bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Flow Field in the HeartMate 3 Using Three-Dimensional Particle Tracking Velocimetry and Comparison to Computational Fluid Dynamics
Authors: Thamsen Bente , Gülan Utku , Wiegmann Lena , Loosli Christian , Schmid Daners Marianne , Kurtcuoglu Vartan , Holzner Markus , Meboldt Mirko
Published: March 2019

Flow fields in rotary blood pumps (RBPs) have a significant influence on hemocompatibility. Because flow characteristics vary with flow rate, different operating conditions play a role. Furthermore, turbulence is crucial in the evaluation of blood damage potential, but the level of turbulence in implantable RBPs is still unknown. In this study, we addressed both research aspects and for the first time measured turbulent flow fields in the HeartMate 3 (HM3) at different operating flows. The averaged, three-dimensional velocity field including fluctuating velocity components in a HM3 with a transparent lower housing was measured using three-dimensional particle tracking velocimetry (3D-PTV). In vitro results were compared with computational fluid dynamic (CFD) simulations for two flow cases, representing the lower and upper physiologic flow range (2.7 and 5.7 L/min), using two different turbulence models that account for fluctuating velocity fields: the k-ω shear stress transport and the Reynolds stress model (RSM). The measurements revealed higher mean and turbulent kinetic energies (TKEs) for the low-flow condition especially within the gap beneath the impeller. Computed mean fields agree well with 3D-PTV for both models, but the RSM predicts the TKE levels better than the k-ω model. Computational fluid dynamic results further show wall shear stresses higher than 150 Pa, a commonly used damage threshold, in the bottom gap for the lower flow condition. In conclusion, the low-flow condition was found to be more prone to blood damage. Furthermore, CFD predictions for turbulence must be carefully experimentally validated.
Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA
Authors: Wijarnpreecha Karn , Kim Donghee , Raymond Pascale , Scribani Melissa , Ahmed Aijaz
Published: March 2019

Background and aim

Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis.

Participants and methods

Cross-sectional data from 11 325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index.

Results

NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01–2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03–1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18–2.72).

Conclusion

Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.
Does Primary Care Provider Supply Influence Medicaid Acceptability?
Authors: Benitez Joseph A. , Tipirneni Renuka , Perez Victoria , Davis Matthew M.
Published: March 2019

Background:

Following the Affordable Care Act’s Medicaid expansions, access to care improved through elevated coverage rates among the low-income population. In Michigan, a major factor contributing to improved access among low-income patients was increased Medicaid acceptance in primary care settings.

Objectives:

Prior evidence shows substantial geographic variation preacceptance and postacceptance of Medicaid. In this study, we determine whether physician’s willingness to accept new Medicaid patients is moderated by the availability of other providers in close proximity.

Methods:

The study uses Michigan simulated patient (ie, “secret shopper”) data collected during 2014 and 2015, and applies a difference-in-differences styled event-study regression approach comparing trends in Medicaid acceptability and appointment scheduling between areas in Michigan with higher densities of primary care providers against those with lower densities of providers that could arguably be classified a health professional shortage areas.

Results:

Through one year after Michigan’s Medicaid expansion, practices in low-supply areas appeared no more likely (P>0.10) to turn away a newly insured Medicaid patient than a practice in a supply-rich area. The wait times for patients in a low-supply area were about a day longer (P<0.05) than for patients in supply-rich areas through 4 months after the expansion, though this difference dissipated through 8 and 12 months after the expansion.

Conclusions:

These results indicate that newly insured Medicaid patients are gaining access to care in settings with limited health care supply.
Priority setting in head and neck oncology in low-resource environments
Authors: Kowalski Luiz P. , Sanabria Alvaro
Published: March 2019

Purpose of review

Most information about priority setting comes from developed countries. In low-resource settings, many factors should be considered to select the best candidate for the treatments that are available. The physician is always under pressure to obtain better results in spite of the lower quantity of resources. This exposes physicians to daily ethical dilemmas and increases their anxiety and burnout.

Recent findings

Most low-resource settings have restrictions in major treatments, and the number of specialized centers that have all the services is low. The surgeon has to navigate through the system as a patient advocate, taking the responsibilities of other health system actors, has to ‘negotiate’ to design a treatment based on outdated results or to wait for new results and has to decide whether to start or to wait for other treatments to be ready to comply with protocol recommendations.

