bluuebunny/crossref_metadata_2025 huggingface dataset:
The HIV‐1 p66 homodimeric RT exhibits different conformations in the binding‐competent and ‐incompetent NNRTI site
Authors: Sharaf Naima G. , Xi Zhaoyong , Ishima Rieko , Gronenborn Angela M.
Published: September 2017

Non‐nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase (RT), NNRTIs, which bind to the p66/p51 heterodimeric RT, also interact with the p66/p66 homodimer, whose structure is unknown. 19F nuclear magnetic resonance of a single 4‐trifluoromethylphenylalanine (tfmF) residue, incorporated into the NNRTI binding pocket of the p66/p66 homodimer at position 181, was used to investigate NNRTI binding. In the NNRTI‐bound homodimer complex, two different 19F signals are observed, with the resonance frequencies matching those of the NNRTI‐bound p66/p51 heterodimer spectra, in which the individual p66‐subunit or p51‐subunit were labeled with tfmF at positions 181. These data suggest that the NNRTI‐bound p66/p66 homodimer conformation, particularly around residue 181, is very similar to that in the p66/p51 heterodimer, explaining why NNRTI binding to p66/p66 enhances dimer formation.
Archaea S‐layer nanotube from a “black smoker” in complex with cyclo‐octasulfur (S8) rings
Authors: McDougall Matthew , Francisco Olga , Harder‐Viddal Candice , Roshko Roy , Meier Markus , Stetefeld Jörg
Published: September 2017

Elemental sulfur exists primarily as an ring and serves as terminal electron acceptor for a variety of sulfur‐fermenting bacteria. Hyperthermophilic archaea from black smoker vents are an exciting research tool to advance our knowledge of sulfur respiration under extreme conditions. Here, we use a hybrid method approach to demonstrate that the proteinaceous cavities of the S‐layer nanotube of the hyperthermophilic archaeon Staphylothermus marinus act as a storage reservoir for cyclo‐octasulfur . Fully atomistic molecular dynamics (MD) simulations were performed and the method of multiconfigurational thermodynamic integration was employed to compute the absolute free energy for transferring a ring of elemental sulfur from an aqueous bath into the largest hydrophobic cavity of a fragment of archaeal tetrabrachion. Comparisons with earlier MD studies of the free energy of hydration as a function of water occupancy in the same cavity of archaeal tetrabrachion show that the sulfur ring is energetically favored over water.
Genetically engineering better fungal biopesticides
Authors: Lovett Brian , St. Leger Raymond John
Published: September 2017

Microbial insect pathogens offer an alternative means of pest control with the potential to wean us off our heavy reliance on chemical pesticides. Insect pathogenic fungi play an important natural role in controlling disease vectors and agricultural pests. Most commercial products employ Ascomycetes in the genera Metarhizium and Beauveria. However, their utilization has been limited by inconsistent field results as a consequence of sensitivity to abiotic stresses and naturally low virulence. Other naturally occurring biocontrol agents also face these hurdles to successful application, but the availability of complete genomes and recombinant DNA technologies have facilitated design of multiple fungal pathogens with enhanced virulence and stress resistance. Many natural and synthetic genes have been inserted into entomopathogen genomes. Some of the biggest gains in virulence have been obtained using genes encoding neurotoxic peptides, peptides that manipulate host physiology and proteases and chitinases that degrade the insect cuticle. Prokaryotes, particularly extremophiles, are useful sources of genes for improving entomopathogen resistance to ultraviolet (UV) radiation. These biological insecticides are environmentally friendly and cost‐effective insect pest control options. © 2017 Society of Chemical Industry
Investigation of the effects of storage and freezing on mixes of heavy‐labeled metabolite and amino acid standards
Authors: Culp‐Hill Rachel , Reisz Julie A. , Hansen Kirk C. , D'Alessandro Angelo
Published: September 2017

Rationale

High‐throughput metabolomics has now made it possible for small/medium‐sized laboratories to analyze thousands of samples/year from the most diverse biological matrices including biofluids, cell and tissue extracts. In large‐scale metabolomics studies, stable‐isotope‐labeled standards are increasingly used to normalize for matrix effects and control for technical reproducibility (e.g. extraction efficiency, chromatographic retention times and mass spectrometry signal stability). However, it is currently unknown how stable mixes of commercially available standards are following repeated freeze/thaw cycles or prolonged storage of aliquots.

Methods

Standard mixes for 13C, 15N or deuterated isotopologues of amino acids and key metabolites from the central carbon and nitrogen pathways (e.g. glycolysis, Krebs cycle, redox homeostasis, purines) were either repeatedly frozen/thawed for up to 10 cycles or diluted into aliquots prior to frozen storage for up to 42 days. Samples were characterized by ultra‐high‐pressure liquid chromatography/mass spectrometry to determine the stability of the aliquoted standards upon freezing/thawing or prolonged storage.

Results

Metabolite standards were stable over up to 10 freeze/thaw cycles, with the exception of adenosine and glutathione, showing technical variability across aliquots in a freeze/thaw‐cycle‐independent fashion. Storage for up to 42 days of mixes of commercially available standards did not significantly affect the stability of amino acid or metabolite standards for the first 2 weeks, while progressive degradation (statistically significant for fumarate) was observed after 3 weeks.

