bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing the additional error caused by the time‐difference method in transit‐time UFMs
Authors: Yazdanshenasshad Behroz , Safizadeh Mir Saeed
Published: May 2019

In transit‐time ultrasonic flow meters (UFMs), one of the most commonly used methods in the time domain is the cross‐correlation method which is a time‐consuming and high computational requirement approach. Hence, the time‐difference approaches are preferred to reduce the computational requirement and increase the response time. However, the time‐difference methods in comparison to conventional ones have been suffering from an additional bias error (ABE). In this study, using a numerical simulation method, the ABE is analysed and some effective factors such as pipe diameter, flow velocity and medium temperature are introduced. Then, an approach for removing or reducing the ABE is presented. Since the time‐difference method has been used for Mach numbers <0.1, it is shown that by using a second‐order approximation, this method can be used for Mach numbers of more than 0.1, and the ABE resulting from this method is reduced to nearly zero. An experiment has been carried out on a 6 in transit‐time UFM with an eight‐path x‐configuration to verify the validity of the second‐order approximation method. The test results confirm that the proposed method can be successfully used in UFMs with the flow velocity greater than Mach 0.1.
Generator‐based threshold for transient stability assessment
Authors: Isbeih Younes J. , El Moursi Mohamed Shawky , Xiao Weidong , El‐Saadany Ehab
Published: May 2019

Power systems are frequently subjected to variations of the operating conditions due to the occurrence of contingencies such as faults, load or generator tripping. These disturbances might enforce the system to enter the instability region and thus deteriorate its overall performance. This paper proposes a systematic approach for transient stability assessment using generator‐based threshold. An individual stability limit is designed for each generator instead of using only one pre‐defined threshold for all generators. The considered contingencies are characterized by a fault type, location, loading condition and critical clearing time to consider wide range of operating conditions. Two fault locations are only considered to reduce the search space for stability limits; the generator terminals and mid of transmission lines. The critical clearing time is used to find the maximum relative rotor angle (MRRA) of individual generators attained during the entire time domain simulation. The MRRA of each generator represents the maximum angle which can be reached without losing synchronism at a given contingency. Conservative stability limits are drawn around the minimum stable drift of each generator which is chosen from the set of MRRAs of all contingencies. The effectiveness of the proposed approach is tested using the modified New‐England, 39‐bus system.
Efficiency loss breakdown for synchronous rectification scheme for automotive applications
Authors: Sarafianos Dimitrios , Llano Danilo X. , McMahon Richard , Flack Timothy , Pickering Stephen
Published: May 2019

This article presents a synchronous rectification scheme using a six‐phase Lundell alternator and a bespoke MOSFET‐based active rectifier. The control of the alternator‐rectifier system is divided into the hysteresis DC‐link voltage control and the switching pattern algorithm. The first allows to keep the DC‐link voltage at the required 14V level, while the latter reproduces the same switching pattern as that of a passive rectifier. The system is tested at three different speeds and the results are compared against the body diodes of the MOSFETs in the active rectifier. The harmonic analysis of the generated waveforms indicates the capability of the control algorithm to generate the same switching pattern of a passive rectifier. Finally, the efficiency measurements illustrate a significant efficiency improvement using a synchronous rectification scheme and MOSFETs with low on‐resistance.
Jigsaw electrode design for electrowetting devices
Authors: Sohail Shiraz , Jaffery Zainul Abdin , Biswas Karabi
Published: May 2019

A new type of electrode design (jigsaw in shape) is presented for actuating inner electrodes in electrowetting‐on‐dielectric devices containing large two‐dimensional array of electrodes. Electrodes are diagonally connected with one external pin to the voltage supply. Each electrode‐pad is made by carving (or cutting) out two triangular sections from the sides and adding two triangular sections on the top and bottom of the traditional square electrode. This modification in electrode shape creates an imbalance of electromechanical force at the three‐phase contact line on applying the supply voltage to the actuating electrode. Droplet moves towards either horizontal or vertical directions depending on the direction of the dominant force. The scheme requires a single layer of metal thin film deposition for device fabrication and also reduces the number of external pin connections to the power supply.
TIG welding-brazing joints of aluminum-stainless steel with different thickness of base metals
Authors: He Huan , Gou Wenqin , Jing Yan , Lin Sanbao , Yang Chunli
Published: May 2019

The aluminum and stainless steel plates with different thickness (1.5, 3 and 4 mm) were joined by TIG welding-brazing process, respectively. The welding procedures, appearance, microstructures and mechanical behavior of the joints were investigated and analyzed. Results showed that reliable welding-brazing joints could be obtained with appropriate welding procedures. The thicker the base metal, the thicker the intermetallic compound (IMC) layer, and the lower the mechanical properties of the joints. There existed obvious microstructure and strength nonhomogeneity along the interface from the top to the bottom of the joint with 3 mm or thicker base metals. The fracture positions of the joints were different from each other. With 1.5 mm base metal, fracture occurred at the aluminum fusion side. While with 3 mm base material, fracture derived from the IMC layer at the root of the steel groove and subsequently occurred at the welded seam. Using 4 mm base metal, crack located mainly at the brazing interface. The differences of the mechanical behavior of the joints were mainly attributed to the change of IMC thickness.
Die Bedeutung des Glykämischen Index und der Glykämischen Last von Kohlenhydraten bei Acne vulgaris
Authors: Abeck F. , Kirsten N. , Zyriax B.-C.
Published: May 2019