The surgeons face the dilemma of offering the best treatment with scarce resources but with a higher possibility of completion. Finally, we must do the best we can with what we have.
Sir Diarmuid Downs CBE. 23 April 1922—12 February 2014
Authors: Morrison David
Published: March 2019

Diarmuid Downs was a one-company man. He started work at Ricardo in 1942, after graduation from the University of London, Northampton Polytechnic (now City University) with a first-class honours degree in engineering, and retired 45 years later. His early meticulously executed research concentrated on spark-ignition combustion phenomena—essentially knock, pre-ignition and the effects of fuel additives— an important understanding in those early days for the oil and additive companies. Later, in the 1970s, his attention moved to engine and vehicle exhaust emission control, a key emerging technology at that time. In his more senior years, he took a broader picture of the industry and technology, building on his detailed pioneering research as he continued to develop his vision and balanced technical judgement. Recognized and encouraged initially by Harry Ricardo, he rose quickly to senior positions in the company, becoming a board member at the age of 35 and managing director 10 years later. In 1976 he became joint chairman and managing director, ultimately to become chairman and finally to retire in 1987. He authored or co-authored some 46 technical papers in his working career. He has been described as a ‘gentleman engineer’ with strong support for his staff at all levels. In the broad spectrum of engineering disciplines, Diarmuid leaned more towards the intellectual/scientific end. He was a deep thinker, with a prodigious memory and love of the arts as well as biographical and historical literature. He inspired respect through his vision, balanced judgement and supreme confidence and was an articulate orator. He was awarded many honours in his lifetime, including a CBE in 1979, a knighthood in 1985 and in the same year Fellowship of the Royal Society. He held appointments in over 30 professional organizations, including four charities, to which he and his wife, Carmel, were dedicated, helping the vulnerable and homeless. He was a lifelong devout Catholic and active supporter of the church and related charities, recognized by a Papal knighthood in 1993.
Free vibration analysis of transmission lines based on the dynamic stiffness method
Authors: Liu Xiaohui , Hu You , Cai Mengqi
Published: March 2019

An improved mathematical model used to study the coupling characteristic of the multi-span transmission lines is developed. Based on the solution method for single-span cable, an expression for the dynamic stiffness of two-span transmission lines with an arbitrary inclination angle is formulated. The continuity of displacements and forces at a suspension point is used to derive the dynamic stiffness. Interactions between insulator strings and adjacent spans are accommodated. Considering the infinite dynamic stiffness corresponds to the natural frequencies of the transmission lines, the finite-element method (FEM) is employed to assess the validity of the dynamic stiffness. In the numerical investigation, attention is focused on the effect of the inclination angles, Irvine parameter, insulator string length and damping parameter. In addition, the modal function corresponding to the natural frequencies is derived. Then, the results of comprehensive parametric studies are presented and discussed. Special attention is paid to the effect of the Irvine parameter and damping parameter on the in-plane modal shapes. Finally, according to the theoretical model of two-span transmission lines, the generalized dynamic stiffness of transmission lines with an arbitrary number of spans and inclination angles is derived. The method can be used as the basis of the vibration analysis on a wide variety of multi-span transmission lines.
Temporal variation in the vocal behaviour of southern right whales in the Auckland Islands, New Zealand
Authors: Webster T. A. , Van Parijs S. M. , Rayment W. J. , Dawson S. M.
Published: March 2019

Autonomous recorders are frequently used for examining vocal behaviour of animals, and are particularly effective in remote habitats. Southern right whales are known to have an extensive acoustic repertoire. A recorder was moored at the isolated sub-Antarctic Auckland Islands for a year to examine whether the acoustic behaviour of southern right whales differed seasonally and throughout the day at their main calving ground in New Zealand. Recordings were made in each month except June, and vocalizations were audible in all months with recordings except January. A total of 35 487 calls were detected, of whichupcallswere the most common (11 623). Call rate peaked in August (288 ± 5.9 [s.e.] calls/hour) and July (194 ± 8.3). Vocal behaviour varied diurnally with highest call rates detected at dusk and night, consistent with the concept thatupcallsfunction primarily as contact calls. Zero-inflated model results confirmed that seasonal variation was the most important factor for explaining differences in vocal behaviour. An automated detector designed to expedite the analysis process for North Atlantic right whales correctly identified 80% ofupcalls,although false detections were frequent, particularly when call rates were low. This study is the first to attempt year-round monitoring of southern right whale presence in New Zealand.
Characterization of cytoplasmic viscosity of hundreds of single tumour cells based on micropipette aspiration
Authors: Wang K. , Sun X. H. , Zhang Y. , Zhang T. , Zheng Y. , Wei Y. C. , Zhao P. , Chen D. Y. , Wu H. A. , Wang W. H. , Long R. , Wang J. B. , Chen J.
Published: March 2019