Conclusions

Refrigerated or frozen preservation for at least 2 weeks of aliquoted heavy‐labeled standard mixes for metabolomics analysis is a feasible and time‐/resource‐saving strategy for standard metabolomics laboratories.
Response to hepatitis B vaccination in patients with liver cirrhosis
Authors: Aggeletopoulou Ioanna , Davoulou Panagiota , Konstantakis Christos , Thomopoulos Konstantinos , Triantos Christos
Published: September 2017

Hepatitis B vaccination is strongly recommended for all infants and children but also for adults who are at risk of HBV infection. Attempts to immunize patients with liver cirrhosis have been proven relatively ineffective, and several strategies have already been used to improve the immune response in this group. The primary aim of this review is to examine, discuss, and summarize the immunogenicity of hepatitis B vaccination in patients with liver cirrhosis. MEDLINE search identified 11 studies (n = 961). The dose of the vaccine and the schedule of the vaccination varied. The response rates to the HBV vaccination ranged from 16% to 87% among patients with cirrhosis regardless of the number and vaccine dose. In particular, patients who received the standard dose of vaccination achieved seroprotection rates ranged from 16% to 79% (mean response rate 38%) and those who received a double dose achieved relatively better seroprotection rates (range: 26%‐87%; mean response rate 53%). The overall mean response rate to the HBV vaccination was 47%. In conclusion, cirrhotic patients achieve lower seroprotection rates after the completion of HBV vaccination series. Several strategies have tried to improve the immunogenicity; however, there is a great need for additional studies to further explore (1) the immune response in relation to poor vaccination responsiveness confounding factors, (2) novel strategies to improve immunogenicity, and (3) the immune mechanism underlying the differences in response rates to HBV vaccination.
Micro–macro compatibility: When does a complex systems approach strongly benefit science learning?
Authors: Samon Sigal , Levy Sharona T.
Published: September 2017

The study explores how a complexity approach empowers science learning. A complexity approach represents systems as many interacting entities. The construct of micro–macro compatibility is introduced, the degree of similarity between behaviors at the micro‐ and macro‐levels of the system. Seventh‐grade students’ learning about gases was studied using questionnaires and interviews. An experimental group (n = 47) learned with a complexity curriculum that included agent‐based computer models, a workbook, class discussions, and laboratory experiments. A comparison group (n = 45) learned with a normative curriculum, incorporating lectures, a textbook, class discussions, and laboratory experiments. Significant learning gains and strong effect sizes were found in the experimental group's overall learning. Diffusion, density, and kinetic molecular theory were learned better with a complexity approach. Pressure, temperature, and the gas laws were learned similarly with both approaches. Learning to notice micro‐level behaviors and their probabilistic nature was greater with the complexity approach. Analysis showed that only concepts that have less “micro–macro compatibility” were learned better with a complexity approach. Thus, a complexity approach helps separate the microbehaviors and then relate them to the macrobehaviors when these behaviors are dissimilar. We discuss how micro–macro compatibility helps point to concepts whose learning would benefit strongly from a complexity approach.
Generalized survival models for correlated time‐to‐event data
Authors: Liu Xing‐Rong , Pawitan Yudi , Clements Mark S.
Published: September 2017

Our aim is to develop a rich and coherent framework for modeling correlated time‐to‐event data, including (1) survival regression models with different links and (2) flexible modeling for time‐dependent and nonlinear effects with rich postestimation. We extend the class of generalized survival models, which expresses a transformed survival in terms of a linear predictor, by incorporating a shared frailty or random effects for correlated survival data. The proposed approach can include parametric or penalized smooth functions for time, time‐dependent effects, nonlinear effects, and their interactions. The maximum (penalized) marginal likelihood method is used to estimate the regression coefficients and the variance for the frailty or random effects. The optimal smoothing parameters for the penalized marginal likelihood estimation can be automatically selected by a likelihood‐based cross‐validation criterion. For models with normal random effects, Gauss‐Hermite quadrature can be used to obtain the cluster‐level marginal likelihoods. The Akaike Information Criterion can be used to compare models and select the link function. We have implemented these methods in the R package rstpm2. Simulating for both small and larger clusters, we find that this approach performs well. Through 2 applications, we demonstrate (1) a comparison of proportional hazards and proportional odds models with random effects for clustered survival data and (2) the estimation of time‐varying effects on the log‐time scale, age‐varying effects for a specific treatment, and two‐dimensional splines for time and age.
Infectious disease prediction with kernel conditional density estimation
Authors: Ray Evan L. , Sakrejda Krzysztof , Lauer Stephen A. , Johansson Michael A. , Reich Nicholas G.
Published: September 2017

