bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Faces of False
Authors: Babcock Matthew , Beskow David M. , Carley Kathleen M.
Published: August 2019

The task of combating false information online appears daunting, in part due to a public focus on how quickly it can spread and the clamor for automated platform-based interventions. While such concerns can be warranted, threat analysis and intervention design both benefit from a fuller understanding of different types of false information and of the community responses to them. Here, we present a study of the most tweeted about movie ever (
Black Panther
) in which the spread of false information of four different types is compared to the ad hoc Twitter community response. We find that (1) false information tweets played a small part in the overall conversation, (2) community-based debunking and shaming responses to false posts about attacks at theaters overwhelmed such posts by orders of magnitude, (3) as another form of community response, one type of false narrative (Satire) was used to attack another (Fake Attacks), and (4) the four types of false-information tweets differed in the use of hashtags and in the role played by originating users and responding users. Overall, this work helps to illustrate the importance of investigating “on-the-ground” community responses to fake news and other types of digital false information and to inform identification and intervention design and implementation.
Approximate Data Reuse-based Accelerator Design for Embedded Processor
Authors: Osawa Hisashi , Hara-Azumi Yuko
Published: August 2019

Due to increasing diversity and complexity of applications in embedded systems, accelerator designs trading-off area/energy-efficiency and design-productivity are becoming a further crucial issue. Targeting applications in the category of Recognition, Mining, and Synthesis (RMS), this study proposes a novel accelerator design to achieve a good trade-off in efficiency and design-productivity (or reusability) by introducing a new computing paradigm called “approximate computing” (AC). Leveraging from the facts that frequently executed parts of applications (i.e., hotspots) are conventionally the target of acceleration and that RMS applications are error-tolerant and often take similar input data repeatedly, our proposed accelerator
reuses previous computational results of similar enough data
to reduce computations. The proposed accelerator is composed of a simple controller and a dedicated memory to store limited sets of previous input data with corresponding computational results in a hotspot. Therefore, this accelerator can be applied to different and/or multiple hotspots/applications only through small extension of the controller, to achieve efficient accelerator design and resolve the design-productivity issue. We conducted quantitative evaluations using a representative RMS application (image compression) to demonstrate the effectiveness of our method over conventional ones with precise computing. Moreover, we provide important findings on parameter exploration for our accelerator design, offering a wider applicability of our accelerator to other applications.
Phylogenetic Comparative Methods and the Evolution of Multivariate Phenotypes
Authors: Adams Dean C. , Collyer Michael L.
Published: August 2019

Evolutionary biology is multivariate, and advances in phylogenetic comparative methods for multivariate phenotypes have surged to accommodate this fact. Evolutionary trends in multivariate phenotypes are derived from distances and directions between species in a multivariate phenotype space. For these patterns to be interpretable, phenotypes should be characterized by traits in commensurate units and scale. Visualizing such trends, as is achieved with phylomorphospaces, should continue to play a prominent role in macroevolutionary analyses. Evaluating phylogenetic generalized least squares (PGLS) models (e.g., phylogenetic analysis of variance and regression) is valuable, but using parametric procedures is limited to only a few phenotypic variables. In contrast, nonparametric, permutation-based PGLS methods provide a flexible alternative and are thus preferred for high-dimensional multivariate phenotypes. Permutation-based methods for evaluating covariation within multivariate phenotypes are also well established and can test evolutionary trends in phenotypic integration. However, comparing evolutionary rates and modes in multivariate phenotypes remains an important area of future development.
Observing the Global Ocean with Biogeochemical-Argo
Authors: Claustre Hervé , Johnson Kenneth S. , Takeshita Yuichiro
Published: August 2019

Biogeochemical-Argo (BGC-Argo) is a network of profiling floats carrying sensors that enable observation of as many as six essential biogeochemical and bio-optical variables: oxygen, nitrate, pH, chlorophyll a, suspended particles, and downwelling irradiance. This sensor network represents today's most promising strategy for collecting temporally and vertically resolved observations of biogeochemical properties throughout the ocean. All data are freely available within 24 hours of transmission. These data fill large gaps in ocean-observing systems and support three ambitions: gaining a better understanding of biogeochemical processes (e.g., the biological carbon pump and air–sea CO2 exchanges) and evaluating ongoing changes resulting from increasing anthropogenic pressure (e.g., acidification and deoxygenation); managing the ocean (e.g., improving the global carbon budget and developing sustainable fisheries); and carrying out exploration for potential discoveries. The BGC-Argo network has already delivered extensive high-quality global data sets that have resulted in unique scientific outcomes from regional to global scales. With the proposed expansion of BGC-Argo in the near future, this network has the potential to become a pivotal observation system that links satellite and ship-based observations in a transformative manner.
Effective glucose metabolism maintains low intracellular glucose in airway epithelial cells after exposure to hyperglycemia
Authors: Bearham Jade , Garnett James P. , Schroeder Victoria , Biggart Matthew G. S. , Baines Deborah L.
Published: August 2019

