bluuebunny/crossref_metadata_2025 huggingface dataset:
FACING A TOUGH PROBLEM? TRY REFRAMING IT
Authors: Wedell‐Wedellsborg Thomas
Published: April 2020

This article discusses the need for leaders to reframe problems, by changing perspectives. Reframing is not a new process; in 1938, Albert Einstein and his fellow physicist Leopold Infeld wrote about the need “to regard old problems from a new angle.” Reframing strategies here are headed into sections: 1. First, frame the Problem 2. Use outsiders to test your problem framing 3. Look outside the frame 4. Devise a hard test. Various examples are provided, in companies such as Cisco, Samsung, and Managed by Q. Also described is the work of Georgina de Rocquigny, founder of the Hong Kong–based branding agency Untapped. She was tapped by a local management consulting firm that wanted to become known as a strategy firm, but her interviews and research turned up something different. The end result was a powerful new positioning around bridging strategy and execution that has resonated with the firm and its clients, and has contributed to the firm's continued growth. As noted in the Samsung example, don't just focus on the product itself, or the problems you already know about. Take a step back and focus on the entire situation, seeking to discover pain points that have hitherto gone unnoticed.
CONSCIOUS LEADERSHIP: MOVING TO AN INTENTIONAL FOCUS FOR A THRIVING WORKPLACE CULTURE
Authors: Wallace Natasha
Published: April 2020

Based on observation and her own experience, the author contends that people who are successful in their functional roles are promoted into management roles and expected to lead. Some organizations figure out that developing leadership capability at the earliest stages is central to success. However, in helping leaders achieve better performance, we're not seeing enough of that investment. The author learned leadership the hard way: through making it up. She draws on her own experience moving from sales into a managerial/leadership role and on research from professors Amy Edmondson of Harvard Business School and Martin Seligman of the University of Pennsylvania. The author expounds on the following steps for new leaders: (1) wise up, (2) accept you'll need to change, (3) leadership is a balancing act, and (4) stay connected. For instance, within point 2; regardless of how good you are at delivering, project managing, and managing efficiency, you won't come into leadership as a fully rounded leader. There are also steps for employers: (1) mentor them, (2) build leadership mind‐set early, (3) promote based on technical and behavioral competence, and (4) create a listening culture. Within point 3, no one should be promoted for technical or professional capability alone.
Selective Control of Cell Activity with Hydrophilic Polymer‐Covered Cationic Nanoparticles
Authors: Lin Hsiu‐Pen , Akimoto Jun , Li Yaw‐Kuen , Ito Yoshihiro
Published: April 2020

Cationic polymers exhibit high cytotoxicity via strong interaction with cell membranes. To reduce cell membrane damage, a hydrophilic polymer is introduced to the cationic nanoparticle surface. The hydrophilic polymer coating of cationic nanoparticles resulted in a nearly neutral nanoparticle. These particles are applied to mouse fibroblast (3T3) and human cervical adenocarcinoma (Hela) cells. Interestingly, nanoparticles with a long cationic segment decrease cell activity regardless of cell type, while those with a short segment only affect 3T3 cell activity at lower concentrations less than 500 µg mL−1. Most nanoparticles are located inside 3T3 cells but on the cell membrane of Hela cells. The short cationic nanoparticle shows negligible cell membrane damage despite its high accumulation on Hela cell membranes. Cell activity changed by hydrophilic polymer‐coated cationic nanoparticles is caused by incorporated nanoparticle accumulation in the cells, not cell membrane damage. To suppress the cytotoxicity from the cationic polymer, cationic nanoparticle needs to completely cover with hydrophilic polymer so as not to exhibit the cationic effect and applies to cell with low concentrations to reduce the nonselective cytotoxicity from the cationic polymer.
A fibrinogen biosensing platform based on plasmonic Ga nanoparticles and aminosilane–titanate antibody trapping
Authors: Magdaleno Alvaro J. , Gordillo Nuria , Pau Jose Luis , Manso Silván Miguel
Published: April 2020

The era of personalized medicine calls for rapid detection of key biomolecules, such as serum proteins, as general indicators of a healthy/sickness state. The fabrication, biofunctionalization and calibration of a fibrinogen biosensing platform based on plasmonic gallium nanoparticles are detailed in the present work. The first step consisted in the deposition of Ga nanoparticles on Si substrates by means of Joule‐effect thermal evaporation technique. A distribution of nanodroplets could be evidenced by scanning electron microscopy. The biofunctionalization of the samples was carried out using aminosilane–titanate thin hybrid layers prepared by a sol–gel route. The integration of functional amino groups could be confirmed by spectroscopic methods. Then, in order to sensitize the platform surface to fibrinogen, specific immunoglobulins have been immobilized. We monitored the plasmon wavelength changes along the fabrication cascade and during detection assays with calibrated fibrinogen solutions in phosphate‐buffered saline. From the ellipsometric analysis, three operational ranges as a function of fibrinogen concentration can be identified, with an out‐of‐range response for low concentration, a linear response behaviour in the 1–10 µM healthy range and a tendency to saturation at high concentration.
Adaptive neuro‐fuzzy inference system to estimate the predictability of visibility during fog over Delhi, India
Authors: Goswami S. , Chaudhuri S. , Das D. , Sarkar I. , Basu D.
Published: April 2020

