions remains notoriously time-consuming ...and difficult to parallelize. Here we demonstrate true parallel fabrication of gold break junctions featuring sub-3 nm gaps on the wafer-scale, by relying on a novel self-breaking mechanism based on controlled crack formation in notched bridge structures. We achieve fabrication densities as high as 7 million junctions per cm
, with fabrication yields of around 7% for obtaining crack-defined break junctions with sub-3 nm gaps of fixed gap width that exhibit electron tunneling. We also form molecular junctions using dithiol-terminated oligo(phenylene ethynylene) (OPE3) to demonstrate the feasibility of our approach for electrical probing of molecules down to liquid helium temperatures. Our technology opens a whole new range of experimental opportunities for nano and molecular electronics applications, by enabling very large-scale fabrication of solid-state break junctions.
Summary
The panzootic caused by A/goose/Guangdong/1/96‐lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 ...viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human‐to‐human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human‐to‐human transmissibility and impact on human health should such human‐to‐human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts.
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