Ziel der Studie Die Darstellung des aktuellen Forschungsstandes zum Zusammenhang zwischen Acne vulgaris und dem Glykämischen Index sowie der Glykämischen Last zielt darauf ab, den Stellenwert der Reduktion hyperglykämischer Kohlenhydrate in der Ernährung zur Prävention und Behandlung der Acne vulgaris zu untersuchen.

Methodik Es erfolgte eine selektive Literaturrecherche zu Acne vulgaris im Zusammenhang mit dem Glykämischen Index und der Glykämischen Last in der Datenbank PubMed.

Ergebnisse Es fanden sich Hinweise auf eine Assoziation zwischen dem Auftreten von Acne vulgaris und einer Ernährung mit hyperglykämischen Kohlenhydraten. Allerdings sind die Auswirkungen einer Ernährungsumstellung auf den klinischen Schweregrad der Acne vulgaris jedoch noch unzureichend geklärt.

Schlussfolgerung Um eine Ernährung mit Reduktion hyperglykämischer Kohlenhydrate als Präventions- oder Behandlungsmöglichkeit bei Acne vulgaris zu etablieren, bedarf es weiterer Untersuchungen. Das mögliche Potenzial einer Ernährungsumstellung bei Acne vulgaris sollte allerdings bereits zum jetzigen Zeitpunkt in der Praxis Beachtung finden.
Surgical and Medical Costs for Fibromyalgia Patients Undergoing Total Knee Arthroplasty
Authors: Moore Tara , Sodhi Nipun , Cohen-Levy Wayne B. , Ehiorobo Joseph , Kalsi Angad , Anis Hiba K. , Dushaj Kristina , Pappas Vivian , Vakharia Rushabh M. , Hepinstall Matthew S. , Roche Martin W. , Mont Michael A.
Published: May 2019

The potential added costs of managing fibromyalgia patients after total knee arthroplasty (TKA) have not been assessed. Therefore, the purpose of this study was to perform a cost analysis of fibromyalgia versus nonfibromyalgia patients who underwent TKA. Specifically, we evaluated the following episodes of care: (1) readmission rates, (2) total costs, (3) total reimbursements, and (4) net losses for surgical and medical complications. Patients who underwent TKAs between 2005 and 2014 from the Medicare Standard Analytical Files of the PearlDiver supercomputer were propensity score matched by patients with and without fibromyalgia in a 1:1 ratio based on age, sex, and the Charlson Comorbidity Index, yielding a total of 305,510 patients distributed equally between the cohorts for analysis. Odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated. Mean costs, total costs, and total reimbursements were assessed as along with total net losses, which were defined as total costs minus total reimbursements. Fibromyalgia patients had similar 90-day readmission rates compared with nonfibromyalgia patients (OR: 1.03; 95% CI: 1.00–1.06; p = 0.06) but incurred lower readmission costs (US$2,318,384,295 vs. US$2,534,482,404; p < 0.001). Although fibromyalgia patients had higher total reimbursements for medical complications ($27,758,057 vs. US$18,780,610; p < 0.001), the increased management costs (US$106,049,870 vs. US$66,080,469; p < 0.001) led to greater net losses (US$78,291,813 vs. US$47,299,859; p < 0.001). Similarly, although fibromyalgia patients had higher total reimbursements for surgical complications (US$94,192,334 vs. US$73,969,026; p < 0.001), the increased surgical costs (US$382,122,613 vs. US$306,359,910; p < 0.001) led to greater net losses (US$287,930,279 vs. US$232,390,884; p < 0.001). This study highlights some of the potential financial discrepancies of managing patients with fibromyalgia. Our findings suggest medical and surgical complication costs to be greater than reimbursement, resulting in overall net financial losses. These findings need to be considered in the light of health care reform and cost structuring.
Reflecting on childhood and child agency in history
Authors: Haring Ute , Sorin Reesa , Caltabiano Nerina J.
Published: May 2019

