bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel pharmacological actions of trequinsin hydrochloride improve human sperm cell motility and function
Authors: McBrinn Rachel C. , Fraser Joanna , Hope Anthony G. , Gray David W. , Barratt Christopher L.R. , Martins da Silva Sarah J. , Brown Sean G.
Published: August 2019

Background and Purpose

Asthenozoospermia is a leading cause of male infertility, but development of pharmacological agents to improve sperm motility is hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high‐throughput screening (HTS) strategy and established in vitro tests can identify and characterise compounds that improve sperm motility. Here, we applied HTS to identify new compounds from a novel small molecule library that increase intracellular calcium ([Ca2+]i), promote human sperm cell motility, and systematically determine the mechanism of action.

Experimental Approach

A validated HTS fluorometric [Ca2+]i assay was used to screen an in‐house library of compounds. Trequinsin hydrochloride (a PDE3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology, and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.

Key Results

Fluorometric assays identified trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone. Functionally, trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. Trequinsin‐induced [Ca2+]i responses were cross‐desensitised consistently by PGE1 but not progesterone. Whole‐cell patch clamp electrophysiology confirmed that trequinsin activated CatSper and partly inhibited potassium channel activity. Trequinsin also increased intracellular cGMP.

Conclusion and Implications

Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new agents to improve patient sperm function and fertilisation potential.
Body mass index and risk of sick leave: A systematic review and meta‐analysis
Authors: Amiri Sohrab , Behnezhad Sepideh
Published: August 2019

Body mass index (BMI) is related to different health dimensions and can be a risk factor for diseases. Our objective was to systematically review and meta‐analysis the association BMI and the risk of sick leave. Four databases were searched for articles until late December 2018 and the results of the studies were extracted and combined using random effects methods. Several sub‐group analyses were conducted as well as bias of publication were measured. A total of 23 longitudinal studies entered into meta‐analysis. BMI ≥ 25 was a risk factor for sick leave; the risk ratio (RR) is equal to 1.20 with confidence interval (CI): 1.14 to 1.28. In the overweight, this result was achieved: RR = 1.09 and CI = 1.04 to 1.15 (P = 0.001) and in the obesity, RR = 1.30 and CI = 1.19 to 1.42 (P < 0.001). In both men and women, overweight and obesity were both a risk factor for sick leave. A high BMI is a risk factor that threatens health in different dimensions and therefore, overweight/obesity prevention and treatment should be given increasing attention. This will reduce the burden of illness and its consequences.
The P429L loss of function mutation of the human glycine transporter 2 associated with hyperekplexia
Authors: Kitzenmaier Alexandra , Schaefer Natascha , Kasaragod Vikram Babu , Polster Tilman , Hantschmann Ralph , Schindelin Hermann , Villmann Carmen
Published: August 2019

Glycine transporter 2 (GlyT2) mutations across the entire sequence have been shown to represent the presynaptic component of the neurological disease hyperekplexia. Dominant, recessive and compound heterozygous mutations have been identified, most of them leading to impaired glycine uptake. Here, we identified a novel loss of function mutation of the GlyT2 resulting from an amino acid exchange of proline 429 to leucine in a family with both parents being heterozygous carriers. A homozygous child suffered from severe neuromotor deficits. We characterised the GlyT2P429L variant at the molecular, cellular and protein level. Functionality was determined by glycine uptake assays. Homology modelling revealed that the mutation localises to α‐helix 5, presumably disrupting the integrity of this α‐helix. GlyT2P429L shows protein trafficking through various intracellular compartments to the cellular surface. However, the protein expression at the whole cell level was significantly reduced. Although present at the cellular surface, GlyT2P429L demonstrated a loss of protein function. Coexpression of the mutant with the wild‐type protein, reflecting the situation in the parents, did not affect transporter function, thus explaining their non‐symptomatic phenotype. Nevertheless, when the mutant was expressed in excess compared with the wild‐type protein, glycine uptake was significantly reduced. Thus, these data demonstrate that the proline residue at position 429 is structurally important for the correct formation of α‐helix 5. The failure in functionality of the mutated GlyT2 is most probably due to structural changes localised in close proximity to the sodium‐binding site of the transporter.
Shortened temperature‐relevant period of spring leaf‐out in temperate‐zone trees
Authors: Fu Yongshuo H. , Geng Xiaojun , Hao Fanghua , Vitasse Yann , Zohner Constantin M. , Zhang Xuan , Zhou Xuancheng , Yin Guodong , Peñuelas Josep , Piao Shilong , Janssens Ivan A.
Published: August 2019