The airway epithelium maintains differential glucose concentrations between the airway surface liquid (ASL, ~0.4 mM) and the blood/interstitium (5–6 mM), which is important for defense against infection. Glucose primarily moves from the blood to the ASL via paracellular movement, down its concentration gradient, across the tight junctions. However, there is evidence that glucose can move transcellularly across epithelial cells. Using a Förster resonance energy transfer sensor for glucose, we investigated intracellular glucose concentrations in airway epithelial cells and the role of hexokinases in regulating intracellular glucose concentrations in normoglycemic and hyperglycemic conditions. Our findings indicated that in airway epithelial cells (H441 or primary human bronchial epithelial cells) exposed to 5 mM glucose (normoglycemia), intracellular glucose concentration is in the micromolar range. Inhibition of facilitative glucose transporters (GLUTs) with cytochalasin B reduced intracellular glucose concentration. When cells were exposed to 15 mM glucose (hyperglycemia), intracellular glucose concentration was reduced. Airway cells expressed hexokinases I, II, and III. Inhibition with 3-bromopyruvate decreased hexokinase activity by 25% and elevated intracellular glucose concentration, but levels remained in the micromolar range. Exposure to hyperglycemia increased glycolysis, glycogen, and sorbitol. Thus, glucose enters the airway cell via GLUTs and is then rapidly processed by hexokinase-dependent and hexokinase-independent metabolic pathways to maintain low intracellular glucose concentrations. We propose that this prevents transcellular transport and aids the removal of glucose from the ASL and that the main route of entry for glucose into the ASL is via the paracellular pathway.
Enteroids expressing a disease-associated mutant of EpCAM are a model for congenital tufting enteropathy
Authors: Das Barun , Okamoto Kevin , Rabalais John , Kozan Philip A. , Marchelletta Ronald R. , McGeough Matthew D. , Durali Nassim , Go Maria , Barrett Kim E. , Das Soumita , Sivagnanam Mamata
Published: August 2019

Congenital tufting enteropathy (CTE) is an autosomal recessive disease characterized by severe intestinal failure in infancy and mutations in the epithelial cell adhesion molecule ( EPCAM) gene. Previous studies of CTE in mice expressing mutant EpCAM show neonatal lethality. Hence, to study the cellular, molecular, and physiological alterations that result from EpCAM mutation, a tamoxifen-inducible mutant EpCAM enteroid model has been generated. The presence of mutant EpCAM in the model was confirmed at both mRNA and protein levels. Immunofluorescence microscopy demonstrated the reduced expression of mutant EpCAM. Mutant enteroids had reduced budding potential as well as significantly decreased mRNA expression for epithelial lineage markers ( Mucin 2, lysozyme, sucrase-isomaltase), proliferation marker Ki67, and secretory pathway transcription factors ( Atoh1, Hnf1b). Significantly decreased numbers of Paneth and goblet cells were confirmed by staining. These findings were correlated with intestinal tissue from CTE patients and the mutant mice model that had significantly fewer Paneth and goblet cells than in healthy counterparts. FITC-dextran studies demonstrated significantly impaired barrier function in monolayers derived from mutant enteroids compared with control monolayers. In conclusion, we have established an ex vivo CTE model. The role of EpCAM in the budding potential, differentiation, and barrier function of enteroids is noted. Our study establishes new facets of EpCAM biology that will aid in understanding the pathophysiology of CTE and role of EpCAM in health and disease.

NEW & NOTEWORTHY Here, we develop a novel ex vivo enteroid model for congenital tufting enteropathy (CTE) based on epithelial cell adhesion molecule ( EPCAM) gene mutations found in patients. With this model we demonstrate the role of EpCAM in maintaining the functional homeostasis of the intestinal epithelium, including differentiation, proliferation, and barrier integrity. This study further establishes a new direction in EpCAM biology that will help in understanding the detailed pathophysiology of CTE and role of EpCAM.
GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis
Authors: Zhang Yingze , Jiang Mao , Nouraie Mehdi , Roth Mark G. , Tabib Tracy , Winters Spencer , Chen Xiaoping , Sembrat John , Chu Yanxia , Cardenes Nayra , Tuder Rubin M. , Herzog Erica L. , Ryu Changwan , Rojas Mauricio , Lafyatis Robert , Gibson Kevin F. , McDyer John F. , Kass Daniel J. , Alder Jonathan K.
Published: August 2019

Idiopathic pulmonary fibrosis (IPF) is the most common and devastating of the interstitial lung diseases. Epithelial dysfunction is thought to play a prominent role in disease pathology, and we sought to characterize secreted signals that may contribute to disease pathology. Transcriptional profiling of senescent type II alveolar epithelial cells from mice with epithelial-specific telomere dysfunction identified the transforming growth factor-β family member, growth and differentiation factor 15 ( Gdf15), as the most significantly upregulated secreted protein. Gdf15 expression is induced in response to telomere dysfunction and bleomycin challenge in mice. Gdf15 mRNA is expressed by lung epithelial cells, and protein can be detected in peripheral blood and bronchoalveolar lavage following bleomycin challenge in mice. In patients with IPF, GDF15 mRNA expression in lung tissue is significantly increased and correlates with pulmonary function. Single-cell RNA sequencing of human lungs identifies epithelial cells as the primary source of GDF15, and circulating concentrations of GDF15 are markedly elevated and correlate with disease severity and survival in multiple independent cohorts. Our findings suggest that GDF15 is an epithelial-derived secreted protein that may be a useful biomarker of epithelial stress and identifies IPF patients with poor outcomes.
Cell fate analysis in fetal mouse lung reveals distinct pathways for TI and TII cell development
Authors: Gonzalez Robert , Leaffer David , Chapin Cheryl , Gillespie Anne Marie , Eckalbar Walter , Dobbs Leland
Published: August 2019