In the present research it was attempted to estimate the predictability of visibility during fog over the airport of the most polluted city Delhi (28 ° 38 ′ N, 77 ° 12 ′ E), India, with an adaptive neuro‐fuzzy inference system (ANFIS). The investigation started with the evaluation of fuzzy membership to categorize the data into different ranges. The output variables of fuzzy membership are used as the input in the multilayer perceptron model of artificial neural networks. In this hybrid computing system, the ANFIS was trained with the data from 2000 to 2010 for estimating the predictability of visibility during fog over Delhi airport. The results show that the ANFIS provides minimum forecast errors (9.09%) with 12 hr lead time in comparison to other neural network models and the existing forecast models. The results were validated with observations from 2011 to 2015. The coupled model ANFIS shows minimum error in visibility forecasting during fog over Delhi airport with validation from observations as well. The study therefore suggests that the ANFIS may be adopted as an alternative operational model for forecasting visibility during fog with 90.91% accuracy for a 12 hr lead time.
Calculated coupling constants 1J(X–Y) and 1K(X–Y), and fundamental relationships among the reduced coupling constants for molecules HmX–YHn, with X, Y ═ 1H, 7Li, 9Be, 11B, 13C, 15N, 17O, 19F, 31P, 33S, and 35Cl
Authors: Elguero José , Alkorta Ibon , Del Bene Janet E.
Published: April 2020

Equation‐of‐motion coupled‐cluster singles and doubles (EOM‐CCSD) calculations have been performed to determine coupling constants 1J(X–Y) for 65 molecules HmX–YHn, with X,Y ═ 1H, 7Li, 9Be, 11B, 13C, 15N, 17O, 19F, 31P, 33S, and 35Cl. The computed 1J(X–Y) values are in good agreement with available experimental data. The reduced coupling constants 1K(X–Y) have been derived from 1J(X–Y) by removing the dependence on the magnetogyric ratios of X and Y. Patterns are found for the reduced coupling constants on a 1K(X–Y) surface that are related to the positions of X and Y in the periodic table.
Ultrasound analysis of cervical paraspinal muscles for needle EMG examination
Authors: Mrkobrada Serge
Published: April 2020

Background

Ultrasound was used to determine optimal needle insertion parameters and assess the vasculature of paraspinal muscles at C5‐T1 spinal levels across patients with different body mass indices (BMIs).

Methods

Thirty patients underwent ultrasound examination of the cervical paraspinal muscles at the C5‐T1 levels. Images were analyzed to determine the optimal distance and angle of needle insertion to reach the base of the right lamina. Color and spectral Doppler analysis were used to identify and map paraspinal blood vessels.

Results

Mean distances and angles varied from 35.1 mm and 17.27 degrees for the low BMI group at C5 to 65.1 mm and 9.85 degrees for the high BMI group at T1. Paraspinal blood vessel mapping revealed a random distribution of vasculature.

Conclusions

Longer distances and steeper angles of needle insertion are required for patients with higher BMIs. Cervical paraspinal arteries vary in distribution and can be visualized with ultrasound.
The Origin of the σ‐Hole in Halogen Atoms: a Valence Bond Perspective
Authors: Franchini Davide , Forni Alessandra , Genoni Alessandro , Pieraccini Stefano , Gandini Enrico , Sironi Maurizio
Published: April 2020

A detailed Valence Bond‐Spin Coupled analysis of a series of halogenated molecules is here reported, allowing to get a rigorous ab initio demonstration of the qualitative models previously proposed to explain the origin of halogen bonding. The concepts of σ‐hole and negative belt observed around the halogen atoms in the electrostatic potential maps are here interpreted by analysis of the relevant Spin Coupled orbitals.
Both Tough and Soft Double Network Hydrogel Nanocomposite Based on O‐Carboxymethyl Chitosan/Poly(vinyl alcohol) and Graphene Oxide: A Promising Alternative for Tissue Engineering
Authors: Pourjavadi Ali , Mazaheri Tehrani Zahra , Salami Hamid , Seidi Farzad , Motamedi Anahita , Amanzadi Amirhossein , Zayerzadeh Ehsan , Shabanian Meisam
Published: April 2020

A reinforced double network (DN) hydrogel as a candidate for skin scaffold was prepared. It consists of O‐carboxymethyl chitosan, polyvinyl alcohol, honey, CaCl2, and graphene oxide. The various concentrations of CaCl2, namely, 30, 45, and 60 wt% were investigated. Besides, the GO content was studied as 3, 5, and 10 wt%. The structure of the DN was characterized by Fourier‐transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, X‐ray diffraction, energy dispersive X‐ray and Brunauer‐Emmett‐Teller were evaluated. The mechanical properties were studied, too. It showed that the DN with 45 wt% CaCl2 was optimized. Also, swelling mechanism was investigated. Moreover, with the increase in GO content, the mechanical strength was increased. The cytotoxicity was evaluated and it was indicated that DN with 45% CaCl2 and 5% GO had an acceptable level of biocompatibility. Moreover, scanning electron microscopy images showed the porous structure of the DN nanocomposite. Thus, the DN has the potential to be applied in tissue engineering as a skin scaffold. POLYM. ENG. SCI., 60:889–899, 2020. © 2020 Society of Plastics Engineers
Development of waste tire‐derived graphene reinforced polypropylene nanocomposites with controlled polymer grade, crystallization and mechanical characteristics via melt‐mixing
Authors: Zanjani Jamal Seyyed Monfared , Poudeh Leila Haghighi , Ozunlu Burcu Girginer , Yagci Yavuz Emre , Menceloglu Yusuf , Saner Okan Burcu
Published: April 2020