Temperature during a particular period prior to spring leaf‐out, the temperature‐relevant period (TRP), is a strong determinant of the leaf‐out date in temperate‐zone trees. Climatic warming has substantially advanced leaf‐out dates in temperate biomes worldwide, but its effect on the beginning and length of the TRP has not yet been explored, despite its direct relevance for phenology modeling. Using 1,551 species–site combinations of long‐term (1951–2016) in situ observations on six tree species (namely, Aesculus hippocastanum, Alnus glutinosa, Betula pendula, Fagus sylvatica, Fraxinus excelsior, and Quercus robur) in central Europe, we found that the advancing leaf‐out was accompanied by a shortening of the TRP. On average across all species and sites, the length of the TRP significantly decreased by 23% (p < .05), from 60 ± 4 days during 1951–1965 to 47 ± 4 days during 2002–2016. Importantly, the average start date of the TRP did not vary significantly over the study period (March 2–5, DOY = 61–64), which could be explained by sufficient chilling over the study period in the regions considered. The advanced leaf‐out date with unchanged beginning of the TRP can be explained by the faster accumulation of the required heat due to climatic warming, which overcompensated for the retarding effect of shortening daylength on bud development. This study shows that climate warming has not yet affected the mean TRP starting date in the study region, implying that phenology modules in global land surface models might be reliable assuming a fixed TRP starting date at least for the temperate central Europe. Field warming experiments do, however, remain necessary to test to what extent the length of TRP will continue to shorten and whether the starting date will remain stable under future climate conditions.
Does curriculum reform influence perceived preparedness for practice of graduates? A comparison of two cohorts
Authors: Parmar Harsha , Schafheutle Ellen , Willis Sarah , Silkstone Victoria
Published: August 2019

Objectives

Using performance standards (PS) set by the General Pharmaceutical Council (GPhC), this study compared the views of two consecutive cohorts of MPharm graduates from one pharmacy school, pre- and postcurriculum reform on preparedness for practice (PFP).

Methods

Preparedness was investigated using the GPhC’s 76 PS, grouped into three domains of practice: professional activity, interpersonal skills and ability to provide an effective pharmaceutical service. Respondents were asked to (dis)agree with how they perceived the MPharm had sufficiently prepared them to meet each of the 76 PS. Differences in mean score between the two cohorts were analysed via the independent-samples t-test. Regression analysis was used to determine whether the year of graduation was a predictor of PFP once other variables were controlled for.

Key findings

A response rate of 30.1 and 42.4% was achieved for the 2014 and 2015 cohort, respectively. Significantly more respondents of the 2015 cohort (postcurricular reform) felt prepared for practice than respondents of the 2014 cohort (precurricular reform), for all domains of preregistration performance standards. Multiple regression analysis demonstrated that year of graduation was the independent variable that made the strongest unique contribution to explaining PFP (β = 0.527, P ≤ 0.005).

Conclusions

Overall findings of this study suggest that increasing adoption of undergraduate active learning opportunities and integrating learning of core subjects may enhance the overall feeling of preparedness for practice.
Effects of ultrasonic treatment on Maillard reaction and product characteristics of enzymatic hydrolysate derived from mussel meat
Authors: Dong Zhou Yong , Liu Wei , Zhou Ya Jun , Ren Hui , Li Meng Yao , Liu Yin
Published: August 2019

Mussel meat is rich in amino acids and is a good source of flavor enhancers. To find a high‐efficiency and suitable method for the Maillard reaction (MR) of enzymatic hydrolysate derived from mussel meat, we studied the changes of Maillard reaction between enzymatic hydrolysate and glucose/xylose under ultrasonic treatment (UsT), heat treatment (HT) and ultrasonic‐assisted heat treatment (Us‐HT). It was found the Us‐HT displayed the highest Maillard reaction rate and a significant increase in intermediate products and melanoidins compared to HT and UsT. The Maillard reaction products (MRPs) derived from the three treatments showed higher antioxidant activity, while the MRPs from Us‐HT had the highest antioxidant activity and ideal sensory properties. Therefore, Us‐HT is a potential method to prepare the Maillard flavor enhancer from mussel meat.

Practical Applications

The ultrasonic technology was applied as a novel food processing technique and can effectively promote the interaction of certain ingredients. Compared with single ultrasonic or heat treatment, ultrasonic‐assisted heat treatment can accelerate the reaction and improve sensory properties and antioxidant activities of MRPs derived from mussel meat hydrolysate. The ultrasonic‐assisted heat treatment is a potential technology for preparing the Maillard flavor enhancer. This efficient method supports the utilization of mussel meat and the development of flavoring essence and functional foods in the future.
Physical Activity and Risk of Postoperative Delirium
Authors: Lee Susie S. , Lo Yungtai , Verghese Joe
Published: August 2019

BACKGROUND/OBJECTIVE

Regular physical activity (PA) has been associated with improved cognitive function, but its effect on postoperative delirium (POD) has not been established. Our objectives were to determine the effect of baseline PA on the incidence of POD in older patients undergoing elective orthopedic surgery and to determine whether these effects were independent of cognitive reserve. We hypothesize that PA protects against POD by bolstering physiologic reserve needed to withstand the stressors of surgery.

DESIGN

Secondary analysis of a prospective, single‐center, cohort study.

SETTING

Urban academic hospital.

PARTICIPANTS

A total of 132 nondemented, English‐speaking adults older than 60 years undergoing elective orthopedic surgery.

MEASUREMENTS

Subjects were screened for POD and delirium severity using the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Baseline cognitive activities and PAs were assessed with a validated Leisure Activity Scale. Regular PA was categorized as 6 to 7 days per week. The association of regular PA with incidence of POD was assessed using multivariable logistic regression, adjusting for age, sex, Charlson Comorbidity Index, cognitive reserve, and cognitive function. Linear regression was used to assess the association of delirium severity with regular PA.

