bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling the actuator line method to the high order meteorological LES model Meso-NH to study wind farm wakes impacts on local meteorology
Authors: Joulin PA , Mayol ML , Blondel F , Masson V , Rodier Q , Lac C
Published: July 2019

Offshore wind energy is now reaching the technological maturity, its capacity is increasing all over the world and this trend is projected to continue for several more years. Given this expectation, a better understanding of the relationship between the presence of wind farms and the atmospheric boundary layer is needed. Turbulent wakes produced by wind turbines can significantly impact the flow dynamics within wind farms and downstream of them. Operating offshore parks have already shown losses on energy production and effects on the local climate. In order to analyse the interactions occurring during these impacts, a new tool has been developed. This numerical tool is a coupling between the Actuator Line Method (ALM) and the open-source, non-hydrostatic mesoscale atmospheric model Meso-NH, based on the Large Eddy Simulation (LES) framework. The coupled Meso-NH + ALM system is first validated by using the experimental data obtained during the New MEXICO experiments. In particular, simulated and experimental loadings along the blades are compared. Then, a simulation of an idealized Horns Rev wind farm is performed using met mast measurements and reanalysis data for the “Horns Rev 1 photo case” as initial conditions. This new coupled system allows the exploration of the impact of wind farms on the lower levels of the atmosphere.
Global Blockage Effects in Wind Farms
Authors: Segalini A , Dahlberg J-Å
Published: July 2019

An experimental and numerical study of wind-farm blockage has been performed to quantify the velocity reduction that the first row of a wind farm experiences due to other turbines downstream. In the present study, an attempt is made to demonstrate the existence of a two-way coupling between individual turbines and wind farm. Several staggered layouts were tested in the wind-tunnel experiments by changing the spacing between rows, spacing between the turbines in the same row and the amount of wind turbines involved. Three turbines located in the first row were monitored to assess their sensitivity to the turbines downstream. One of the experiments was replicated by means of numerical simulations performed in ORFEUS, a linearised code developed at KTH, in order to complement the experimental results. Simulations were performed at the same thrust coefficient and with a more distant ceiling to assess the eventual interference of the ceiling on the experimental results. Additionally, simulations performed at different thrust coefficients were done to assess its effect on the blockage phenomenon.
Benchmarks for Model Validation based on LiDAR Wake Measurements
Authors: Doubrawa P , Debnath M , Moriarty P J , Branlard E , Herges T G , Maniaci D C , Naughton B
Published: July 2019

Technology development and design decisions in wind energy are often based on results from simulations performed for individual wind turbines or entire wind plants. It is therefore critical to ensure that the models being used for research and industry applications in wind energy be thoroughly validated against measurements. A full-system validation of wind plant simulations must consider the atmospheric inflow, the response of the wind turbines, and their wakes. This task is complicated by the lack of freely available, quality-controlled, high-quality measurements. Here, such measurements are used to offer a validation exercise that can be used to assess the accuracy of models of any fidelity level. When it comes to real-world measurements, the dataset considered herein is simple in terms of terrain but exhibits pronounced diurnal cycles. Instead of a full-scale wind plant, we consider an individual research-scale, utility wind turbine instrumented for power and loads measurements. Three benchmarks are defined, with increasing levels of complexity: near neutral, slightly unstable, and very stable atmospheric stratification. Through comparisons between observations and simulations, the benchmarks provide complementary information about the model performance and its ability to reproduce mean and dynamic wake characteristics. This article describes the measurements and methodology used to define these benchmarks and provides the information required to perform simulations and conduct the model-measurement comparison. The objective is to provide a robust wake model validation exercise open to anyone, which will serve to minimize uncertainty in model validation practices related to varying methodologies across simulation tools and users.
Wind Farm Wakes Simulated Using WRF
Authors: Pryor S C , Shepherd T J , Barthelmie R J , Hahmann A N , Volker P
Published: July 2019

Optimization of wind turbine (WT) arrays to maximize system-wide power production (i.e. minimize ‘wind-theft’) requires high-fidelity simulations of array-array interactions at the regional scale. This study systematically compares two parameterizations (Fitch and EWP) developed to describe wind farm impacts on atmospheric flow in the Weather Research and Forecasting (WRF) model. We present new year-long simulations for a nested domain centred on Iowa (the state with highest WT density) in the US Midwest that employ real WT characteristics and locations. Simulations with Fitch and EWP indicate similar seasonality in system-wide gross capacity factors (CF) for WT operating in Iowa, but the gross CF are systematically higher in simulations using EWP. The mean gross CF from the Fitch scheme is 44.1%, while that from EWP is 46.4%. These differences in CF are due to marked differences in the intensity and vertical profile of wakes simulated by the two approaches. Output from EWP also indicates much smaller near-surface climate impacts from WT. For example, when summertime hourly near-surface temperature (T2m) from the 299 WT grid cells are compared (i.e. EWP or Fitch minus noWT) the results show warming of nocturnal temperatures (lowest decile of T2m) but the maximum warming is considerably larger in simulations with the Fitch scheme.
Why curved wind turbine rows are better than straight ones
Authors: Krabben I G W , van der Laan M P , Koivisto M. , Larsen T J , Pedersen M M , Hansen K S
Published: July 2019

