bluuebunny/crossref_metadata_2025 huggingface dataset:
HNF4αpathway mapping identifies wild-typeIDH1as a targetable metabolic node in gastric cancer
Authors: Xu Chang , Ooi Wen Fong , Qamra Aditi , Tan Jing , Chua Benjamin Yan-Jiang , Ho Shamaine Wei Ting , Das Kakoli , Adam Isa Zul Fazreen , Li Zhimei , Yao Xiaosai , Yan Tingdong , Xing Manjie , Huang Kie Kyon , Lin Joyce Suling , Nandi Tannistha , Tay Su Ting , Lee Ming Hui , Tan Angie Lay Keng , Ong Xuewen , Ashktorab Hassan , Smoot Duane , Li Shang , Ng Shyh-Chang , Teh Bin Tean , Tan Patrick
Published: May 2019

Objective

Gastric cancer (GC) is a leading cause of cancer mortality. Previous studies have shown thathepatocyte nuclear factor-4α (HNF4α)is specifically overexpressed in GC and functionally required for GC development. In this study, we investigated, on a genome-wide scale, target genes of HNF4α and oncogenic pathways driven by HNF4α and HNF4α target genes.

Design

We performed HNF4α chromatin immunoprecipitation followed by sequencing across multiple GC cell lines, integrating HNF4α occupancy data with (epi)genomic and transcriptome data of primary GCs to define HNF4α target genes ofin vitroandin vivorelevance. To investigate mechanistic roles ofHNF4αand HNF4α targets, we performed cancer metabolic measurements, drug treatments and functional assays including murine xenograft experiments.

Results

Gene expression analysis across 19 tumour types revealedHNF4αto be specifically upregulated in GCs. Unbiased pathway analysis revealed organic acid metabolism as the topHNF4α-regulated pathway, orthogonally supported by metabolomic analysis. Isocitrate dehydrogenase 1 (IDH1) emerged as a convergentHNF4αdirect target gene regulating GC metabolism. We show that wild-typeIDH1is essential for GC cell survival, and that certain GC cells can be targeted by IDH1 inhibitors.

Conclusions

Our results highlight a role forHNF4αin sustaining GC oncogenic metabolism, through the regulation ofIDH1. Drugs targeting wild-typeIDH1may thus have clinical utility in GCs exhibitingHNF4αoverexpression, expanding the role ofIDH1in cancer beyondIDH1/2mutated malignancies.
Use of polyhalite mineral as an acidogenic ingredient for prepartum diets of non-lactating dairy cows
Authors: Ferreira Gonzalo , Teets Christy L. , Meakin Robert J.
Published: May 2019

We measured urine pH from cows fed a prepartum diet containing polyhalite mineral as an acidogenic salt. At 21 d before expected calving date (ECD), cows were transferred from the far-off to the close-up group. The polyhalite mineral was incorporated into a pelleted concentrate to provide 500 g d−1. Urine pH at −21, −14, −7, and 0 d relative to ECD was 8.26, 5.18, 5.12, and 5.15, respectively. These results indicate that a metabolic acidosis could be effectively induced when polyhalite mineral is included as an acidogenic source in close-up rations for pregnant and non-lactating dairy cows.
The early developmental stages of gall-inducing insects define final gall structural and histochemical profiles: the case of Bystracoccus mataybae galls on Matayba guianensis
Authors: Silva Ana Flávia de Melo , Kuster Vinícius Coelho , Rezende Uiara Costa , Oliveira Denis Coelho de
Published: May 2019

Gall morphotypes depend on continuous chemical and feeding stimuli of the gall inducer, which promotes specific structural and metabolic changes in plant tissues. The galling insect manipulates host-plant tissues and may stimulate the production of primary and secondary metabolites. The type of chemical arsenal and the storage site varies according to the developmental potentials of the host plant and the insect’s feeding habit. Here, we investigated whether the structural and histochemical profiles of the gall system Matayba guianensis Aubl. (Sapindaceae) – Bystracoccus mataybae (Eriococcidae) are dependent on the instars of the galling insect. Standard anatomical analyses were carried out, as well as histochemical evaluation of reactive oxygen species and primary and secondary metabolites. Structural changes induced by the first instar nymphs were detected on the stem, while deep changes induced by the second instar nymphs and adult females were detected in leaflet galls, indicating that the host-plant tissue can impose more limits on gall development and complexity than the stages of galling insect development. The compartmentalization of primary and secondary compounds is established during the early stages of development of the leaflet gall by the second instar nymphs. Despite deep structural differences between stem and leaflet galls, there were no significant changes in the establishment of the histochemical profiles.
A review of methodological approaches for saturation flow estimation at signalized intersections
Authors: Mondal Satyajit , Gupta Ankit
Published: May 2019

