bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Solvent Evaporation Time and Casting Thickness on the Separation Performance of Cellulose Acetate Butyrate Blend Membrane
Authors: Manimaran Darvin , Jawad Zeinab Abbas , Thiam Leng Chew
Published: July 2019

Global warming and climate change due to greenhouse gases (GHGs) emission, mostly carbon dioxide (CO2), have induced global efforts to minimize the concentration of atmospheric CO2. To reduce the effects of this problem, membrane technology is selected for the separation of CO2 due to the energy efficiency and economic advantages exhibited. In this study, the chosen polymeric material, cellulose acetate butyrate (CAB) is optimized using a wet phase inversion method with various molecular weight and different casting conditions due to its outstanding film-forming specifications and capabilities of fabricating a defect-free layer of neat membrane. The membrane was synthesized by blending three different molecular weights (Mn) of 12,000, 30,000 and 70,000 at different casting thickness, 150 µm to 300 µm and solvent evaporation time of 3.5 to 5 min. The results of these predominant parameters were then utilized to determine a high performance CAB membrane suitable for an enhanced CO2/Nitrogen (N2) separation. Eventually, a high separation performance CAB membrane was successfully synthesized with a CO2/N2 selectivity of 1.5819 ± 0.0775 when the solvent evaporation time and casting thickness was optimized at 4.5 min and 300 µm, respectively. Through this study, an improved understanding between membrane casting conditions and membrane performance has been achieved, for future development and progress.
Machine Learning to Aid Tuning of Numerical Parameters in Topology Optimization
Authors: Lynch Matthew E. , Sarkar Soumalya , Maute Kurt
Published: July 2019

Recent advances in design optimization have significant potential to improve the function of mechanical components and systems. Coupled with additive manufacturing, topology optimization is one category of numerical methods used to produce algorithmically generated optimized designs making a difference in the mechanical design of hardware currently being introduced to the market. Unfortunately, many of these algorithms require extensive manual setup and control, particularly of tuning parameters that control algorithmic function and convergence. This paper introduces a framework based on machine learning approaches to recommend tuning parameters to a user in order to avoid costly trial and error involved in manual tuning. The algorithm reads tuning parameters from a repository of prior, similar problems adjudged using a dissimilarity metric based on problem metadata and refines them for the current problem using a Bayesian optimization approach. The approach is demonstrated for a simple topology optimization problem with the objective of achieving good topology optimization solution quality and then with the additional objective of finding an optimal “trade” between solution quality and required computational time. The goal is to reduce the total number of “wasted” tuning runs that would be required for purely manual tuning. With more development, the framework may ultimately be useful on an enterprise level for analysis and optimization problems—topology optimization is one example but the framework is also applicable to other optimization problems such as shape and sizing and in high-fidelity physics-based analysis models—and enable these types of advanced approaches to be used more efficiently.
Nitrogen gas (N2), by near-ambient pressure XPS
Authors: Shah Dhruv , Bahr Stephan , Dietrich Paul , Meyer Michael , Thißen Andreas , Linford Matthew R.
Published: July 2019

Near-ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) is a less traditional form of XPS that allows samples to be analyzed at relatively high pressures, i.e., at ca. 2500 Pa, or even higher in some cases. With NAP-XPS, XPS can probe moderately volatile liquids, biological samples, porous materials, and/or polymeric materials that outgas significantly. In this submission, we show NAP-XPS survey and narrow scans from nitrogen gas (N2), a material that could not be analyzed at moderate pressures by conventional approaches. Nitrogen gas is an important reference material for NAP-XPS because residual N2 from the air and/or venting produces an N 1s signal in many NAP-XPS spectra. Nitrogen gas may also be deliberately employed as the gaseous background for NAP-XPS experiments. The survey spectrum of N2 gas contains N 1s, N 2s, N KLL (Auger), and valence band signals. This submission is part of a series of articles on NAP-XPS that has been submitted to Surface Science Spectra.
Listeners normalize speech for contextual speech rate even without an explicit recognition task
Authors: Maslowski Merel , Meyer Antje S. , Bosker Hans Rutger
Published: July 2019