Creating statistical models that generate accurate predictions of infectious disease incidence is a challenging problem whose solution could benefit public health decision makers. We develop a new approach to this problem using kernel conditional density estimation (KCDE) and copulas. We obtain predictive distributions for incidence in individual weeks using KCDE and tie those distributions together into joint distributions using copulas. This strategy enables us to create predictions for the timing of and incidence in the peak week of the season. Our implementation of KCDE incorporates 2 novel kernel components: a periodic component that captures seasonality in disease incidence and a component that allows for a full parameterization of the bandwidth matrix with discrete variables. We demonstrate via simulation that a fully parameterized bandwidth matrix can be beneficial for estimating conditional densities. We apply the method to predicting dengue fever and influenza and compare to a seasonal autoregressive integrated moving average model and HHH4, a previously published extension to the generalized linear model framework developed for infectious disease incidence. The KCDE outperforms the baseline methods for predictions of dengue incidence in individual weeks. The KCDE also offers more consistent performance than the baseline models for predictions of incidence in the peak week and is comparable to the baseline models on the other prediction targets. Using the periodic kernel function led to better predictions of incidence. Our approach and extensions of it could yield improved predictions for public health decision makers, particularly in diseases with heterogeneous seasonal dynamics such as dengue fever.
I can do that alone…or not? How idea generators juggle between the pros and cons of teamwork
Authors: Deichmann Dirk , Jensen Michael
Published: September 2017

Research summary: The advantages of working with a team to develop an idea are well established, but surprisingly, little is known about why some idea generators ignore these advantages by developing their ideas alone. To answer this question, we study two important trade‐offs. First, working with a team provides access to additional resources but also leads to increased coordination costs. Second, sharing the risks and costs of developing an idea necessitates sharing the potential rewards of a successful idea. We use unique data on idea generators and their submission of ideas to an innovation program in a large European company between 1996 and 2008 to show how the two different trade‐offs affect the decision of idea generators to collaborate with a team.

Managerial summary: Organizations usually form teams to develop and execute innovative ideas. When people have the choice, however, will they also form a team or will they develop ideas alone? By studying idea generators and their voluntary submissions of breakthrough ideas to an innovation program, we find that the success rate is much higher for team ideas. Although teamwork has important benefits, idea generators will often develop incremental ideas alone and only accept increased coordination costs for developing radical ideas—this is even more so when they have prior team experiences. Moreover, only when idea generators were successful before and—even more so—when they developed that idea alone, will they be more open to sharing the rewards and risks of developing another idea with a team.
Highly Efficient Perovskite Solar Cells Using Non‐Toxic Industry Compatible Solvent System
Authors: Wang Junke , Di Giacomo Francesco , Brüls Jim , Gorter Harrie , Katsouras Ilias , Groen Pim , Janssen René A. J. , Andriessen Ronn , Galagan Yulia
Published: September 2017

Perovskite solar cells attract a lot attention as alternative energy sources for the future energy market. With the remarkable lab‐scale achievements, the investigations into a high‐throughput large‐scale production of perovskite devices are now on the agenda. The first step towards mass manufacturing should be a replacement of toxic solvents used in the manufacturing of perovskite layer. In this study, a non‐toxic and up‐scaling compatible solvent system is developed. The impact of the solvent properties on the perovskite crystallization kinetics has been systematically investigated, which is found to be crucial in controlling the surface coverage and layer crystallinity. By optimizing the processing conditions, a stabilized efficiency of 16.0% is achieved with the developed non‐toxic solvent system.
Increasing the fish diversity of the Triassic faunas of Gondwana: a new redfieldiiform (Actinopterygii) from the Middle Triassic of Argentina and its palaeobiogeographical implications
Authors: Gouiric‐Cavalli Soledad , Zavattieri Ana M. , Gutierrez Pedro R. , Cariglino Bárbara , Balarino Lucía
Published: September 2017

A new actinopterygian, Calaichthys tehul gen. et sp. nov. is described on the basis of a few, well‐preserved specimens from the Anisian Cerro de Las Cabras Formation, Cuyo Basin in Mendoza Province. The new genus shows a combination of primitive characters (e.g. deep posterior region of the maxilla contacting the preopercle, a suspensorium backwardly oriented) and more advanced characters (e.g. distally segmented fin rays, hemiheterocercal caudal fin) and is thus considered to be a ‘subholostean’ fish. The new taxon is assigned to Redfieldiiformes on the basis of its single branchiostegal plate‐like ray, a median gular plate, pectoral fins with stout, stiff, mainly non‐segmented and distally branched fin rays, long and robust fringing fulcra in all fins, basal fulcra bordering both lobes of the caudal fin, and opposite dorsal and anal fins. Calaichthys is characterized by a combination of characters some of which are unique among redfieldiiforms (i.e. strongly ornamented but thin scales with a serrated posterior margin, smooth skull roof bones, extrascapulars with a bifid posterior margin, three suborbital bones, a hatchet‐shaped preopercle, rectangular and slender opercle, deep mouth gape, entopterygoid and ectopterygoid with small pointed teeth disposed in several series, unornamented rostral bone, massive pectoral fins and delicate dorsal, pelvic and anal fins). Calaichthys provides novel information about the anatomy of redfieldiiforms, in particular in relation with the fins and associated scaly elements, as well as the scale morphology and their disposition over the body. Our work confirms for the first time that redfieldiiforms occur in South America. Redfieldiiforms seem to have originated in Gondwana and shown two diversity peaks: in the Anisian and the Carnian. Calaichthys is coeval with those redfieldiiforms of the Middle Triassic (Anisian) of Africa and Australia dwelling in ephemeral lakes.
Human mating strategies: from past causes to present consequences
Authors: Marzoli Daniele , Havlíček Jan , Roberts S. Craig
Published: September 2017