The estimation of the saturation flow is the utmost component for performance evaluation of a signalized intersection. The flow rate estimation procedure includes the analysis of the vehicles headway, vehicles discharge rate, passenger car unit, effective green time and cycle length of the signalling system. This study attempts to exhaustively review the existing literature and its suitability along with the multiple factors affecting the performance of signalized intersection. Different methodological approaches and soft computing techniques used worldwide by the researchers both in developed and developing countries are emphasized. This study also highlights the several influencing factors that have a significant impact on saturation flow value and several methodological approaches to determine the flow value through normalizing the influencing factors, which lead to a better way for planning and designing of a signalized intersection.
Stability of Solutions and Continuity of Solution Maps of Tensor Complementarity Problems
Authors: Bai Xue-Li , Huang Zheng-Hai , Li Xia
Published: May 2019

Recently, tensor complementarity problems are becoming more and more popular. There are various literatures considering all kinds of properties of tensor complementarity problems, however, the stability of solutions and the continuity of solution maps are rarely mentioned so far. In the present paper, we study these two properties for tensor complementarity problems. We propose conditions under which the solutions of tensor complementarity problems are stable with the help of the tensor variational inequality or structured tensors. We also show that the solution maps of tensor complementarity problems are upper semicontinuous with the involved tensors being [Formula: see text]-tensors. Meanwhile, we establish the relationship between the uniqueness of solutions and the continuity of solution maps of tensor complementarity problems.
Edge-Cuts of Optimal Average Weights
Authors: Payne Scott , Fuller Edgar , Zhang Cun-Quan
Published: May 2019

Let [Formula: see text] be a directed graph associated with a weight [Formula: see text]. For an edge-cut [Formula: see text] of [Formula: see text], the average weight of [Formula: see text] is denoted and defined as [Formula: see text]. An optimal edge-cut with average weight is an edge-cut [Formula: see text] such that [Formula: see text] is maximum among all edge-cuts (or minimum, symmetrically). In this paper, a polynomial algorithm for this problem is proposed for finding an optimal edge-cut in a rooted tree separating the root and the set of all leafs. This algorithm enables us to develop an automatic clustering method with more accurate detection of community output.
An Inexact Projected Gradient Method for Sparsity-Constrained Quadratic Measurements Regression
Authors: Fan Jun , Wang Liqun , Yan Ailing
Published: May 2019

In this paper, we employ the sparsity-constrained least squares method to reconstruct sparse signals from the noisy measurements in high-dimensional case, and derive the existence of the optimal solution under certain conditions. We propose an inexact sparse-projected gradient method for numerical computation and discuss its convergence. Moreover, we present numerical results to demonstrate the efficiency of the proposed method.
Tachyonic braneworld mimetic cosmology
Authors: Sadatian S. Davood , Sepehri Alireza
Published: May 2019

Recently, some authors have generalized the idea of mimetic gravity to a Randall–Sundrum II braneworld model [L. Randall and R. Sundrum, Phys. Rev. Lett. 83, 3370 (1999); L. Randall and R. Sundrum, Phys. Rev. Lett. 83, 4690 (1999)] and introduced Braneworld Mimetic Cosmology. In this paper, we extend their new cosmological model to brane–anti-brane systems and obtain the explicit form of potential which appeared in their action. This potential depends on the tachyonic fields, the separation distance between two branes and time. On the other hand, our universe is located on one of the branes and its evolution is controlled by the potential between two branes. By passing time and decreasing the separation distance between branes, more energy dissolves into branes and the universe expands. In the following, we presented the physical applications such as late time accelerating phase, inflation model and behavior of perturbations, with respect to brane–anti-brane system. Finally, we briefly discussed the moduli stabilization of the model.
Collective classical motion on hyperbolic spacetimes of any dimensions
Authors: Cotăescu Ion I.
Published: May 2019

The geodesics equations on de Sitter (dS) and anti-de Sitter (AdS) spacetimes of any dimensions, are the starting point for deriving the general form of the Boltzmann equation in terms of conserved quantities. The simple equation for the non-equilibrium Marle and Anderson–Witting models are derived and the distributions of the Boltzmann–Marle model on these manifolds are written down first in terms of conserved quantities and then as functions of canonical variables.
Understanding of two-zero textures of neutrino mass matrices in minimal extended seesaw mechanism and their symmetry realization
Authors: Patgiri Mahadev , Kumar Priyanka
Published: May 2019

We study the texture zeros of [Formula: see text] neutrino mass matrices [Formula: see text] in the minimal extended type-I seesaw (MES) mechanism, incorporating one extra gauge singlet field “[Formula: see text]”. The [Formula: see text]  MES model deals with [Formula: see text]  [Formula: see text], [Formula: see text]  [Formula: see text] and [Formula: see text] mass matrix [Formula: see text] which couples the right-handed neutrinos and the singlet field “[Formula: see text]”. We carry out the mapping of all possible zero textures of [Formula: see text], [Formula: see text] and [Formula: see text] with the restriction to phenomenologically predictive cases having total eight zeros of [Formula: see text] and [Formula: see text] studied in the literature. If [Formula: see text], the sterile neutrino mass, is subject to any limit, further block diagonalization of [Formula: see text] shall not be allowed to reduce it to a [Formula: see text] matrix. In [Formula: see text]  [Formula: see text] scenario, the study of texture zero is totally different and interesting. With this motivation, we consider the [Formula: see text] scheme where the digits of the pair represent the number of zeros of [Formula: see text] and [Formula: see text], respectively, along with the one/two-zero textures of [Formula: see text]. There are a large number of possibilities of zeros of fermion mass matrices, but the implementation of [Formula: see text] transformations reduces it to a very minimum number of basic structures. As the [Formula: see text] MES matrix is a matrix of rank 3, so we consider only those textures with two zeros which are of rank 3 whereby the number of feasible zero textures reduces to 12, out of 15. On realizing these 12 textures under MES mechanism with [Formula: see text] picture, we arrive at certain correlations for each texture. We examine the viability of each texture by scanning their respective correlations under recent neutrino oscillation data. Also, we discuss the interplay of Dirac and Majorana CP phases in determining the viability of a texture. The allowed two-zero textures are finally realized using a discrete Abelian flavor symmetry group [Formula: see text] with the extension of Standard Model to include some scalar fields.
Performance assessments of the fully submerged sphere and cylinder point absorber wave energy converters
Authors: Xu Qianlong , Li Ye , Xia Yingkai , Chen Weixing , Gao Feng
Published: May 2019