In today’s fast changing and unpredictable world we tend to rely upon children’s agency to ensure their survival following traumatic events. Because of this, parents and teachers need to be conversant with ways of encouraging children’s agency to support their health and efficacy throughout the lifespan. This paper takes the form of a literature review covering historical and recent developments in the field of childhood, child abuse and child agency. It offers the findings of a qualitative document study that aimed to explore how childhood and child agency have been conceptualized historically in the Western world. It begins with a summary of theories and typologies of childhood throughout history, exploring the unique social and historical concepts in which theories of childhood and child agency developed. Furthermore, a paradigm shift in Western society towards women achieving agency is revealed. With this came greater attention to the child, especially the abused child. Focusing on abuse to which children have been exposed, this study looks at child agency and how it can be actualized for children’s wellbeing. Research findings make a strong case for the arts to provide valuable tools of resilience for the developing child. Arts-based activities have been increasingly appreciated as providing a voice for traumatized or abused children. Therefore, the findings of this study into agency and child abuse were distilled into a poem to demonstrate the potential impact on a child and to help adults better understand the historically perceived voiceless victim. The poem, as seen from the perspective of the child, offers a distinctive contribution to the literature on child abuse. Key findings of this study are discussed, including the importance of increasing understanding of children’s agency. It is argued that a shift in childrearing, incorporated child protection laws and agentic experiences build children’s confidence to challenge the traditional adult-child power relationship. The results of this research help to contribute to teacher knowledge about the intricate background to child abuse and child agency.
Entrainment of aperiodic and periodic oscillations in the Mercury Beating Heart system using external periodic forcing
Authors: Kumar Pawan , Parmananda P. , Verma Dinesh Kumar , Singla Tanu , de Nicolás Iram , Escalona J. , Rivera M.
Published: May 2019

We report experimental results indicating entrainment of aperiodic and periodic oscillatory dynamics in the Mercury Beating Heart (MBH) system under the influence of superimposed periodic forcing. Aperiodic oscillations in MBH were controlled to generate stable topological modes, namely, circle, ellipse, and triangle, evolving in a periodic fashion at different parameters of the forcing signal. These periodic dynamics show 1:1 entrainment for circular and elliptical modes, and additionally the controlled system exhibits 1:2 entrainment for elliptical and triangular modes at a different set of parameters. The external periodic forcing of the periodic MBH system reveals the existence of domains of entrainment (1:1, 1:2, 1:3, and 1:4) represented in the Arnold tongue structures. Moreover, Devil’s staircase is obtained when the amplitude-frequency space of parameters of the applied signal is scanned.
Multivalent “attacker and guard” strategy for targeting surfaces with low receptor density
Authors: Tito Nicholas B.
Published: May 2019

Multivalent particles, i.e., microscopic constructs having multiple ligands, can be used to target surfaces selectively depending on their receptor density. Typically, there is a sharp onset of multivalent binding as the receptor density exceeds a given threshold. However, the opposite case, selectively binding to surfaces with a receptor density below a given threshold, is much harder. Here, we present a simple strategy for selectively targeting a surface with a low density of receptors, within a system also having a surface with a higher density of the same receptors. Our strategy exploits competitive adsorption of two species. The first species, called “guards,” are receptor-sized monovalent particles designed to occupy the high-density surface at equilibrium, while the second multivalent “attacker” species outcompetes the guards for binding onto the low-density surface. Surprisingly, the recipe for attackers and guards yields more selective binding with stronger ligand-receptor association constants, in contrast to standard multivalency. We derive explicit expressions for the attacker and guard molecular design parameters and concentrations, optimized within bounds of what is experimentally accessible, thereby facilitating implementation of the proposed approach.
Numerical study of natural convection in a differentially heated square cavity filled with nanofluid in the presence of fins attached to walls in different locations
Authors: Bendaraa A. , Charafi M. M. , Hasnaoui A.
Published: May 2019

The phenomenon of natural convection in a square cavity filled with a copper-water nanofluid is investigated numerically. The studied domain is a square cavity with hot and cold isothermal walls at x = 0 and x = L, respectively, while the other walls are adiabatic. The fins are considered perfectly conductive with different lengths (Lf) and positioned at different locations. We examined the situation for Rayleigh numbers ranging between 104 and 106. The governing equations are expressed in the vorticity, stream function, and temperature formulation. The system of equations was solved by the finite difference method, using the upwind scheme. The computation code thus developed was used to analyze the effect of the different locations of the fins on the thermal performances. The obtained results were validated by comparing with those of a previously published work and with those obtained using COMSOL Multiphysics. It has been found that adding fins on the cold and adiabatic walls results in an increase in the average Nusselt number, while it decreases when the fin is located on the hot wall. That is to say, placing the fins on the cold and adiabatic walls increases the thermal performances of the transfer.
A complex network theory analytical approach to power system cascading failure—From a cyber-physical perspective
Authors: Guo Hengdao , Yu Samson S. , Iu Herbert H. C. , Fernando Tyrone , Zheng Ciyan
Published: May 2019

The modern electric power grid is evolving rapidly into such a state that distributed controllers and two-way energy and information flow are replacing the traditional paradigm of electricity distribution and energy management. Therefore, a power grid coupled with a communication network is playing a pivotal role in establishing modern electric power systems. Previous cascading failure analysis in power systems focused more on the physical network, while falling short of investigations on the coupling effect of interdependency of the integrated electricity and communication networks, i.e., cyber-physical power systems. To address such a pressing issue, this study introduces a novel stochastic cascading failure model, considering the interdependency between the cyber network and power network. A multiagent system and a novel protection relay model are incorporated into the proposed model. To apply the proposed analytical method, a test power system, the IEEE 68-bs power system, is used to study the impacts of a range of interdependencies and cyber network topological structures on the cascading failure. Simulation results show the necessity and effects of consideration of cyber communication network when investigating power system cascading failures. The study also provides useful information on robustness and vulnerability of a particular power grid, given different communication topologies and interdependencies.
Droplet encapsulation of particles in different regimes and sorting of particle-encapsulating-droplets from empty droplets
Authors: Jayaprakash K. S. , Sen A. K.
Published: May 2019