Alveolar type I (TI) cells are large squamous cells that cover >95% of the internal surface area of the lung; type II (TII) cells are small cuboidal cells with distinctive intracellular surfactant storage organelles. Based on autoradiographic studies in the 1970s, the long-held paradigm of alveolar epithelial development has been a linear progression from undifferentiated progenitor cells through TII cells to TI cells. Subsequent data support the existence of more complex pathways. Recently, a bipotent TI/TII progenitor cell at embryonic day E18 has been inferred both from marker expression in developing airways and from statistical analyses of gene expression data obtained from single-lung embryonic cells. To study cell lineage directly by fate mapping, we developed new transgenic mouse models in which rtTA is driven either by the rat podoplanin or the mouse Sftpc gene to mark cells irreversibly in development. Using these models, we found two distinct lineage pathways. One pathway, evident as early as E12–15, is devoted almost exclusively to TI cell development; a second pathway gives rise predominantly to TII cells but also a subpopulation of TI cells. We have defined the molecular phenotypes of these distinct progenitor populations and have identified potential regulatory factors in TI and TII cell differentiation. By analyzing gene pathways in mature TI and TII cells, we identified potential novel functions of each cell type. These results provide novel insights into lung development and suggest a basis for testing strategies to promote alveolar differentiation and repair, including potential transplantation of lineage-specific progenitor cells.
Antagonism of major histocompatibility complex class II invariant chain peptide during chronic lipopolysaccharide treatment rescues autoregulatory behavior
Authors: Van Beusecum Justin P. , Zhang Shali , Beltran Estevan , Cook Anthony K. , Tobin Richard P. , Newell-Rogers M. Karen , Inscho Edward W.
Published: August 2019

Toll-like receptor 4 (TLR4) activation contributes to vascular dysfunction in pathological conditions such as hypertension and diabetes, but the role of chronic TLR4 activation on renal autoregulatory behavior is unknown. We hypothesized that subclinical TLR4 stimulation with low-dose lipopolysaccharide (LPS) infusion increases TLR4 activation and blunts renal autoregulatory behavior. We assessed afferent arteriolar autoregulatory behavior in male Sprague-Dawley rats after prolonged LPS (0.1 mg·kg−1·day−1 sq) infusion via osmotic minipump for 8 or 14 days. Some rats also received daily cotreatment with either anti-TLR4 antibody (1 μg ip), competitive antagonist peptide (CAP; 3 mg/kg ip) or tempol (2 mmol/l, drinking water) throughout the 8-day LPS treatment period. Autoregulatory behavior was assessed using the in vitro blood-perfused juxtamedullary nephron preparation. Selected physiological measures, systolic blood pressure and baseline diameters were normal and similar across groups. Pressure-dependent vasoconstriction averaged 72 ± 2% of baseline in sham rats, indicating intact autoregulatory behavior. Eight-day LPS-treated rats exhibited significantly impaired pressure-mediated vasoconstriction (96 ± 1% of baseline), whereas it was preserved in rats that received anti-TLR4 antibody (75 ± 3%), CAP (84 ± 2%), or tempol (82 ± 2%). Using a 14-day LPS (0.1 mg·kg−1·day−1 sq) intervention protocol, CAP treatment started on day 7, where autoregulatory behavior is already impaired. Systolic blood pressures were normal across all treatment groups. Fourteen-day LPS treatment retained the autoregulatory impairment (95 ± 2% of baseline). CAP intervention starting on day 7 rescued pressure-mediated vasoconstriction with diameters decreasing to 85 ± 1% of baseline. These data demonstrate that chronic subclinical TLR4 activation impairs afferent arteriolar autoregulatory behavior through mechanisms involving reactive oxygen species and major histocompatibility complex class II activation.
Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease
Authors: Liu Chang , Gidlund Eva-Karin , Witasp Anna , Qureshi Abdul Rashid , Söderberg Magnus , Thorell Anders , Nader Gustavo A. , Barany Peter , Stenvinkel Peter , von Walden Ferdinand
Published: August 2019