Fully submerged sphere and cylinder point absorber (PA), wave energy converters (WECs) are analyzed numerically based on linearized potential flow theory. A boundary element method (BEM) (a radiation–diffraction panel program for wave-body interactions) is used for the basic wave-structure interaction analysis. In the present numerical model, the viscous damping is modeled by an equivalent linearized damping which extracts the same amount of wave energy over one cycle as the conventional quadratic damping term. The wave power capture width in each case is predicted. Comparisons are also made between the sphere and cylinder PAs which have identical geometrical scales and submerged depths. The results show that: (i) viscous damping has a greater influence on wave power performance of the cylinder PA than that of the sphere PA; (ii) the increasing wave height reduces wave power performance of PAs; (iii) the cylinder PA has a better wave power performance compared to the sphere PA in larger wave height scenarios, which indicates that fully submerged cylinder PA is a preferable prototype of WEC.
Effect of triangle behavior on topological properties of weighted networks
Authors: An Qi , Zhou Yajing , Chen Kehua , Chen Weilong , Yan Guan , Liu Zhidong
Published: May 2019

As an essential dynamic evolving mechanism, triangle behavior can be observed ubiquitously in the real world. Combining transfer mechanism with weighted dynamic, in this paper, we propose a new community model and deduce the strength distribution. Consistent with the theoretical results, numerical simulations show decent right-skewed scale-free characters of strength distribution. Moreover, we calculate some important coefficients to analyze the correlations of nodes and demonstrate the disassortative property of this model. Finally, the process of epidemic spreading with different weighted transmission rate is introduced on the weighted community network, and the results indicate that the triangle behavior has a significant influence on the dynamic of the epidemic spreading. Composed with the models proposed already, our model is supposed to be closer to the realistic network and imitate the real system more accurately and exactly.
CORPORATE CHAMPIONS OF EARLY-STAGE PROJECT PROPOSALS AND THE INSTITUTIONALISATION OF ORGANISATIONAL INERTIA
Authors: BERTELS HEIDI M. J. , MITHANI MURAD , ZHU SIWEI , KOEN PETER A.
Published: May 2019

This study looks at the role of champions in the early stages of the product development process, when employees try to secure initial funding for project proposals. Project proposals that fail to receive funding never become part of the firm’s project pipeline; hence, it is critical to understand the champion’s role early on. Existing research on corporate champions is mostly focused on the later stages of the new product development process and has generally identified corporate champions as key to projects likely to face organisational resistance. However, several recent studies suggest that champions may prefer projects less likely to face organisational resistance. Using data from project proposals of executive MBA students across 78 large organisations, we find that champion support for the team is weaker for project proposals likely to evoke resistance and that such lower champion support further reduces the likelihood of high-resistance early-stage proposals to receive initial funding.
The Enhancement of Upconversion Luminescence of Gd2O3:Yb,Er Nanoparticles by Ca2+ Codoping for Temperature Sensing at Room and High Temperatures
Authors: Liu Haiquan , Rong Jianing , Song Yao , Shen Guoqiong , Gu Wen , Liu Xin
Published: May 2019

We prepared a series of Gd2O3:Yb,Er,Ca (3/1/[Formula: see text][Formula: see text]mol.%, [Formula: see text] represents the nominal concentration of Ca element including 0, 2, 3, 4, 5, 7, 10) upconversion nanoparticles (UCNPs) with regular morphology via a wet-chemical route. We observed a simultaneous enhancement of upconversion luminescence (UCL) emission of Gd2O3:Yb,Er after Ca[Formula: see text] ions were doped. When the doping level of Ca[Formula: see text] reaches its optimal concentrate at 5[Formula: see text]mol.%, the red and green emissions increased by 6.3 and 11 times, respectively. The potential application of Gd2O3:Yb,Er,Ca material as a noninvasion optical thermometry based on FIR technique was investigated. The sensing of temperature at both high and room temperatures was realized by choosing different parameters. The absolute temperature sensitivity ([Formula: see text]) of Gd2O3:Yb,Er nanoparticles at 293[Formula: see text]K reached 0.0875[Formula: see text]K[Formula: see text], whereas Gd2O3:Yb,Er, 5[Formula: see text]mol.%Ca was chosen as sensor of high temperature due to its considerable Sa of 0.0060[Formula: see text]K[Formula: see text] at 573[Formula: see text]K. The resultant UCNPs provided a new way for sensitive thermal detection at various target temperatures.
Wedge Cameras for Minimally Invasive Archaeology
Authors: Crespel Thomas , Travis Adrian , Reuter Patrick , Granier Xavier
Published: May 2019