RESULTS

Of 132 patients, 41 (31.1%) developed POD. Regular PA was associated with a 74% lower odds of developing POD (odds ratio [OR] = 0.26; 95% confidence interval [CI] = 0.08‐0.82). There was no significant interaction between PA and cognitive reserve (P = .70). Of 85 women, 25 (29.4%), and of 47 men, 16 (34.0%) developed POD. In stratified analysis, women who engaged in regular PA had dramatically lower odds of POD (OR = 0.08; 95% CI = 0.01‐0.63) compared with men (OR = 0.93; 95% CI = 0.18‐4.97).

CONCLUSIONS

Regular PA is associated with decreased incidence of POD, especially among women. Future studies should address the basis of sex differences in PA benefits on delirium. J Am Geriatr Soc 67:2260–2266, 2019
Usefulness of cardiac parasympathetic index in CPAP‐treated patients with obstructive sleep apnea: A preliminary study
Authors: Salsone Maria , Marelli Sara , Vescio Basilio , Quattrone Andrea , Gambardella Antonio , Castelnuovo Alessandra , Quattrone Aldo , Ferini Strambi Luigi
Published: August 2019

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full‐night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability‐polysomnographic study included 16 never‐treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full‐night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high‐frequency and low‐frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea–hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single‐night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea–hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice.
Evolution of l‐DOPA 4,5‐dioxygenase activity allows for recurrent specialisation to betalain pigmentation in Caryophyllales
Authors: Sheehan Hester , Feng Tao , Walker‐Hale Nathanael , Lopez‐Nieves Samuel , Pucker Boas , Guo Rui , Yim Won C. , Badgami Roshani , Timoneda Alfonso , Zhao Lijun , Tiley Helene , Copetti Dario , Sanderson Michael J. , Cushman John C. , Moore Michael J. , Smith Stephen A. , Brockington Samuel F.
Published: August 2019

The evolution of l‐DOPA 4,5‐dioxygenase activity, encoded by the gene DODA, was a key step in the origin of betalain biosynthesis in Caryophyllales. We previously proposed that l‐DOPA 4,5‐dioxygenase activity evolved via a single Caryophyllales‐specific neofunctionalisation event within the DODA gene lineage. However, this neofunctionalisation event has not been confirmed and the DODA gene lineage exhibits numerous gene duplication events, whose evolutionary significance is unclear.

To address this, we functionally characterised 23 distinct DODA proteins for l‐DOPA 4,5‐dioxygenase activity, from four betalain‐pigmented and five anthocyanin‐pigmented species, representing key evolutionary transitions across Caryophyllales. By mapping these functional data to an updated DODA phylogeny, we then explored the evolution of l‐DOPA 4,5‐dioxygenase activity.

We find that low l‐DOPA 4,5‐dioxygenase activity is distributed across the DODA gene lineage. In this context, repeated gene duplication events within the DODA gene lineage give rise to polyphyletic occurrences of elevated l‐DOPA 4,5‐dioxygenase activity, accompanied by convergent shifts in key functional residues and distinct genomic patterns of micro‐synteny.

In the context of an updated organismal phylogeny and newly inferred pigment reconstructions, we argue that repeated convergent acquisition of elevated l‐DOPA 4,5‐dioxygenase activity is consistent with recurrent specialisation to betalain synthesis in Caryophyllales.
The antiquity and evolution of the neural bases of rhythmic activity
Authors: Lieberman Philip
Published: August 2019

The evolution of the anatomy and neural circuits that regulate the rhythm of speech can be traced back to the Devonian age, 400 million years ago. Epigenetic processes 100 million years later modified these circuits. Natural selection on similar genetic processes occurred during the evolution of archaic hominins and humans. The lungs and larynx—anatomy that produces the rhythmic fundamental frequency patterns of speech—have a deep evolutionary history. Neural circuits linking the cortex, basal ganglia, and other subcortical structures plan, sequence, and execute motor as well as cognitive acts. These neural circuits generate the rhythm of speech, singing, and chanting. The human form of the transcription factor FOXP2 increased synaptic connectivity and plasticity in basal ganglia circuits, enhancing motor control and cognitive and linguistic capabilities in humans as well as Neanderthals. The archeological record also suggests that Neanderthals passed spoken language. Homologous circuits existed in amphibians. In songbirds, the avian form of FOXP2 acted on similar neural circuits allowing birds to learn and produce new songs. Current studies point to natural selection on genetic events enhancing these and other neural circuits to yield fully human rhythmic speech, and motor, cognitive, and linguistic capabilities, rather than the saltation proposed by Noam Chomsky.
Characterization of the novel HLA‐DQA1*01:27 allele by sequencing‐based typing
Authors: Ralazamahaleo Mamy , Andreani Marco , Di Luzio Andrea , Guidicelli Gwendaline , Visentin Jonathan
Published: August 2019