In both humans and nonhuman animals, mating strategies represent a set of evolutionary adaptations aimed at promoting individual fitness by means of reproduction with the best possible partners. Given this critical role, mating strategies influence numerous aspects of human life. In particular, between‐sex divergence in the intensity of intrasexual competition could account for robust cross‐cultural sex differences in psychology and behavior (e.g., personality, psychiatric disorders, social behavior, violence). Several other factors (including individual differences, relationship type and environment) affect—in an evolutionarily consistent manner—variation in mating strategy that individuals pursue (as one example, awareness of one's own attractiveness impinges on mating standards). Here we provide an overview of relevant theoretical frameworks and empirical evidence on variation in mating strategies. Given its multifaceted nature and intense research interest over several decades, this is a challenging task, and we highlight areas where further investigation is warranted in order to achieve a clearer picture and resolve apparent inconsistencies. However, we suggest that addressing outstanding questions using a variety of different methodological approaches, a deeper understanding of the cognitive representations involved in mating strategies is within reach.WIREs Cogn Sci2018, 9:e1456. doi: 10.1002/wcs.1456

This article is categorized under:

Cognitive Biology > Evolutionary Roots of Cognition

Neuroscience > Behavior

Neuroscience > Cognition
Synthesis, Crystal Structure, DNA‐binding Properties and Antioxidant Activity of a Copper(II) Complex with Naphthalimide Schiff Base
Authors: Chen Ying , Mao Shanshan , Shi Xinkui , Shen Kesheng , Wu Huilu
Published: September 2017

The Schiff N‐allylamine‐4‐(ethylenediamine‐5‐methylsalicylidene)‐1,8‐naphthalimide (H2L) and its copper(II) complex, [Cu(HL)2]·0.5DMF, were synthesized and characterized. The crystal structure of the CuII complex reveals a slightly distorted square‐planar arrangement provided by two N and O donors from two deprotonated ligands. In addition, the DNA‐binding properties of the ligand and CuII complex were investigated by fluorescence spectra, electronic absorption, and viscosity measurements. The experimental studies of the DNA‐binding properties indicated that the ligand and CuII complex reacted with DNA via intercalation binding mode, and binding affinity for DNA takes the order: ligand > CuII complex. The antioxidant assay in vitro suggested that both exhibited potential intensely antioxidant properties, and the ligand is more effective than its CuII complex.
Normal hematology and serum chemistry of northern fur seals (Callorhinus ursinus) in captivity
Authors: Kohyama Kaoru , Inoshima Yasuo
Published: September 2017

Northern fur seals (Callorhinus ursinus) are endemic to the North Pacific Ocean. They were hunted for their fur and became endangered in the late 1800s, but their populations recovered following the introduction of protection laws. Recently, populations have been decreasing again, although the reasons are unclear. For individuals that are bred and reared in captivity as part of ex situ conservation projects, details of blood characteristics are essential to ensure good health. However, the normal ranges of hematology and serum chemistry of captive northern fur seals have not been defined. This study determined the normal ranges of hematology and serum chemistry of captive fur seals. Blood samples were collected every month for 2 years from four captive northern fur seals in Japan (three born in an aquarium and one kept in the same aquarium following rescue). Fifteen blood characteristics and 29 serum chemistry properties were compared with those previously reported for wild northern fur seals in the USA. Several parameters were not within the normal ranges reported previously in wild northern fur seals. In particular, levels of alkaline phosphatase was outside of the normal ranges previously reported. The hematological and serum chemistry ranges in this study can help provide a guideline for understanding the health of northern fur seals in captivity.
Impaired fertility and motor function in a zebrafish model for classic galactosemia
Authors: Vanoevelen Jo M. , van Erven Britt , Bierau Jörgen , Huang Xiaoping , Berry Gerard T. , Vos Rein , Coelho Ana I. , Rubio‐Gozalbo M. Estela
Published: September 2017

Classic galactosemia is a genetic disorder of galactose metabolism, caused by severe deficiency of galactose‐1‐phosphate uridylyltransferase (GALT) enzyme activity due to mutations of the GALT gene. Its pathogenesis is still not fully elucidated, and a therapy that prevents chronic impairments is lacking. In order to move research forward, there is a high need for a novel animal model, which allows organ studies throughout development and high‐throughput screening of pharmacologic compounds. Here, we describe the generation of a galt knockout zebrafish model and present its phenotypical characterization. Using a TALEN approach, a galt knockout line was successfully created. Accordingly, biochemical assays confirm essentially undetectable galt enzyme activity in homozygotes. Analogous to humans, galt knockout fish accumulate galactose‐1‐phosphate upon exposure to exogenous galactose. Furthermore, without prior exposure to exogenous galactose, they exhibit reduced motor activity and impaired fertility (lower egg quantity per mating, higher number of unsuccessful crossings), resembling the human phenotype(s) of neurological sequelae and subfertility. In conclusion, our galt knockout zebrafish model for classic galactosemia mimics the human phenotype(s) at biochemical and clinical levels. Future studies in our model will contribute to improved understanding and management of this disorder.
The Effect of Sr Modifier Additions on Double Oxide Film Defects in 2L99 Alloy Castings
Authors: Chen Qi , Griffiths W. D.
Published: September 2017