Cytoplasmic viscosity (μc) is a key biomechanical parameter for evaluating the status of cellular cytoskeletons. Previous studies focused on white blood cells, but the data of cytoplasmic viscosity for tumour cells were missing. Tumour cells (H1299, A549 and drug-treated H1299 with compromised cytoskeletons) were aspirated continuously through a micropipette at a pressure of −10 or −5 kPa where aspiration lengths as a function of time were obtained and translated to cytoplasmic viscosity based on a theoretical Newtonian fluid model. Quartile coefficients of dispersion were quantified to evaluate the distributions of cytoplasmic viscosity within the same cell type while neural network-based pattern recognitions were used to classify different cell types based on cytoplasmic viscosity. The single-cell cytoplasmic viscosity with three quartiles and the quartile coefficient of dispersion were quantified as 16.7 Pa s, 42.1 Pa s, 110.3 Pa s and 74% for H1299 cells at −10 kPa (ncell= 652); 144.8 Pa s, 489.8 Pa s, 1390.7 Pa s, and 81% for A549 cells at −10 kPa (ncell= 785); 7.1 Pa s, 13.7 Pa s, 31.5 Pa s, and 63% for CD-treated H1299 cells at −10 kPa (ncell= 651); and 16.9 Pa s, 48.2 Pa s, 150.2 Pa s, and 80% for H1299 cells at −5 kPa (ncell= 600), respectively. Neural network-based pattern recognition produced successful classification rates of 76.7% for H1299 versus A549, 67.0% for H1299 versus drug-treated H1299 and 50.3% for H1299 at −5 and −10 kPa. Variations of cytoplasmic viscosity were observed within the same cell type and among different cell types, suggesting the potential role of cytoplasmic viscosity in cell status evaluation and cell type classification.
Plastic multicellular development ofMyxococcus xanthus: genotype–environment interactions in a physical gradient
Authors: Rivera-Yoshida Natsuko , Arzola Alejandro V. , Arias Del Angel Juan A. , Franci Alessio , Travisano Michael , Escalante Ana E. , Benítez Mariana
Published: March 2019

In order to investigate the contribution of the physical environment to variation in multicellular development ofMyxococcus xanthus, phenotypes developed by different genotypes in a gradient of substrate stiffness conditions were quantitatively characterized. Statistical analysis showed that plastic phenotypes result from the genotype, the substrate conditions and the interaction between them. Also, phenotypes were expressed in two distinguishable scales, the individual and the population levels, and the interaction with the environment showed scale and trait specificity. Overall, our results highlight the constructive role of the physical context in the development of microbial multicellularity, with both ecological and evolutionary implications.
Complex interactions between local adaptation, phenotypic plasticity and sex affect vulnerability to warming in a widespread marine copepod
Authors: Sasaki Matthew , Hedberg Sydney , Richardson Kailin , Dam Hans G.
Published: March 2019

Predicting the response of populations to climate change requires an understanding of how various factors affect thermal performance. Genetic differentiation is well known to affect thermal performance, but the effects of sex and developmental phenotypic plasticity often go uncharacterized. We used common garden experiments to test for effects of local adaptation, developmental phenotypic plasticity and individual sex on thermal performance of the ubiquitous copepod,Acartia tonsa(Calanoida, Crustacea) from two populations strongly differing in thermal regimes (Florida and Connecticut, USA). Females had higher thermal tolerance than males in both populations, while the Florida population had higher thermal tolerance compared with the Connecticut population. An effect of developmental phenotypic plasticity on thermal tolerance was observed only in the Connecticut population. Our results show clearly that thermal performance is affected by complex interactions of the three tested variables. Ignoring sex-specific differences in thermal performance may result in a severe underestimation of population-level impacts of warming because of population decline due to sperm limitation. Furthermore, despite having a higher thermal tolerance, low-latitude populations may be more vulnerable to warming as they lack the ability to respond to increases in temperature through phenotypic plasticity.
A rational framework for dynamic homogenization at finite wavelengths and frequencies
Authors: Guzina Bojan B. , Meng Shixu , Oudghiri-Idrissi Othman
Published: March 2019

In this study, we establish an inclusive paradigm for the homogenization of scalar wave motion in periodic media (including the source term) at finite frequencies and wavenumbers spanning the first Brillouin zone. We take the eigenvalue problem for the unit cell of periodicity as a point of departure, and we consider the projection of germane Bloch wave function onto a suitable eigenfunction as descriptor of effective wave motion. For generality the finite wavenumber, finite frequency homogenization is pursued in

R

d

via second-order asymptotic expansion about the apexes of ‘wavenumber quadrants’ comprising the first Brillouin zone, at frequencies near given (acoustic or optical) dispersion branch. We also consider the junctures of dispersion branches and ‘dense’ clusters thereof, where the asymptotic analysis reveals several distinct regimes driven by the parity and symmetries of the germane eigenfunction basis. In the case of junctures, one of these asymptotic regimes is shown to describe the so-called Dirac points that are relevant to the phenomenon of topological insulation. On the other hand, the effective model for nearby solution branches is found to invariably entail a Dirac-like system of equations that describes the interacting dispersion surfaces as ‘blunted cones’. For all cases considered, the effective description turns out to admit the same general framework, with differences largely being limited to (i) the eigenfunction basis, (ii) the reference cell of medium periodicity, and (iii) the wavenumber–frequency scaling law underpinning the asymptotic expansion. We illustrate the analytical developments by several examples, including Green's function near the edge of a band gap and clusters of nearby dispersion surfaces.
Self-sustaining dual critical layer states in plane Poiseuille–Couette flow at large Reynolds number
Authors: Kumar Rishi , Walton Andrew
Published: March 2019