HLA‐DQA1*01:27 differs from HLA‐DQA1*01:01:01:01 by one nucleotide substitution in codon 221 in exon 4.
Characterization of the novel HLA‐DPA1*01:20 allele by sequencing‐based typing
Authors: Cargou Marine , Andreani Marco , Testa Giuseppe , Guidicelli Gwendaline , Visentin Jonathan
Published: August 2019

HLA‐DPA1*01:20 differs from HLA‐DPA1*01:03:01:01 by one nucleotide substitution in codon 5 in exon 2.
A mixed methods approach to Schrödinger equation: Finite difference method and quartic B-spline based differential quadrature method
Authors: Başhan Ali
Published: August 2019

The present manuscript include, finite difference method and quartic B-spline based differential quadrature method (FDM-DQM) to obtain the numerical solutions for the nonlinear Schr¨odinger (NLS) equation. For this purpose, firstly Schrödinger equation has been converted into coupled real value differential equations and then they have been discretized using special type of classical finite difference method namely, Crank-Nicolson scheme. After that, Rubin and Graves linearization techniques have been utilized and differential quadrature method has been applied. So, partial differential equation turn into algebraic equation system. Next, in order to be able to test the accuracy of the newly hybrid method, the error norms L2 and L? as well as the two lowest invariants I1 and I2 have been calculated. Besides those, the relative changes in those invariants have been given. Finally, the newly obtained numerical results have been compared with some of those available in the literature for similar parameters. This comparison has clearly indicated that the currently utilized method, namely FDM-DQM, is an effective and efficient numerical schemeand allowed us to propose to solve a wide range of nonlinear equations.
Meet Your Robotic Coworkers
Authors: González Carlos M.
Published: August 2019

Engineers are already using inspection robots to identify hot spots on refinery exhausts, check boilers for metal loss and corrosion, and examine machinery without disassembling it. Yet, despite their sophisticated sensors and machine learning algorithms, few can do anything about a problem once they spot it. It still takes a human technician to maintain or repair a structure. This is beginning to change. A handful of inspection robots have begun to evolve into robots that can do maintenance tasks and even make the occasional repair on the spot. This special report delves deeper into how this will change the relationship between robots and workers.
Computational Creativity Via Assisted Variational Synthesis of Mechanisms Using Deep Generative Models
Authors: Deshpande Shrinath , Purwar Anurag
Published: August 2019

Computational methods for kinematic synthesis of mechanisms for motion generation problems require input in the form of precision positions. Given the highly nonlinear nature of the problem, solutions to these methods are overly sensitive to the input—a small perturbation to even a single position of a given motion can change the topology and dimensions of the synthesized mechanisms drastically. Thus, the synthesis becomes a blind iterative process of maneuvering precision positions in the hope of finding good solutions. In this paper, we present a deep-learning-based framework which manages the uncertain user input and provides the user with a higher level control of the design process. The framework also imputes the input with missing information required by the computational algorithms. The approach starts by learning the probability distribution of possible linkage parameters with a deep generative modeling technique, called variational auto encoder (VAE). This facilitates capturing salient features of the user input and relating them with possible linkage parameters. Then, input samples resembling the inferred salient features are generated and fed to the computational methods of kinematic synthesis. The framework postprocesses the solutions and presents the concepts to the user along with a handle to visualize the variants of each concept. We define this approach as variational synthesis of mechanisms. In addition, we also present an alternate end-to-end deep neural network architecture for variational synthesis of linkages. This end-to-end architecture is a conditional-VAE, which approximates the conditional distribution of linkage parameters with respect to a coupler trajectory distribution. The outcome is a probability distribution of kinematic linkages for an unknown coupler path or motion. This framework functions as a bridge between the current state of the art theoretical and computational kinematic methods and machine learning to enable designers to create practical mechanism design solutions.
A Case Study of Deep Reinforcement Learning for Engineering Design: Application to Microfluidic Devices for Flow Sculpting
Authors: Lee Xian Yeow , Balu Aditya , Stoecklein Daniel , Ganapathysubramanian Baskar , Sarkar Soumik
Published: August 2019

Efficient exploration of design spaces is highly sought after in engineering applications. A spectrum of tools has been proposed to deal with the computational difficulties associated with such problems. In the context of our case study, these tools can be broadly classified into optimization and supervised learning approaches. Optimization approaches, while successful, are inherently data inefficient, with evolutionary optimization-based methods being a good example. This inefficiency stems from data not being reused from previous design explorations. Alternately, supervised learning-based design paradigms are data efficient. However, the quality of ensuing solutions depends heavily on the quality of data available. Furthermore, it is difficult to incorporate physics models and domain knowledge aspects of design exploration into pure-learning-based methods. In this work, we formulate a reinforcement learning (RL)-based design framework that mitigates disadvantages of both approaches. Our framework simultaneously finds solutions that are more efficient compared with supervised learning approaches while using data more efficiently compared with genetic algorithm (GA)-based optimization approaches. We illustrate our framework on a problem of microfluidic device design for flow sculpting, and our results show that a single generic RL agent is capable of exploring the solution space to achieve multiple design objectives. Additionally, we demonstrate that the RL agent can be used to solve more complex problems using a targeted refinement step. Thus, we address the data efficiency limitation of optimization-based methods and the limited data problem of supervised learning-based methods. The versatility of our framework is illustrated by utilizing it to gain domain insights and to incorporate domain knowledge. We envision such RL frameworks to have an impact on design science.
Mining and Representing the Concept Space of Existing Ideas for Directed Ideation
Authors: He Yuejun , Camburn Bradley , Liu Haowen , Luo Jianxi , Yang Maria , Wood Kristin
Published: August 2019

