Expanding and Testing a Computational Method for Predicting the Ground State Reduction Potentials of Organic Molecules on the Basis of Empirical Correlation to Experiment

A method for predicting the ground state reduction potentials of organic molecules on the basis of the correlation of computed energy differences between the starting S-0 and one-electron-reduced D-0 species with experimental reduction potentials in acetonitrile has been expanded to cover 3.5 V of potential range and 74 compounds across 6 broad families of molecules. Utilizing the conductor-like polarizable continuum model of implicit solvent allows a global correlation that is computationally efficient and has improved accuracy, with r(2) \u3e 0.98 in all cases and root mean square deviation errors of(mean absolute deviationsmV) for either B3LYP/6-311+G(d,p) or B3LYP//6-31G(d) with an appropriate choice of radii (UAKS or UA0). The correlations are proven to be robust across a wide range of structures and potentials, including four larger (27-28 heavy atoms) and more conformationally flexible photochromic molecules not used in calibrating the correlation. The method is also proven to be robust to a number of minor student mistakes or methodological inconsistencies

Visualizing the 3D collagen structure of human atherosclerotic plaques using Diffusion Tensor Imaging

Introduction Ischemic strokes and heart attacks are mainly caused by rupture of the fibrous cap of an atherosclerotic plaque. Reliable prediction of the fibrous cap rupture is, therefore, crucial to prevent these potentially lethal cardiovascular events. Since cap rupture occurs when the stresses in the cap exceed the strength of the cap, biomechanical modeling may help to improve cap rupture prediction. Biomechanical models depend strongly on the material parameters used as input. Previous studies focused on the anisotropic mechanical behaviour of atherosclerotic plaques and produced stiffness values for the collagen fibers in plaques [1]. However, for a more complete characterization knowledge of the global 3D collagen architecture in atherosclerotic plaques is required. Therefore, for the first time diffusion tensor imaging (DTI) was used to investigate the 3D collagen structure of human atherosclerotic plaques. Methods Until now five human carotid atherosclerotic plaques were obtained from endarterectomy patients and embedded in 4 % type VII agarose. The samples were placed in a 9.4 T horizontal-bore MRI scanner to conduct DTI. DTI enabled the tracking of the fiber directions and visualisation of the collagen fibers [2]. Results The consistent results of five different plaques suggest that collagen fibers are deposited in a new layer in a different direction during the development of atherosclerosis (see figure for one representative result). Two distinct layers of collagen fibers were found; an outer layer, where the collagen is aligned in the circumferential direction (14.5°±28.0°), similar to healthy arteries [2], and an inner layer where the collagen follows a longitudinal direction (77.4°±22.4°). Conclusions DTI allowed the visualization of the global 3D collagen architecture of atherosclerotic plaques. The inner collagen layer showed a surprising result and implies a change of strain distribution in the artery during the later stage of atherosclerosis, possibly due to the thickening and stiffening of the diseased intimal tissue. These data, combined with collagen stiffness data found in previous studies [1], will be used as input for biomechanical models including the anisotropic mechanical behaviour of plaque tissue. Models using general over-simplified assumptions like isotropic behaviour can be replaced by models including the anisotopic behavior and thereby improve the stress analysis of plaques. Improved models might help in the diagnosis and treatment of plaque rupture preventing heart attacks and ischemic strokes. References [1] Chai C-K, Akyildiz AC, Speelman L, Gijsen FJH, Oomens CWJ, Sambeek MRHM, van der Lugt A, Baaijens FTP, Anisotropic mechanical behaviour of carotid atherosclerotic plaques at large strain, The 8th international symposium on Biomechanics in Vascular Biology and Cardiovascular Disease, Rotterdam, 2013. [2] Ghazanfari S, Driessen-Mol A, Strijkers GJ, Kanters FMW, Baaijens FPT, Bouten CVC, A comparative analysis of the collagen architecture in the carotid artery: Second harmonic generation versus diffusion tensor imaging, Biochemical and Biophysical Research Communications, 426(1): 54-58, 2012

Synthesis and Structural Investigation of an \u27Oxazinoquinolinespirohexadienone\u27 That Only Exists as Its Long-Wavelength Ring-Opened Quinonimine Isomer

The spirocyclic oxazinoquinolinespirohexadienone (OSHD) photochromes are computationally predicted to be an attractive target as electron deficient analogues of the perimidinespirohexadienone (PSHD) photochromes, for eventual application as photochromic photooxidants. We have found the literature method for their preparation unsuitable and present an alternative synthesis. Unfortunately the product of this synthesis is the long wavelength (LW) ring-opened quinonimine isomer of the OSHD. We have found this isomer does not close to the spirocyclic short wavelength isomer (SW) upon prolonged standing in the dark, unlike other PSHD photochromes. The structure of this long wavelength isomer was found by NMR and X-ray crystallography to be exclusively the quinolinone (keto) tautomer, though experimental cyclic voltammetry supported by our computational methodology indicates that the quinolinol (enol) tautomer (not detected by other means) may be accessible through a fast equilibrium lying far toward the keto tautomer. Computations also support the relative stability order of keto LW over enol LW over SW