Wind turbine wake effects in wind farms not only reduce the wind farm power production but also influence the wind farm power dependency on wind direction. In this paper, the wake effects in wind farm layouts consisting of curved and straight wind turbine rows are studied using engineering wake models and a Reynolds-averaged Navier-Stokes model. These models predict a similar annual energy production for both wind farm layouts, but show stronger wake losses in the aligned wind directions for a rectangular wind farm layout, while the wake losses for a curved wind farm layout are more spread out over a larger wind direction sector. An energy system level simulation predicts that the enhanced spreading of wake losses over wind directions results in less hourly variability in energy generation on a Danish energy system level. Thus, our results show that a curved wind farm layout is more favorable compared to a wind farm layout with straight rows.
Investigation of oxygen vacancy migration energy in yttrium doped cerium
Authors: Lam Le Thu , Hung Vu Van
Published: July 2019

Using the statistical moment method, the analytic expression of vacancy migration energy in yttria doped cerium (YDC) is derived within the fourth order moment approximation. This expression depends strongly on the interaction potentials between the diffusing oxygen ion and the surrounding cations. Our results show the predominant direction of oxygen vacancy migration and the influence of cation barriers on oxygen vacancy diffusion. The dependences of the migration energy on temperature and dopant concentration are evaluated in detail. Calculated results are compared with other theoretical results.
Zero bias anomaly in the two-site Anderson-Hubbard model with Gaussian distribution for disorder
Authors: Nguyen Oanh K. T. , Tran Nam Van , Bach Giang Huong
Published: July 2019

The Anderson-Hubbard model considers the correlation between disorder and other interactions in a strongly correlated electron system. Both disorder and correlations drive the metal-insulator transition but the densities of states behave in different ways. The zero bias anomaly (ZBA) referring to the V-dip shape of the density of states at the Fermi energy occurs in the strong disorder and strong interaction regime instead of a hard Coulomb gap in an insulator phase of strongly correlated interacting systems. In this paper, we use a Gaussian distribution for disorder to examine a two-site Anderson-Hubbard model. We also explain comprehensively the relationship between the phase diagram of ground states with various numbers of electrons and the behavior of the density of states. Furthermore, we want to investigate the effect of disorder distribution on the formation of the ZBA which originates from a hopping mechanism in two specific configurations.
Theoretical predictions of two-dimensional covalent organic frameworks (COF) with hexagonal topologies
Authors: Duong Le Nam , Tuoc Vu Ngoc , Thao Nguyen Thi
Published: July 2019

Recently, covalent organic frameworks (COFs) - a new class of highly ordered organic crystalline porous polymers, have attracted huge research interest because of their unique structures and potential applications in gas separation/storage, catalysis, energy strorage and optoelectronic materials development. We have studied several structure’s series of hexagonal shapes to explore the applicability of the formation of two-dimensional (2D) COFs from various pre-defined individual building blocks using Density Functional based tight-binding (DFTB) method. Different high-symmetry stackings, e.g. AA and AB stacking sequence are also designed and investigated. The designed series’s band gaps are found to be ranging from 1.7 to 4.0 eV. Further, the COF series, revealing a variety of promising mechanical and electronic properties, which can potentially find future realistic applications.
Cluster-root bearing Proteaceae species show a competitive advantage over non-cluster root species
Authors: Fajardo Alex , Piper Frida I
Published: July 2019

Background and aims

Cluster roots (CRs) constitute a special root adaptation that enables plants to take up nutrients, especially phosphorus (P), from soils with low nutrient availability, including recent volcanic deposits. It is unclear, however, how CR species interact with non-cluster root (NCR) species, and how substrates’ fertility modulates potential interactions.

Methods

We experimentally assessed the net interaction between CR and NCR species using two substrates of contrasting fertility: nutrient-rich nursery mix and tephra (low P availability). We planted seedlings of two southern South America (SSA) Proteaceae species and two NCR Nothofagus species in pairs (conspecifics and heterospecifics) and as singles. We analysed the effect of seedling neighbours on survival, growth performance (e.g. total biomass and leaf area), and leaf and substrate nutrient concentrations (including manganese [Mn], a proxy for P-acquisition efficiency through CR activity) using the relative interaction index (RII).