In this paper, Sr modifier (300 ppm) was added to 2L99 alloy sand castings to investigate its effect on bifilm defects in the castings. Two different sand molds were used in this study, with good and bad running system designs, to introduce different amounts of bifilm defects into the castings. The mechanical properties of the modified 2L99 castings were compared to the properties of unmodified castings and showed that with high bifilm defect contents (H) the Sr addition reduced the Weibull modulus of the UTS by 67 pct and the Position Parameter by 5 pct, and introduced a bimodal distribution into the Weibull plot of the pct Elongation. However, for castings with low bifilm defect content (L), the Weibull moduli of both the UTS and pct Elongation were significantly improved (by 78 and 73 pct, respectively) with the addition of Sr. The Position Parameter of the pct Elongation was improved by 135 pct. The results suggested that a desirable modification effect can only be achieved while the bifilm defect content in a casting was low.
Widening of Laths in Bainite
Authors: Yin Jiaqing , Hillert Mats , Borgenstam Annika
Published: September 2017

Units of bainite in Fe-C alloys from the upper temperature range inherit their shape from Widmanstätten plates of ferrite, which are lathlike. The thickness increases by long-range diffusion of carbon and the length by short-range diffusion of carbon from the advancing edge of the tip. Both have been studied extensively and are fairly well understood. Widening growth seems to have been much neglected, but a study of some aspects of widening is now presented. The present report is the last one in a series of four morphological studies of bainite, isothermally formed in Fe-C alloys with 0.3 or 0.7 mass pct carbon, mainly in the upper temperature range. It contains a number of morphological observations made on cross sections of packets of bainite, and it elucidated a number of interesting questions about bainite and resulted in some proposals. The ferrite plates in a packet are nucleated as a group on a grain boundary, not each one separately on the side of a prior plate. Lengthening occurs by advancement of a short edge that is formed in close contact to the grain boundary. Widening of laths does not start spontaneously. It is initiated by a modification of the structure of the long edge of the lath. When it then moves, the lattice of the new ferrite is rotated relative to the ferrite formed by lengthening and the habit plane is different. In a section through the length direction, it is difficult to recognize what part of ferrite has formed by widening growth. Furthermore, it is proposed that the individual plates in a microstructure, previously used to illustrate subunits formed by repeated nucleation, were nucleated on a hidden grain boundary.
Metabolic pathway databases and model repositories
Authors: Labena Abraham A. , Gao Yi‐Zhou , Dong Chuan , Hua Hong‐li , Guo Feng‐Biao
Published: September 2017

Background

The number of biological Knowledge bases/databases storing metabolic pathway information and models has been growing rapidly. These resources are diverse in the type of information/data, the analytical tools, and objectives. Here we present a review of the most popular metabolic pathway databases and model repositories, focusing on their scope, content including reactions, enzymes, compounds, and genes, and applicability. The review aims to help researchers choose a suitable database or model repository according to the information and data required, by providing an insight look of each pathway resource.

Results

Four pathways databases and three model repositories were selected on the basis of popularity and diversity. Our review showed that the pathway resources vary in many aspects, such as their scope, content, access to data and the tools. In addition, inconsistencies have been observed in nomenclature and representation of database entities. The three model repositories reviewed do not offer a brief description of the models’ characteristics such as simulation conditions.

Conclusions

The inconsistencies among the databases in representing their contents may hamper the maximal use of the knowledge accumulated in these databases in particular and the area of systems biology at large. Therefore, it is strongly recommended that the database creators and the metabolic network models developers should follow international standards for the nomenclature of reactions and metabolites. Besides, computationally generated models that could be obtained from model repositories should be utilized with manual curations as they lack some important components that are necessary for full functionality of the models.
Knowledge‐driven computational modeling in Alzheimer's disease research: Current state and future trends
Authors: Geerts Hugo , Hofmann‐Apitius Martin , Anastasio Thomas J. ,   Brain Health Modeling Initiative
Published: September 2017