Speech can be produced at different rates. Listeners take this rate variation into account by normalizing vowel duration for contextual speech rate: An ambiguous Dutch word /m?t/ is perceived as short /mɑt/ when embedded in a slow context, but long /ma:t/ in a fast context. While some have argued that this rate normalization involves low-level automatic perceptual processing, there is also evidence that it arises at higher-level cognitive processing stages, such as decision making. Prior research on rate-dependent speech perception has only used explicit recognition tasks to investigate the phenomenon, involving both perceptual processing and decision making. This study tested whether speech rate normalization can be observed without explicit decision making, using a cross-modal repetition priming paradigm. Results show that a fast precursor sentence makes an embedded ambiguous prime (/m?t/) sound (implicitly) more /a:/-like, facilitating lexical access to the long target word “maat” in a (explicit) lexical decision task. This result suggests that rate normalization is automatic, taking place even in the absence of an explicit recognition task. Thus, rate normalization is placed within the realm of everyday spoken conversation, where explicit categorization of ambiguous sounds is rare.
Genomic and Seasonal Variations among Aquatic Phages Infecting the Baltic Sea GammaproteobacteriumRheinheimerasp. Strain BAL341
Authors: Nilsson E. , Li K. , Fridlund J. , Šulčius S. , Bunse C. , Karlsson C. M. G. , Lindh M. , Lundin D. , Pinhassi J. , Holmfeldt K.
Published: July 2019

Phages are important in aquatic ecosystems as they influence their microbial hosts through lysis, gene transfer, transcriptional regulation, and expression of phage metabolic genes. Still, there is limited knowledge of how phages interact with their hosts, especially at fine scales. Here, aRheinheimeraphage-host system constituting highly similar phages infecting one host strain is presented. This relatively limited diversity has previously been seen only when smaller numbers of phages have been isolated and points toward ecological constraints affecting theRheinheimeraphage diversity. The variation of metabolic genes among the species points toward various fitness advantages, opening up possibilities for future hypothesis testing. Phage-host dynamics monitored over several years point toward recurring “kill-the-winner” oscillations and an ecological niche fulfilled by this system in the Baltic Sea. Identifying and quantifying ecological dynamics of such phage-host model systemsin situallow us to understand and study the influence of phages on aquatic ecosystems.
Generality of Post-Antimicrobial Treatment Persistence of
Borrelia burgdorferi
Strains N40 and B31 in Genetically Susceptible and Resistant Mouse Strains
Authors: Hodzic Emir , Imai Denise M. , Escobar Edlin
Published: July 2019

A basic feature of infection caused by
Borrelia burgdorferi
, the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge.
Whole-Genome Sequencing Reveals a Prolonged and Persistent Intrahospital Transmission of Corynebacterium striatum, an Emerging Multidrug-Resistant Pathogen
Authors: Wang Xuebing , Zhou Haijian , Chen Dongke , Du Pengcheng , Lan Ruiting , Qiu Xiaotong , Hou Xuexin , Liu Zhiguo , Sun Lina , Xu Shuai , Ji Xingzhao , Li Heqiao , Li Dan , Zhang Jingshan , Zeng Hui , Li Zhenjun
Published: July 2019

Corynebacterium striatum
is an emerging multidrug-resistant (MDR) pathogen that occurs primarily among immunocompromised and chronically ill patients. However, little is known about the genomic diversity of
C. striatum
, which contributes to its long-term persistence and transmission in hospitals.
Early Neoproterozoic continental arc system at the central Jiangnan Orogen, South China: Geochronological and geochemical constraints on the key igneous rock-association
Authors: Zhang Yuzhi , Wang Yuejun
Published: July 2019