Advanced chronic kidney disease (CKD) is characterized by a premature aging phenotype of multifactorial origin. Mitochondrial dysfunction is prevalent in CKD and has been proposed as a major contributor to poor muscle function. Although the mitochondria-derived peptides (MDPs) humanin and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis, and glucose control, the implications of MDP in CKD are unknown. We investigated humanin and MOTS-c protein expression in skeletal muscle and serum levels in CKD at stage 5 (glomerular filtration rate: <15 ml/min) patients and age-matched controls with normal renal function. Whereas circulating levels of humanin were increased in CKD, local muscle expression was reduced. In contrast, MOTS-c levels were reduced in both skeletal muscle and serum in CKD. Humanin in serum correlated positively to circulating TNF levels. Reduced MDP levels in skeletal muscle were associated with lower mitochondrial density and evidence of oxidative stress. These results indicate a differential regulation of MDPs in CKD and suggest an alternative site for humanin production than skeletal muscle in the uremic milieu. MDP levels were linked to systemic inflammation and evidence of oxidative stress in the muscle, two hallmark features of premature aging and uremia.
Rho kinase inhibitors reduce voltage-dependent Ca2+channel signaling in aortic and renal microvascular smooth muscle cells
Authors: Guan Zhengrong , Baty Joshua J. , Zhang Shali , Remedies Colton E. , Inscho Edward W.
Published: August 2019

Voltage-dependent L-type Ca2+channels (L-VDCCs) and the RhoA/Rho kinase pathway are two predominant intracellular signaling pathways that regulate renal microvascular reactivity. Traditionally, these two pathways have been thought to act independently; however, recent evidence suggests that these pathways could be convergent. We hypothesized that Rho kinase inhibitors can influence L-VDCC signaling. The effects of Rho kinase inhibitors Y-27632 or RKI-1447 on KCl-induced depolarization or the L-VDCC agonist Bay K8644 were assessed in afferent arterioles using an in vitro blood-perfused rat juxtamedullary nephron preparation. Superfusion of KCl (30–90 mM) led to concentration-dependent vasoconstriction of afferent arterioles. Administration of Y-27632 (1, 5, and 10 µM) or RKI-1447 (0.1, 1, and 10 µM) significantly increased the starting diameter by 16–65%. KCl-induced vasoconstriction was markedly attenuated with 5 and 10 µM Y-27632 and with 10 µM RKI-1447 ( P < 0.05 vs. KCl alone). Y-27632 (5 µM) also significantly attenuated Bay K8644-induced vasoconstriction ( P < 0.05). Changes in intracellular Ca2+concentration ([Ca2+]i) were estimated by fura-2 fluorescence during KCl-induced depolarization in cultured A7r5 cells and in freshly isolated preglomerular microvascular smooth muscle cells. Administration of 90 mM KCl significantly increased fura-2 fluorescence in both cell types. KCl-mediated elevation of [Ca2+]iin A7r5 cells was suppressed by 1–10 µM Y-27632 ( P < 0.05), but 10 µM Y-27632 was required to suppress Ca2+responses in preglomerular microvascular smooth muscle cells. RKI-1447, however, significantly attenuated KCl-mediated elevation of [Ca2+]i. Y-27632 markedly inhibited Bay K8644-induced elevation of [Ca2+]iin both cell types. The results of the present study indicate that the Rho kinase inhibitors Y-27632 and RKI-1447 can partially inhibit L-VDCC function and participate in L-VDCC signaling.
A Meshless WCSPH Boundary Treatment for Open‐Channel Flow over Small‐Scale Rough Bed
Authors: Shi Yang , Wei Jiahua , Li Shaowu , Song Peng , Zhang Bangwen
Published: August 2019

A weakly compressible smoothed particle hydrodynamics (WCSPH) method was developed to model open‐channel flow over rough bed. An improved boundary treatment is proposed to quantitatively characterize bed roughness based on the ghost boundary particles (GBPs). In this model, the velocities of GBPs are explicitly calculated by using evolutionary polynomial regression with a multiobjective genetic algorithm. The simulation results show that the proposed boundary treatment can well reflect the influence of wall roughness on the vertical flow structure. A fully developed open channel is established, and its flume length, processing time, and turbulent model are discussed. The mixed‐length‐based subparticle scale (SPS) turbulence model is adopted to simulate uniform flow in open channel, and this model is compared with the Smagorinsky‐based one. For the modified WCSPH model, the results show that the calculated vertical velocity and turbulent shear stress distribution are in good agreement with experimental data and fit better than the calculations obtained from the traditional Smagorinsky‐based model.
An Ontology-Enabled Case-Based Reasoning Decision Support System for Manufacturing Process Selection
Authors: Mabkhot Mohammed M. , Al-Samhan Ali M. , Hidri Lotfi
Published: August 2019

In nowadays industry 4.0 and changeable manufacturing context, designers and manufacturing engineers struggle to determine appropriate quick, accurate (with flawless quality), and cost-effective processes to design highly customized products to meet customer requirements. To determine manufacturing processes, the matching between product features, material characteristics, and process capabilities needs to be optimized. Finding such an optimized matching is usually referred to as manufacturing process selection (MPS), which is not an easy task because of the infinite combinations of product features, numerous material characteristics, and various manufacturing processes. Although problems associated with MPS have received considerable attention, semantic web technologies are still underexplored and their potential is still uncovered. Almost no previous study has considered combining case-based reasoning (CBR) with ontologies, a famous and powerful semantic web enabler, to achieve MPS. In this study, we developed a decision support system (DSS) for MPS based on ontology-enabled CBR. By applying automatic reasoning and similarity retrieving on an industrial case study, we show that ontologies enable process selection by determining competitive matching between product features, material characteristics, and process capabilities and by endorsing effective case retrieval.
Artificial Potential Function Safety and Obstacle Avoidance Guidance for Autonomous Rendezvous and Docking with Noncooperative Target
Authors: Liu Jianghui , Li Haiyang
Published: August 2019