Encapsulation of microparticles in droplets has profound applications in biochemical assays. We investigate encapsulation of rigid particles (polystyrene beads) and deformable particles (biological cells) inside aqueous droplets in various droplet generation regimes, namely, squeezing, dripping, and jetting. Our study reveals that the size of the positive (particle-encapsulating) droplets is larger or smaller compared to that of the negative (empty) droplets in the dripping and jetting regimes but no size contrast is observed in the squeezing regime. The size contrast of the positive and negative droplets in the different regimes is characterized in terms of capillary number Ca and stream width ratio ω (i.e., ratio of stream width at the throat to particle diameter ω=w/dp). While for deformable particles, the positive droplets are always larger compared to the negative droplets, for rigid particles, the positive droplets are larger in the dripping and jetting regimes for 0.50≤ω≤0.80 but smaller in the jetting regime for ω<0.50. We exploit the size contrast of positive and negative droplets for sorting across the fluid–fluid interface based on noninertial lift force (at Re≪1), which is a strong function of droplet size. We demonstrate sorting of the positive droplets encapsulating polystyrene beads and biological cells from the negative droplets with an efficiency of ∼95% and purity of ∼65%. The proposed study will find relevance in single-cell studies, where positive droplets need to be isolated from the empty droplets prior to downstream processing.
Real-time observation shows new hybrid writing method is fast and reliable in spin-based memory
Authors: Patrick Chris
Published: May 2019

Authors observe fast and reliable magnetization switching in real-time by combining existing methods in voltage-control spintronics memory.
Nitrogen fertilisation improves the grain production efficiency and sustainability of out-of-season corn and Congo grass intercropping
Authors: Batista Karina , Giacomini Alessandra Aparecida , Gerdes Luciana , Teixeira de Mattos Waldssimiler , Otsuk Ivani Pozar
Published: May 2019

Intercropping is a method for straw production and maintenance during the dry season in no-tillage systems. Among the crops used for intercropping are corn and grasses. However, nitrogen can interfere with the production capacity of these plants. The objective of this study was to evaluate the macronutrient accumulations and efficiency values of out-of-season corn and Congo grass intercropped under a no-tillage system as a function of the nitrogen fertilisation applied by side dressing. The experimental design was a randomised complete block with four replicates of four nitrogen application rates: 0, 30, 60 and 90 kg ha−1. The evaluations were carried out when the corn was physiologically mature. The phosphorus and potassium accumulation and nitrogen utilisation efficiency of the out-of-season corn did not respond to the nitrogen rates. The nitrogen recovery efficiency and the nitrogen to biomass conversion efficiency of the Congo grass also did not respond to nitrogen application rates. Nitrogen fertilisation as side dressing in the rows of the out-of-season corn and Congo grass intercropping improves the nutrient cycling in the no-tillage system. Side dressing fertilisation with nitrogen improves the agronomic efficiency and physiological efficiency of the out-of-season corn and Congo grass intercropping under a no-tillage system.
Disorder raises the critical temperature of a cuprate superconductor
Authors: Leroux Maxime , Mishra Vivek , Ruff Jacob P. C. , Claus Helmut , Smylie Matthew P. , Opagiste Christine , Rodière Pierre , Kayani Asghar , Gu G. D. , Tranquada John M. , Kwok Wai-Kwong , Islam Zahirul , Welp Ulrich
Published: May 2019

Significance

The origin of high-temperature superconductivity remains unknown. Over the past two decades, spatial oscillations of the electronic density known as charge-density waves (CDWs) have been found to coexist with high-temperature superconductivity in most prominent cuprate superconductors. The debate on whether CDWs help or hinder high-temperature superconductivity in cuprates is still ongoing. In principle, disorder at the atomic scale should strongly suppress both high-temperature superconductivity and CDWs. In this work, however, we find that disorder created by irradiation increases the superconducting critical temperature by 50% while suppressing the CDW order, showing that CDWs strongly hinder bulk superconductivity. We provide indications that this increase occurs because the CDWs could be part of a pair-density wave frustrating the superconducting coupling between atomic planes.
Hydrogel-based transparent soils for root phenotyping in vivo
Authors: Ma Lin , Shi Yichao , Siemianowski Oskar , Yuan Bin , Egner Timothy K. , Mirnezami Seyed Vahid , Lind Kara R. , Ganapathysubramanian Baskar , Venditti Vincenzo , Cademartiri Ludovico
Published: May 2019