To better reveal the tectonic process of the Jiangnan Orogen in creating the united South China Block (SCB), a set of new geochronological, geochemical, and Sr-Nd-Hf-O isotopic data is herein presented for the coeval early Neoproterozoic mafic to acid rocks in the Lengjiaxi Group and its equivalents. Our data show that these rocks belong to subalkaline basalt, basaltic andesite, andesite, and dacite in composition, and can be geochemically classified into N-MORB- and arc-like mafic (Group 1 and Group 2, respectively), along with high-Mg andesitic-dacitic (Group 3) rocks. They yield zircon U-Pb ages of 837 ± 4 Ma, 832 ± 11 Ma, and 835 ± 7 Ma, respectively, suggesting their early Neoproterozoic (ca. 835 Ma) origin. Group 1 has SiO2 = 47.21–52.45 wt%, MgO = 7.36–10.07 wt% with Mg-number of 56–68, 87Sr/86Sr(t) = 0.7062–0.7136 and εNd(t) = +1.3–+9.4, along with N-MORB-like REE- (rare earth element) and PM (primitive mantle)-normalized patterns, suggesting its derivation from a refractory MORB-like source newly introduced by slab-derived fluid. The Group 2 samples are classified as tholeiitic basalt and basaltic andesite with SiO2 = 48.78–55.75 wt%, MgO = 7.70–12.74 wt%, Mg-number = 63–77, 87Sr/86Sr(t) = 0.7046–0.7098 and εNd(t) = –1.6 to –0.4. They exhibit similar “spiky” REE- and PM-normalized patterns to typical arc basalt, with pronounced enrichment in (large ion lithophile elements) and sharp depletion in (high field strength elements), probably inheriting from a sub-arc source modified by fluids and/or melts released from recycled sedimentary component. The Group 3 rocks show SiO2 = 57.74–66.30 wt%, FeOt = 6.22–8.59 wt%, Mg-number = 43–66, K2O+Na2O = 3.18–6.17 wt% with K2O/Na2O of 0.59–3.28, classified as high-Mg andesites and dacites. Diagnostic elemental and isotopic ratios of Group 3 include (La/Yb)cn = 7.7–11.4, (Gd/Yb)cn = 1.44–1.87, Eu/Eu* = 0.49–0.80, Nb/La = 0.27–0.42 and εNd(t) = –7.3 to –5.4, resembling to those of other early Neoproterozoic high-Mg intermediate rocks in the SCB, originating from a mantle wedge source with proportional addition of the recycled SCB sediment-derived components. In combination with the available data and geological observations, it is concluded that the N-MORB- and arc-like mafic, along with high-Mg andesitic rocks are coeval in the Lengjiaxi Group and its equivalents along the central Jiangnan Orogen and formed at ca. 847–832 Ma of the early Neoproterozoic period. The synthesis of these observations suggests the development of an early Neoproterozoic continental arc-basin setting. The arc-basin system westerly subducted and finally closed at ca. 830 Ma and the assembly of the Yangtze and Cathaysia blocks terminated at ca. 810 Ma along the central Jiangnan Orogen.
The Xiaoqinling metamorphic core complex: A record of Early Cretaceous backarc extension along the southern part of the North China Craton
Authors: Li Yunjian , Zhu Guang , Su Nan , Xiao Shiye , Zhang Shuai , Liu Cheng , Xie Chenglong , Yin Hao , Wu Xiaodong
Published: July 2019

Many metamorphic core complexes (MCCs) of Early Cretaceous age are documented in the northern part of the North China Craton (NCC), which formed in a backarc extensional setting. However, whether or not the MCCs are also present in the southern part of the NCC, and where the western boundary of backarc extension lies, remain unclear. We present new structural and geochronological data to show that Early Cretaceous structures in the Xiaoqinling region (China) lying in the southern part of the central NCC represent a Cordilleran-type MCC. The NW-dipping detachment zone on the northwestern edge of the Xiaoqinling MCC is a ductile extensional shear zone that is overprinted by a later brittle detachment fault. The footwall (lower plate) consists of Archean metamorphic rocks and Mesozoic plutonic rocks, and was cut by a series of ductile normal sense shear belts and later brittle normal faults that strike predominantly NE-SW. Both the ductile and brittle structures indicate that NW-SE extension was responsible for the development of the MCC. Geochronological data suggest that the MCC initiated at 138 Ma and lasted until 100 Ma, recording a protracted extensional history. The MCC experienced an early phase of crustal-scale normal faulting (138–126 Ma) and later isostatic doming (125–100 Ma), consistent with the “rolling-hinge” model. The Xiaoqinling MCC shows similar features and a similar evolution to other intraplate MCCs in the northern and southeastern parts of the NCC, and shows that the southern part of the NCC was also involved in intense backarc extension and magmatism. Distribution of these intraplate MCCs indicates synchronous backarc extension over a length of around 1800 km. Delamination of a flat oceanic slab during roll-back is consistent with such large-scale, synchronous extension in the overriding plate.
Pressure induced skin and soft tissue injury in the emergency department
Authors: Gamston Julia
Published: July 2019

The incidence of pressure ulcers or injuries is a global healthcare issue and in the top six most common adverse events in healthcare. Pressure injuries also are symptomatic of wider system failure and poor care. Recognition of these injuries and prevention strategies must start in the emergency department. This article will detail best practice in relation to both assessment of these injuries and their prevention in the emergency department.
Whose values? Whose reasons? A commentary on ‘Rethinking disease: a fresh diagnosis and a new philosophical treatment’ by Powell and Scarffe
Authors: Carel Havi
Published: July 2019

In this short commentary, I reflect on the new definition of disease proposed by Powell and Scarffe. I suggest that the method they appeal to as objective, namely, rational justification, is open to several criticisms, which I outline and discuss.
Thoracolumbar myelopathy with diffuse vertebral involvement in a dog secondary to aleukaemic lymphocytic leukaemia
Authors: Doran Caitlin Elizabeth , Platt Simon , Lau Vivian , Camus Melinda
Published: July 2019