Key Results

After three growing seasons, we found that 1) Proteaceae species had fewer CRs, lower CR biomass, and grew less in the tephra than in the nursery substrate; 2) Nothofagus species did not improve their survival and growth in the presence of Proteaceae species in any substrate; 3) contrary to Nothofagus, Proteaceae species improved their growth more when planted with any neighbour (including conspecifics) than when planted alone, which was accompanied by a significant accretion of leaf P; and 4) the presence of a neighbour increased the final N and P concentrations in the nursery substrate, regardless of species identity.

Conclusions

CRs provide Proteaceae a competitive advantage over NCR species at the seedling stage, which may have important consequences for species coexistence and community structuring. The investigated SSA Proteaceae, which have not evolved in nutrient-impoverished soils as their relatives in southwestern Australia and South Africa, improve their growth when cultivated in pairs, especially in nutrient-rich substrates.
Fast glacier melting threatens water supply
Authors: Kumar Adarsh
Published: July 2019

Adarsh Kumar reports on a study of glacier melting and what it means for water in the Indian Himalayan region.
Beyond Jodrell Bank: astronomical heritage
Authors: Ruggles Clive
Published: July 2019

In July, UNESCO added two very different astronomical places to its World Heritage List. Clive Ruggles explains the background to this decision and what it means for our astronomical heritage.
Lame Ducks and Local Fiscal Policy: Quasi-Experimental Evidence from Portugal
Authors: da Fonseca Mariana Lopes
Published: July 2019

I use the introduction of mayoral term limits in Portugal to identify how an exogenous variation in eligibility for office affects policy decisions. Relying on a quasi-experimental difference-in-differences approach, I find that term-limited incumbents pursue more conservative fiscal policies than those who are eligible for re-election. Heterogeneous effects show that the treatment effects primarily reflect the behaviour of right-leaning, term-limited incumbents. Results are in line with a model in which right-leaning officeholders try to maintain a good reputation by pleasing an electorate prone to redistribution while they are eligible, but adopt policies closer to their true preferences when term-limited.
Inflammatory bowel disease- and Barrett’s esophagus-associated neoplasia: the old, the new, and the persistent struggles
Authors: Karamchandani Dipti M , Zhang Qin , Liao Xiao-Yan , Xu Jing-Hong , Liu Xiu-Li
Published: July 2019

Early diagnosis of and adequate therapy for premalignant lesions in patients with inflammatory bowel disease (IBD) and Barrett's esophagus (BE) has been shown to decrease mortality. Endoscopic examination with histologic evaluation of random and targeted biopsies remains the gold standard for early detection and adequate treatment of neoplasia in both these diseases. Although eventual patient management (including surveillance and treatment) depends upon a precise histologic assessment of the initial biopsy, accurately diagnosing and grading IBD- and BE-associated dysplasia is still considered challenging by many general as well as subspecialized pathologists. Additionally, there are continuing updates in the literature regarding the diagnosis, surveillance, and treatment of these disease entities. This comprehensive review discusses the cancer risk, detailed histopathological features, diagnostic challenges, and updates as well as the latest surveillance and treatment recommendations in IBD- and BE-associated dysplasia.
An Introduction to Pathology in Biomedical Research: A Mission-Critical Specialty for Reproducibility and Rigor in Translational Research
Authors: Brayton Cory F , Boyd Kelli L , Everitt Jeffrey L , Meyerholz David K , Treuting Piper M , Bolon Brad
Published: July 2019

This issue of ILAR Journal focusses on pathology and pathologists in biomedical research, more specifically in preclinical translational research involving (nonhuman) animals, emphasizing academic settings. Considerations in study design and planning to maximize benefit from pathologists and pathology resources are reviewed. Adjunctive technologies including molecular techniques, digital pathology, and imaging are highlighted. Additional considerations regarding safety and regulatory concerns, and veterinary clinical trials are reviewed as well. Pathology has been fundamental to understanding clinical disease, remains fundamental to diagnosing disease, and is required in drug and device development. Broader integration of pathology expertise and well-designed pathology investigations have much to offer research rigor and reproducibility, and successful translation from biomedical research.
What Is the Evidence to Support a Correlate of Protection for Measles? A Systematic Review
Authors: Bolotin Shelly , Hughes Stephanie L , Gul Nazish , Khan Sumaiya , Rota Paul A , Severini Alberto , Hahné Susan , Tricco Andrea , Moss William J , Orenstein Walter , Turner Nikki , Durrheim David , Heffernan Jane M , Crowcroft Natasha
Published: July 2019

Background

Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection.

Methods

We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria.

Results

We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold.