Acquiring images of archaeological artifacts is an essential step for the study and preservation of cultural heritage. In constrained environments, traditional acquisition techniques may fail or be too invasive. We present an optical device including a camera and a wedge waveguide that is optimized for imaging within confined spaces in archeology. The major idea is to redirect light by total internal reflection to circumvent the lack of room, and to compute the final image from the raw data. We tested various applications on site during an archaeological mission in Medamoud (Egypt). Our device was able to successfully record images of the underground from slim trenches of about 15cm wide, including underwater trenches, and between rocks composing a wall temple. Experts agreed that the acquired images were good enough to get useful information that cannot be obtained as easily with traditional techniques.
A Survey of Opinion Mining in Arabic
Authors: Badaro Gilbert , Baly Ramy , Hajj Hazem , El-Hajj Wassim , Shaban Khaled Bashir , Habash Nizar , Al-Sallab Ahmad , Hamdi Ali
Published: May 2019

Opinion-mining or sentiment analysis continues to gain interest in industry and academics. While there has been significant progress in developing models for sentiment analysis, the field remains an active area of research for many languages across the world, and in particular for the Arabic language, which is the fifth most-spoken language and has become the fourth most-used language on the Internet. With the flurry of research activity in Arabic opinion mining, several researchers have provided surveys to capture advances in the field. While these surveys capture a wealth of important progress in the field, the fast pace of advances in machine learning and natural language processing (NLP) necessitates a continuous need for a more up-to-date literature survey. The aim of this article is to provide a comprehensive literature survey for state-of-the-art advances in Arabic opinion mining. The survey goes beyond surveying previous works that were primarily focused on classification models. Instead, this article provides a comprehensive system perspective by covering advances in different aspects of an opinion-mining system, including advances in NLP software tools, lexical sentiment and corpora resources, classification models, and applications of opinion mining. It also presents future directions for opinion mining in Arabic. The survey also covers latest advances in the field, including deep learning advances in Arabic Opinion Mining. The article provides state-of-the-art information to help new or established researchers in the field as well as industry developers who aim to deploy an operational complete opinion-mining system. Key insights are captured at the end of each section for particular aspects of the opinion-mining system giving the reader a choice of focusing on particular aspects of interest.
Approximation Schemes for Machine Scheduling with Resource (In-)dependent Processing Times
Authors: Jansen Klaus , Maack Marten , Rau Malin
Published: May 2019

We consider two related scheduling problems: single resource-constrained scheduling on identical parallel machines and a generalization with resource-dependent processing times. In both problems, jobs require a certain amount of an additional resource and have to be scheduled on machines minimizing the makespan, while at every point in time a given resource capacity is not exceeded. In the first variant of the problem, the processing times and resource amounts are fixed, while in the second the former depends on the latter.

Both problems contain bin packing with cardinality constraint as a special case, and, therefore, these problems are strongly NP-complete even for a constant number of machines larger than three, which can be proven by a reduction from 3-Partition. Furthermore, if the number of machines is part of the input, then we cannot hope for an approximation algorithm with absolute approximation ratio smaller than 3/2.

We present asymptotic fully polynomial time approximation schemes (AFPTAS) for the problems: For any ε > 0, a schedule of length at most (1+ε) times the optimum plus an additive term of
O
(
p
max
log (1/ε)/ε) is provided, and the running time is polynomially bounded in 1/ε and the input length. Up to now, only approximation algorithms with absolute approximation ratios were known. Furthermore, the AFPTAS for resource-constrained scheduling on identical parallel machines directly improves the additive term of the best AFPTAS for bin packing with cardinality constraint so far.
Variant Grassmann Manifolds
Authors: Hong Junyuan , Li Yang , Chen Huanhuan
Published: May 2019

In classification tasks, classifiers trained with finite examples might generalize poorly to new data with unknown variance. For this issue, data augmentation is a successful solution where numerous artificial examples are added to training sets. In this article, we focus on the data augmentation for improving the accuracy of action recognition, where action videos are modeled by linear dynamical systems and approximately represented as linear subspaces. These subspace representations lie in a non-Euclidean space, named Grassmann manifold, containing points as orthonormal matrixes. It is our concern that poor generalization may result from the variance of manifolds when data come from different sources or classes. Thus, we introduce infinitely many
variant Grassmann manifolds
(VGM) subject to a known distribution, then represent each action video as different Grassmann points leading to augmented representations. Furthermore, a prior based on the stability of subspace bases is introduced, so the manifold distribution can be adaptively determined, balancing discrimination and representation. Experimental results of multi-class and multi-source classification show that VGM softmax classifiers achieve lower test error rates compared to methods with a single manifold.
The Relationship between Online Social Network Ties and User Attributes
Authors: Mahmoudi Amin , Yaakub Mohd Ridzwan , Bakar Azuraliza Abu
Published: May 2019