Incidence rate of lymphocytic leukaemia is unknown in canine patients; neurological manifestations and imaging findings are rarely reported. In human medicine, acute lymphocytic leukaemia is known to have a high rate of meningeal metastasis prompting the use of intrathecal chemotherapy for newly diagnosed cases regardless of neurological signs. This report documents the clinical presentation and diagnostic findings in a dog presenting with paraparesis and pain, ultimately diagnosed with aleukaemic lymphocytic leukaemia. MRI findings with diffuse vertebral involvement secondary to lymphocytic leukaemia have not been documented in the veterinary literature. This report adds to the clinical presentations of leukaemia in canines and highlights a neurological sequela of the disease. Further investigation into neurological involvement of leukaemia is needed in veterinary medicine and necropsy, with meningeal histopathology, is recommended for all cases of acute lymphocytic leukaemia in canines to assess the metastatic rate and direct further research.
SMA/Py/ZnO as a new biocompatible polymer supported nanocatalyst for the synthesis of chromeno[2,3-d] pyrimidine-diones through a novel and efficient pathway
Authors: Daraie Mansoureh , Heravi Majid M.
Published: July 2019

An efficient and simple method for the synthesis of chromeno[2,3-d]pyrimidine-diones using SMA/Py/ZnO catalyst has been reported. Zinc oxide nanoparticles were coordinated on a modified poly(styrene-comaleic anhydride) (SMA) support to prevent agglomeration and reduction catalytic activity. The polymer support was easily prepared from the reaction of 3-aminopyridine with SMA. The catalyst was characterized by using various characterization techniques such as FTIR, 1H NMR, SEM, and EDX. The catalytic activity of SMA/Py/ZnO for the synthesis of chromeno[2,3-d]pyrimidine-diones through a multicomponent reaction of 6-amino-1,3-dimethyl uracil, 3,4-methylenedioxyphenol, and an appropriate aryl aldehyde under solvent-free conditions was also studied.
A discrete-event simulation model to test multimodal strategies for a greener and more resilient wood supply
Authors: Kogler Christoph , Rauch Peter
Published: July 2019

Increasing occurrences of natural disturbances, including windstorms and high snow cover, and supply chain risks lead to severe irregularities in wood harvest and transport. To overcome resulting supply difficulties, innovative multimodal systems via rail terminals are promising options offering the potential to increase buffer capacity, improve supply chain resilience, and reduce greenhouse gas emissions. Therefore, a train terminal is included in a virtual simulation environment spanning the entire wood supply chain from forest to industry to test, analyze, and evaluate a complex multimodal system in different scenario settings. Furthermore, the simulation model provides intuitive decision support through animation and a cockpit of key performance indicators, facilitating hands-on workshops with supply chain managers. Results show the advantage of a combination of unimodal and multimodal transport in the wood supply chain of the observed case-study region. This combination proves to be resilient and outperforms other tested supply chain strategies by avoiding both bottlenecks and ill-timed plans and reducing carbon dioxide (CO2) emissions. Furthermore, workshops conducted with industry experts indicate that adapting collaborative supply chain control strategies by means of a participatory simulation environment enhances the development of advanced risk management and therefore improves supply chain resilience, efficiency, and sustainability.
Atiyah–Hitchin in five-dimensional Einstein–Gauss–Bonnet gravity
Authors: Butler M. , Ghezelbash A. M. , Massaeli E. , Motaharfar M.
Published: July 2019

We construct a new class of stationary exact solutions to five-dimensional Einstein–Gauss–Bonnet gravity. The solutions are based on four-dimensional self-dual Atiyah–Hitchin geometry. We find analytical solutions to the five-dimensional metric function that are regular everywhere. We find some constraints on the possible physical solutions by investigating the solutions numerically. We also study the behavior of the solutions in the extremal limits of the Atiyah–Hitchin geometry. In the extremal limits, the Atiyah–Hitchin metric reduces to a bolt structure and Euclidean Taub–NUT space, respectively. In these limits, the five-dimensional metric function approaches to a constant value and infinity, respectively. We find that the asymptotic metrics are regular everywhere.
Dirac oscillator in a uniform electric field: Path integral treatment
Authors: Bada Hassene , Aouachria Mekki
Published: July 2019

In this paper, the propagator of a two-dimensional Dirac oscillator in the presence of a uniform electric field is derived by using the path integral technique. The fact that the globally named approach is used in this work redirects, beforehand, our search for the propagator of the Dirac equation to that of the propagator of its quadratic form. The internal motions relative to the spin are represented by two fermionic oscillators, which are described by Grassmannian variables, according to Schwinger’s fermionic model. Once the integration over the anticommuting variables (Grassmannian variables) is accomplished, the problem becomes the one of finding a non-relativistic propagator with only bosonic variables. The energy spectrum of the electron and the corresponding eigenspinors are also obtained in this work.
Canonical relativistic formulation to calculate the Casimir force four-vector on anisotropic conductor polarizable and magnetizable media
Authors: Amooshahi Majid
Published: July 2019