Conclusions

Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.
Intrahousehold Bargaining, Female Autonomy, and Labor Supply: Theory and Evidence from India
Authors: Heath Rachel , Tan Xu
Published: July 2019

Standard models of labor supply predict that unearned income decreases labor supply. We propose an alternative noncooperative household model in which a woman’s unearned income improves her autonomy within the household, which raises her gains from working and can increase her labor supply. We find empirical support for this model, using women’s exposure to the Hindu Succession Act in India as a source of exogenous variation in their unearned income. Exposure to the Hindu Succession Act increases a woman’s labor supply by between 3.8 and 6.1 percentage points, particularly into high-paying jobs. Autonomy increased by 0.17 standard deviations, suggesting that control of income is a potential channel for these effects. Thus, policies that empower women can have an additional impact on the labor market, which can further reinforce autonomy increases.
Sleep in Huntington’s disease: a systematic review and meta-analysis of polysomongraphic findings
Authors: Zhang Ye , Ren Rong , Yang Linghui , Zhou Junying , Li Yun , Shi Jie , Lu Lin , Sanford Larry D , Tang Xiangdong
Published: July 2019

Study Objectives

Disturbed overnight sleep is a prominent feature of advanced stage Huntington’s disease (HD). Several polysomnography (PSG) studies have reported significant changes of sleep in HD patients, but the findings are not unequivocal. To date, no meta-analysis has investigated the PSG changes in HD patients. The present study meta-analyzed results from studies examining the PSG changes in HD patients compared with controls.

Methods

A literature search performed in MEDLINE, EMBASE, All EBM databases, PsycINFO, and CINAHL databases identified seven studies involving 152 HD patients and 144 controls which were included in our meta-analysis.

Results

Pooled results indicated decreased sleep efficiency, percentage of slow wave sleep and rapid eye movement sleep, and increased percentage of N1 sleep, wake time after sleep onset, and rapid eye movement sleep latency in HD patients compared with controls. We found high heterogeneity in the effect sizes and no indication of systematic publication biases across studies. Meta-regression analyses showed that some of the heterogeneity was explained by age, body mass index (BMI), CAG repeat length, and disease severity of HD patients.

Conclusions

Our study showed that polysomnographic abnormalities are present in HD. Our findings also underscore the need for a comprehensive PSG assessment of sleep changes in patients with HD. Furthermore, the effects of age, BMI and CAG repeat length on sleep changes should be carefully considered and closely monitored in the management of HD.
Beyond sleepy: structural and functional changes of the default-mode network in idiopathic hypersomnia
Authors: Pomares Florence B , Boucetta Soufiane , Lachapelle Francis , Steffener Jason , Montplaisir Jacques , Cha Jungho , Kim Hosung , Dang-Vu Thien Thanh
Published: July 2019

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness but, in contrast to narcolepsy, does not involve cataplexy, sleep-onset REM periods, or any consistent hypocretin-1 deficiency. The pathophysiological mechanisms of IH remain unclear. Because of the involvement of the default-mode network (DMN) in alertness and sleep, our aim was to investigate the structural and functional modifications of the DMN in IH. We conducted multimodal magnetic resonance imaging (MRI) in 12 participants with IH and 15 good sleeper controls (mean age ± SD: 32 ± 9.6 years, range 22–53 years, nine males). Self-reported as well as objective measures of daytime sleepiness were collected. Gray matter volume and cortical thickness were analyzed to investigate brain structural differences between good sleepers and IH. Structural covariance and resting-state functional connectivity were analyzed to investigate changes in the DMN. Participants with IH had greater volume and cortical thickness in the precuneus, a posterior hub of the DMN. Cortical thickness in the left medial prefrontal cortex was positively correlated with thickness of the precuneus, and the strength of this correlation was greater in IH. In contrast, functional connectivity at rest was lower within the anterior DMN (medial prefrontal cortex) in IH, and correlated with self-reported daytime sleepiness. The present results show that IH is associated with structural and functional differences in the DMN, in proportion to the severity of daytime sleepiness, suggesting that a disruption of the DMN contributes to the clinical features of IH. Larger volume and thickness in this network might reflect compensatory changes to lower functional connectivity in IH.
Bidirectional associations between insomnia, posttraumatic stress disorder, and depressive symptoms among adolescent earthquake survivors: a longitudinal multiwave cohort study
Authors: Geng Fulei , Liang Yingxin , Li Yuanyuan , Fang Yi , Pham Tien Sy , Liu Xianchen , Fan Fang
Published: July 2019

Study Objectives

To assess insomnia symptoms in adolescents with probable posttraumatic stress disorder (PTSD) and to determine whether there are longitudinal and reciprocal associations between insomnia, PTSD, and depressive symptoms.

Methods

Participants were 1,492 adolescent survivors who had been exposed to the 2008 Wenchuan earthquake in China. Insomnia, PTSD, and depressive symptoms were measured at 12 months (T1, n = 1407), 18 months (T2, n = 1335), and 24 months (T3, n = 1361) postearthquake by self-report questionnaires. Generalized estimating equation (GEE) models were used to examine the cross-sectional and longitudinal associations of insomnia with PTSD and depression.