In the present work, single layer graphene nanoplatelets (GNPs) derived from waste tires by recycling and upcycling approaches were integrated in homopolymer (Homo‐) and copolymer (Copo‐) polypropylene (PP) matrices by fast and efficient mixing in the melt phase. The effect of GNP content on crystallization and mechanical behaviors was investigated in detail at different loading levels. Regarding isothermal and non‐isothermal crystallization experiments, GNPs significantly accelerated the nucleation and growth of crystallites, and the crystallization degree in Homo‐PP nanocomposites was slightly higher than that of Copo‐PP based nanocomposites. Also, there was significant improvement in mechanical and thermal properties of GNP reinforced polymers compared to neat polymers. As the GNP concentration increased from 1 to 5 wt%, there was a gradual increase in flexural modulus and strength values. In tensile tests, an increase in GNP content in both polymer grades led to a slight increase in yield strength coming from the proper distribution of nano‐reinforcement by creating stress concentration sites. After the yield point, Homo‐PP based nanocomposites showed higher strain hardening than GNP reinforced Copo‐PP owing to a high crystallization degree and linear chains of Homo‐PP. This work showed that functionalized graphene can act as both nucleating and reinforcing agent in the compounding process and its exfoliation through polymer chains is much better in homopolymers at a faster and high shear rate. © 2020 Society of Chemical Industry
Microplasma direct writing of a copper thin film in the atmospheric condition with a novel copper powder electrode
Authors: Wang Tao , Lv Li , Shi Liping , Tong Baohong , Zhang Xingquan , Zhang Guotao , Liu Jingquan
Published: April 2020

This study presents the microplasma direct writing of copper film in the open air using a novel copper powder electrode. The powder electrode acted as a high‐voltage electrode and the precursor source. The deposition process is realized through ion sputtering of the powder in the microplasma. The bombarded copper nanoparticles were deposited and accumulated on a silicon substrate. The deposited film is composed of copper nanoparticles with sizes in the range from tens to hundreds of nanometers, and its electrical conductivity could reach 3.96 × 105 S/m. The morphologies, chemical compositions and electrical property of the thin film can be adjusted by changing the input current, and maskless film deposition with different micropatterns can be achieved by direct microplasma scanning.
Deep learning for automated detection of Drosophila suzukii: potential for UAV‐based monitoring
Authors: Roosjen Peter PJ , Kellenberger Benjamin , Kooistra Lammert , Green David R , Fahrentrapp Johannes
Published: April 2020

BACKGROUND

The fruit fly Drosophila suzukii, or spotted wing drosophila (SWD), is a serious pest worldwide, attacking many soft‐skinned fruits. An efficient monitoring system that identifies and counts SWD in crops and their surroundings is therefore essential for integrated pest management (IPM) strategies. Existing methods, such as catching flies in liquid bait traps and counting them manually, are costly, time‐consuming and labour‐intensive. To overcome these limitations, we studied insect trap monitoring using image‐based object detection with deep learning.

RESULTS

Based on an image database with 4753 annotated SWD flies, we trained a ResNet‐18‐based deep convolutional neural network to detect and count SWD, including sex prediction and discrimination. The results show that SWD can be detected with an area under the precision recall curve (AUC) of 0.506 (female) and 0.603 (male) in digital images taken from a static position. For images collected using an unmanned aerial vehicle (UAV), the algorithm detected SWD individuals with an AUC of 0.086 (female) and 0.284 (male). The lower AUC for the aerial imagery was due to lower image quality caused by stabilisation manoeuvres of the UAV during image collection.

CONCLUSION

Our results indicate that it is possible to monitor SWD using deep learning and object detection. Moreover, the results demonstrate the potential of UAVs to monitor insect traps, which could be valuable in the development of autonomous insect monitoring systems and IPM. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Ameliorative effects of Magnolia sieboldii buds hexane extract on experimental reflux esophagitis
Authors: Nan Li , Nam Hyeon Hwa , Park Byung Yong , Kim Beom Tae , Choo Byung Kil
Published: April 2020

Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing into esophagus causes symptoms and/or complications. The study was working to find natural plant extracts with good effects and small side effects to treat reflux esophagitis (RE). The anti‐inflammatory effects of hexane extract of Magnolia sieboldii (MsHE) were conducted on lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cells. The ameliorative effects of MsHE on esophageal damage in rats induced by gastric acid reflux was explored in vivo. The results showed that MsHE decreased the production of nitric oxide (NO) and expression levels of iNOS, COX‐2 and TNF‐α on LPS‐stimulated RAW 264.7 cells and MsHE treatment ameliorated the rats' esophageal tissue damage induced by gastric acid and inhibited the increase of inflammatory mediators and pro‐inflammatory cytokines by regulating NF‐κB signaling pathway. In addition, MsHE protected the function of barrier of epithelial cells against inflammatory conditions through increasing the expression of tight junctions. Furthermore, liquid chromatography‐mass spectrometry analysis was used for determine the active ingredients contained in MsHE. The results show that MsHE can alleviate experimental rat RE by regulating NF‐κB signaling pathway. In summary, MsHE may be used as a source material of drug candidate for the treatment of RE.
Regularized Dawid–Sebastiani score for multivariate ensemble forecasts
Authors: Wilks Daniel S.
Published: April 2020

The Dawid–Sebastiani score (DSS) is a theoretically attractive tool for evaluating the accuracy of multivariate ensemble forecasts, wherein each ensemble member produces a vector of forecasts. It has been little used to date mostly because its computation requires calculation and inversion of the ensemble covariance matrix for each forecast occasion. These matrices are not invertible unless the ensemble size is larger than the dimension of the forecast vectors. Moreover, these matrices are poorly estimated unless the ensemble size is quite large relative to the dimension of the vectors. This article describes application to the inverse correlation matrix in the DSS of a relatively recently developed regularization procedure called the graphical lasso (“glasso”), which not only suppresses the sampling variability of the score for relatively small ensemble sizes but also allows its computation even when the ensemble size is smaller than the dimension of the forecast and observation vectors. Use of glasso regularization with the DSS, and its performance in comparison to the Energy Score and the Variogram Score, are illustrated using a novel statistical model for multivariate ensemble forecasts which allows separate manipulation of bias, univariate calibration, multivariate calibration, and multivariate correlation characteristics.
A feasible strategy based on high ultrasound frequency and mass spectrometry for discriminating individuals diagnosed with bipolar disorder and schizophrenia through ionomic profile
Authors: de Jesus Jemmyson Romário , Arruda Marco Aurélio Zezzi
Published: April 2020

Rationale

A viable and accurate method based on high‐power ultrasound‐assisted microextraction and inductively coupled plasma mass spectrometry was developed to determine metals in human serum from patients with bipolar disorder and schizophrenia.

Methods

A simple and rapid sample preparation method using a cup–horn sonoreactor was developed. The acid concentration of HNO3 (10, 20, and 40% v/v) and HCl (1, 5, 15, and 30% v/v) of the extraction solution, the sonication time (1, 3, 6, and 10 min), and the sonication amplitude (20, 40, 60, and 80%) were evaluated. Cd, Cu, Fe, Li, Pb, and Zn were determined in serum samples from patients with bipolar disorder and schizophrenia, and from healthy controls. Quantitative metal recoveries using the proposed method were compared under the same conditions using an ultrasonic bath, magnetic stirring, and microwave‐assisted digestion.

Results

Optimum extraction conditions were obtained using HNO3 (40% v/v) + HCl (30% v/v) as the extraction solution with 3 min sonication time and 60% sonication amplitude. Significant differences were observed among the methods compared. On application of the sample preparation method based on high‐power ultrasound‐assisted microextraction coupled with inductively coupled plasma mass spectrometry, Pb and Cd in all the studied samples were below the limit of detection of our method. Compared with healthy controls, the concentration of Cu, Li, Fe, and Zn was found to be significantly higher for the bipolar disorder group, while these metals and Li were found at a lower level for the group diagnosed with schizophrenia.

Conclusions

Principal component analysis showed a significant separation for the groups studied based on their ionomic profiles after the application of high‐power ultrasound‐assisted microextraction as a sample preparation strategy.
A machine learning method for selection of genetic variants to increase prediction accuracy of type 2 diabetes mellitus using sequencing data
Authors: Jung Luann C. , Wang Haiyan , Li Xukun , Wu Cen
Published: April 2020

Type 2 diabetes mellitus (T2DM) affects millions of people through its life‐altering complications. Worldwide, 3.4 million people die of diabetes annually. Studying the effect of genetic polymorphism on T2DM has been plagued by the available sample size. A 2016 Nature Reviews article summarized that the accuracy of predicting future type 2 diabetes from genetic polymorphism is very low at the population level. Innumerable associations between genes, environmental factors, and type 2 diabetes remain to be discovered. This research presents a method to identify subtle effects of genetic variants using whole genome sequencing data and improve prediction accuracy of T2DM at the population level. To achieve this, a new feature selection procedure and a classifier are proposed. The method involves (a) first applying sparse principal component analysis to genotype data to obtain orthogonal features; (b) building a new classifier using single nucleotide polymorphism (SNP)‐specific regularization parameters to reduce the false positive rate of feature selection; (c) verifying feature relevance through penalized logistic regression. After application to a dataset containing 625 597 SNPs and 23 environmental variables from each of 3326 humans, the method identified 271 genetic variants with subtle effects on T2DM prediction. These variants led to greatly improved prediction accuracy for new patients at the population level. The proposed method also has the advantage of computational efficiency, over 15 times faster than random forest and extreme gradient boosting (XGBoost) classifiers, and thus provides a promising tool for large‐scale genome‐wide association studies.
STRATOS guidance document on measurement error and misclassification of variables in observational epidemiology: Part 2—More complex methods of adjustment and advanced topics
Authors: Shaw Pamela A. , Gustafson Paul , Carroll Raymond J. , Deffner Veronika , Dodd Kevin W. , Keogh Ruth H. , Kipnis Victor , Tooze Janet A. , Wallace Michael P. , Küchenhoff Helmut , Freedman Laurence S.
Published: April 2020