A canonical relativistic formulation to calculate the Casimir force four-vector exerted on anisotropic conductor polarizable and magnetizable media is provided. The anisotropic conductor polarizable and magnetizable medium is modeled by a continuum collection of the antisymmetric tensor fields of the second rank and a continuum collection of the vector fields in Minkowski spacetime. The collection of the antisymmetric tensor fields describes the polarization and the magnetization properties of the medium. The collection of the vector fields describes the conductivity property of the medium. The quantum relativistic wave equation of the four-vector potential of the electromagnetic field is solved using an iteration method. According to the conservation principle of the energy–momentum four-vector and using of the energy–momentum tensors of the relativistic dynamical fields, contained in the theory, the Casimir force four-vector on the anisotropic conductor polarizable and magnetizable medium is obtained. The Casimir force four-vector is obtained in terms of the relativistic dynamical fields, contained in the theory and the coupling tensors that couple the electromagnetic field to the anisotropic conductor polarizable and magnetizable medium. The Casimir force four-vector exerted on the medium is calculated in the vacuum state of the total system. As a special case, the formulation is applied to a multilayer medium. The tangential component of the Casimir force exerted on a multilayer medium vanish when the anisotropic conductor polarizable and magnetizable medium is converted to an isotropic one.
Application Research of KNN Algorithm Based on Clustering in Big Data Talent Demand Information Classification
Authors: Xiao Qingtao , Zhong Xin , Zhong Chenghua
Published: July 2019

With the growth of massive data in the current mobile Internet, network recruitment is gradually growing into a new recruitment channel. How to effectively mine available information in the massive network recruitment data has become the technical bottleneck of current education and social supply and demand development. The renewal of talent demand information is carried out every day, which produces a large amount of text data. How to manage these talents’ demand information reasonably becomes more and more important. Artificial classification is time-consuming and laborious, which is unrealistic naturally. Therefore, using automatic text categorization technology to classify and manage this information becomes particularly important. To break through the bottleneck of this technology, a heuristic KNN text categorization algorithm based on ABC (artificial bee colony) is proposed to adjust the weight of features, and the similarity between test observation and training observation is measured by using the method of fuzzy distance measurement. Firstly, the recruitment information is segmented and feature selection and noise data elimination are carried out by using term frequency-inverse document frequency (TF-IDF) algorithm and AP (affinity propagation) clustering algorithm. Finally, the text information is classified by using KNN algorithm combined with heuristic search and fuzzy distance measurement. The experimental results show that this method effectively solves the problem of poor stability and low classification accuracy of traditional KNN algorithm in text categorization method for talent demand.
Proper Vertex Connection and Graph Operations
Authors: ZHANG YINGYING , ZHU XIAOYU
Published: July 2019

A path in a vertex-colored graph is a vertex-proper path if any two internal adjacent vertices differ in color. A vertex-colored graph is proper vertex k-connected if any two vertices of the graph are connected by k disjoint vertex-proper paths of the graph. For a k-connected graph G, the proper vertex k-connection number of G, denoted by pvck(G), is defined as the smallest number of colors required to make G proper vertex k-connected. A vertex-colored graph is strong proper vertex-connected, if for any two vertices u, v of the graph, there exists a vertex-proper u-v geodesic. For a connected graph G, the strong proper vertex-connection number of G, denoted by spvc(G), is the smallest number of colors required to make G strong proper vertex-connected. In this paper, we study the proper vertex k-connection number and the strong proper vertex-connection number on the join of two graphs, the Cartesian, lexicographic, strong and direct product, and present exact values or upper bounds for these operations of graphs. Then we apply these results to some instances of Cartesian and lexicographic product networks.
Programming Embodied Interactions with a Remotely Controlled Educational Robot
Authors: Merkouris Alexandros , Chorianopoulos Konstantinos
Published: July 2019

Contemporary research has explored educational robotics, but it has not examined the development of computational thinking in the context of programming embodied interactions. Apart from the goal of the robot and how the robot will interact with its environment, another important aspect that should be taken into consideration is whether and how the user will physically interact with the robot. We recruited 36 middle school students to participate in a six-session robotics curriculum in an attempt to expand their learning in computational thinking. Participants were asked to develop interfaces for the remote control of a robot using diverse interaction styles from low-level to high-level embodiment, such as touch, speech, and hand and full-body gestures. We measured students’ perception of computing, examined their computational practices, and assessed the development of their computational thinking skills by analyzing the sophistication of the projects they created during a problem-solving task. We found that students who programmed combinations of low embodiment interfaces or interfaces with no embodiment produced more sophisticated projects and adopted more sophisticated computational practices compared to those who programmed full-body interfaces. These findings suggest that there might be a tradeoff between the appeal and the cognitive benefit of rich embodied interaction with a remotely controlled robot. In further work, educational robotics research and competitions might be complemented with a hybrid approach that blends the traditional autonomous robot movement with student enactment.
Infinite-duration Bidding Games
Authors: Avni Guy , Henzinger Thomas A. , Chonev Ventsislav
Published: July 2019