Results

Insomnia, PTSD, and depressive symptoms were common among adolescent survivors. Among participants with probable PTSD, approximately 47% (48.5%, T1; 48.1%, T2; and 44.2%, T3) reported difficulty falling asleep or difficulty maintaining sleep. Cross-sectional analyses showed that insomnia co-occurred with PTSD (odds ratio [OR] = 2.04) and depressive symptoms (OR = 2.10). Longitudinal analyses revealed that probable PTSD (OR = 1.50) and depression (OR = 1.42) predicted the incidence of insomnia; in turn, insomnia predicted the incidence of depression (OR = 1.65) over time. Furthermore, PTSD predicted (OR = 3.11) and was predicted (OR = 3.25) by depressive symptoms.

Conclusions

There is a bidirectional relationship between insomnia, PTSD, and depressive symptoms. This suggests that insomnia, PTSD, and depression are intertwined over time.
Development and evaluation of the SPeeding Research-tested INTerventions (SPRINT) training program
Authors: Gaysynsky Anna , Vinson Cynthia A , Oh April
Published: July 2019

The National Cancer Institute established a dissemination and implementation accelerator program called SPeeding Research-tested INTerventions (SPRINT) to improve the uptake of evidence-based interventions. The purpose of this study was to describe the origin, structure, and goals of the SPRINT program, and present evaluation results from the first two cohorts of the program. Qualitative (focus group) and quantitative (survey) data collected from participants were used to evaluate the course and inform program improvement efforts. The majority of the participants (over 90% in both cohorts) rated the course highly, and over 80% would recommend the course to other researchers. Most participants indicated knowing relatively little about business model concepts before SPRINT, but after SPRINT, nearly all respondents felt that they had at least “some” knowledge of each business model component. Participants also indicated that they learned about the product–market fit of their intervention and gained insights from customer discovery interviews that would enable them to make their intervention more “stakeholder focused”. Participants also indicated that they plan to use the knowledge and skills they gained during the SPRINT program in their future work. Feedback from participants was used by the management team to implement various program improvements to better serve the next cohort of participants. While behavioral researchers face significant barriers to commercializing their interventions, they recognize the importance of translating their research into practice. Training researchers to consider scale-up, implementation, and commercialization from the outset can help reduce the number of proven interventions that are never used in practice.
Acting together, destabilizing influences can stabilize human balance
Authors: Milton John , Insperger Tamas
Published: July 2019

The causes of falling in the elderly are multi-factorial. Three factors that influence balance stability are the time delay, a sensory dead zone and the maximum ankle torque that can be generated by muscular contraction. Here, the effects of these contributions are evaluated in the context of a model of an inverted pendulum stabilized by time-delayed proportional–derivative (PD) feedback. The effect of the sensory dead zone is to produce a hybrid type of control in which the PD feedback is switched ON or OFF depending on whether or not the controlled variable is larger or smaller than the detection threshold,Π. It is shown that, asΠincreases, the region in the plane of control parameters where the balance time (BT) is greater than 60 s is increased slightly. However, when maximum ankle torque is also limited, there is a dramatic increase in the parameter region associated with BTs greater than 60 s. This increase is due to the effects of a torque limitation on over-control associated with bang-bang type switching controllers. These observations show that acting together influences, which are typically thought to destabilize balance, can actually stabilize balance.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Complex partial synchronization patterns in networks of delay-coupled neurons
Authors: Nikitin D. , Omelchenko I. , Zakharova A. , Avetyan M. , Fradkov A. L. , Schöll E.
Published: July 2019

We study the spatio-temporal dynamics of a multiplex network of delay-coupled FitzHugh–Nagumo oscillators with non-local and fractal connectivities. Apart from chimera states, a new regime of coexistence of slow and fast oscillations is found. An analytical explanation for the emergence of such coexisting partial synchronization patterns is given. Furthermore, we propose a control scheme for the number of fast and slow neurons in each layer.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Geometric analysis of synchronization in neuronal networks with global inhibition and coupling delays
Authors: Ryu Hwayeon , Campbell Sue Ann
Published: July 2019

We study synaptically coupled neuronal networks to identify the role of coupling delays in network synchronized behaviour. We consider a network of excitable, relaxation oscillator neurons where two distinct populations, one excitatory and one inhibitory, are coupled with time-delayed synapses. The excitatory population is uncoupled, while the inhibitory population is tightly coupled without time delay. A geometric singular perturbation analysis yields existence and stability conditions for periodic solutions where the excitatory cells are synchronized and different phase relationships between the excitatory and inhibitory populations can occur, along with formulae for the periods of such solutions. In particular, we show that if there are no delays in the coupling, oscillations where the excitatory population is synchronized cannot occur. Numerical simulations are conducted to supplement and validate the analytical results. The analysis helps to explain how coupling delays in either excitatory or inhibitory synapses contribute to producing synchronized rhythms.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Fast consensus in a large-scale multi-agent system with directed graphs using time-delayed measurements
Authors: Ramírez Adrián , Sipahi Rifat , Mondié Sabine , Garrido Rubén
Published: July 2019