The nonlinear stability of plane Poiseuille–Couette flow subjected to three-dimensional disturbances is studied asymptotically at large Reynolds number
R
. By analysing the nature of the instability for increasing disturbance size Δ, the scaling Δ = 
O
(
R
−1/3
) is identified at which a strongly nonlinear neutral wave structure emerges, involving the interaction of two inviscid critical layers. The striking feature of this structure is that the travelling wave disturbances have both streamwise and spanwise wavelengths comparable to the channel width, with an associated phase speed of
O
(1). An alternative method to the classical balancing of phase shifts is proposed, involving vorticity jumps, that uses a global property of the flow-field and enables the amplitude-dependence of the neutral modes to be determined in terms of the wavenumbers and the properties of the basic flow. Numerical computation of the Rayleigh equation which governs the flow outside of the critical layers shows that neutral solutions exist for non-dimensional wall sliding speeds in the range 0 ≤ 
V
 < 2. It transpires that the critical layers merge and the asymptotic structure referred to above breaks down both in the large-amplitude limit and the limit

V
→
2

when the maximum of the basic flow becomes located at the upper wall.
Species richness and disparity of parareptiles across the end-Permian mass extinction
Authors: MacDougall Mark J. , Brocklehurst Neil , Fröbisch Jörg
Published: March 2019

The amniote clade Parareptilia is notable in that members of the clade exhibited a wide array of morphologies, were successful in a variety of ecological niches and survived the end-Permian mass extinction. In order to better understand how mass extinction events can affect clades that survive them, we investigate both the species richness and morphological diversity (disparity) of parareptiles over the course of their history. Furthermore, we examine our observations in the context of other metazoan clades, in order to identify post-extinction survivorship patterns that are present in the clade. The results of our study indicate that there was an early increase in parareptilian disparity, which then fluctuated over the course of the Permian, before it eventually declined sharply towards the end of the Permian and into the Triassic, corresponding with the end-Permian mass extinction event. Interestingly, this is a different trend to what is observed regarding parareptile richness, that shows an almost continuous increase until its overall peak at the end of the Late Permian. Moreover, richness did not experience the same sharp drop at the end of the Permian, reaching a plateau until the Anisian, before dropping sharply and remaining low, with the clade going extinct at the end of the Triassic. This observed pattern is likely to be due to the fact that, despite the extinction of several morphologically distinct parareptile clades, the procolophonoids, one of the largest parareptilian clades, were diversifying across the Permian–Triassic boundary. With the clade's low levels of disparity and eventually declining species richness, this pattern most resembles a ‘dead clade walking’ pattern.
Sexual selection, body mass and molecular evolution interact to predict diversification in birds
Authors: Iglesias-Carrasco Maider , Jennions Michael D. , Ho Simon Y. W. , Duchêne David A.
Published: March 2019

Sexual selection is a powerful agent of evolution, driving microevolutionary changes in the genome and macroevolutionary rates of lineage diversification. The mechanisms by which sexual selection might influence macroevolution remain poorly understood. For example, sexual selection might drive positive selection for key adaptations that facilitate diversification. Furthermore, sexual selection might be a general driver of molecular evolutionary rate. We lay out some of the potential mechanisms that create a link between sexual selection and diversification, based on causal effects on other life-history traits such as body mass and the rate of molecular evolution. Birds are ideally suited for testing the importance of these relationships because of their diverse reproductive systems and the multiple evolutionary radiations that have produced their astounding modern diversity. We show that sexual selection (measured as the degree of polygyny) interacts with the rate of molecular evolution and with body mass to predict species richness at the genus level. A high degree of polygyny and rapid molecular evolution are positively associated with the net rate of diversification, with the two factors being especially important for explaining diversification in large-bodied taxa. Our findings further suggest that mutation rates underpin some of the macroevolutionary effects of sexual selection. We synthesize the existing theory on sexual selection as a force for diversity and propose avenues for exploring this association using genome data.
Sexual conflict and intrasexual polymorphism promote assortative mating and halt population differentiation
Authors: Iversen Lars Lønsmann , Svensson Erik I. , Christensen Søren Thromsholdt , Bergsten Johannes , Sand-Jensen Kaj
Published: March 2019

Sexual conflict is thought to be an important evolutionary force in driving phenotypic diversification, population divergence, and speciation. However, empirical evidence is inconsistent with the generality that sexual conflict enhances population divergence. Here, we demonstrate an alternative evolutionary outcome in which sexual conflict plays a conservative role in maintaining male and female polymorphisms locally, rather than promoting population divergence. In diving beetles, female polymorphisms have evolved in response to male mating harassment and sexual conflict. We present the first empirical evidence that this female polymorphism is associated with (i) two distinct and sympatric male morphological mating clusters (morphs) and (ii) assortative mating between male and female morphs. Changes in mating traits in one sex led to a predictable change in the other sex which leads to predictable within-population evolutionary dynamics in male and female morph frequencies. Our results reveal that sexual conflict can lead to assortative mating between male offence and female defence traits, if a stable male and female mating polymorphisms are maintained. Stable male and female mating polymorphisms are an alternative outcome to an accelerating coevolutionary arms race driven by sexual conflict. Such stable polymorphisms challenge the common view of sexual conflict as an engine of rapid speciation via exaggerated coevolution between sexes.
Future suitability of habitat in a migratory ungulate under climate change
Authors: Rivrud Inger Maren , Meisingset Erling L. , Loe Leif Egil , Mysterud Atle
Published: March 2019