The distance between users has an effect on the formation of social network ties, but it is not the only or even the main factor. Knowing all the features that influence such ties is very important for many related domains such as location-based recommender systems and community and event detection systems for online social networks (OSNs). In recent years, researchers have analyzed the role of user geo-location in OSNs. Researchers have also attempted to determine the probability of friendships being established based on distance, where friendship is not only a function of distance. However, some important features of OSNs remain unknown. In order to comprehensively understand the OSN phenomenon, we also need to analyze users’ attributes. Basically, an OSN functions according to four main user properties: user geo-location, user weight, number of user interactions, and user lifespan. The research presented here sought to determine whether the user mobility pattern can be used to predict users’ interaction behavior. It also investigated whether, in addition to distance, the number of friends (known as user weight) interferes in social network tie formation. To this end, we analyzed the above-stated features in three large-scale OSNs. We found that regardless of a high degree freedom in user mobility, the fraction of the number of outside activities over the inside activity is a significant fraction that helps us to address the user interaction behavior. To the best of our knowledge, research has not been conducted elsewhere on this issue. We also present a high-resolution formula in order to improve the friendship probability function.
Good markets (really do) make good neighbors
Authors: Kominers Scott Duke
Published: May 2019

This article gives a (very) brief exposition of what market design is, along with four examples of market design in action. Loosely themed after Robert Frost's poem "Mending Wall," the examples demonstrate ways in which market design can break barriers---physical, political, and/or metaphorical. Each example also illustrates one of four broader classes of ways that market design can create positive change: marketplace mechanism (re-)design, information provision, (re-)shaping the extensive margin, and market(place) creation.
Game dynamics as the meaning of a game
Authors: Papadimitriou Christos , Piliouras Georgios
Published: May 2019

Learning dynamics have traditionally taken a secondary role to Nash equilibria in game theory. We propose a new approach that places the understanding of game dynamics over mixed strategy profiles as the central object of inquiry. We focus on the stable recurrent points of the dynamics,
i.e.
states which are likely to be revisited infinitely often; obviously, pure Nash equilibria are a special case of such behavior. We propose a new solution concept, the Markov-Conley Chain (MCC), which has several favorable properties: It is a simple randomized generalization of the pure Nash equilibrium, just like the mixed Nash equilibrium; every game has at least one MCC; an MCC is invariant under additive constants and positive multipliers of the players' utilities; there is a polynomial number of MCCs in any game, and they can be all computed in polynomial time; the MCCs can be shown to be, in a well defined sense, surrogates or traces of an important but elusive topological object called the sink chain component of the dynamics; finally, it can be shown that a natural game dynamics surely ends up at one of the MCCs of the game.
Integrated proteomics and metabolomics analysis reveals differential lipid metabolism in human umbilical vein endothelial cells under high and low shear stress
Authors: Venturini Gabriela , Malagrino Pamella Araujo , Padilha Kallyandra , Tanaka Leonardo Yuji , Laurindo Francisco Rafael , Dariolli Rafael , Carvalho Valdemir Melechco , Cardozo Karina Helena Morais , Krieger Jose Eduardo , Pereira Alexandre da Costa
Published: May 2019

Atherosclerotic plaque development is closely associated with the hemodynamic forces applied to endothelial cells (ECs). Among these, shear stress (SS) plays a key role in disease development since changes in flow intensity and direction could stimulate an atheroprone or atheroprotective phenotype. ECs under low or oscillatory SS (LSS) show upregulation of inflammatory, adhesion, and cellular permeability molecules. On the contrary, cells under high or laminar SS (HSS) increase their expression of protective and anti-inflammatory factors. The mechanism behind SS regulation of an atheroprotective phenotype is not completely elucidated. Here we used proteomics and metabolomics to better understand the changes in endothelial cells (human umbilical vein endothelial cells) under in vitro LSS and HSS that promote an atheroprone or atheroprotective profile and how these modifications can be connected to atherosclerosis development. Our data showed that lipid metabolism, in special cholesterol metabolism, was downregulated in cells under LSS. The low-density lipoprotein receptor (LDLR) showed significant alterations both at the quantitative expression level as well as regarding posttranslational modifications. Under LSS, LDLR was seen at lower concentrations and with a different glycosylation profile. Finally, modulating LDLR with atorvastatin led to the recapitulation of a HSS metabolic phenotype in EC under LSS. Altogether, our data suggest that there is significant modulation of lipid metabolism in endothelial cells under different SS intensities and that this could contribute to the atheroprone phenotype of LSS. Statin treatment was able to partially recover the protective profile of these cells.
Wnt signaling regulates cytosolic translocation of connexin 43
Authors: Hou Xiaoming , Khan Mohammad R. A. , Turmaine Mark , Thrasivoulou Christopher , Becker David L , Ahmed Aamir
Published: May 2019