The problem of artificial potential function (APF) safety and obstacle avoidance guidance for autonomous rendezvous and docking of chaser spacecraft with noncooperative spacecraft is studied. The relative motion equation of the chaser and the target is established based on the line‐of‐sight coordinate system, the reference state is designed, and the corresponding state error is deduced. The attitude motion equation of the noncooperative target spacecraft in space is established. The safety and obstacle avoidance guidance problem of autonomous rendezvous and docking with noncooperative target is transformed into a path planning problem in a dynamic environment. The attractive potential function is designed according to the state error. In order to ensure that the chaser can safely approach the noncooperative target spacecraft, a safe corridor with ellipse cissoid is designed in the final approaching stage of autonomous rendezvous and docking. The obstacle is assumed to be a sphere with a certain radius to avoid its influence in the approach, and the obstacle potential function is designed based on the Gaussian function method. The total potential function of the system is designed according to the attractive potential function, the safe potential function, and the obstacle potential function. The total potential function of the system is modified to ensure that the reference state is the minimum of the total potential function of the system. The stability of the system is proven according to the Lyapunov stability principle, and the conditions for satisfying the monotonic decrease in the total potential function of the system are deduced. Finally, the effectiveness of the proposed method is verified by three sets of numerical simulations.
Identifying Protein Complexes from Dynamic Temporal Interval Protein-Protein Interaction Networks
Authors: Zhang Jinxiong , Zhong Cheng , Lin Hai Xiang , Wang Mian
Published: August 2019

Identification of protein complex is very important for revealing the underlying mechanism of biological processes. Many computational methods have been developed to identify protein complexes from static protein-protein interaction (PPI) networks. Recently, researchers are considering the dynamics of protein-protein interactions. Dynamic PPI networks are closer to reality in the cell system. It is expected that more protein complexes can be accurately identified from dynamic PPI networks. In this paper, we use the undulating degree above the base level of gene expression instead of the gene expression level to construct dynamic temporal PPI networks. Further we convert dynamic temporal PPI networks into dynamic Temporal Interval Protein Interaction Networks (TI-PINs) and propose a novel method to accurately identify more protein complexes from the constructed TI-PINs. Owing to preserving continuous interactions within temporal interval, the constructed TI-PINs contain more dynamical information for accurately identifying more protein complexes. Our proposed identification method uses multisource biological data to judge whether the joint colocalization condition, the joint coexpression condition, and the expanding cluster condition are satisfied; this is to ensure that the identified protein complexes have the features of colocalization, coexpression, and functional homogeneity. The experimental results on yeast data sets demonstrated that using the constructed TI-PINs can obtain better identification of protein complexes than five existing dynamic PPI networks, and our proposed identification method can find more protein complexes accurately than four other methods.
Removal Properties, Mechanisms, and Performance of Methyl Green from Aqueous Solution Using Raw and Purified Sejnane Clay Type
Authors: Satlaoui Yosra , Trifi Mariem , Fkih Romdhane Dalila , Charef Abdelkrim , Azouzi Rim
Published: August 2019

Adsorption of cationic methyl green (MG) on nontreated (AB) and purified (AP) natural Sejnane clay type was studied in an equilibrium batch process. This work reported the application of kaolinite-rich heterogeneous clay for the removal of a cationic dye. Effects of contact time, initial dye concentration, mass adsorbent, pH, and temperature on the MG removal were checked. The adsorbent before and after adsorption processes was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and atomic adsorption spectrophotometer. Equilibrium data were mathematically modeled using the Freundlich, Langmuir, and intraparticle diffusion models. Kinetic of adsorption was determined by pseudo-first-order and pseudo-second-order models. The free energy (ΔG°), standard enthalpy (ΔH°), and standard entropy (ΔS°) were calculated. A fast increase in the equilibrium removal of the cationic dye was obtained at a pH ranging between 3 and 11 and moderate temperature. This rapid MG adsorption proved the efficiency of kaolinite clay in cationic dye removal. Decolorizing yields were 73.3% for AB and 99.8% for AP. Thus, the adsorption capacity of purified clay was clearly higher than of H2SO4 and thermic activated clays. The data more closely resembled a pseudo-second-order model process, and the clay had reasonable Freundlich adsorption capacity. Adsorption process was endothermic and spontaneous chemisorption. SEM analysis showed that the adsorbed MG had remarkably changed the morphology of raw and purified clay surface. The low desorption rates confirmed effectiveness of this type of material for the retention of methyl green molecules. Thus, tested clays have no environmental impact.
Three‐Dimensional Aerodynamic Optimization of Single‐Layer Reticulated Cylindrical Roofs Subjected to Mean Wind Loads
Authors: San Bingbing , Xu Chen , Qiu Ye
Published: August 2019