Neurodegenerative diseases such as Alzheimer's disease (AD) follow a slowly progressing dysfunctional trajectory, with a large presymptomatic component and many comorbidities. Using preclinical models and large‐scale omics studies ranging from genetics to imaging, a large number of processes that might be involved in AD pathology at different stages and levels have been identified. The sheer number of putative hypotheses makes it almost impossible to estimate their contribution to the clinical outcome and to develop a comprehensive view on the pathological processes driving the clinical phenotype. Traditionally, bioinformatics approaches have provided correlations and associations between processes and phenotypes. Focusing on causality, a new breed of advanced and more quantitative modeling approaches that use formalized domain expertise offer new opportunities to integrate these different modalities and outline possible paths toward new therapeutic interventions. This article reviews three different computational approaches and their possible complementarities. Process algebras, implemented using declarative programming languages such as Maude, facilitate simulation and analysis of complicated biological processes on a comprehensive but coarse‐grained level. A model‐driven Integration of Data and Knowledge, based on the OpenBEL platform and using reverse causative reasoning and network jump analysis, can generate mechanistic knowledge and a new, mechanism‐based taxonomy of disease. Finally, Quantitative Systems Pharmacology is based on formalized implementation of domain expertise in a more fine‐grained, mechanism‐driven, quantitative, and predictive humanized computer model. We propose a strategy to combine the strengths of these individual approaches for developing powerful modeling methodologies that can provide actionable knowledge for rational development of preventive and therapeutic interventions. Development of these computational approaches is likely to be required for further progress in understanding and treating AD.
Accelerated Return to Sport After Anterior Cruciate Ligament Reconstruction and Early Knee Osteoarthritis Features at 1 Year: An Exploratory Study
Authors: Culvenor Adam G. , Patterson Brooke E. , Guermazi Ali , Morris Hayden G. , Whitehead Timothy S. , Crossley Kay M.
Published: September 2017

Background

A timely return to competitive sport is a primary goal of anterior cruciate ligament reconstruction (ACLR). It is not known whether an accelerated return to sport increases the risk of early‐onset knee osteoarthritis (KOA).

Objective

To determine whether an accelerated return to sport post‐ACLR (ie, <10 months) is associated with increased odds of early KOA features on magnetic resonance imaging (MRI) 1 year after surgery and to evaluate the relationship between an accelerated return to sport and early KOA features stratified by type of ACL injury (isolated or concurrent chondral/meniscal injury) and lower limb function (good or poor).

Design

Cross‐sectional study.

Setting

Private radiology clinic and university laboratory.

Participants

A total of 111 participants (71 male; mean age 30 ± 8 years) 1‐year post‐ACLR.

Methods

Participants completed a self‐report questionnaire regarding postoperative return‐to‐sport data (specific sport, postoperative month first returned), and isotropic 3‐T MRI scans were obtained.

Outcome Measures

Early KOA features (bone marrow, cartilage and meniscal lesions, and osteophytes) assessed with the MRI OA Knee Score. Logistic regression analyses evaluated the odds of early KOA features with an accelerated return to sport (<10 months post‐ACLR versus ≥10 months or no return to sport) in the total cohort and stratified by type of ACL injury and lower limb function.

Results

Forty‐six (41%) participants returned to competitive sport <10 months post‐ACLR. An early return to sport was associated with significantly increased odds of bone marrow lesions (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3‐6.0) but not cartilage (OR 1.2, 95% CI 0.5‐2.6) or meniscal lesions (OR 0.8, 95% CI 0.4‐1.8) or osteophytes (OR 0.6, 95% CI 0.3‐1.4). In those with poor lower limb function, early return to sport exacerbated the odds of bone marrow lesions (OR 4.6, 95% CI 1.6‐13.5), whereas stratified analyses for type of ACL injury did not reach statistical significance.

Conclusion

An accelerated return to sport, particularly in the presence of poor lower limb function, may be implicated in posttraumatic KOA development.

Level of evidence

IV
Computational analysis of vortex dynamics and performance enhancement due to body–fin and fin–fin interactions in fish-like locomotion
Authors: Liu Geng , Ren Yan , Dong Haibo , Akanyeti Otar , Liao James C. , Lauder George V.
Published: September 2017

Numerical simulations are used to investigate the hydrodynamic benefits of body–fin and fin–fin interactions in a fish model in carangiform swimming. The geometry and kinematics of the model are reconstructed in three-dimensions from high-speed videos of a live fish, Crevalle Jack (Caranx hippos), during steady swimming. The simulations employ an immersed-boundary-method-based incompressible Navier–Stokes flow solver that allows us to quantitatively characterize the propulsive performance of the fish median fins (the dorsal and the anal fins) and the caudal fin using three-dimensional full body simulations. This includes a detailed analysis of associated performance enhancement mechanisms and their connection to the vortex dynamics. Comparisons are made using three different models containing different combinations of the fish body and fins to provide insights into the force production. The results indicate that the fish produces high performance propulsion by utilizing complex interactions among the fins and the body. By connecting the vortex dynamics and surface force distribution, it is found that the leading-edge vortices produced by the caudal fin are associated with most of the thrust production in this fish model. These vortices could be strengthened by the vorticity capture from the vortices generated by the posterior body during undulatory motion. Meanwhile, the pressure difference between the two sides of posterior body resulting from the posterior body vortices (PBVs) helps with the alleviation of the body drag. The appearance of the median fins in the posterior region further strengthens the PBVs and caudal-fin wake capture mechanism. This work provides new physical insights into how body–fin and fin–fin interactions enhance thrust production in swimming fishes, and emphasizes that movements of both the body and fins contribute to overall swimming performance in fish locomotion.
Electrohydrodynamics of viscous drops in strong electric fields: numerical simulations
Authors: Das Debasish , Saintillan David
Published: September 2017