The availability of intracellular, stabilized β-catenin, a transcription factor coactivator, is tightly regulated; β-catenin is translocated into the nucleus in response to Wnt ligand binding to its cell membrane receptors. Here we show that Wnt signal activation in mammalian cells activates intracellular mobilization of connexin 43 (Cx43), which belongs to a gap junction protein family, a new target protein in response to extracellular Wnt signal activation. Transmission electron microscopy showed that the nuclear localization of Cx43 was increased by 8- to 10-fold in Wnt5A- and 9B-treated cells compared with controls; this Wnt-induced increase was negated in the cells where Cx43 and β-catenin were knocked down using shRNA. There was a significant ( P < 0.001) and concomitant depletion of the cell membrane and cytosolic signal of Cx43 in Wnt-treated cells with an increase in the nuclear signal for Cx43; this was more obvious in cells where β-catenin was knocked down using shRNA. Conversely, Cx43 knockdown resulted in increased β-catenin in the nucleus in the absence of Wnt activation. Coimmunoprecipitation of Cx43 and β-catenin proteins with a casein kinase (CKIδ) antibody showed that Cx43 interacts with β-catenin and may form part of the so-called destruction complex. Functionally, Wnt activation increased the rate of wound reepithelization in rat skin in vivo.
Motor module generalization across balance and walking is impaired after stroke
Authors: Allen Jessica L. , Kesar Trisha M. , Ting Lena H.
Published: May 2019

Muscle coordination is often impaired after stroke, leading to deficits in the control of walking and balance. In this study, we examined features of muscle coordination associated with reduced walking performance in chronic stroke survivors using motor module (a.k.a. muscle synergy) analysis. We identified differences between stroke survivors and age-similar neurotypical controls in the modular control of both overground walking and standing reactive balance. In contrast to previous studies that demonstrated reduced motor module number poststroke, our cohort of stroke survivors did not exhibit a reduction in motor module number compared with controls during either walking or reactive balance. Instead, the pool of motor modules common to walking and reactive balance was smaller, suggesting reduced generalizability of motor module function across behaviors. The motor modules common to walking and reactive balance tended to be less variable and more distinct, suggesting more reliable output compared with motor modules specific to either behavior. Greater motor module generalization in stroke survivors was associated with faster walking speed, more normal step length asymmetry, and narrower step widths. Our work is the first to show that motor module generalization across walking and balance may help to distinguish important and clinically relevant differences in walking performance across stroke survivors that would have been overlooked by examining only a single behavior. Finally, because similar relationships between motor module generalization and walking performance have been demonstrated in healthy young adults and individuals with Parkinson’s disease, this suggests that motor module generalization across walking and balance may be important for well-coordinated walking.

NEW & NOTEWORTHY This is the first work to simultaneously examine neuromuscular control of walking and standing reactive balance in stroke survivors. We show that motor module generalization across these behaviors (i.e., recruiting common motor modules) is reduced compared with controls and is associated with slower walking speeds, asymmetric step lengths, and larger step widths. This is true despite no between-group differences in module number, suggesting that motor module generalization across walking and balance is important for well-coordinated walking.
Discovery of DNA Motif Utilising an Integrated Strategy Based on Random Projection and Particle Swarm Optimization
Authors: Ge Hongwei , Yu Jinghong , Sun Liang , Wang Zhen , Yao Yao
Published: May 2019

During the process of gene expression and regulation, the DNA genetic information can be transferred to protein by means of transcription. The recognition of transcription factor binding sites can help to understand the evolutionary relations among different sequences. Thus, the problem of recognition of transcription factor binding sites, i.e., motif recognition, plays an important role for understanding the biological functions or meanings of sequences. However, when the established search space processes much noise subsequences, many optimization algorithms tend to be trapped into local optimum. In order to solve this problem, a particle swarm optimization and random projection‐based algorithm (PSORPS) is proposed for recognizing DNA motifs. First, a random projection strategy is employed to filter the noise subsequences for constructing the objective space. Moreover, the sequence segments distributed in the majority of DNA sequences can be obtained and used for the population initialization of PSO. Then, the motifs of DNA sequences can be automatically searched by using a designed PSO algorithm in the constructed l‐mer objective space. Finally, to alleviate the base deviation and further improve the recognition accuracy, the two operators of associated drift and independent drift are performed on the optimization results obtained by PSO. The experiments are conducted on real‐world biological datasets, and the experimental results verify the effectiveness of the proposed algorithm.
The Evaluation of Different Radiological Measurement Parameters of the Degree of Collapse of the Vertebral Body in Vertebral Compression Fractures
Authors: Hsu Wei-En , Su Kuo-Chih , Chen Kun-Hui , Pan Chien-Chou , Lu Wen-Hsien , Lee Cheng-Hung
Published: May 2019