This article is on fast-consensus reaching in a class of multi-agent systems (MAS). We present an analytical approach to tune controllers for the agents based on the premise that delayed measurements in the controller can be preferable to standard controllers relying only on current measurements. Controller tuning in this setting is however challenging due to the presence of delays. To tackle this problem, we propose an analytic geometry approach. The key contribution is that the tuning can be implemented for complex eigenvalues of the arising graph Laplacian of the network, complementing the current state of the art, which is limited to real eigenvalues. Results, therefore, extend our knowledge beyond symmetric graphs and enable the study of the MAS under directed graphs.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Nonlinear dynamics of delay systems: an overview
Authors: Otto A. , Just W. , Radons G.
Published: July 2019

Time delays play an important role in many fields such as engineering, physics or biology. Delays occur due to finite velocities of signal propagation or processing delays leading to memory effects and, in general, infinite-dimensional systems. Time delay systems can be described by delay differential equations and often include non-negligible nonlinear effects. This overview article introduces the theme issue ‘Nonlinear dynamics of delay systems’, which contains new fundamental results in this interdisciplinary field as well as recent developments in applications. Fundamentally, new results were obtained especially for systems with time-varying delay and state-dependent delay and for delay system with noise, which do often appear in real systems in engineering and nature. The applications range from climate modelling over network dynamics and laser systems with feedback to human balancing and machine tool chatter.

This article is part of the theme issue ‘Nonlinear dynamics of delay systems’.
Brefeldin A and Cytochalasin B reduce dengue virus replication in cell cultures but do not protect mice against viral challenge
Authors: Farias Kleber Juvenal Silva , Machado Paula Renata Lima , de Almeida Júnior Renato Ferreira , Lopes da Fonseca Benedito Antônio
Published: July 2019

Background. Dengue is an emerging arboviral disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae and genus Flavivirus. No specific anti-DENV drugs are currently available.

Methods. We investigated the antiviral activity of Brefeldin A (BFA) and Cytochalasin B (CB) against this infection. The drugs BFA and CB were used in the in vitro treatment of dengue-2 virus (DENV-2) infections in Vero cell cultures and in protection from lethality by post-challenge administration in Swiss mice. Viral load was quantified by qRT-PCR and plaque assay in Vero cell cultures, post-infection, treated or not with the drugs. Post-challenge drug levels were evaluated by survival analysis.

Results. Our results indicate that doses of 5 µg ml−1 of BFA and 10 µg ml−1 of CB are not toxic to the cells and induce a statistically significant inhibition of DENV-2 replication in Vero cells when compared to control. No BFA- or CB-treated mice survived the challenge with DENV-2.

Conclusion. These data suggest that BFA and CB have an antiviral action against DENV-2 replication in Vero cell culture, but do not alter infected mice mortality.
Genomics of vancomycin-resistant Enterococcus faecium
Authors: Gorrie Claire , Higgs Charlie , Carter Glen , Stinear Timothy P. , Howden Benjamin
Published: July 2019

Vancomycin-resistant

Enterococcus faecium

(VREfm) is a globally significant public health threat and was listed on the World Health Organization’s 2017 list of high-priority pathogens for which new treatments are urgently needed. Treatment options for invasive VREfm infections are very limited, and outcomes are often poor. Whole-genome sequencing is providing important new insights into VREfm evolution, drug resistance and hospital adaptation, and is increasingly being used to track VREfm transmission within hospitals to detect outbreaks and inform infection control practices. This mini-review provides an overview of recent data on the use of genomics to understand and respond to the global problem of VREfm.
Homologous recombination-based genome editing by clade F AAVs is inefficient in the absence of a targeted DNA break
Authors: Rogers Geoffrey L. , Chen Hsu-Yu , Morales Heidy , Cannon Paula M.
Published: July 2019

Adeno-associated virus (AAV) vectors are frequently used as donor templates for genome editing by homologous recombination. Although modification rates are typically under 1%, they are greatly enhanced by targeted double-stranded DNA breaks (DSBs). A recent report described clade F AAVs mediating high-efficiency homologous recombination-based editing in the absence of DSBs. The clade F vectors included AAV9 and a series isolated from human hematopoietic stem/progenitor cells (HSPCs). We evaluated these vectors by packaging homology donors into AAV9 and an AAVHSC capsid and examining their ability to insert GFP at the CCR5 or AAVS1 loci in human HSPCs and cell lines. As a control we used AAV6, which effectively edits HSPCs, but only when combined with a targeted DSB. Each AAV vector promoted GFP insertion in the presence of matched CCR5 or AAVS1 zinc finger nucleases (ZFNs), but none supported detectable editing in the absence of the nucleases. Rates of editing with ZFNs correlated with transduction efficiencies for each vector, implying no differences in the ability of donor sequences delivered by the different vectors to direct genome editing. Our results therefore do not support that clade F AAVs can perform high efficiency genome editing in the absence of a DSB.
Reduced sleep pressure in young children with autism
Authors: Arazi Ayelet , Meiri Gal , Danan Dor , Michaelovski Analya , Flusser Hagit , Menashe Idan , Tarasiuk Ariel , Dinstein Ilan
Published: July 2019