We continue our review of issues related to measurement error and misclassification in epidemiology. We further describe methods of adjusting for biased estimation caused by measurement error in continuous covariates, covering likelihood methods, Bayesian methods, moment reconstruction, moment‐adjusted imputation, and multiple imputation. We then describe which methods can also be used with misclassification of categorical covariates. Methods of adjusting estimation of distributions of continuous variables for measurement error are then reviewed. Illustrative examples are provided throughout these sections. We provide lists of available software for implementing these methods and also provide the code for implementing our examples in the Supporting Information. Next, we present several advanced topics, including data subject to both classical and Berkson error, modeling continuous exposures with measurement error, and categorical exposures with misclassification in the same model, variable selection when some of the variables are measured with error, adjusting analyses or design for error in an outcome variable, and categorizing continuous variables measured with error. Finally, we provide some advice for the often met situations where variables are known to be measured with substantial error, but there is only an external reference standard or partial (or no) information about the type or magnitude of the error.
Green Light‐Based Photobiomodulation with an Implantable and Biodegradable Fiber for Bone Regeneration
Authors: Jiang Yuxi , Qi Wei , Zhang Qianyi , Liu Hao , Zhang Jianyun , Du Ning , Nazempour Roya , Su Yuanzhe , Fu Ruxing , Zhang Kaiyuan , Lyu Peijun , Dong Fan , Yin Lan , Sheng Xing , Wang Yuguang
Published: April 2020

Photobiomodulation (PBM) has recently started to gain popularity in clinical therapeutics. Visible light, in particular, plays a critical role in osteogenesis modulation. However, the limited penetration depth of visible light in biological tissues has constrained the application of this technology in vivo. Herein a green light‐based PBM technique with implantable and biodegradable poly(L‐lactic acid) & poly(L‐actic‐co‐glycolic acid) optical fibers to achieve accelerated bone regeneration is explored. Facilitated with experimental characterizations as well as numerical simulations, optical and thermal behaviors of fibers operated in the biological environment are understood. The optical regulation of bone regeneration is systematically studied both in vitro and in vivo. Under green light irradiation, biochemical activities of bone marrow‐derived mesenchymal stem cells and their expression of osteogenic‐related factors are significantly elevated. By introducing green light into defective bone structures via fibers in a rodent model, the process of bone regeneration and repair is accelerated. Furthermore, fibers exhibit ideal biocompatibility with both cultured cells and living tissues and undergo complete degradation in vivo after ≈1 month. Assisted with degradable optical materials and devices, such as photobiomodulation technique provides a promising solution to tissue regeneration in various biomedical applications.
New vortex‐lift and tangential‐force models for HAWT aerodynamic load prediction
Authors: Elgammi Moutaz , Schepers Gerard , Osta‐Omar Salem
Published: April 2020

Horizontal axis wind turbines (HAWTs) experience three‐dimensional rotational and unsteady aerodynamic phenomena at the rotor blades sections. These highly unsteady three‐dimensional effects have a dramatic impact on the aerodynamic load distributions on the blades, in particular, when they occur at high angles of attack due to stall delay and dynamic stall. Unfortunately, there is no complete understanding of the flow physics yet at these unsteady 3D flow conditions, and hence, the existing published theoretical models are often incapable of modelling the impact on the turbine response realistically. The purpose of this paper is to provide an insight on the combined influence of the stall delay and dynamic stall on the blade load history of wind turbines in controlled and uncontrolled conditions. New dynamic stall vortex and nonlinear tangential force coefficient modules, which integrally take into account the three dimensional rotational effect, are also proposed in this paper. This module along with the unsteady influence of turbulent wind speed and tower shadow is implemented in a blade element momentum (BEM) model to estimate the aerodynamic loads on a rotating blade more accurately. This work presents an important step to help modelling the combined influence of the stall delay and dynamic stall on the load history of the rotating wind turbine blades which is vital to have lighter turbine blades and improved wind turbine design systems.
The full four-loop cusp anomalous dimension in $$ \mathcal{N} $$ = 4 super Yang-Mills and QCD
Authors: Henn Johannes M. , Korchemsky Gregory P. , Mistlberger Bernhard
Published: April 2020

Abstract

We present the complete formula for the cusp anomalous dimension at four loops in QCD and in maximally supersymmetric Yang-Mills. In the latter theory it is given by

$$ {\left.{\Gamma}_{\mathrm{cusp},\mathrm{A}}\right|}_{\alpha_s^4}=-{\left(\frac{\alpha_sN}{\pi}\right)}^4\left[\frac{73{\pi}^6}{20160}+\frac{\zeta_3^2}{8}+\frac{1}{N^2}\left(\frac{31{\pi}^6}{5040}+\frac{9{\zeta}_3^2}{4}\right)\right]. $$

Γ

cusp
,
A

α
s
4

=
−

α
s

N

π

4

73

π
6

20160

+

ζ
3
2

8

+

1

N
2

31

π
6

5040

+

9

ζ
3
2

4

.