For compression fracture, vertebral body height loss (VBHL) and kyphotic angle (KA) are two important imaging parameters for determining the prognosis and appropriate treatment. This study used previous measurement methods to assess the degree of VBHL and KA, compare and examine differences between various measurement methods, and examine the correlation between relevant measurement parameters and intravertebral cleft (IVC) in the vertebral body. The radiographic images (lateral view of the T-L spine) of 18 patients with a single-level vertebral compression fracture were reviewed. We measured 9 characteristic lengths and angles on plain radiographs, including anterior vertebral height (AVH) and AVH of the adjacent upper and lower levels, middle vertebral height (MVH) and MVH of the adjacent upper and lower levels, posterior vertebral height (PVH), and vertebral body width, and assessed 6 parameters, including vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), percentage of middle height compression (PMHC), kyphotic angle (KA), calculated kyphotic angle (CKA), and IVC. The results showed that VBCR is a simple and rapid method of VBHL assessment, but it may result in an underestimation of the degree of VBHL compared to PAHC. WhenPMHC<40%orkyphotic angle>15°, the probability of IVC occurring on the vertebral body was higher which means the higher risk of vertebral body instability. The results of this study could provide a reference for surgeons when using imaging modalities to assess the degree of vertebral body collapse.
Desired Terminal State Concept in Model Predictive Control: A Case Study
Authors: Dušek František , Honc Daniel
Published: May 2019

The paper deals with an online optimization control method for dynamical processes called Model Predictive Control (MPC). It is a popular control method in industry and frequently treated in academic areas as well. The standard predictive controllers usually do not guarantee stability especially for the case of short horizons and large control error penalization. Terminal state is one way to ensure stability or at least increase the controller robustness. In the paper, deviation of the predicted terminal state from the desired terminal state is considered as one term of the cost function. Effect of the stability and control quality is demonstrated in the simulated experiments. The application area for online optimization methods is very broad including various logistics and transport problems. If the dynamics of the controlled processes cannot be neglected, the optimization problem must be solved not only for steady state but also for transient behaviour, e.g., by MPC.
Analysis of Retinal Perfusion in Children, Adolescents, and Young Adults with Type 1 Diabetes Using Optical Coherence Tomography Angiography
Authors: Mameli Chiara , Invernizzi Alessandro , Bolchini Alice , Bedogni Giorgio , Giani Elisa , Macedoni Maddalena , Zuccotti Gianvincenzo , Preziosa Chiara , Pellegrini Marco
Published: May 2019

We performed a cross-sectional study to analyze the retinal vasculature in children, adolescent, and young adults with type 1 diabetes using optical coherence tomography angiography (OCTA). Patients underwent funduscopic examination for diabetic retinopathy (DR) screening during an annual visit for the screening of diabetes-related complications which included the evaluation of glycated hemoglobin (HbA1c), microalbuminuria, lipid profile, arterial pressure, and neurological assessment. In addition, OCTA of the retinal vasculature was performed. Quantitative analysis of the OCTA images evaluated the vessel density at the superficial (SCP) and deep (DCP) capillary plexus of the retina. Structural vascular alterations were evaluated qualitatively. Results were compared to those obtained in a group of healthy age-, sex-, and pubertal stage-matched controls. The effect of age, disease duration, age at the disease onset, mean HbA1c since the onset, and lipid profile on vascular density was tested. Fifty-three patients (median age 15.5, IQR 12.4-19.4 years; 57% females) with type 1 diabetes and 48 controls were enrolled. The median (IQR) HbA1c was 7.6% (60 mmol/mol) (6.9-8.1%, 52-65 mmol/mol), and the median (IQR) duration of disease was 6.0 (3.3-10.3) years. Mean vessel density measured with OCTA was lower in patients compared to controls with the temporal sector showing the highest difference both in the SCP (0.55 vs. 0.57, p<0.001) and the DCP (0.63 vs. 0.65, p<0.001). None of the predictors was associated with the superficial and deep vascular densities. Only 2 patients had clinically detectable DR. Microvascular structural changes were found on OCTA in both of these patients and in one without funduscopic alterations. In conclusion, patients with type 1 diabetes without clinically detectable DR had decreased capillary density compared to controls on OCTA images. These findings may provide useful information for the screening and the management of patients with type 1 diabetes. Further studies are needed to confirm our results and their clinical relevance.
Quantitative Phase-Field Simulation of Composition Partition and Separation Kinetics of Nanoscale Phase in Fe-Cr-Al Alloy
Authors: Chen Shi , Li Yongsheng , Shi Shujing , Jin Shengshun
Published: May 2019

Phase separation of the Cr-enriched nanoscaleα′phase in the Fe-38 at.% Cr-10 at.% Al alloy is studied by utilizing phase-field simulation. The partition of elements in theαandα′phases is clarified with the composition evolution through theα/α′phase interface, and the separation kinetics is quantitatively investigated by the temporal evolution of the size and volume fraction of theα′phase. Aluminum partitions into the Fe-enrichedαphase and depletes in theα′phase, and the partition coefficient decreases as the temperature changes from 720 K to 760 K for the steady-state coarsening stage. As the temperature increases, the initial change rate of the volume fraction of theα′phase is faster, indicating an accelerated phase separation. At the coarsening stage, the average particle distance and coarsening rate constant of theα′phase increase with increased temperature, and the ratio of the Ostwald ripening is dominating compared with coalescence coarsening. The element partition and kinetics evolution of theα′phase with temperature are helpful for the morphology and property predication of nanoscale precipitates.
SPH Simulation on the Coupled Failure of Slope‐Building Adjacent to Water Triggered by the Rapid Drawdown of Water Level
Authors: Zhou Yundong , Qu Zhangcheng , Zhang Weijie , Wang Zhanbin
Published: May 2019