Study Objectives

Sleep disturbances and insomnia are highly prevalent in children with Autism Spectrum Disorder (ASD). Sleep homeostasis, a fundamental mechanism of sleep regulation that generates pressure to sleep as a function of wakefulness, has not been studied in children with ASD so far, and its potential contribution to their sleep disturbances remains unknown. Here, we examined whether slow wave activity (SWA), a measure that is indicative of sleep pressure, differs in children with ASD.

Methods

In this case-control study, we compared overnight electroencephalogram (EEG) recordings that were performed during Polysomnography (PSG) evaluations of 29 children with ASD and 23 typically developing children.

Results

Children with ASD exhibited significantly weaker SWA power, shallower SWA slopes, and a decreased proportion of slow wave sleep in comparison to controls. This difference was largest during the first two hours following sleep onset and decreased gradually thereafter. Furthermore, SWA power of children with ASD was significantly, negatively correlated with the time of their sleep onset in the lab and at home, as reported by parents.

Conclusions

These results suggest that children with ASD may have a dysregulation of sleep homeostasis that is manifested in reduced sleep pressure. The extent of this dysregulation in individual children was apparent in the amplitude of their SWA power, which was indicative of the severity of their individual sleep disturbances. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances in children with ASD.

Statement of significance

Sleep disturbances are apparent in 40-80% of children with autism. Homeostatic sleep regulation, a mechanism that increases the pressure to sleep as a function of prior wakefulness, has not been studied in children with autism. Here, we compared Polysomnography exams of 29 children with autism and 23 matched controls. We found that children with autism exhibited reduced slow-wave-activity power and shallower slopes, particularly during the first two hours of sleep. This suggests that they develop less pressure to sleep. Furthermore, the reduction in slow-wave-activity was associated with the severity of sleep disturbances as observed in the laboratory and as reported by parents. We, therefore, suggest that disrupted homeostatic sleep regulation may contribute to sleep disturbances of children with autism.
The genomics of mimicry: gene expression throughout development provides insights into convergent and divergent phenotypes in a Müllerian mimicry system
Authors: Stuckert Adam M M , Chouteau Mathieu , McClure Melanie , LaPolice Troy M , Linderoth Tyler , Nielsen Rasmus , Summers Kyle , MacManes Matthew D
Published: July 2019

A common goal in evolutionary biology is to discern the mechanisms that produce the astounding diversity of morphologies seen across the tree of life. Aposematic species, those with a conspicuous phenotype coupled with some form of defense, are excellent models to understand the link between vivid color pattern variations, the natural selection shaping it, and the underlying genetic mechanisms underpinning this variation. Mimicry systems in which multiple species share the same conspicuous phenotype can provide an even better model for understanding the mechanisms of color production in aposematic species, especially if comimics have divergent evolutionary histories. Here we investigate the genetic mechanisms by which vivid color and pattern are produced in a Müllerian mimicry complex of poison frogs. We did this by first assembling a high-quality de novo genome assembly for the mimic poison frogRanitomeya imitator. This assembled genome is 6.8 Gbp in size, with a contig N50 of 300 Kbp and 93% of expected tetrapod genes. We then leveraged this genome to conduct gene expression analyses throughout development of four color morphs ofR. imitatorand two color morphs from bothR. fantasticaandR. variabiliswhichR. imitatormimics. We identified a large number of pigmentation and patterning genes that are differentially expressed throughout development, many of them related to melanocyte development, melanin synthesis, iridophore development, and guanine synthesis. In addition, we identify the pteridine synthesis pathway (including genes such asqdprandxdh) as a key driver of the variation in color between morphs of these species. Finally, we hypothesize that genes in the keratin family are important for producing different structural colors within these frogs.
How many different clonotypes do immune repertoires contain?
Authors: Mora Thierry , Walczak Aleksandra M.
Published: July 2019

Immune repertoires rely on diversity of T-cell and B-cell receptors to protect us against foreign threats. The ability to recognize a wide variety of pathogens is linked to the number of different clonotypes expressed by an individual. Out of the estimated ∼ 1012different B and T cells in humans, how many of them express distinct receptors? We review current and past estimates for these numbers. We point out a fundamental limitation of current methods, which ignore the tail of small clones in the distribution of clone sizes. We show that this tail strongly affects the total number of clones, but it is impractical to access experimentally. We propose that combining statistical models with mechanistic models of lymphocyte clonal dynamics offers possible new strategies for estimating the number of clones.
A Minimally Invasive Technique for Serial Intraosseous Perfusion Measurements in the Murine Tibia Using Laser Doppler Flowmetry
Authors: Hanne Nicholas J , Easter Elizabeth D , Stangeland-Molo Sandra , Cole Jacqueline H
Published: July 2019