With climate change, the effect of global warming on snow cover is expected to cause range expansion and enhance habitat suitability for species at their northern distribution limits. However, how this depends on landscape topography and sex in size-dimorphic species remains uncertain, and is further complicated for migratory animals following climate-driven seasonal resource fluctuations across vast landscapes. Using 11 years of data from a partially migratory ungulate at their northern distribution ranges, the red deer (Cervus elaphus), we predicted sex-specific summer and winter habitat suitability in diverse landscapes under medium and severe global warming. We found large increases in future winter habitat suitability, resulting in expansion of winter ranges as currently unsuitable habitat became suitable. Even moderate warming decreased snow cover substantially, with no suitability difference between warming scenarios. Winter ranges will hence not expand linearly with warming, even for species at their northern distribution limits. Although less pronounced than in winter, summer ranges also expanded and more so under severe warming. Summer habitat suitability was positively correlated with landscape topography and ranges expanded more for females than males. Our study highlights the complexity of predicting future habitat suitability for conservation and management of size-dimorphic, migratory species under global warming.
Unsupervised deep learning on biomedical data with BoltzmannMachines.jl
Authors: Lenz Stefan , Hess Moritz , Binder Harald
Published: March 2019

Deep Boltzmann machines (DBMs) are models for unsupervised learning in the field of artificial intelligence, promising to be useful for dimensionality reduction and pattern detection in clinical and genomic data. Multimodal and partitioned DBMs alleviate the problem of small sample sizes and make it possible to combine different input data types in one DBM model. We present the package “BoltzmannMachines” for the Julia programming language, which makes this model class available for practical use in working with biomedical data.

Availability

Notebook with example data: http://github.com/stefan-m-lenz/BMs4BInf2019 Julia package: http://github.com/stefan-m-lenz/BoltzmannMachines.jl
Knowledge and attitudes among life scientists towards reproducibility within journal articles: a research survey
Authors: Samota Evanthia Kaimaklioti , Davey Robert P.
Published: March 2019

We constructed a survey to understand how authors and scientists view the issues around reproducibility, focusing on interactive elements such as interactive figures embedded within online publications, as a solution for enabling the reproducibility of experiments. We report the views of 251 researchers, comprising authors who have published in eLIFE Sciences, and those who work at the Norwich Biosciences Institutes (NBI). The survey also outlines to what extent researchers are occupied with reproducing experiments themselves. Currently, there is an increasing range of tools that attempt to address the production of reproducible research by making code, data, and analyses available to the community for reuse. We wanted to collect information about attitudes around the consumer end of the spectrum, where life scientists interact with research outputs to interpret scientific results. Static plots and figures within articles are a central part of this interpretation, and therefore we asked respondents to consider various features for an interactive figure within a research article that would allow them to better understand and reproduce a published analysis. The majority (91%) of respondents reported that when authors describe their research methodology (methods and analyses) in detail, published research can become more reproducible. The respondents believe that having interactive figures in published papers is a beneficial element to themselves, the papers they read as well as to their readers. Whilst interactive figures are one potential solution for consuming the results of research more effectively to enable reproducibility, we also review the equally pressing technical and cultural demands on researchers that need to be addressed to achieve greater success in reproducibility in the life sciences.
Critical Variables to be Considered when Attempting to Estimate Blood Ethanol Concentrations in Rats from g/kg Exposure Data
Authors: Dannenhoffer Carol A. , Hosová Dominika , Dang Sanjeena , Dang Utkarsh , Spear Linda P. ,   Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium
Published: March 2019

Background

In rodent studies of ethanol (EtOH) consumption where blood sample collection does not occur, there is often mention of likely BECs based on prior studies. These studies may vary in dose(s) used, age/sex/species, or administration route. Often, intake studies may presume that binge-levels were achieved without knowing that BECs exceeded 80 mg% (binge threshold). In human studies, estimated BECs (eBECs) have been derived using complex formulas that consider EtOH consumption level and the weight and sex of the individual.

Method

Three datasets were used to derive eBECs using a conversion factor (CF) that considers gram (g) of EtOH per kilogram (kg) of animal weight and other variables that may influence BECs such as age, sex, dose, route, vehicle, chronicity, and timing post-exposure. Regression analyses were also conducted for each dataset, building regression models with BEC as the response and other variables in the study specific to each dataset as predictor variables.