Design innovation projects often generate large numbers of design ideas from designers, users, and, increasingly, the crowd over the Internet. Such idea data are often used for selection and implementation but, in fact, can 1also be used as sources of inspiration for further idea generation. In particular, the elementary concepts that underlie the original ideas can be recombined to generate new ideas. But it is not a trivial task to retrieve concepts from raw lists of ideas and data sources in a manner that can stimulate or generate new ideas. A significant difficulty lies in the fact that idea data are often expressed in unstructured natural languages. This paper develops a methodology that uses natural language processing to extract key words as elementary concepts embedded in massive idea descriptions and represents the elementary concept space in a core–periphery structure to direct the recombination of elementary concepts into new ideas. We apply the methodology to mine and represent the concept space underlying massive crowdsourced ideas and use it to generate new ideas for future transportation system designs in a real public sector-sponsored project via humans and automated computer programs. Our analysis of the human and computer recombination processes and outcomes sheds light on future research directions for artificial intelligence in design ideation.
A Machine Learning Enabled Multi-Fidelity Platform for the Integrated Design of Aircraft Systems
Authors: Garriga Ana Garcia , Mainini Laura , Ponnusamy Sangeeth Saagar
Published: August 2019

The push toward reducing the aircraft development cycle time motivates the development of collaborative frameworks that enable the more integrated design of aircraft and their systems. The ModellIng and Simulation tools for Systems IntegratiON on Aircraft (MISSION) project aims to develop an integrated modelling and simulation framework. This paper focuses on some recent advancements in the MISSION project and presents a design framework that combines a filtering process to down-select feasible architectures, a modeling platform that simulates the power system of the aircraft, and a machine learning-based clustering and optimization module. This framework enables the designer to prioritize different designs and offers traceability on the optimal choices. In addition, it enables the integration of models at multiple levels of fidelity depending on the size of the design space and the accuracy required. It is demonstrated for the electrification of the Primary Flight Control System (PFCS) and the landing gear braking system using different electric actuation technologies. The performance of different architectures is analyzed with respect to key performance indicators (fuel burn, weight, power). The optimization process benefits from a data-driven localization step to identify sets of similar architectures. The framework demonstrates the capability of optimizing across multiple, different system architectures in an efficient way that is scalable for larger design spaces and larger dimensionality problems.
Multiscale Mesoscale Modeling of Porosity Evolution in Oxide Fuels
Authors: Welland M. J. , Colins K. D. , Ofori-Opoku N. , Prudil A. A. , Thomas E. S.
Published: August 2019

The behavior of fission gas, notably accommodation within intra- and intergranular bubbles, influences the macroscopic properties and overall performance of oxide fuels. This work discusses progress to capture key fission gas-related phenomena with modern mesoscale techniques: the interaction of grain growth and irradiation by a phase-field crystal (PFC) method; overpressurized intragranular bubble migration in a vacancy gradient by a linearized phase-field model; and intergranular bubble interlinkage and percolation by the included phase model (IPM). An outlook on the impact of these models for the investigation of unit mechanisms of fission gas behavior and integration of them into fuel-performance codes is presented.
Estimation of Flow-Accelerated Corrosion Rate in Nuclear Piping System
Authors: Hazra Indranil , Pandey Mahesh D. , Jyrkama Mikko I.
Published: August 2019

Flow-accelerated corrosion (FAC) is a life-limiting factor for the piping network of the primary heat transport system (PHTS) in CANDU® reactors. The pipe wall thinning caused by FAC is monitored by carrying out periodic in-service inspections (ISI) to ensure the fitness-for-service of the piping system. Accurate prediction of the lifetime of various components in the PHTS piping network requires estimation of FAC thinning rate. The traditional Bayesian inference techniques commonly employed for parameter estimation are computationally costly. This paper presents an inexpensive and intuitive simulation-based Bayesian approach to FAC rate estimation, called approximate Bayesian computation using Markov chain Monte Carlo (ABC-MCMC). ABC-MCMC is a likelihood-free Bayesian computation scheme that generates samples directly from an approximate posterior distribution by simulating data sets from a forward model. The efficiency of ABC-MCMC is demonstrated by presenting a comparison with a likelihood-based Bayesian computation scheme, Metropolis-Hastings (MH) algorithm, using a practical data-based example. Furthermore, an innovative step has been proposed for reducing the Markov chain burn-in time in the proposed scheme. To indicate the need of a Bayesian approach in quantifying the uncertainties related to the FAC model parameters, results from the linear regression method, a common industrial approach, are also presented in this study. The numerical results show a notable reduction in computational time, suggesting that ABC-MCMC is an efficient alternative to the traditional Bayesian inference methods, specifically for handling noisy degradation data.
Experimental Evaluation of Critical Heat Flux in Downward-Facing Boiling on SS304 L Flat Plate Relevant to In-Calandria Retention in PHWRs
Authors: Prasad Sumit V. , Nayak A. K.
Published: August 2019