Our approach is based on computing the correlation function of a rectangular light-like Wilson loop with a Lagrangian insertion, normalized by the expectation value of the Wilson loop. In maximally supersymmetric Yang-Mills theory, this ratio is a finite function of a cross-ratio and the coupling constant. We compute it to three loops, including the full colour dependence. Integrating over the position of the Lagrangian insertion gives the four-loop Wilson loop. We extract its leading divergence, which determines the four-loop cusp anomalous dimension. Finally, we employ a supersymmetric decomposition to derive the last missing ingredient in the corresponding QCD result.
Emerging roles of infiltrating granulocytes and monocytes in homeostasis
Authors: Groeneweg Linda , Hidalgo Andres , A-Gonzalez Noelia
Published: April 2020

The infiltration of naïve tissues by myeloid cells has been long related to their clearance and the physiological cell turnover, however, increasing evidence shows that they can additionally fulfill specific, non-immune functions in different tissues. There is also growing evidence to support that infiltrated granulocytes and monocytes respond to different environments by modulating gene expression and cytokine production, which in turn contribute to the normal function of the host tissue. This review will address the roles of immigrated myeloid cells in different tissues and their crosstalk with the host tissue environments.
GAD-alum immunotherapy in type 1 diabetes expands bifunctional Th1/Th2 autoreactive CD4 T cells
Authors: Arif Sefina , Gomez-Tourino Iria , Kamra Yogesh , Pujol-Autonell Irma , Hanton Emily , Tree Timothy , Melandri Daisy , Hull Caroline , Wherrett Diane K. , Beam Craig , Roep Bart O. , Lorenc Anna , Peakman Mark
Published: April 2020

Aims/hypothesis

Antigen-specific therapy aims to modify inflammatory T cell responses in type 1 diabetes and restore immune tolerance. One strategy employs GAD65 conjugated to aluminium hydroxide (GAD-alum) to take advantage of the T helper (Th)2-biasing adjuvant properties of alum and thereby regulate pathological Th1 autoimmunity. We explored the cellular and molecular mechanism of GAD-alum action in the setting of a previously reported randomised placebo-controlled clinical trial conducted by Type 1 Diabetes TrialNet.

Methods

In the clinical trial conducted by Type 1 Diabetes TrialNet, participants were immunised with 20 μg GAD-alum (twice or three times) or alum alone and peripheral blood mononuclear cell samples were banked at baseline and post treatment. In the present study, GAD-specific T cell responses were measured in these samples and GAD-specific T cell lines and clones were generated, which were then further characterised.

Results

At day 91 post immunisation, we detected GAD-specific IL-13+CD4 T cell responses significantly more frequently in participants immunised with GAD-alum (71% and 94% treated twice or three times, respectively) compared with those immunised with alum alone (38%;p = 0.003 andp = 0.0002, respectively) accompanied by high secreted levels of IL-13, IL-4 and IL-5, confirming a GAD-specific, GAD-alum-induced Th2 response. Of note, GAD-specific, IL-13+CD4 T cells observed after immunisation co-secreted IFN-γ, displaying a bifunctional Th1/Th2 phenotype. Single-cell transcriptome analysis identifiedIL13andIFNGexpression in concert with the canonical Th2 and Th1 transcription factor genesGATA3andTBX21, respectively. T cell receptor β-chain (TCRB) CDR3 regions of GAD-specific bifunctional T cells were identified in circulating naive and central memory CD4 T cell pools of non-immunised participants with new-onset type 1 diabetes and healthy individuals, suggesting the potential for bifunctional responses to be generated de novo by GAD-alum immunisation or via expansion from an existing public repertoire.

Conclusions/interpretation

GAD-alum immunisation activates and propagates GAD-specific CD4 T cells with a distinctive bifunctional phenotype, the functional analysis of which might be important in understanding therapeutic responses.
Incremental diagnostic value of [18F]tetrafluoroborate PET-CT compared to [131I]iodine scintigraphy in recurrent differentiated thyroid cancer
Authors: Dittmann Matthias , Gonzalez Carvalho José Manuel , Rahbar Kambiz , Schäfers Michael , Claesener Michael , Riemann Burkhard , Seifert Robert
Published: April 2020

Introduction

Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([131I]iodine) or limited availability ([124I]iodine). In contrast, [18F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [18F]TFB-PET to the clinical reference standard [131I]iodine scintigraphy in patients with recurrent DTC.

Methods

Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [18F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [131I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [18F]FDG-PET-CT was present for 21 patients. Histological verification of [18F]TFB positive findings was available in 4 patients.

Results

[18F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [131I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [131I]iodine scintigraphy was changed: [18F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [18F]TFB-PET-CT/MRI with [18F]FDG-PET-CT (64%).