Significance

Imaging of plant roots is severely limited by the opacity of soil media. Hydroponic (or gel) conditions provide transparency but nonphysiological root phenotypes. Here, we develop a “transparent soil” with high transparency, good mechanical stability, tunable pore sizes, low cost, and easy scalability. This porous media can support root growth in the presence of air, water, and nutrients, and allows for the imaging of unconstrained root systems in vivo by both photography and microscopy. Our study provides evidence that the roots of soybean developed in this medium are significantly more similar to those developed in real soil than those developed in hydroponic conditions and do not show signs of hypoxia.
Electrochemical nanoimprinting of silicon
Authors: Sharstniou Aliaksandr , Niauzorau Stanislau , Ferreira Placid M. , Azeredo Bruno P.
Published: May 2019

Significance

The indirect nature of existing parallel micromachining strategies that combine sacrificial templates with top-down processes to etch 3D micro- and nanostructures inherently produces poor out-of-plane patterning fidelity. Here, the patterning fidelity of our process is measured for microscale curvilinear 3D objects to be less than 20 nm in rms averaged over features as wide as 10 µm. These results are attributed to increased pathways for diffusion, which increase the kinetics of the anodic reaction. Using this approach, arrays of nanotextured silicon lenses are deterministically imprinted to illustrate Mac-Imprint’s ability to directly pattern hierarchical micro- and nanostructures and enable fabrication of biomimetic optical designs on silicon.
Climate change mitigation potential of carbon capture and utilization in the chemical industry
Authors: Kätelhön Arne , Meys Raoul , Deutz Sarah , Suh Sangwon , Bardow André
Published: May 2019

Significance

Carbon dioxide (CO
2
) drives climate change when released to the atmosphere. Alternatively, CO
2
could be captured and utilized as carbon source for chemicals. Here, we provide a global assessment of the technical climate change mitigation potential of carbon capture and utilization (CCU) in the chemical industry. We develop an engineering-level model of the global chemical industry representing 75% of current greenhouse gas (GHG) emissions. The model allows us to analyze the potential disruptive changes through large-scale CO
2
utilization and resulting emission reductions. Our study shows that CCU has the technical potential to lead to a carbon-neutral chemical industry and decouple chemical production from fossil resources. This transition, however, would cause largely increased mass flows and demand for low-carbon electricity.
Temporal virus serological profiling of kidney graft recipients using VirScan
Authors: Isnard Pierre , Kula Tomasz , Avettand Fenoel Véronique , Anglicheau Dany , Terzi Fabiola , Legendre Christophe , Elledge Stephen J. , Canaud Guillaume
Published: May 2019

Significance

Viral infections after organ transplantation remain a significant cause of morbidity, reducing both allograft and patient survival. At this time, pretransplant screening of potential donors and recipients is based on serological status and is limited to certain viruses. Recently, a multiplex unbiased array, called VirScan, was developed. This tool allows the detection of antibodies against viruses, using a synthetic human virome. Here, we tested the value of VirScan in the follow-up of a cohort of kidney transplant recipients. We found that VirScan is easy to use, cost-effective, safe, and reproducible, and gives an unbiased approach to monitor patients after transplantation, but in addition, the anti-viral antibody responses were largely conserved in patients, regardless of immunosuppressive treatment.
Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination
Authors: Ufimtsev Ivan S. , Almagor Lior , Weis William I. , Levitt Michael
Published: May 2019

Significance

Determination of macromolecular crystal structures by molecular replacement (MR) uses a related structure to generate approximate phases for the unknown crystal. MR fails if the search model is too dissimilar to the unknown structure. In an accompanying paper, we described a method that generates many ensembles of possible solutions and refines them against the diffraction data without human intervention, and demonstrated its ability to solve test cases of known structure. Here, we apply this method to crystals of the epithelial cell polarity protein lethal giant larvae, which had resisted structure solution using conventional MR or experimental phasing. The results show that our method of unsupervised protein structure solution can be applied to a very large and difficult phasing problem.
Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis
Authors: Sui Wenhai , Li Hongshi , Yang Yunlong , Jing Xu , Xue Fei , Cheng Jing , Dong Mei , Zhang Meng , Pan Huazheng , Chen Yuguo , Zhang Yunjian , Zhou Qingjun , Shi Weiyun , Wang Xinsheng , Zhang Han , Zhang Cheng , Zhang Yun , Cao Yihai
Published: May 2019

Significance

Mirabegron as a β3-adrenoceptor agonist is a routinely prescribed drug for treating overactive bladder syndrome. However, the effect of this drug on off-targeted tissues and organs is largely unknown. In this study, we provide mechanistic insights on mirabegron-triggered atherosclerosis in causing potential cardiovascular and cerebrovascular diseases by activation of brown fat. Given that mirabegron can induce brown fat activation in adult human subjects, these findings are clinically relevant. Moreover, genetic mutations of low-density lipoprotein receptor (LDLR) frequently occur in human populations (1 in 300 humans carries LDLR mutations). If this population of patients receive mirabegron therapy, it would be of a high risk. This important issue has not been explored in clinical studies, and warrants further investigation.
On the cause of sleep: Protein fragments, the concept of sentinels, and links to epilepsy
Authors: Varshavsky Alexander
Published: May 2019