Weakly conducting dielectric liquid drops suspended in another dielectric liquid and subject to an applied uniform electric field exhibit a wide range of dynamical behaviours contingent on field strength and material properties. These phenomena are best described by the Melcher–Taylor leaky dielectric model, which hypothesizes charge accumulation on the drop–fluid interface and prescribes a balance between charge relaxation, the jump in ohmic currents from the bulk and charge convection by the interfacial fluid flow. Most previous numerical simulations based on this model have either neglected interfacial charge convection or restricted themselves to axisymmetric drops. In this work, we develop a three-dimensional boundary element method for the complete leaky dielectric model to systematically study the deformation and dynamics of liquid drops in electric fields. The inclusion of charge convection in our simulations permits us to investigate drops in the Quincke regime, in which experiments have demonstrated a symmetry-breaking bifurcation leading to steady electrorotation. Our simulation results show excellent agreement with existing experimental data and small-deformation theories.
Stability of three-dimensional columnar convection in a porous medium
Authors: Hewitt Duncan R. , Lister John R.
Published: September 2017

The stability of steady convective exchange flow with a rectangular planform in an unbounded three-dimensional porous medium is explored. The base flow comprises a balance between vertical advection with amplitude $A$ in interleaving rectangular columns with aspect ratio $\unicode[STIX]{x1D709}\leqslant 1$ and horizontal diffusion between the columns. Columnar flow with a square planform ($\unicode[STIX]{x1D709}=1$) is found to be weakly unstable to a large-scale perturbation of the background temperature gradient, irrespective of $A$, but to have no stronger instability on the scale of the columns. This result provides a stark contrast to two-dimensional columnar flow (Hewitt et al., J. Fluid Mech., vol. 737, 2013, pp. 205–231), which, as $A$ is increased, is increasingly unstable to a perturbation on the scale of the columnar wavelength. For rectangular planforms with $\unicode[STIX]{x1D709}<1$, a critical aspect ratio is identified, below which a perturbation on the scale of the columns is the fastest growing mode, as in two dimensions. Scalings for the growth rate and the structure of this mode are identified, and are explained by means of an asymptotic expansion in the limit $\unicode[STIX]{x1D709}\rightarrow 0$. The difference between the stabilities of two-dimensional and three-dimensional exchange flow provides a potential explanation for the apparent difference in dominant horizontal scale observed in direct numerical simulations of two-dimensional and three-dimensional statistically steady ‘Rayleigh–Darcy’ convection at high Rayleigh numbers.
Film spreading from a miscible drop on a deep liquid layer
Authors: Dandekar Raj , Pant Anurag , Puthenveettil Baburaj A.
Published: September 2017

We study the spreading of a film from ethanol–water droplets of radii$0.9~\text{mm}<r_{d}<1.1~\text{mm}$on the surface of a deep water layer for various concentrations of ethanol in the drop. Since the drop is lighter ($\unicode[STIX]{x1D709}=\unicode[STIX]{x1D70C}_{l}/\unicode[STIX]{x1D70C}_{d}>1.03$), it stays at the surface of the water layer during the spreading of the film from the drop; the film is more viscous than the underlying water layer since$\unicode[STIX]{x1D712}=\unicode[STIX]{x1D707}_{l}/\unicode[STIX]{x1D707}_{d}>0.38$. Inertial forces are not dominant in the spreading since the Reynolds numbers based on the film thickness$h_{f}$are in the range$0.02<Re_{f}<1.4$. The spreading is surface-tension-driven since the film capillary numbers are in the range$0.0005<Ca_{f}<0.0069$and the drop Bond numbers are in the range$0.19<Bo_{d}<0.56$. We observe that, when the drop is brought in contact with the water surface, capillary waves propagate from the point of contact, followed by a radially expanding, thin circular film of ethanol–water mixture. The film develops instabilities at some radius to form outward-moving fingers at its periphery while it is still expanding, till the expansion stops at a larger radius. The film then retracts, during which time the remaining major part of the drop, which stays at the centre of the expanding film, thins and develops holes and eventually mixes completely with water. The radius of the expanding front of the film scales as$r_{f}\sim t^{1/4}$and shows a dependence on the concentration of ethanol in the drop as well as on$r_{d}$, and is independent of the layer height$h_{l}$. Using a balance of surface tension and viscous forces within the film, along with a model for the fraction of the drop that forms the thin film, we obtain an expression for the dimensionless film radius$r_{f}^{\ast }=r_{f}/r_{d}$, in the form$fr_{f}^{\ast }={t_{\unicode[STIX]{x1D707}d}^{\ast }}^{1/4}$, where$t_{\unicode[STIX]{x1D707}d}^{\ast }=t/t_{\unicode[STIX]{x1D707}d}$, with the time scale$t_{\unicode[STIX]{x1D707}d}=\unicode[STIX]{x1D707}_{d}r_{d}/\unicode[STIX]{x0394}\unicode[STIX]{x1D70E}$and$f$is a function of$Bo_{d}$. Similarly, we show that the dimensionless velocity of film spreading,$Ca_{d}=u_{f}\unicode[STIX]{x1D707}_{d}/\unicode[STIX]{x0394}\unicode[STIX]{x1D70E}$, scales as$4f^{4}Ca_{d}={r_{f}^{\ast }}^{-3}$.
A Lagrangian fluctuation–dissipation relation for scalar turbulence. Part I. Flows with no bounding walls
Authors: Drivas Theodore D. , Eyink Gregory L.
Published: September 2017