Conclusion

In the present cohort, [18F]TFB-PET shows higher sensitivity and accuracy than [131I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [18F]TFB-PET with [18F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [18F]TFB-PET in recurrent DTC are warranted.
Mechanisms of enhanced ocean surface warming in the Kuroshio region for 1951–2010
Authors: Toda Masaki , Watanabe Masahiro
Published: April 2020

Since the early twentieth century, observations have shown that the ocean surface has warmed almost globally, but the rate of sea surface temperature (SST) rise in the Kuroshio region (KR) has been twice that of the global-mean. This study focuses on the mechanisms driving long-term changes in SST in the KR during the period 1951–2010 using observations, reanalysis data, and 10-member ensembles of historical simulations based on a global climate model (GCM) called MIROC 5.2. The observational data indicates that SST in the KR slightly decreased until around 1980, but rapidly increased afterwards. The MIROC5.2 historical experiment reproduced the observed multidecadal changes in the KR SST, and a signal-to-noise analysis showed that one third to half of the changes were attributable to a forced component, represented by the ensemble mean. Comparison of historical runs with another ensemble in which sulfate aerosols were fixed at preindustrial levels, highlighted that multidecadal SST changes in the KR were primarily driven by sulfate aerosols, contributing to the warming for 1981–2010 as much as greenhouse gases. Analyses of the MIROC5.2 ensemble mean revealed that the key factor for enhanced warming after the 1980s in the KR was a high-pressure trend over the North Pacific. This is because it advects warm air to the northwestern Pacific in the lower troposphere and causes a northward shift in the Kuroshio current. The presence of this mechanism was supported by a significant correlation between SST trends in the KR and high-pressure trends over the North Pacific based on historical simulations from 27 GCMs, and a large ensemble of historical simulations using MIROC6. These results demonstrate the importance of an externally forced atmospheric circulation response over the North Pacific as it relates to enhanced ocean surface warming in the KR.
A comparison of the satiating properties of medium-chain triglycerides and conjugated linoleic acid in participants with healthy weight and overweight or obesity
Authors: Maher Tyler , Deleuse Martina , Thondre Sangeetha , Shafat Amir , Clegg Miriam E.
Published: April 2020

Purpose

Inconsistent evidence exists for greater satiety after medium-chain triglycerides (MCT) or conjugated linoleic acid (CLA) compared to long-chain triglycerides (LCT). Furthermore, the mechanisms are poorly understood and effects in people with a healthy weight and those with overweight/obesity have not been compared. This study aimed to compare appetite responses in these groups and examine the mechanisms behind any differences.

Methods

Fifteen participants with healthy weight (BMI: 22.7 ± 1.9 kg·m−2) and fourteen participants with overweight/obesity (BMI: 30.9 ± 3.9 kg·m−2) consumed a breakfast containing either 23.06 g vegetable oil (CON), 25.00 g MCT oil (MCT), or 6.25 g CLA and 16.80 g vegetable oil (CLA). Appetite, peptide YY (PYY), total ghrelin (TG), β-hydroxybutyrate, and gastric emptying (GE) were measured throughout. Energy intake was assessed at an ad libitum lunch and throughout the following ~ 36 h.

Results

Neither MCT nor CLA decreased ad libitum intake; however MCT decreased day 1 energy intake (P = 0.031) and the 48-h period (P = 0.005) compared to CON. MCT delayed GE (P ≤ 0.01) compared to CON, whereas CLA did not. PYY and TG concentrations were not different (P = 0.743 and P = 0.188, respectively), but MCT increased β-hydroxybutyrate concentrations compared to CON (P = 0.005) and CLA (P < 0.001). β-hydroxybutyrate concentrations were higher in participants with overweight/obesity (P = 0.009).

Conclusion

Consumption of MCT reduces energy intake in the subsequent 48 h, whereas CLA does not. Delayed gastric emptying or increased β-hydroxybutyrate concentrations may mediate this.
Structural variations in a non-coding region at 1q32.1 are responsible for the NYS7 locus in two large families
Authors: Sun Wenmin , Li Shiqiang , Jia Xiaoyun , Wang Panfeng , Hejtmancik J. Fielding , Xiao Xueshan , Zhang Qingjiong
Published: April 2020

Congenital motor nystagmus (CMN) is characterized by early-onset bilateral ocular oscillations without other ocular deficits. To date, mutations in only one gene have been identified to be responsible for CMN, i.e., FRMD7 for X-linked CMN. Four loci for autosomal dominant CMN, including NYS7 (OMIM 614826), have been mapped but the causative genes have yet to be identified. NYS7 was mapped to 1q32.1 based on independent genome-wide linkage scan on two large families with CMN. In this study, mutations in all known protein-coding genes, both intronic sequence with predicted effect and coding sequence, in the linkage interval were excluded by whole-genome sequencing. Then, long-read genome sequencing based on the Nanopore platform was performed with a sample from each of the two families. Two deletions with an overlapping region of 775,699 bp, located in a region without any known protein-coding genes, were identified in the two families in the linkage region. The two deletions as well as their breakpoints were confirmed by Sanger sequencing and co-segregated with CMN in the two families. The 775,699 bp deleted region contains uncharacterized non-protein-coding expressed sequences and pseudogenes but no protein-coding genes. However, Hi-C data predicted that the deletions span two topologically associated domains and probably lead to a change in the 3D genomic architecture. These results provide novel evidence of a strong association between structural variations in non-coding genomic regions and human hereditary diseases like CMN with a potential mechanism involving changes in 3D genome architecture, which provides clues regarding the molecular pathogenicity of CMN.
Missing heritability in Parkinson’s disease: the emerging role of non-coding genetic variation
Authors: Ohnmacht Jochen , May Patrick , Sinkkonen Lasse , Krüger Rejko
Published: April 2020