In biomedical and preclinical research, the current standard method for measuring blood perfusion inside murine bone, radiolabeled microspheres, is a terminal procedure that cannot be used to monitor longitudinal perfusion changes. Laser Doppler flowmetry (LDF) can quantify perfusion within the proximal tibial metaphysis of mice in vivo but requires a surgical procedure to place the measurement probe directly onto the bone surface. Sustained inflammation for over a month following this technique was previously reported, and previous studies have used LDF as an endpoint-only procedure. We developed a modified, minimally invasive LDF procedure to measure intraosseous perfusion in the murine tibia without stimulating local or systemic inflammation or inducing gait abnormalities. This modified technique can be used to measure perfusion weekly for up to at least a month.

Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibia

The modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery
Quantitative three-dimensional nondestructive imaging of whole anaerobic ammonium-oxidizing bacteria
Authors: Peng M-W. , Guan Y. , Liu J-H. , Chen L. , Wang H. , Xie Z-Z. , Li H-Y. , Chen Y-P. , Liu P. , Yan P. , Guo J-S. , Liu G. , Shen Y. , Fang F.
Published: July 2019

Anaerobic ammonium-oxidizing (anammox) bacteria play a key role in the global nitrogen cycle and the treatment of nitrogenous wastewater. These functions are closely related to the unique biophysical structure of anammox bacteria. However, the research on the biophysical ultrastructure of intact anammox bacteria is lacking. In this study,in-situthree-dimensional nondestructive ultrastructure imaging of whole anammox cell was performed using synchrotron soft X-ray nano-computed tomography and the total variation-based simultaneous algebraic reconstruction technique (TV-SART). Statistical and quantitative analyses of the ultrastructures of intact anammox bacteria were performed. The linear absorption coefficient values of the ultrastructures of anammox bacteria were calculated and the asymmetric structure of the anammox bacteria was quantified. On this basis, the shape adaptation of the anammox bacteria responses to Fe2+were explored, and the underlying regulation mechanism of Fe2+on anammox bacteria was explored. Furthermore, a promising method to study the biophysical properties of cells in different environments and engineering processes was proposed.

Graphical Abstract

Statement of Significance

Anaerobic ammonium-oxidizing (anammox) bacteria play key role in global nitrogen cycle, and this physiological function depends on the unique morphology of anammox bacteria. In this study, synchrotron soft-X ray imaging technique coupled with simultaneous algebraic reconstruction technique with total variation (SART-TV) algorithm were performed to quantify the three-dimensional ultrastructure of the whole anammox bacteria for the first time. On this basis, the shape adaptation and mechanism of the anammox bacteria responses to Fe2+ were explored and a promising method for detecting the physiological properties of anammox bacteria was proposed.
Acidic fibroblast growth factor underlies microenvironmental regulation of MYC in pancreatic cancer
Authors: Bhattacharyya Sohinee , Oon Chet , Kothari Aayush , Horton Wesley , Link Jason , Sears Rosalie C. , Sherman Mara H.
Published: July 2019

Despite a critical role for MYC as an effector of oncogenic RAS, strategies to target MYC activity in RAS-driven cancers are lacking. Oncogenic KRAS is insufficient to drive tumorigenesis, while addition of modest overexpression of MYC drives robust tumor formation, suggesting that mechanisms beyond the RAS pathway play key roles in MYC regulation and RAS-driven tumorigenesis. Here we show that acidic fibroblast growth factor (FGF1) derived from cancer-associated fibroblasts (CAFs) cooperates with cancer cell-autonomous signals to increase MYC level, promoter occupancy, and activity. FGF1 is necessary and sufficient for paracrine regulation of MYC protein stability, signaling through AKT and GSK-3β. These signals cooperate with, but are distinct from, cell-autonomous signals from oncogenic KRAS which stabilize MYC. Human pancreatic cancer specimens reveal a strong correlation between stromal CAF content and MYC protein level in the neoplastic compartment, and identify CAFs as the specific source of FGF1 in the tumor microenvironment. Together, our findings demonstrate that MYC is coordinately regulated by cell-autonomous and microenvironmental signals, and establish CAF-derived FGF1 as a novel paracrine regulator of oncogenic transcription.

Statement of significance

Our work highlights an unanticipated role for the tumor microenvironment in the regulation of MYC protein stability in pancreatic cancer cells and identifies CAF-derived FGF1 as a novel, specific paracrine regulator of MYC.
Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics
Authors: Horns Felix , Dekker Cornelia L. , Quake Stephen R.
Published: July 2019

Antibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profiled the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling revealed a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicited an antibody clone which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.