Retention of corium inside the calandria vessel (CV) by externally cooling it by calandria vault water is essential to mitigate severe accidents in pressurized heavy water reactor (PHWR). The thermal failure of CV can be prevented by effective decay heat removal on the outer surface of CV using vault water, which depends on the heat transfer behavior from the outer surface of CV to the vault water. Determination of limiting heat removal capability of vault subcooled water through outer surface of CV is very important. Since the CV has a very large diameter and length, the bottom most part of the CV almost behaves as a flat plate with downward natural convection boiling heat transfer. The natural convection heat transfer is lesser on the flat surface as compared to the curved surface of the CV. Thus, the critical heat flux (CHF) on the flat surface under downward boiling condition is the limiting CHF of the CV under external surface boiling scenario. In order to estimate CHF in this configuration with local boiling, experiments were carried out on a downward facing SS304 L flat plate simulating the conditions of CV of 700 MWel Indian PHWR. The pool boiling CHF obtained in this study is also compared with other earlier works.
Inside the circle of trust
Authors: Cohen Jon
Published: August 2019

The scientist who created the first gene-edited babies did not hide his plans from all—but regulations and colleagues failed to stop him.
A three-dimensional map of the Milky Way using classical Cepheid variable stars
Authors: Skowron Dorota M. , Skowron Jan , Mróz Przemek , Udalski Andrzej , Pietrukowicz Paweł , Soszyński Igor , Szymański Michał K. , Poleski Radosław , Kozłowski Szymon , Ulaczyk Krzysztof , Rybicki Krzysztof , Iwanek Patryk
Published: August 2019

Cepheids help to map the Galaxy

Cepheid variable stars pulsate, which allows their distances to be determined from the periodic variations in brightness. Skowron
et al.
constructed a catalog of thousands of Cepheids covering a large fraction of the Milky Way. They combined optical and infrared data to determine the stars' pulsation periods and mapped the distribution of Cepheids and the associated young stellar populations across the Galaxy. Their three-dimensional map demonstrates the warping of the Milky Way's disc. A simple model of star formation in the spiral arms reproduced the positions and ages of the Cepheid population.

Science
, this issue p.
478
Bright and photostable chemigenetic indicators for extended in vivo voltage imaging
Authors: Abdelfattah Ahmed S. , Kawashima Takashi , Singh Amrita , Novak Ondrej , Liu Hui , Shuai Yichun , Huang Yi-Chieh , Campagnola Luke , Seeman Stephanie C. , Yu Jianing , Zheng Jihong , Grimm Jonathan B. , Patel Ronak , Friedrich Johannes , Mensh Brett D. , Paninski Liam , Macklin John J. , Murphy Gabe J. , Podgorski Kaspar , Lin Bei-Jung , Chen Tsai-Wen , Turner Glenn C. , Liu Zhe , Koyama Minoru , Svoboda Karel , Ahrens Misha B. , Lavis Luke D. , Schreiter Eric R.
Published: August 2019

Visualizing neuronal activity in vivo

Imaging the changes in fluorescence of voltage-sensitive reagents would enable monitoring of the activity of neurons in vivo. Abdelfattah
et al.
created such a voltage indicator by designing a protein that combines the voltage sensor domain from microbial rhodopsin with a domain that captures a dye molecule with exceptional brightness and photostability. When the protein was expressed in mice, flies, or zebrafish, they could monitor single action potentials in dozens of neurons simultaneously for many minutes.

Science
, this issue p.
699
3D bioprinting of collagen to rebuild components of the human heart
Authors: Lee A. , Hudson A. R. , Shiwarski D. J. , Tashman J. W. , Hinton T. J. , Yerneni S. , Bliley J. M. , Campbell P. G. , Feinberg A. W.
Published: August 2019

If I only had a heart

3D bioprinting is still a fairly new technique that has been limited in terms of resolution and by the materials that can be printed. Lee
et al.
describe a 3D printing technique to build complex collagen scaffolds for engineering biological tissues (see the Perspective by Dasgupta and Black). Collagen gelation was controlled by modulation of pH and could provide up to 10-micrometer resolution on printing. Cells could be embedded in the collagen or pores could be introduced into the scaffold via embedding of gelatin spheres. The authors demonstrated successful 3D printing of five components of the human heart spanning capillary to full-organ scale, which they validated for tissue and organ function.

Science
, this issue p.
482
; see also p.
446
Observation of a symmetry-protected topological phase of interacting bosons with Rydberg atoms
Authors: de Léséleuc Sylvain , Lienhard Vincent , Scholl Pascal , Barredo Daniel , Weber Sebastian , Lang Nicolai , Büchler Hans Peter , Lahaye Thierry , Browaeys Antoine
Published: August 2019

An interacting topological phase

Most topologically nontrivial systems discovered to date consist of noninteracting particles. Their properties can therefore be explained within a single-particle picture. De Léséleuc
et al.
engineered a topological phase of bosonic atoms in which interactions play a crucial role. The atoms, which were in highly excited Rydberg states, were held in an array of optical tweezers. Depending on the spatial arrangement of the tweezers, the dipole-dipole interactions between the atoms gave rise to two configurations with different topological properties.