This paper presents a procedure to optimize the rise‐to‐span ratio of single‐layer reticulated cylindrical roofs to improve their aerodynamic performance, by coupling the optimization method with computational fluid dynamics (CFD) and finite element analysis (FEA). Four turbulence models (standard k‐ε, RNG k‐ε, SST k‐ω, and RSM) were used to predict the mean wind loads on cylindrical roofs. The simulation results were compared with wind tunnel data, and the RSM turbulence model was employed. The aim of this paper is to determine the best performing rise‐to‐span ratio of cylindrical roofs based on the gradient algorithm. Two objective functions were considered to minimize the highest mean suction on the roof surface and the maximum response displacement of the single‐layer reticulated cylindrical shell subjected to mean wind loads. The results revealed that a cylindrical roof with a rise‐to‐span ratio (R/S) of 1/6.25 seems to be most effective in attenuating high suctions on the roof surface. In addition, a single‐layer reticulated cylindrical shell with R/S = 1/5.5 gives the best performance in reducing the maximum response displacement against wind loads.
Quadrilateral Interval Type‐2 Fuzzy Regression Analysis for Data Outlier Detection
Authors: Gao Pingping , Gao Yabin
Published: August 2019

This paper presents a fuzzy regression analysis method based on a general quadrilateral interval type‐2 fuzzy numbers, regarding the data outlier detection. The Euclidean distance for the general quadrilateral interval type‐2 fuzzy numbers is provided. In the sense of Euclidean distance, some parameter estimation laws of the type‐2 fuzzy linear regression model are designed. Then, the data outlier detection‐oriented parameter estimation method is proposed using the data deletion‐based type‐2 fuzzy regression model. Moreover, based on the fuzzy regression model, by using the root mean squared error method, an impact evaluation rule is designed for detecting data outlier. An example is finally provided to validate the presented methods.
Prediction of Protein-Protein Interactions Based on Domain
Authors: Li Xue , Yang Lifeng , Zhang Xiaopan , Jiao Xiong
Published: August 2019

Protein-protein interactions (PPIs) play a crucial role in various biological processes. To better comprehend the pathogenesis and treatments of various diseases, it is necessary to learn the detail of these interactions. However, the current experimental method still has many false-positive and false-negative problems. Computational prediction of protein-protein interaction has become a more important prediction method which can overcome the obstacles of the experimental method. In this work, we proposed a novel computational domain-based method for PPI prediction, and an SVM model for the prediction was built based on the physicochemical property of the domain. The outcomes of SVM and the domain-domain score were used to construct the prediction model for protein-protein interaction. The predicted results demonstrated the domain-based research can enhance the ability to predict protein interactions.
EM Duality and Quasinormal Modes from Higher Derivatives with Homogeneous Disorder
Authors: Fu Guoyang , Wu Jian-Pin
Published: August 2019

We study the electromagnetic (EM) duality from 6 derivative theory with homogeneous disorder. We find that, with the change of the sign of the coupling parameter γ1 of the 6 derivative theory, the particle-vortex duality with homogeneous disorder holds better than that without homogeneous disorder. The properties of quasinormal modes (QNMs) of this system are also explored. When the homogeneous disorder is introduced, some modes emerge at the imaginary frequency axis for negative γ1 but not for positive γ1. In particular, with an increase in the magnitude of α^, new branch cuts emerge for positive γ1. These emerging modes violate the duality related to the change of the sign of γ1. With the increase of α^, this duality is getting violated more.
Finite Element- and Design of Experiment-Derived Optimization of Screw Configurations and a Locking Plate for Internal Fixation System
Authors: Sheng Wei , Ji Aimin , Fang Runxin , He Gang , Chen Changsheng
Published: August 2019

Objectives. The optimization for the screw configurations and bone plate parameters was studied to improve the biomechanical performances such as reliable internal fixation and beneficial callus growth for the clinical treatment of femoral shaft fracture. Methods. The finite element analysis (FEA) of internal fixation system under different screw configurations based on the orthogonal design was performed and so was for the different structural parameters of the locking plate based on the combination of uniform and orthogonal design. Moreover, orthogonal experiment weight matrixes for four evaluation indexes with FEA were analyzed. Results. The analytical results showed the optimal scheme of screw configuration was that screws are omitted in the thread holes near the fracture site, and single cortical screws are used in the following holes to the distal end, while the double cortical screws are fixed in thread holes that are distal to the fracture; in the other words, the length of the screws showed an increasing trend from the fracture site to the distal end in the optimized configuration. The plate structure was optimized when thread holes gap reached 13 mm, with a width of 11 mm and 4.6 mm and 5 mm for thickness and diameter of the screw, respectively. The biomechanical performance of the internal fixation construct was further improved by about 10% based on the optimal strain range and lower stress in the internal fixation system. Conclusions. The proposed orthogonal design and uniform design can be used in a more efficient way for the optimization of internal fixation system, which can reduce the simulation runs to about 10% compared with comprehensive test, and the methodology can be also used for other types of fractures to achieve better internal fixation stability and optimal healing efficiency, which may provide a method for an orthopedist in choosing the screw configurations and parameters for internal fixation system in a more efficient way.
Context Attention Heterogeneous Network Embedding
Authors: Zhuo Wei , Zhan Qianyi , Liu Yuan , Xie Zhenping , Lu Jing
Published: August 2019