A continuous-discontinuous model for crack branching

This is the peer reviewed version of the following article: Tamayo, E. [et al.]. A continuous-discontinuous model for crack branching. "International journal for numerical methods in engineering", 5 Octubre 2019, vol. 120, núm. 1, p. 86-104, which has been published in final form at https://doi.org/10.1002/nme.6125. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.A new continuous-discontinuous model for fracture that accounts for crack branching in a natural manner is presented. It combines a gradient-enhanced damage model based on nonlocal displacements to describe diffuse cracks and the extended finite element method (X-FEM) for sharp cracks. Its most distinct feature is a global crack tracking strategy based on the geometrical notion of medial axis: the sharp crack propagates following the direction dictated by the medial axis of a damage isoline. This means that, if the damage field branches, the medial axis automatically detects this bifurcation, and a branching sharp crack is thus easily obtained. In contrast to other existing models, no special crack-tip criteria are required to trigger branching. Complex crack patterns may also be described with this approach, since the X-FEM enrichment of the displacement field can be recursively applied by adding one extra term at each branching event. The proposed approach is also equipped with a crack-fluid pressure, a relevant feature in applications such as hydraulic fracturing or leakage-related events. The capabilities of the model to handle propagation and branching of cracks are illustrated by means of different two-dimensional numerical examples.Peer ReviewedPostprint (author's final draft

High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

AbstractBackground and aimsCarotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons.MethodsParticipants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness.ResultsThe study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015).ConclusionsHigher maximum shear stress is associated with intraplaque haemorrhage and calcifications

High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

Background and aims Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. Methods Participants (n = 74) from the population-based

A Large Outbreak of Legionnaires’ Disease at a Flower Show, the Netherlands, 1999

In 1999, an outbreak of Legionnaires’ disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails

Physicians Report Barriers to Deliver Best Practice Care for Asplenic Patients: A Cross-Sectional Survey

Background: Current management of asplenic patients is not in compliance with best practice standards, such as defined by the British Committee for Standards in Haematology. To improve quality of care, factors inhibiting best practice care delivery need to be identified first. With this study, we aimed to identify and quantify physicians' barriers to adhere to best practice management of asplenic patients in the Netherlands. Methods and Principal Findings: A cross-sectional survey, preceded by multiple focus group discussions, was performed among Dutch physicians responsible for prevention of infections in asplenic patients, including specialists ( of Internal medicine and Surgery) and general practitioners (GPs). Forty seven GPs and seventy three hospital specialists returned the questionnaire, yielding response rates of 47% and 36,5% respectively. Physicians reported several barriers to deliver best practice. For both GPs and specialists, the most frequently listed barriers were: poor patient knowledge (> 80% of hospital specialists and GPs) and lack of clarity about which physician is responsible for the management of asplenic patients (50% of Internists, 46% of Surgeons, 55% of GPs). Both GPs and hospital specialists expressed to experience a lack of mutual trust: specialists were uncertain whether the GP would follow their advice given on patient discharge (33-59%), whereas half of GPs was not convinced that specialists' discharge letters contained the correct recommendations. Almost all physicians (> 90%) indicated that availability of a national guideline would improve adherence to best practice, especially if accessible online. Conclusion: This study showed that, in accordance with reports on international performance, care delivery for asplenic patients in the Netherlands is suboptimal. We identified and quantified perceived barriers by physicians that prevent adherence to post-splenectomy guidelines for the first time. Better transmural collaboration and better informed patients are likely to improve the quality of care of the asplenic patient population. A national, online-available guideline is urgently require

Large Isoforms of UNC-89 (Obscurin) Are Required for Muscle Cell Architecture and Optimal Calcium Release in Caenorhabditis elegans

Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction

Assessing Order Effects in Online Community-based Health Forums

Measuring the quality of health content in online health forums is a challenging task. The majority of the existing measures are based on evaluations of forum users and may not be reliable. We employed machine learning techniques, text mining methods, and Big Data platforms to construct four measures of textual quality to automatically determine the similarity of a given answer to professional answers. We then used them to assess the quality of 66,888 answers posted on Yahoo! Answers Health section. All four measures of textual quality revealed a higher quality for asker-selected best answers indicating that askers, to some extent, have a proper judgment to select the best answers. We also studied the presence of order effects in online health forums. Our results suggest that the textual quality of the first answer positively influences the mean textual quality of the subsequent answers and negatively influences the quantity of subsequent answers