Science
, this issue p.
775
Identification of a T follicular helper cell subset that drives anaphylactic IgE
Authors: Gowthaman Uthaman , Chen Jennifer S. , Zhang Biyan , Flynn William F. , Lu Yisi , Song Wenzhi , Joseph Julie , Gertie Jake A. , Xu Lan , Collet Magalie A. , Grassmann Jessica D. S. , Simoneau Tregony , Chiang David , Berin M. Cecilia , Craft Joseph E. , Weinstein Jason S. , Williams Adam , Eisenbarth Stephanie C.
Published: August 2019

Thirteen is the charm in anaphylaxis

Immunoglobulin E (IgE) is a type of antibody associated with allergies and response to parasites such as worms. When high-affinity, allergen-specific IgE binds its target, it can cross-link receptors on mast cells that induce anaphylaxis. It remains unclear, however, how B cells are instructed to generate high-affinity IgE. Gowthaman
et al.
discovered a subset of T follicular helper cells (T
FH
13) that direct B cells to do just that. T
FH
13 cells are induced by allergens but not during parasite infection. Transgenic mice lacking these cells show impaired production of high-affinity, anaphylactic IgE. T
FH
13 cells, which are elevated in patients with food and aeroallergies, may be targeted in future antianaphylaxis therapies.

Science
, this issue p.
eaaw6433
The geologic history of seawater oxygen isotopes from marine iron oxides
Authors: Galili Nir , Shemesh Aldo , Yam Ruth , Brailovsky Irena , Sela-Adler Michal , Schuster Elaine M. , Collom Christopher , Bekker Andrey , Planavsky Noah , Macdonald Francis A. , Préat Alain , Rudmin Maxim , Trela Wieslaw , Sturesson Ulf , Heikoop Jeffrey M. , Aurell Marcos , Ramajo Javier , Halevy Itay
Published: August 2019

Not as hot as we thought

Earth's early oceans appear not to have been as hot as some have suggested. The oxygen isotope composition of marine carbonates has changed markedly over the past 3.5 billion years. However, it has been difficult to determine whether that is because of a cooling of the seawater (from temperatures as high as 70°C) or an actual change in the isotope composition of the water. Galili
et al.
calibrated the temperature-dependent oxygen isotope fractionation between iron oxides and aqueous solutions and constructed an oxygen isotope record in marine iron oxides covering the past 2 billion years. Their findings suggest that a change in the isotope composition of the water, rather than its cooling, underlies the observed geological trend.

Science
, this issue p.
469
The pigment-protein network of a diatom photosystem II–light-harvesting antenna supercomplex
Authors: Pi Xiong , Zhao Songhao , Wang Wenda , Liu Desheng , Xu Caizhe , Han Guangye , Kuang Tingyun , Sui Sen-Fang , Shen Jian-Ren
Published: August 2019

A light-harvesting array in diatoms

Photosynthetic organisms use huge arrays of pigments to draw light energy into the core of photosystem II. The arrangement of these pigments influences how much energy reaches the reaction center. Pi
et al.
determined the structure of photosystem II from a diatom in complex with an antenna of fucoxanthin–chlorophyll a/c binding proteins (FCPs) (see the Perspective by Büchel). The specialized pigments in this complex allow microalgae to harvest light within a wide range of the visible spectrum. The FCPs are arranged in a pattern analogous to light-harvesting complexes in plants.

Science
, this issue p.
eaax4406
; see also p.
447
Time's up, CO
2
Authors: McNutt Marcia
Published: August 2019

Forty years ago this summer, a small group of atmospheric and ocean scientists met in Woods Hole, Massachusetts, to project the future impacts on Earth's climate from atmospheric release of carbon dioxide (CO
2
) from fossil fuel combustion. Frank Press, head of the United States Office of Science and Technology Policy and Science Adviser to President Carter, requested that the National Academy of Sciences conduct the study for the benefit of policymakers. On the basis of then-current trends, the 1979 committee, led by Jule Charney of the Massachusetts Institute of Technology, assumed that atmospheric CO
2
concentrations would reach double the preindustrial values sometime in the first half of the 21st century. They calculated that as a result, the average global surface temperature would increase by 3° ± 1.5°C, with the greatest warming at high latitudes—the first assessment of its kind. The Charney committee also noted in the models a lag on the order of decades between CO
2
release and the resulting temperature rise. This delay, from disequilibrium effects with the ocean, masks pending temperature increases long before they are apparent.
Evaluation of an Indirect Enzyme-Linked Immunosorbent Assay Based on Recombinant Baculovirus-Expressed Rift Valley Fever Virus Nucleoprotein as the Diagnostic Antigen
Authors: Faburay Bonto , Wilson William C. , Secka Arss , Drolet Barbara , McVey D. Scott , Richt Juergen A.
Published: August 2019