Two-player games on graphs are widely studied in formal methods, as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the
bidding
mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. The following bidding rule was previously defined and called Richman bidding. Both players have separate
budgets
, which sum up to 1. In each turn, a bidding takes place: Both players submit bids simultaneously, where a bid is legal if it does not exceed the available budget, and the higher bidder pays his bid to the other player and moves the token. The central question studied in bidding games is a necessary and sufficient initial budget for winning the game: a
threshold
budget in a vertex is a value
t
∈ [0, 1] such that if Player 1’s budget exceeds
t
, he can win the game; and if Player 2’s budget exceeds 1 −
t
, he can win the game. Threshold budgets were previously shown to exist in every vertex of a reachability game, which have an interesting connection with
random-turn
games—a sub-class of simple stochastic games in which the player who moves is chosen randomly. We show the existence of threshold budgets for a qualitative class of infinite-duration games, namely parity games, and a quantitative class, namely mean-payoff games. The key component of the proof is a quantitative solution to strongly connected mean-payoff bidding games in which we extend the connection with random-turn games to these games, and construct explicit optimal strategies for both players.
Risk of Malignant Neoplasia with Glucagon-Like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis
Authors: Liu Yufang , Zhang Xiaomei , Chai Sanbao , Zhao Xin , Ji Linong
Published: July 2019

Background. Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs, but there is concern that they may increase the risk of malignant neoplasia. The present meta-analysis examined the safety of GLP-1 receptor agonists with regard to malignant neoplasia. Methods. We analyzed data from randomized controlled trials with a minimum duration of 24 weeks that assessed the incidence of neoplasms in type 2 diabetes patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs. We searched the MEDLINE, Embase, and Cochrane databases with a language restriction of English through October 1, 2018, and carried out a meta-analysis of the available trial data using a fixed effects model to calculate odds ratios (ORs) for neoplasia. Results. Thirty-four relevant articles, providing data for 50452 patients, were included in the meta-analysis. Compared with the incidence of malignant neoplasia with placebo or other interventions, no increase in malignant neoplasm formation was observed with the use of GLP-1 receptor agonists (OR 1.04, 95% confidence interval (CI) 0.94–1.15; p=0.46), liraglutide (OR 1.08, 95% CI 0.91–1.27; p=0.38), exenatide (OR 1.00, 95% CI 0.86–1.16; p=1.00), semaglutide (OR 0.89, 95% CI 0.35–2.22; p=0.80), or albiglutide (OR 1.07, 95% CI 0.23–4.88; p=0.93). A subanalysis of trials lasting longer than 3 years also showed no increase in the neoplasia risk with GLP-1 receptor agonist use (OR 1.03, 95% CI 0.92–1.15; p=0.60). Between-trial statistical heterogeneity was low for all comparisons. Conclusion. GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes.
Applying Two Simplified Ellipse‐Based Tangential Models to Wheel‐Rail Contact Using Three Alternative Nonelliptic Adaptation Approaches: A Comparative Study
Authors: An Boyang , Wang Ping , Zhou Jiayi , Chen Rong , Xu Jingmang , Wu Bing
Published: July 2019

In the modeling of railway vehicle‐track dynamics and wheel‐rail damage, simplified tangential contact models based on ellipse assumption are usually used due to strict limitation of computational cost. Since most wheel‐rail contact cases appear to be nonelliptic shapes, a fast and accurate tangential model for nonelliptic contact case is in demand. In this paper, two ellipse‐based simplified tangential models (i.e., FASTSIM and FaStrip) using three alternative nonelliptic adaptation approaches, together with Kalker’s NORM algorithm, are applied to wheel‐rail rolling contact cases. It aims at finding the best approach for dealing with nonelliptic rolling contact. Compared to previous studies, the nonelliptic normal contact solution in the present work is accurately solved rather than simplification. Therefore, it can avoid tangential modeling evaluation affected by inaccurate normal contact solution. By comparing with Kalker’s CONTACT code, it shows both FASTSIM‐based and FaStrip‐based models can provide accurate global creep force. With regard to local rolling contact solution, only the accuracy of FaStrip‐based models is satisfactory. Moreover, Ayasse‐Chollet’s local ellipse approach appears to be the best choice for nonelliptic adaptation.
Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to SLE and SSc
Authors: Petrackova Anna , Horak Pavel , Radvansky Martin , Skacelova Martina , Fillerova Regina , Kudelka Milos , Smrzova Andrea , Mrazek Frantisek , Kriegova Eva
Published: July 2019

Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (n=36, DAS28≥3.2), SLE (n=28, SLEDAI>6), and SSc (n=22, revised EUSTAR index>2.25). Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (Pcorr<0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (Pcorr<0.02). Applying the association rule analysis, six rules (combinations and expression of genes describing disease) were identified for RA (most frequently included high TLR3 and/or IL1RAP/IL1R3) and three rules for SLE (low IL1RN and IL18R1) and SSc (low TLR5 and IL18R1). This first cross-disease study identified emerging heterogeneity in the innate signature of RA patients with many upregulated innate genes compared to that of SLE and SSc.
Impacts of Denture Retention and Stability on Oral Health-Related Quality of Life, General Health, and Happiness in Elderly Thais
Authors: Limpuangthip Nareudee , Somkotra Tewarit , Arksornnukit Mansuang
Published: July 2019

Purpose. This study investigated denture and patient related factors associated with oral health-related quality of life (OHRQoL) of complete denture wearers and their association with general health and happiness. Methods. This retrospective cohort study comprised 130 participants with complete edentulism, with maxillary and mandibular complete dentures treated at Chulalongkorn University Dental School during 2010-2017. The primary outcome was the presence of overall and domain-specific Oral Impacts on Daily Performances (OIDP). Secondary outcomes were diagnosed and perceived general health, and happiness. Denture retention and stability were classified as acceptable or unacceptable following the CU-modified Kapur criteria. Five esthetic-assessment criteria of the harmonization and proportions between facial and dental anatomical landmarks were measured from patient’s photographs. Age, sex, previous complete denture experience, and denture age were recorded. The associations between each variable and oral impacts were analyzed using bivariate logistic regression, and the factors with p < 0.25 were further adjusted using multivariable analysis. Associations between oral impact scores and general health and happiness were assessed using Spearman’s rank correlation. Results. The most frequent oral impacts were on physical domain, while social domain was the least affected. Denture retention/stability was significantly associated with both overall and specific domains of oral impact. Happiness was found to be strongly correlated with perceived general health, but marginally with oral impact scores. Conclusions. Unacceptable complete denture retention and stability are substantial risk factors for impaired OHRQoL in complete edentulism. Maintaining optimal denture retention and stability in denture wearers is essential for good oral health and well-being with the goal of enhancing happiness.
Fluoxetine Attenuated Anxiety-Like Behaviors in Streptozotocin-Induced Diabetic Mice by Mitigating the Inflammation
Authors: Yuan Peng , Zhang Jian , Li Liang , Song Zhendi
Published: July 2019

Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.
Measurement and Adaptive Identification of Nonstationary Acoustic Impulse Responses
Authors: Mekarzia M.
Published: July 2019

In this work, we present a method of measurement of nonstationary acoustic impulse responses identified by the fast version of the Recursive Least Squares algorithm (FRLS), using professional acoustic equipment. This measurement bench realized in a deaf room presents several tests of capability of adaptive algorithm to tracking the nonstationarities of true system to be identified. The tests of tracking capability obtained are stronger compared to what is encountered in real life and can be used in several applications.
Kinesio Taping for Balance Function after Stroke: A Systematic Review and Meta-Analysis
Authors: Hu Yijuan , Zhong Dongling , Xiao Qiwei , Chen Qiang , Li Juan , Jin Rongjiang
Published: July 2019