Network embedding (NE), which maps nodes into a low-dimensional latent Euclidean space to represent effective features of each node in the network, has obtained considerable attention in recent years. Many popular NE methods, such as DeepWalk, Node2vec, and LINE, are capable of handling homogeneous networks. However, nodes are always fully accompanied by heterogeneous information (e.g., text descriptions, node properties, and hashtags) in the real-world network, which remains a great challenge to jointly project the topological structure and different types of information into the fixed-dimensional embedding space due to heterogeneity. Besides, in the unweighted network, how to quantify the strength of edges (tightness of connections between nodes) accurately is also a difficulty faced by existing methods. To bridge the gap, in this paper, we propose CAHNE (context attention heterogeneous network embedding), a novel network embedding method, to accurately determine the learning result. Specifically, we propose the concept of node importance to measure the strength of edges, which can better preserve the context relations of a node in unweighted networks. Moreover, text information is a widely ubiquitous feature in real-world networks, e.g., online social networks and citation networks. On account of the sophisticated interactions between the network structure and text features of nodes, CAHNE learns context embeddings for nodes by introducing the context node sequence, and the attention mechanism is also integrated into our model to better reflect the impact of context nodes on the current node. To corroborate the efficacy of CAHNE, we apply our method and various baseline methods on several real-world datasets. The experimental results show that CAHNE achieves higher quality compared to a number of state-of-the-art network embedding methods on the tasks of network reconstruction, link prediction, node classification, and visualization.
The Cdk2–c-Myc–miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin
Authors: Zhang Yi , Li Zhuqing , Hao Qiang , Tan Wei , Sun Jing , Li Jing , Chen Chi-wei , Li Zongzhu , Meng Yunxiao , Zhou Yuan , Han Zhiyong , Pei Huadong , DePamphilis Melvin L. , Zhu Wenge
Published: August 2019

DNA rereplication leads to genomic instability and has been implicated in the pathology of a variety of human cancers. Eukaryotic DNA replication is tightly controlled to ensure it occurs only once during each cell cycle. Geminin is a critical component of this control, it prevents DNA rereplication from occurring during S, G2, and early M phases by preventing MCM helicases from forming prereplication complexes. Geminin is targeted for degradation by the anaphase-promoting complex (APC/C) from anaphase through G1-phase, however, accumulating evidence indicates that Geminin is downregulated in late S-phase due to an unknown mechanism. Here, we used a high-throughput screen to identify miRNAs that can induce excess DNA replication and found that miR-571 could reduce the protein level of Geminin in late S-phase independent of the APC/C. Furthermore, miR-571 regulated efficient DNA replication and S-phase cell-cycle progression. Strikingly, c-Myc suppressed miR-571 expression by binding directly to the miR-571 promoter. At the beginning of S-phase, Cdk2 phosphorylated c-Myc at Serine 62, promoting its association with the miR-571 promoter region. Collectively, we identify miR-571 as the first miRNA that prevents aberrant DNA replication and the Cdk2–c-Myc–miR-571 axis as a new pathway for regulating DNA replication, cell cycle, and genomic stability in cancer cells.

Significance:

These findings identify a novel regulatory mechanism that is critical for maintaining genome integrity by regulating DNA replication and cell-cycle progression.
MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1
Authors: Chuang Huai-Chia , Chang Chih-Chi , Teng Chiao-Fang , Hsueh Chia-Hsin , Chiu Li-Li , Hsu Pu-Ming , Lee Ming-Ching , Hsu Chung-Ping , Chen Yi-Rong , Liu Yi-Chung , Lyu Ping-Chiang , Tan Tse-Hua
Published: August 2019

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1.

Significance:

These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.
A Tumor Agnostic Therapeutic Strategy for Hexokinase 1–Null/Hexokinase 2–Positive Cancers
Authors: Xu Shili , Herschman Harvey R.
Published: August 2019