The increasing risk of Rift Valley fever virus (RVFV) infection as a global veterinary and public health threat demands the development of safe and accurate diagnostic tests. The aim of this study was to assess the suitability of a baculovirus expression system to produce recombinant RVFV nucleoprotein (N) for use as serodiagnostic antigen in an indirect enzyme-linked immunosorbent assay (ELISA).
Vascular leiomyosarcoma of the femoral vein: an unusual cause of a femoral triangle mass
Authors: Narayanen Neegam , O’Hanlon Deirdre , Murphy Michael , O’Brien Noel
Published: August 2019

Lumps in the femoral triangle are common. The differential diagnosis includes lymphadenopathy and femoral hernias. Rarer causes of lumps are saphena varix, femoral artery aneurysm or a psoas abscess. We present a leiomyosarcoma of the femoral vein that presented as a femoral triangle mass.
A prospective trial of adjuvant therapy for high-risk uveal melanoma: assessing 5-year survival outcomes
Authors: Binkley Elaine , Triozzi Pierre L , Rybicki Lisa , Achberger Susan , Aldrich Wayne , Singh Arun
Published: August 2019

Background/aims

Survival after diagnosis of metastasis from uveal melanoma is poor. Identifying individuals at high risk for metastasis and developing adjuvant therapy to prevent clinically apparent metastasis could improve survival. We conducted an adjuvant trial of sequential, low-dose dacarbazine (DTIC) and interferon-alpha-2b (IFN-α−2b) in patients with cytogenetic high-risk uveal melanoma.

Methods

Patients diagnosed with iris, ciliary body or choroidal melanoma with high-risk tumour cytogenetics (monosomy 3) were offered adjuvant treatment with low-dose DTIC and IFN-α−2b following primary therapy. Eligible but not enrolled patients were observed for comparison. DTIC was administered at 850 mg/m2 intravenously on days 1 and 28. IFN-α−2b was administered at 3 million units three times a week subcutaneously for 24 weeks beginning at week 9. Hepatic imaging was performed prior to adjuvant therapy and then at least every 6 months. Survival data were collected for 5 years after enrolment.

Results

33 patients (22%) were enrolled (treatment group), 29 (19%) were eligible but did not enrol (observation group) and 88 (59%) were not eligible. The 5-year metastasis-free survival (MFS) was 64%±9% for treated and 33%±10% for observed patients (p=0.05). The 5-year overall survival (OS) rate was 66%±9% for treated and 37%±10% for observed patients (p=0.02).

Conclusions

When adjusted for differences in age, tumour size and initial treatment, survival between treated and observed patients was no longer significant (p=0.56 MFS and p=0.92 OS). Differences in baseline tumour characteristics between treated and observed patients can influence interpretation of results.

Trial registration number

NCT01100528.
Can even experienced orthopaedic surgeons predict who will benefit from surgery when patients present with degenerative meniscal tears? A survey of 194 orthopaedic surgeons who made 3880 predictions
Authors: van de Graaf Victor A , Bloembergen Coen H , Willigenburg Nienke W , Noorduyn Julia C A , Saris Daniel BF , Harris Ian A , Poolman Rudolf W
Published: August 2019

Objectives

To examine the ability of surgeons to predict the outcome of treatment for meniscal tears by arthroscopic partial meniscectomy (APM) and exercise therapy in middle-aged patients.

Design and setting

Electronic survey. Orthopaedic surgeon survey participants were presented 20 patient profiles. These profiles were derived from a randomised clinical trial comparing APM with exercise therapy in middle-aged patients with symptomatic non-obstructive meniscal tears. From each treatment group (APM and exercise therapy), we selected five patients with the best (responders) and five patients with the worst (non-responders) knee function after treatment. 1111 orthopaedic surgeons and residents in the Netherlands and Australia were invited to participate in the survey.

Interventions

For each of the 20 patient profiles, surgeons (unaware of treatment allocation) had to choose between APM and exercise therapy as preferred treatment and subsequently had to estimate the expected change in knee function for both treatments on a 5-point Likert Scale. Finally, surgeons were asked which patient characteristics affected their treatment choice.

Main outcomes

The primary outcome was the surgeons’ percentage correct predictions. We also compared this percentage between experienced knee surgeons and other orthopaedic surgeons, and between treatment responders and non-responders.

Results

We received 194 (17%) complete responses for all 20 patient profiles, resulting in 3880 predictions. Overall, 50.0% (95% CI 39.6% to 60.4%) of the predictions were correct, which equals the proportion expected by chance. Experienced knee surgeons were not better in predicting outcome than other orthopaedic surgeons (50.4% vs 49.5%, respectively; p=0.29). The percentage correct predictions was lower for patient profiles of non-responders (34%; 95% CI 21.3% to 46.6%) compared with responders (66.0%; 95% CI 57.0% to 75.0%; p=0.01).

In general, bucket handle tears, knee locking and failed non-operative treatment directed the surgeons’ choice towards APM, while higher level of osteoarthritis, degenerative aetiology and the absence of locking complaints directed the surgeons’ choice towards exercise therapy.

Conclusions

Surgeons’ criteria for deciding that surgery was indicated did not pass statistical examination. This was true regardless of a surgeon’s experience. These results suggest that non-surgical management is appropriate as first-line therapy in middle-aged patients with symptomatic non-obstructive meniscal tears.

Clinical trial registration

ClinicalTrials.gov Identifier:
NCT03462134
.