With the development of economy, more and more buildings are constructed on both sides of rivers. The rapid drawdown of water level may induce the change of groundwater seepage in the river bank, thus affecting the stability of buildings on the bank. In this study, the right bank of Qinhuai river with its ancillary building from the Dinghuai Gate to the Qingliang Gate in Nanjing City is analyzed to reveal the failure mechanism and coupled failure mode of slope and building adjacent to water. The soil‐water coupled SPH program considering the interaction between soil and structure has been proposed. Then this model is used to study the evolutionary deformation mechanism of slope and building under the rapid drawdown of water level. The results indicate that the potential slip surface of slope and the asymmetrical distribution of plastic zone in the foundation of building become more obvious under the rapid drawdown of water level. Besides, the differential settlement of building induced by the rapid drawdown causes the building tilt. When the sliding surface of the slope passes the building, the differential settlement will become larger. This study is conducive to reveal the coupled failure mechanism of slope and building and also to provide scientific basis for the prevention of such disasters.
NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma
Authors: Jones Martin R. , Williamson Laura M. , Topham James T. , Lee Michael K.C. , Goytain Angela , Ho Julie , Denroche Robert E. , Jang GunHo , Pleasance Erin , Shen Yaoquing , Karasinska Joanna M. , McGhie John P. , Gill Sharlene , Lim Howard J. , Moore Malcolm J. , Wong Hui-li , Ng Tony , Yip Stephen , Zhang Wei , Sadeghi Sara , Reisle Carolyn , Mungall Andrew J. , Mungall Karen L. , Moore Richard A. , Ma Yussanne , Knox Jennifer J. , Gallinger Steven , Laskin Janessa , Marra Marco A. , Schaeffer David F. , Jones Steven J.M. , Renouf Daniel J.
Published: May 2019

Purpose:

Gene fusions involving neuregulin 1 (NRG1) have been noted in multiple cancer types and have potential therapeutic implications. Although varying results have been reported in other cancer types, the efficacy of the HER-family kinase inhibitor afatinib in the treatment of NRG1 fusion–positive pancreatic ductal adenocarcinoma is not fully understood.

Experimental Design:

Forty-seven patients with pancreatic ductal adenocarcinoma received comprehensive whole-genome and transcriptome sequencing and analysis. Two patients with gene fusions involving NRG1 received afatinib treatment, with response measured by pretreatment and posttreatment PET/CT imaging.

Results:

Three of 47 (6%) patients with advanced pancreatic ductal adenocarcinoma were identified as KRAS wild type by whole-genome sequencing. All KRAS wild-type tumors were positive for gene fusions involving the ERBB3 ligand NRG1. Two of 3 patients with NRG1 fusion–positive tumors were treated with afatinib and demonstrated a significant and rapid response while on therapy.

Conclusions:

This work adds to a growing body of evidence that NRG1 gene fusions are recurrent, therapeutically actionable genomic events in pancreatic cancers. Based on the clinical outcomes described here, patients with KRAS wild-type tumors harboring NRG1 gene fusions may benefit from treatment with afatinib.

See related commentary by Aguirre, p. 4589
Reprogramming of Isocitrate Dehydrogenases Expression and Activity by the Androgen Receptor in Prostate Cancer
Authors: Gonthier Kevin , Poluri Raghavendra Tejo Karthik , Weidmann Cindy , Tadros Maude , Audet-Walsh Étienne
Published: May 2019

Mutations of the isocitrate dehydrogenase genes IDH1 and IDH2, key enzymes involved in citrate metabolism, are important oncogenic events in several cancer types, including in 1%–3% of all prostate cancer cases. However, if IDH1 and other IDH isoforms are associated with prostate cancer progression, as well as the regulatory factors controlling their expression and activity, remain mostly unknown. Using publicly available datasets, we showed that prostate cancer harbors the highest IDH1 expression across the human cancer spectrum and that IDH1 expression is altered during prostate cancer progression. We showed that the androgen receptor (AR), a key oncogene in prostate cancer, controls multiple IDH isoforms in both in vitro and in vivo models, predominantly positively regulating IDH1. Chromatin immunoprecipitation experiments confirmed the recruitment of AR at several regulatory regions of IDH1 and enzymatic assays demonstrated that AR significantly induces IDH activity. Genetic blockade of IDH1 significantly impaired prostate cancer cell proliferation, consistent with IDH1 having a key function in these cancer cells. Importantly, knockdown of IDH1 blocked the AR-mediated induction in IDH activity, indicating that AR promotes a mitochondrial to cytoplasmic reprogramming of IDH activity. Overall, our study demonstrates that IDH1 expression is associated with prostate cancer progression, that AR signaling integrates one of the first transcriptional mechanisms shown to regulate IDH1, and that AR reprograms prostate cancer cell metabolism by selectively inducing extra-mitochondrial IDH activity.

Implications:

The discovery that AR reprograms IDH activity highlights a novel metabolic reprogramming necessary for prostate cancer growth and suggests targeting IDH activity as a new therapeutic approach for prostate cancer treatment.