Significance

The molecular-level cause of sleep is unknown. According to the fragment generation (FG) hypothesis discussed in the present paper, protease-generated protein fragments can be beneficial but toxic as well, and some fragments are eliminated slowly during wakefulness. We propose specific and experimentally verifiable ideas that allow a rigorous testing of the FG hypothesis. In particular, it is suggested that a major function of sleep involves a partial and reversible expansion of postsynaptic densities (PSDs) in excitatory synapses of the brain, thereby allowing an accelerated destruction of PSD-localized protein fragments by the ubiquitin/proteasome system. This and related suggestions, described in the paper, are compatible with current evidence about sleep and lead to testable predictions.
Effect of Dilute-acid Hydrolysis Conditions on Sugar and Productions from Paragrass
Authors: Thongtus Vipa , Nuchdang Sasikarn , Chirathivat Papin , Moore Elvin J. , Phalakornkule Chantaraporn
Published: May 2019

In this study, the productions of sugars as well as inhibitory compounds, e.g hydroxymethylfurfural (HMF) and furfural, from paragrass (Brachiaria mutica) were investigated using dilute acid hydrolysis. Sulphuric acid concentration of 1.0, 1.2, 1.5 and 2.0 wt% and reaction temperature of 120, 130, 140 and 150 °C for either 30 or 60 min were investigated. Xylose was found to be the major product at a maximum yield of 99±3 mg/g grass using 1.2 wt% H2SO4 and reaction temperature of 140 °C for 30 min. Analysis of variance (ANOVA) showed that for the reaction temperature between 120-140 °C, sulphuric acid concentration was the most important factor affecting the yields of hemicellulose sugars from paragrass. However, the temperature ≥ 150 °C caused the marked drop in all sugar compounds. At the optimal condition, the concentration of HMF was 0.16 g/l and furfural 0.09 g/l. The formation of HMF and furfural was almost linearly increased with increasing hydrolysis temperature between 120 and 150 °C. Furthermore, longer reaction times led to higher levels of HMF and furfural. The dilute acid hydrolysis in series with enzyme saccharification of paragrass yielded 122 mg total reducing sugar (TRS) per g grass in the enzyme hydrolysate.
Early-Life Growth and Benign Breast Disease
Authors: Goldberg Mandy , Cohn Barbara A , Houghton Lauren C , Flom Julie D , Wei Ying , Cirillo Piera , Michels Karin B , Terry Mary Beth
Published: May 2019

Using prospective data from the Early Determinants of Mammographic Density study (United States, 1959–2008, n = 1121), we examined the associations between maternal body size, birth size, and infant and early childhood growth during 3 time periods (0–4 months, 4–12 months, and 1–4 years) and benign breast disease (BBD) using multivariable logistic regression with generalized estimating equations. A total of 197 women (17.6%) reported receiving a diagnosis of BBD by a physician. Higher body mass index at age 7 years was inversely associated with BBD risk. Rapid weight gain from age 1 year to 4 years, defined as an increase of least 2 major percentiles (e.g., 5th, 10th, 25th, 50th, 75th, and 95th) relative to stable growth, defined as remaining within 2 percentiles, was also inversely associated with BBD (odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.23, 1.15). In contrast, rapid weight gain in infancy was positively associated with BBD relative to stable growth (from 0 to 4 months, OR = 1.65, 95% CI: 1.04, 2.62; from 4 to 12 months, 1.85, 95% CI: 0.89, 3.85), independent of birth weight, which was not associated with BBD. Our results suggest that patterns of early-life weight gain are important to BBD risk. Thus, susceptibility to BBD, like susceptibility to breast cancer, might start in early life.
Egg discrimination is mediated by individual differences in queen olfactory responsiveness and boldness
Authors: Wright Colin M , McEwen Brendan L , Fisher David N , Lichtenstein James L L , Antoun Angelle , Tibbetts Elizabeth A , Pruitt Jonathan N
Published: May 2019

Nest parasites attempt to shift the cost of rearing young from themselves to others. Despite strong selection to avoid this exploitation, there is considerable variation among-individuals in susceptibility to nest parasites. We evaluated the effects of individual variation in boldness, aggressiveness, and olfactory responsiveness on egg discrimination in wasps: Polistes metricus, which founds nests as singleton individuals, and P. dominula, which founds nests in small coalitions. Aggressiveness and boldness were evaluated using individuals’ response to mechanical disturbance, and olfactory responsiveness was evaluated using individuals’ tendency to respond to a novel rewarding stimulus. Egg discrimination was evaluated by presenting each queen with a variety of foreign eggs: 1) unaltered eggs laid by the resident (negative control group), 2) eggs produced by the resident female that were removed and replaced (procedural control), 3) eggs of foreign conspecifics (conspecific egg), and 4) eggs of a heterospecific congener (heterospecific egg). Females of both species never rejected untampered eggs and rejected procedural controls in only 35% of cases. Both species were twice as likely (70% rejection rate) to reject eggs of foreign conspecifics or heterospecifics. In P. dominula, bolder individuals and those with low olfactory responsiveness were more likely to reject foreign eggs. In P. metricus, boldness was not associated with egg rejection, but individuals with heightened olfactory responsiveness were more likely to reject foreign eggs. Thus, there are contrasting associations between behavioral phenotypes and egg rejection across species. These results are discussed in light of differences in the colony founding behavior of these species.
Inferring signalling dynamics by integrating interventional with observational data
Authors: Cardner Mathias , Meyer-Schaller Nathalie , Christofori Gerhard , Beerenwinkel Niko
Published: May 2019