Since Warburg's observation that most cancers exhibit elevated glycolysis, decades of research have attempted to reduce tumor glucose utilization as a therapeutic approach. Hexokinase (HK) activity is the first glycolytic enzymatic step; despite many attempts to inhibit HK activity, none has reached clinical application. Identification of HK isoforms, and recognition that most tissues express only HK1 while most tumors express HK1 and HK2, stimulated reducing HK2 activity as a therapeutic option. However, studies using HK2 shRNA and isogenic HK1+HK2− and HK1+HK2+ tumor cell pairs demonstrated that tumors expressing only HK1, while exhibiting reduced glucose consumption, progressed in vivo as well as tumors expressing both HK1 and HK2. However, HK1−HK2+ tumor subpopulations exist among many cancers. shRNA HK2 suppression in HK1−HK2+ liver cancer cells reduced xenograft tumor progression, in contrast to HK1+HK2+ cells. HK2 inhibition, and partial inhibition of both oxidative phosphorylation and fatty acid oxidation using HK2 shRNA and small-molecule drugs, prevented human liver HK1−HK2+ cancer xenograft progression. Using human multiple myeloma xenografts and mouse allogeneic models to identify potential clinical translational agents, triple therapies that include antisense HK2 oligonucleotides, metformin, and perhexiline prevent progression. These results suggest an agnostic approach for HK1−HK2+ cancers, regardless of tissue origin.
Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma
Authors: Panowski Siler H. , Kuo Tracy C. , Zhang Yi , Chen Amy , Geng Tao , Aschenbrenner Laura , Kamperschroer Cris , Pascua Edward , Chen Wei , Delaria Kathy , Farias Santiago , Bateman Marjorie , Dushin Russell G. , Chin Sherman M. , Van Blarcom Thomas J. , Yeung Yik Andy , Lindquist Kevin C. , Chunyk Allison G. , Kuang Bing , Han Bora , Mirsky Michael , Pardo Ingrid , Buetow Bernard , Martin Thomas G. , Wolf Jeffrey L. , Shelton David , Rajpal Arvind , Strop Pavel , Chaparro-Riggers Javier , Sasu Barbra J.
Published: August 2019

The restricted expression pattern of B-cell maturation antigen (BCMA) makes it an ideal tumor-associated antigen (TAA) for the treatment of myeloma. BCMA has been targeted by both CD3 bispecific antibody and antibody–drug conjugate (ADC) modalities, but a true comparison of modalities has yet to be performed. Here we utilized a single BCMA antibody to develop and characterize both a CD3 bispecific and 2 ADC formats (cleavable and noncleavable) and compared activity both in vitro and in vivo with the aim of generating an optimal therapeutic. Antibody affinity, but not epitope was influential in drug activity and hence a high-affinity BCMA antibody was selected. Both the bispecific and ADCs were potent in vitro and in vivo, causing dose-dependent cell killing of myeloma cell lines and tumor regression in orthotopic myeloma xenograft models. Primary patient cells were effectively lysed by both CD3 bispecific and ADCs, with the bispecific demonstrating improved potency, maximal cell killing, and consistency across patients. Safety was evaluated in cynomolgus monkey toxicity studies and both modalities were active based on on-target elimination of B lineage cells. Distinct nonclinical toxicity profiles were seen for the bispecific and ADC modalities. When taken together, results from this comparison of BCMA CD3 bispecific and ADC modalities suggest better efficacy and an improved toxicity profile might be achieved with the bispecific modality. This led to the advancement of a bispecific candidate into phase I clinical trials.
ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells
Authors: Jimenez-Pascual Ana , Hale James S. , Kordowski Anja , Pugh Jamie , Silver Daniel J. , Bayik Defne , Roversi Gustavo , Alban Tyler J. , Rao Shilpa , Chen Rui , McIntyre Thomas M. , Colombo Giorgio , Taraboletti Giulia , Holmberg Karl O. , Forsberg-Nilsson Karin , Lathia Justin D. , Siebzehnrubl Florian A.
Published: August 2019

Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSC), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs consisting of an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly solubilizes FGF2 to stimulate FGFR1 expressed on GSCs. FGFR1 signaling induces upregulation of ZEB1 via ERK1/2 that regulates ADAMDEC1 expression through miR-203, creating a positive feedback loop. Genetic or pharmacologic targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM.

Significance:

Cancer stem cells (CSC) drive tumor growth in many cancers including GBM. We identified a novel sheddase, ADAMDEC1, which initiates an FGF autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce GBM growth.

This article is highlighted in the In This Issue feature, p. 1469
Immediate Manifestation of Ocular Decompression Retinopathy following Anterior Chamber Paracentesis
Authors: Prince Jamie , Fleischman David
Published: August 2019

Ocular decompression retinopathy (ODR) is a complication of rapid lowering of intraocular pressure (IOP) resulting in hemorrhages in multiple retinal layers. We report a case of ODR that developed within minutes following anterior chamber paracentesis in an adult female with primary open-angle glaucoma. A 61-year-old Black woman with primary open-angle glaucoma presented with marked elevation of IOP (46 mm Hg in the right eye and 30 mm Hg in the left) despite maximal medical therapy and bilateral selective laser trabeculoplasty. Vision in the right eye decreased from counting fingers at 3 feet 1 week earlier to no light perception at the time of presentation. Anterior chamber paracentesis was performed on the right eye to reduce IOP and stabilize the eye until further surgical intervention could be performed. IOP in the right eye decreased to 6 mm Hg postoperatively. Within minutes of the procedure, several intraretinal blot hemorrhages appeared in the periphery of the right eye. During this time, visual acuity remained at no light perception. The findings were consistent with decompression retinopathy. By 12 weeks postoperatively, the ODR had resolved with visual acuity of light perception and normal fundoscopy except for profound cupping. Our case demonstrates how rapidly ocular decompression can form following IOP reduction.