Results

Dataset1 assessed age, sex and post-injection time point. Both CF and regression analyses determined that different CFs should be used for 10- and 30-min post-administration time points. Dataset2 assessed age, dose, vehicle and post-intubation time point. Depending on the post-intubation time point, several CFs were used to derive eBECs. When weight was not used as a regression variable, data across approaches corresponded, with age differences emerging later in elimination phase. In Dataset3 that used BECs from a repeated intake study, chronic exposure influenced CFs, although regression analysis did not yield similar findings.

Conclusions

Although eBECs can be derived, critical variables vary with subject and test conditions and do not always concur with results of regression analyses. Although, not designed to replace assessment of BECs when sample collection is possible, the CF approach may prove useful when estimating BECs in studies where assessments are not feasible.
Cell Cycle Asynchrony Generates DNA Damage at Mitotic Entry in Polyploid Cells
Authors: Nano Maddalena , Simon Anthony , Pennetier Carole , Fraisier Vincent , Marthiens Veronique , Basto Renata
Published: March 2019

Polyploidy arises from the gain of complete chromosomes sets [1] and is known to promote cancer genome evolution. Recent evidence suggests that a large proportion of human tumours experience whole genome duplications (WGDs), which might favour the generation of highly abnormal karyotypes within a short time frame, rather than in a stepwise manner [2–6]. However, the molecular mechanisms linking whole genome duplication to genetic instability remain poorly understood. Further, possible mechanisms responsible for rapid genome reshuffling have not been described yet. Using repeated cytokinesis failure to induce polyploidization ofDrosophilaneural stem cells (NSCs, also called neuroblasts - NBs), we investigated the consequences of polyploidyin vivo. Here, we show that polyploid NSCs accumulate high levels of chromosome instability. Surprisingly, we found that DNA damage is generated in a subset of nuclei of polyploid NBs during mitosis, in an asymmetric manner. Importantly, our observations in flies were confirmed in mouse NSCs (mNSCs) after acute cytokinesis inhibition. Interestingly, DNA damage occurs in nuclei that were not ready to enter mitosis but were forced to do so when exposed to the mitotic environment of neighbouring nuclei within the same cell. Additionally, we found that polyploid cells are cell cycle asynchronous and forcing cell cycle synchronization is sufficient to lower the levels of DNA damage generated during mitosis. Overall, this work supports a model in which DNA damage at mitotic entry can generate a mutated genetic landscape that contributes to the onset of genetic instability.
A Critique of Pure Learning: What Artificial Neural Networks can Learn from Animal Brains
Authors: Zador Anthony M.
Published: March 2019

ABSTRACT

Over the last decade, artificial neural networks (ANNs), have undergone a revolution, catalyzed in large part by better tools for supervised learning. However, training such networks requires enormous data sets of labeled examples, whereas young animals (including humans) typically learn with few or no labeled examples. This stark contrast with biological learning has led many in the ANN community posit that instead of supervised paradigms, animals must rely instead primarily on unsupervised learning, leading the search for better unsupervised algorithms. Here we argue that much of an animal’s behavioral repertoire is not the result of clever learning algorithms—supervised or unsupervised—but arises instead from behavior programs already present at birth. These programs arise through evolution, are encoded in the genome, and emerge as a consequence of wiring up the brain. Specifically, animals are born with highly structured brain connectivity, which enables them learn very rapidly. Recognizing the importance of the highly structured connectivity suggests a path toward building ANNs capable of rapid learning.
StretchfMRI: a new technique to quantify the contribution of the reticular formation to long-latency responses via fMRI
Authors: Zonnino Andrea , Farrens Andria J. , Ress David , Sergi Fabrizio
Published: March 2019

Increased reticulospinal (RS) function has been observed to cause both positive and negative outcomes in the recovery of motor function after corticospinal lesions such as stroke. Current knowledge of RF function is limited by the lack of accurate, noninvasive methods for measuring RS function. Recent studies suggest that the RS tract may be involved in processing and generating Long Latency Responses (LLRs). LLRs, elicited by applying precisely controlled perturbations, can act as a reliable stimulus to measure LLR-related brainstem function using fMRI with high signal-to-noise ratio.

In this paper, we present StretchfMRI, a new technique that enables simultaneous recording of neural and muscular activity during motor responses conditioned by velocity-controlled robotic perturbations, which allows for direct investigation of the neural correlates of LLRs using fMRI.