Motivation

In order to infer a cell signalling network, we generally need interventional data from perturbation experiments. If the perturbation experiments are time-resolved, then signal progression through the network can be inferred. However, such designs are infeasible for large signalling networks, where it is more common to have steady-state perturbation data on the one hand, and a non-interventional time series on the other. Such was the design in a recent experiment investigating the coordination of epithelial–mesenchymal transition (EMT) in murine mammary gland cells. We aimed to infer the underlying signalling network of transcription factors and microRNAs coordinating EMT, as well as the signal progression during EMT.

Results

In the context of nested effects models, we developed a method for integrating perturbation data with a non-interventional time series. We applied the model to RNA sequencing data obtained from an EMT experiment. Part of the network inferred from RNA interference was validated experimentally using luciferase reporter assays. Our model extension is formulated as an integer linear programme, which can be solved efficiently using heuristic algorithms. This extension allowed us to infer the signal progression through the network during an EMT time course, and thereby assess when each regulator is necessary for EMT to advance.

Availability and implementation

R package at https://github.com/cbg-ethz/timeseriesNEM. The RNA sequencing data and microscopy images can be explored through a Shiny app at https://emt.bsse.ethz.ch.

Supplementary information

Supplementary data are available at Bioinformatics online.
Estimating the strength of expression conservation from high throughput RNA-seq data
Authors: Gu Xun , Ruan Hang , Yang Jingwen
Published: May 2019

Motivation

Evolution of gene across species is usually subject to the stabilizing selection to maintain the optimal expression level. While it is generally accepted that the resulting expression conservation may vary considerably among genes, statistically reliable estimation remains challenging, due to few species included in current comparative RNA-seq data with high number of unknown parameters.

Results

In this paper, we develop a gamma distribution model to describe how the strength of expression conservation (denoted by W) varies among genes. Given the high throughput RNA-seq datasets from multiple species, we then formulate an empirical Bayesian procedure to estimate W for each gene. Our case studies showed that those W-estimates are useful to study the evolutionary pattern of expression conservation.

Availability and implementation

Our method has been implemented in the R-package software, TreeExp, which is publically available at Github develop site https://github.com/hr1912/TreeExp. It involves three functions: estParaGamma, estParaQ and estParaWBayesian. The manual for software TreeExp is available at https://github.com/hr1912/TreeExp/tree/master/vignettes. For any question, one may contact Dr Hang Ruan (Hang.Ruan@uth.tmc.edu).
Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging
Authors: Jenkins Peter O , De Simoni Sara , Bourke Niall J , Fleminger Jessica , Scott Gregory , Towey David J , Svensson William , Khan Sameer , Patel Maneesh C , Greenwood Richard , Friedland Daniel , Hampshire Adam , Cole James H , Sharp David J
Published: May 2019

Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = −16 ms; 95% confidence interval (CI): −28 to −3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change −19 ms; 95% CI: −23 to −7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03 and P = 0.007). The cognitive effects of methylphenidate after traumatic brain injury were only seen in patients with low caudate dopamine transporter levels. This shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy.
Comparison of Adalimumab Serum Drug Levels When Delivered by Pen Versus Syringe in Patients With Inflammatory Bowel Disease. An International, Multicentre Cohort Analysis
Authors: Little Robert D , Chu Isabel E , van der Zanden Esmerij P , Flanagan Emma , Bell Sally J , Gibson Peter R , Sparrow Miles P , Shelton Edward , Connor Susan J , Roblin Xavier , Ward Mark G
Published: May 2019

Background

Adalimumab is administered via a pre-filled syringe or spring-loaded pen. In a previous study in Crohn’s disease, higher drug levels were observed in syringe users. The aim of this study was to evaluate the impact of delivery device on adalimumab drug levels in patients with Crohn’s disease.

Methods

Consecutive Crohn’s disease patients treated with maintenance adalimumab [40 mg fortnightly] were recruited from five centres. The first recorded drug level with matched clinical and biochemical markers of disease activity was compared between pen and syringe users.