An exact relation is derived between scalar dissipation due to molecular diffusivity and the randomness of stochastic Lagrangian trajectories for flows without bounding walls. This ‘Lagrangian fluctuation–dissipation relation’ equates the scalar dissipation for either passive or active scalars to the variance of scalar inputs associated with initial scalar values and internal scalar sources, as these are sampled backward in time by the stochastic Lagrangian trajectories. As an important application, we reconsider the phenomenon of ‘Lagrangian spontaneous stochasticity’ or persistent non-determinism of Lagrangian particle trajectories in the limit of vanishing viscosity and diffusivity. Previous work on the Kraichnan (Phys. Fluids, 1968, vol. 11, pp. 945–953) model of turbulent scalar advection has shown that anomalous scalar dissipation is associated in that model with Lagrangian spontaneous stochasticity. There has been controversy, however, regarding the validity of this mechanism for scalars advected by an actual turbulent flow. We here completely resolve this controversy by exploiting the fluctuation–dissipation relation. For either a passive or an active scalar advected by any divergence-free velocity field, including solutions of the incompressible Navier–Stokes equation, and away from walls, we prove that anomalous scalar dissipation requires Lagrangian spontaneous stochasticity. For passive scalars, we prove furthermore that spontaneous stochasticity yields anomalous dissipation for suitable initial scalar fields, so that the two phenomena are there completely equivalent. These points are illustrated by numerical results from a database of homogeneous isotropic turbulence, which provide both additional support to the results and physical insight into the representation of diffusive effects by stochastic Lagrangian particle trajectories.
A Lagrangian fluctuation–dissipation relation for scalar turbulence. Part II. Wall-bounded flows
Authors: Drivas Theodore D. , Eyink Gregory L.
Published: September 2017

We derive here Lagrangian fluctuation–dissipation relations for advected scalars in wall-bounded flows. The relations equate the dissipation rate for either passive or active scalars to the variance of scalar inputs from the initial values, boundary values and internal sources, as those are sampled backward in time by stochastic Lagrangian trajectories. New probabilistic concepts are required to represent scalar boundary conditions at the walls: the boundary local-time density at points on the wall where scalar fluxes are imposed and the boundary first hitting time at points where scalar values are imposed. These concepts are illustrated both by analytical results for the problem of pure heat conduction and by numerical results from a database of channel-flow turbulence, which also demonstrate the scalar mixing properties of near-wall turbulence. As an application of the fluctuation–dissipation relation, we examine for wall-bounded flows the relation between anomalous scalar dissipation and Lagrangian spontaneous stochasticity, i.e. the persistent non-determinism of Lagrangian particle trajectories in the limit of vanishing viscosity and diffusivity. In Part I of this series, we showed that spontaneous stochasticity is the only possible mechanism for anomalous dissipation of passive or active scalars, away from walls. Here it is shown that this remains true when there are no scalar fluxes through walls. Simple examples show, on the other hand, that a distinct mechanism of non-vanishing scalar dissipation can be thin scalar boundary layers near the walls. Nevertheless, we prove for general wall-bounded flows that spontaneous stochasticity is another possible mechanism of anomalous scalar dissipation.
Forcing symmetry exchanges and flow reversals in turbulent wakes
Authors: Barros Diogo , Borée Jacques , Cadot Olivier , Spohn Andreas , Noack Bernd R.
Published: September 2017

Turbulent wakes past bluff bodies commonly present asymmetric flow states reminiscent of bifurcations in the laminar regime. Understanding the sensitivity of these states to flow forcing is crucial to the modelling and control of flow symmetry properties. In this study, the near wake of a rectangular bluff body in proximity to a wall is disturbed by the use of passive devices located between the model and the wall, upstream of the massive flow separation occurring at the blunt trailing edges. Due to the proximity to the boundary, the wake initially presents wall-normal asymmetry and a negative wall-normal pressure gradient along the base. The application of disturbances with variable size, however, sets flow symmetry along the wall-normal plane, leading to the intermittent spanwise wake reversals reported recently in the literature. A further increase in the size of perturbation suppresses wake switching, and wall-normal asymmetry is recovered, but with a positive wall-normal pressure gradient. The dynamical features of this bifurcation scenario can be retrieved using two coupled symmetry-breaking models for spanwise and wall-normal pressure gradients. This confirms the high sensitivity of the separated flow to external perturbations. More importantly, the results unify observations of the bluff-body wake topologies covered in previous investigations.