Via preliminary validation experiments, we demonstrate that our technique can reliably elicit and identify LLRs in two wrist muscles–FCR and ECU. Moreover, via a single-subject pilot experiment, we show that the occurrence of an LLR in a flexor and extensor muscle modulates neural activity in distinct regions of the brainstem. The observed somatotopic organization is in agreement with the double reciprocal model of RS function observed in animal models, in which the right medullary and left pontine reticular formation are responsible for control of the motor activity in flexors and extensors, respectively.
Single-stride exposure to pulse torque assistance provided by a robotic exoskeleton at the hip and knee joints
Authors: McGrath Robert L. , Sergi Fabrizio
Published: March 2019

Robot assisted gait retraining is an increasingly common method for supporting restoration of walking function after neurological injury. Gait speed, an indicator of walking function, is correlated with propulsive force, a measure modulated by the posture of the trailing limb at push-off. With the ultimate goal of improving efficacy of robot assisted gait retraining, we sought to directly target gait propulsion, by exposing subjects to pulses of joint torque applied at the hip and knee joints to modulate push-off posture. Our previous work investigated changes in joint moments associated with push-off posture modulation, which informed the composition of 16 joint torque pulse conditions.

In this work, we utilized a robotic exoskeleton to apply pulses of torque to the hip and knee joints, during individual strides, of 16 healthy control subjects, and quantified the effects of this intervention on hip extension and propulsive impulse during and after application of these pulses.

We observed significant effects in the outcome measures primarily at the stride of pulse application. Specifically, when pulses were applied at late stance, we observed a significant increase in propulsive impulse when knee and/or hip flexion pulses were applied and a significant increase in hip extension angle when hip extension torque pulses were applied. When pulses were applied at early stance, we observed a significant increase in propulsive impulse associated with hip extension torque.
Phosphatidylinositol 4,5 bisphosphate controls the cis and trans interactions of synaptotagmin 1
Authors: Nyenhuis S.B. , Thapa A. , Cafiso D. S.
Published: March 2019

Synaptotagmin 1 acts as the Ca2+-sensor for synchronous neurotransmitter release; however, the mechanism by which it functions is not understood and is presently a topic of considerable interest. Here we describe measurements on full-length membrane reconstituted synaptotagmin 1 using site-directed spin labeling where we characterize the linker region as well as thecis(vesicle membrane) andtrans(cytoplasmic membrane) binding of its two C2 domains. In the full-length protein, the C2A domain does not undergo membrane insertion in the absence of Ca2+; however, the C2B domain will bind to and penetrate intransto a membrane containing phosphatidylinositol 4,5 bisphosphate (PIP2), even if phosphatidylserine (PS) is present in the cis membrane. In the presence of Ca2+, the Ca2+-binding loops of C2A and C2B both insert into the membrane interface; moreover, C2A preferentially inserts into PS containing bilayers and will bind in acisconfiguration to membranes containing PS even if a PIP2membrane is presented intrans. The data are consistent with a bridging activity for Syt1 where the two domains bind to opposing vesicle and plasma membranes. The failure of C2A to bind membranes in the absence of Ca2+and the long unstructured segment linking C2A to the vesicle membrane indicates that synaptotagmin 1 could act to significantly shorten the vesicle-plasma membrane distance with increasing levels of Ca2+.
The menstrual cycle is a primary contributor to cyclic variation in women’s mood, behavior, and vital signs
Authors: Pierson Emma , Althoff Tim , Thomas Daniel , Hillard Paula , Leskovec Jure
Published: March 2019

Female mood, behavior, and vital signs exhibit cycles which fundamentally affect health and happiness. However, it is unclear which dimensions of mood, behavior, and vital signs vary cyclically, how cycles at different timescales compare in magnitude, and how cycles vary across countries. Here we separate female mood, behavior, and vital signs into four simultaneous cycles – daily, weekly, seasonal, and menstrual. We analyze nine mood dimensions, three behavior dimensions, and three vital signs using a dataset of 241 million observations from 3.3 million women in 109 countries. We find that the menstrual cycle is a primary contributor to cyclic variation: it is the cycle with the largest amplitude for all three vital signs, sexual activity, and 7 out of 9 dimensions of mood. The amplitude of the menstrual happiness cycle is 1.4x the amplitude of the daily cycle, 3.3x the amplitude of the weekly cycle, 2.3x the amplitude of the seasonal cycle, and 1.7x the Christmas increase in happiness. Menstrual cycle effects are directionally consistent across countries, demonstrating that they occur across cultures. Overall, our results demonstrate the primacy of the menstrual cycle and necessitate better accounting for it in clinical data and practice.
Composition variation of agarwood-associated microbial communities from Aquilaria sinensis
Authors: Mo Qigui , Fan Chenyang , Zhou Gao , Fu Huiying , Wang Youwei
Published: March 2019