Results

Of 218 patients, 64% used pen, with a median faecal calprotectin 110 μg/g and serum C-reactive protein 4 mg/L. In comparison to pen, syringe users had higher albumin [39 vs 42 g/L; p = 0.016], lower Harvey-Bradshaw Index [2 vs 1; p = 0.017], and higher rates of concomitant immunomodulation [54% vs 71%; p = 0.014]. Drug levels were equivalent between pen and syringe users [median 5.3 vs 5.2 μg/ml; p = 0.584], even after controlling for disease activity and immunomodulation. Syringe users at Alfred Health had higher drug levels than pen [6.1 vs 4.5 μg/ml; p = 0.039]; a greater proportion achieved therapeutic levels [75% vs 44%; p = 0.045]. A higher proportion of pen users from Saint-Étienne had therapeutic levels [79% vs 42%; p = 0.027], yet no significant difference in drug levels [7.9 vs 4.5 μg/ml; p = 0.119].

Conclusions

Delivery device does not appear to significantly affect adalimumab drug levels. Given differences between study sites, studies evaluating administration education and technique are warranted.
Optimization with levosimendan improves outcomes after left ventricular assist device implantation
Authors: Kocabeyoglu Sinan Sabit , Kervan Umit , Sert Dogan Emre , Karahan Mehmet , Aygun Emre , Beyazal Osman Fehmi , Unal Ertekin Utku , Akin Yesim , Demirkan Burcu , Pac Mustafa
Published: May 2019

OBJECTIVES

The aim of this study was to examine the haemodynamic effects of preoperative levosimendan infusion in patients who underwent left ventricular assist device implantation and evaluate the prognoses.

METHODS

Between May 2013 and October 2018, 85 adult patients who underwent left ventricular assist device implantation were included; 44 and 41 patients suffered from dilated cardiomyopathy and ischaemic cardiomyopathy, respectively. Patients were divided into 2 groups: group A (58 patients) included those who received levosimendan infusion in addition to other inotropes and group B (27 patients) included those who received inotropic agents other than levosimendan. Levosimendan infusion was started at a dose of 0.1 µg⋅kg−1⋅min−1 for a maximum of 48 h without a bolus. The primary outcome was early right ventricular failure (RVF). The secondary outcomes were in-hospital mortality, need for right ventricular assist device, late RVF and recovery of end-organ functions. The safety end points of levosimendan included hypotension, atrial fibrillation, ventricular tachycardia or fibrillation and resuscitated cardiac arrest.

RESULTS

Patient characteristics were similar in both groups. No significant differences between groups were observed in the rates of early mortality, RVF, need for right ventricular assist device, cardiopulmonary bypass time and intensive care unit stay. Survival rates at 30 days, 1 year and 3 years and freedom from late RVF were similar between the groups. Administration of levosimendan was safe, generally well-tolerated and not interrupted because of side effects.

CONCLUSIONS

Levosimendan therapy was well-tolerated in patients who received permanent left ventricular assist devices. Combined preoperative therapy with inotropes and levosimendan significantly improves end-organ functions.
Cardiac arrhythmias in the emergency settings of acute coronary syndrome and revascularization: an European Heart Rhythm Association (EHRA) consensus document, endorsed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Acute Cardiovascular Care Association (ACCA)
Authors: Kalarus Zbigniew , Svendsen Jesper Hastrup , Capodanno Davide , Dan Gheorghe-Andrei , De Maria Elia , Gorenek Bulent , Jędrzejczyk-Patej Ewa , Mazurek Michał , Podolecki Tomasz , Sticherling Christian , Tfelt-Hansen Jacob , Traykov Vassil , Lip Gregory Y H , Fauchier Laurent , Boriani Giuseppe , Mansourati Jacques , Blomström-Lundqvist Carina , Mairesse Georges H , Rubboli Andrea , Deneke Thomas , Dagres Nikolaos , Steen Torkel , Ahrens Ingo , Kunadian Vijay , Berti Sergio
Published: May 2019

Despite major therapeutic advances over the last decades, complex supraventricular and ventricular arrhythmias (VAs), particularly in the emergency setting or during revascularization for acute myocardial infarction (AMI), remain an important clinical problem. Although the incidence of VAs has declined in the hospital phase of acute coronary syndromes (ACS), mainly due to prompt revascularization and optimal medical therapy, still up to 6% patients with ACS develop ventricular tachycardia and/or ventricular fibrillation within the first hours of ACS symptoms. Despite sustained VAs being perceived predictors of worse in-hospital outcomes, specific associations between the type of VAs, arrhythmia timing, applied treatment strategies and long-term prognosis in AMI are vague. Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia that may be asymptomatic and/or may be associated with rapid haemodynamic deterioration requiring immediate treatment. It is estimated that over 20% AMI patients may have a history of AF, whereas the new-onset arrhythmia may occur in 5% patients with ST elevation myocardial infarction. Importantly, patients who were treated with primary percutaneous coronary intervention for AMI and developed AF have higher rates of adverse events and mortality compared with subjects free of arrhythmia. The scope of this position document is to cover the clinical implications and pharmacological/non-pharmacological management of arrhythmias in emergency presentations and during revascularization. Current evidence for clinical relevance of specific types of VAs complicating AMI in relation to arrhythmia timing has been discussed.