Parkinson’s disease (PD) is a neurodegenerative disorder caused by a complex interplay of genetic and environmental factors. For the stratification of PD patients and the development of advanced clinical trials, including causative treatments, a better understanding of the underlying genetic architecture of PD is required. Despite substantial efforts, genome-wide association studies have not been able to explain most of the observed heritability. The majority of PD-associated genetic variants are located in non-coding regions of the genome. A systematic assessment of their functional role is hampered by our incomplete understanding of genotype–phenotype correlations, for example through differential regulation of gene expression. Here, the recent progress and remaining challenges for the elucidation of the role of non-coding genetic variants is reviewed with a focus on PD as a complex disease with multifactorial origins. The function of gene regulatory elements and the impact of non-coding variants on them, and the means to map these elements on a genome-wide level, will be delineated. Moreover, examples of how the integration of functional genomic annotations can serve to identify disease-associated pathways and to prioritize disease- and cell type-specific regulatory variants will be given. Finally, strategies for functional validation and considerations for suitable model systems are outlined. Together this emphasizes the contribution of rare and common genetic variants to the complex pathogenesis of PD and points to remaining challenges for the dissection of genetic complexity that may allow for better stratification, improved diagnostics and more targeted treatments for PD in the future.
Nonlinear electromechanical coupling in ferroelectric materials: large deformation and hysteresis
Authors: Humer Alexander , Pechstein Astrid S. , Meindlhumer Martin , Krommer Michael
Published: April 2020

Smart materials respond to external stimuli, e.g., electric fields, which enables their use as sensors and actuators. The electromechanical coupling of the direct and converse piezoelectric effects, for instance, is used for both actuation and sensing in diverse engineering applications. The response of ferroelectric materials depends on their state of remanent polarization and the presence of an external electric field. To extend the operational range of sensors and actuators, an accurate understanding of the evolution of the material’s state of polarization is imperative, which requires both physical and geometric nonlinearities to be taken into account. Moreover, polymeric smart materials like PVDF allow significantly larger deformation as compared to conventional piezoelectric ceramics. The electromechanical coupling in piezoelectric materials manifests in ferroelectric and ferroelastic hystereses, which are related to both reversible and irreversible processes. Focusing on the latter, we transfer phenomenological models for domain switching in ferroelectric materials to the geometrically nonlinear regime. For this purpose, we follow related concepts of geometrically nonlinear elastoplasticity, where the concept of a multiplicative decomposition of the deformation gradient plays a key role. Accordingly, an additional deformation path that describes the evolution of the poled state from the unpoled referential configuration is introduced. The constitutive response of the material to mechanical and electrical loads is discussed, and dissipative internal forces that drive the evolution of the remanent polarization are derived within a thermodynamical framework and the principle of maximum dissipation.
Purine tautomeric preferences and bond-length alternation in relation with protonation-deprotonation and alkali metal cationization
Authors: Raczyńska Ewa D. , Gal Jean-François , Maria Pierre-Charles , Kamińska Beata , Igielska Małgorzata , Kurpiewski Julian , Juras Weronika
Published: April 2020

Quantum chemical calculations were carried out for deprotonated (P−) and protonated purine (PH+) and for adducts with one alkali metal cation (P−M+ and PM+, where M+ is Li+ or Na+) in the gas phase {B3LYP/6-311+G(d,p)}, a model of perfectly apolar environment, and for selected structures in aqueous solution {PCM(water)//B3LYP/6-311+G(d,p)}, a reference polar medium for biological studies. All potential isomers of purine derivatives were considered, the favored structures indicated, and the preferred sites for protonation/deprotonation and cationization reactions determined. Proton and metal cation basicities of purine in the gas phase were discussed and compared with those of imidazole and pyrimidine. Bond-length alternations in the P, PH+, P−M+, and PM+ forms were quantitatively measured using the harmonic oscillator model of electron delocalization (HOMED) indices and compared with those for P. Variations of the HOMED values when proceeding from the purine structural building blocks, pyrimidine and imidazole, to the bicyclic purine system were also examined. Generally, the isolated NH isomers exhibit a strongly delocalized π-system (HOMED > 0.8). Deprotonation slightly increases the HOMED values, whereas protonation and cationization change the HOMED indices in different way. For bidentate M+-adducts, the HOMED values are larger than 0.9 like for the largely delocalized P−. The HOMED values correlate well in a comprehensive relationship with the relative Gibbs energies (ΔG) calculated for individual isomers whatever the purine form is, neutral, protonated, or cationized. When PCM-DFT model was utilized for P−, PH+, PM+, and P−M+ (M+ = Li+) both electron delocalization and relative stability are different from those for the molecules in vacuo. The solvation effects cause a slight increase in HOMEDs, whereas the ΔEs decrease, but in different ways. Hence, contribution of particular isomers in the isomeric mixtures of PH+, PM+, and P−M+ also varies.