Agarwood, derived from Aquilaria sinensis and Aquilaria malaccensis, is of medicinal and ecological value and religious importance as incense. The existing imbalance between short supply and increasing demand of this product remains to be solved. Thus, the biologically artificial agarwood-inducing methods commonly called whole-tree agarwood-inducing techniques (agar-wit) have been established to dramatically improve agarwood yield within a short period. However, several studies reported a lower content of ethanol-soluble extractive in the agar-wit agarwood than in the natural agarwood. To further understand the role of microorganisms in agarwood formation, we investigated and contrasted the endophytic bacteria and fungi between different types of agarwood from A. sinensis through high-throughput sequencing. Results showed that the same dominant phyla of bacteria consisting of Proteobacteria, Actinobacteria, and Acidobacteria were shared by the natural agarwood and agar-wit agarwood. Meanwhile, Ascomycota and Basidiomycota constituted the similar dominant fungal phyla of these two kinds of agarwood. However, the principal microbial communities at the genus or order level evidently varied from natural agarwood to agar-wit agarwood. Moreover, the bacterial communities are closely connected with terpenoid and carbohydrate metabolism, which indicated that the bacterial communities also play a vital role in agarwood formation. In conclusion, the higher concentrated abundance of the dominant microbial communities in agar-wit agarwood than in natural agarwood may promote agarwood formation, however, the low evenness of microbial communities also lowers the content of ethanol-soluble extractive.

IMPORTANCE

Agarwood has become an indispensable product in modern life because of medicinal value, ecological and religious importance as incense. Nevertheless, the enormous demand for agarwood markedly exceeds the supply because of the dramatically declining population of genus Aquilaria. Agarwood formation occurring slowly and infrequently in a natural environment, so various artificial techniques were developed to promote the formation of agarwood, such as the physical methods and chemical methods. However, these techniques still are insufficient to compensate for the agarwood shortage. In this case, a novel biological method called the whole-tree agarwood-inducing technique (Agar-wit) induces agarwood production. However, several studies have shown that agarwood harvested from biological technology contains lower content of ethanol-soluble extractive compared with natural agarwood. So to further expose and understand the endophytic bacteria and fungi in agarwood formation is important for the improvement of biological method.
Structural investigation of one- and three-dimensional lanthanide(III) coordination polymers based on functionalized terpyridine carboxylate and aromatic dicarboxylate ligands
Authors: Bai Chao , Liu Bin , Hu Huai-Ming , Li Jin-Dian , Wang Xiaofang , Xue Ganglin
Published: March 2019

Three series of lanthanide coordination polymers, namely catena-poly[[lanthanide(III)-μ2-(benzene-1,2-dicarboxylato)-μ2-[2-(2,2′:6′,2′′-terpyridin-4′-yl)benzoato]] monohydrate], {[Ln(C8H4O4)(C22H14N3O2)]·H2O}
n
or {[Ln(1,2-bdc)(L)]·H2O}
n
, with lanthanide (Ln) = dysprosium (Dy, 1), holmium (Ho, 2) and erbium (Er, 3), poly[bis(μ2-benzene-1,3-dicarboxylato)bis[μ2-2-(2,2′:6′,2′′-terpyridin-4′-yl)benzoato]dilanthanide(III)], [Ln2(C8H4O4)2(C22H14N3O2)2]
n
or [Ln2(1,3-bdc)2(L)2]
n
, with Ln = gadolinium (Gd, 4), Ho (5) and Er (6), and poly[(μ2-benzene-1,4-dicarboxylato)[μ2-2-(2,2′:6′,2′′-terpyridin-4′-yl)benzoato]lanthanide(III)], [Ln(C8H4O4)(C22H14N3O2)]
n
or [Ln(1,4-bdc)(L)]
n
, with Ln = Dy (7), Ho (8), Er (9) and ytterbium (Yb, 10), were synthesized under hydrothermal conditions and characterized by elemental analysis, IR and single-crystal X-ray diffraction. Compounds 1–3 possess one-dimensional loop chains with Ln2(COO)2 units, which are extended into three-dimensional (3D) supramolecular structures by π–π interactions. Isostructural compounds 5 and 6 show 6-connected 3D networks, with pcu topology consisting of Ln2(COO)2 units. Compounds 7–10 display 8-connected 3D frameworks with the topological type rob, consisting of Ln2(COO)2 units. The influence of the coordination orientations of the aromatic dicarboxylate groups on the crystal structures is discussed.
Time rationalities
Authors: Chakhovich Terhi
Published: March 2019

Purpose

The temporality of performance measurement systems has been claimed to affect actors’ time orientation, such as that of listed company managers. The purpose of this paper is to explore this view.

Design/methodology/approach

The study uses constructivist data gathered from executives in one listed and one non-listed company.

Findings

The study shows that the research on performance measurement is based on a linear-quantitative view on time that assumes that humans orient towards the future from one point, the present; this view excludes other time-related constructs, particularly the past, and highlights a choice between the short term and the long term, idealising the long term. It is shown that the performance measurement of non-listed company executives is constructed through past-based, present-based and future-based rationalities: executives acknowledge the past as a basis for present and future performance, present actions as shaping future performance and future plans and performance targets as bases for present actions. Listed company executives’ performance measurement is constructed predominantly through the present-based time rationality.

Research limitations/implications

“The orientation from the present” and the “short” and “long terms” could be enhanced with time rationalities.

Practical implications

The evaluation periods within performance measurement systems do not determine the time orientations of the actors subjected to those systems; time rationalities could be considered when designing such systems.

Originality/value

The paper provides a novel view on performance measurement and time.