Objective. With the increasing social and economic burdens of balance impairment after stroke, the treatment for balance impairment after stroke becomes a major public health problem worldwide. Kinesio taping (KT) as a part of clinical practice has been used widely in the treatment of balance impairment after stroke. However, the clinical effects of KT for balance function have not been confirmed. The objective of this study is to investigate the effects and safety of KT for balance impairment after stroke. Methods. We conducted a systematic review (SR) and meta-analysis of randomized controlled trials (RCTs) on the effects of KT for balance impairment after stroke. We searched the following databases: (1) English databases: EMBASE (via Ovid), MEDLINE (via Ovid), the Cochrane library, PubMed, and PEDro; (2) Chinese databases: China Biology Medicine (CBM), Wan Fang database, China National Knowledge Infrastructure (CNKI), and VIP. Besides, hand searches of relevant references were also conducted. We systematically searched from the inception to December 2018, using the keywords (Kinesio, Kinesio Tape, tape, or Orthotic Tape) and (stroke, hemiplegia, or hemiplegic paralysis) and (balance or stability). The search strategies were adjusted for each database. The reference lists of included articles were reviewed for relevant trials. For missing data, we contacted the authors to get additional information. Results. 22 RCTs involved 1331 patients, among which 667 patients in the experimental group and 664 patients in the control group were included. Results of meta-analysis showed that, compared with conventional rehabilitation (CR), there was significant difference in Berg Balance Scale (BBS) (MD=4.46, 95%CI 1.72 to 7.19, P=0.001), Time Up and Go Test (TUGT) (MD=-4.62, 95%CI -5.48 to -3.79, P < 0.00001), functional ambulation category scale (FAC) (MD=0.53, 95%CI 0.38 to 0.68, P < 0.00001), Fugl-Meyer assessment (FMA-L) (MD=4.20, 95%CI 3.17 to 5.24, P < 0.00001), and Modified Ashworth Scale (MAS) (MD=-0.38, 95%CI -0.49 to -0.27, P < 0.00001). The results of subgroup analysis showed that there was no significant difference between KT and CR with ≤4 weeks treatment duration (< 4 weeks: MD=5.03, 95%CI -1.80 to 11.85, P=0.15; =4 weeks: MD=4.33, 95%CI -1.50 to 10.15, P=0.15), while there was significant difference with more than 4-week treatment duration (MD=4.77, 95%CI 2.58 to 6.97, P < 0.0001). Conclusions. Based on current evidence, KT was more effective than CR for balance function, lower limb function, and walking function in poststroke patients. Longer treatment duration may be associated with better effects. However, more well-conducted RCTs are required in the future.
Metastasis Suppressors NME1 and NME2 Promote Dynamin 2 Oligomerization and Regulate Tumor Cell Endocytosis, Motility, and Metastasis
Authors: Khan Imran , Gril Brunilde , Steeg Patricia S.
Published: July 2019

NM23 (NME) is a metastasis suppressor that significantly reduces metastasis without affecting primary tumor size, however, the precise molecular mechanisms are not completely understood. We examined the role of dynamin (DNM2), a GTPase regulating membrane scission of vesicles in endocytosis, in NME1 and NME2 regulation of tumor cell motility and metastasis. Overexpression of NMEs in MDA-MB-231T and MDA-MB-435 cancer cell lines increased endocytosis of transferrin and EGF receptors (TfR and EGFR) concurrent with motility and migration suppression. The internalized vesicles, costained with Rab5, had AP2 depleted from the cell surface and exhibited increased Rab5-GTP levels, consistent with endocytosis. Dynamin inhibitors Iminodyn-22 and Dynole-34-2, or shRNA-mediated downregulation of DNM2, impaired NME's ability to augment endocytosis or suppress tumor cell motility. In a lung metastasis assay, NME1 overexpression failed to significantly suppress metastasis in the DNM2 knockdown MDA-MB-231T cells. Using the EGF–EGFR signaling axis as a model in MDA-MB-231T cells, NME1 decreased pEGFR and pAkt expression in a DNM2-dependent manner, indicating the relevance of this interaction for downstream signaling. NME–DNM2 interaction was confirmed in two-way coimmunoprecipitations. Transfection of a NME1 site–directed mutant lacking histidine protein kinase activity but retaining nucleoside diphosphate kinase (NDPK) activity showed that the NDPK activity of NME was insufficient to promote endocytosis or inhibit EGFR signaling. We show that addition of NME1 or NME2 to DNM2 facilitates DNM2 oligomerization and increases GTPase activity, both required for vesicle scission. NME–DNM2 interaction may contribute to metastasis suppression by altering tumor endocytic and motility phenotypes.

Significance:

NME1 suppresses metastasis via changes in tumor endocytosis and motility, mediated by dynamin (DNM2) GTPase activity.
MALAT1 rs664589 Polymorphism Inhibits Binding to miR-194-5p, Contributing to Colorectal Cancer Risk, Growth, and Metastasis
Authors: Wu Shenshen , Sun Hao , Wang Yajie , Yang Xi , Meng Qingtao , Yang Hongbao , Zhu Haitao , Tang Weiyan , Li Xiaobo , Aschner Michael , Chen Rui
Published: July 2019

Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is an evolutionarily highly conserved lncRNA that contributes to colorectal cancer development. However, the exact molecular mechanisms connecting MALAT1 to colorectal cancer have not been fully elucidated. Here, we performed a case–control study in 1,078 patients with colorectal cancer and 1,175 healthy controls to evaluate the association between potentially functional genetic variants of MALAT1 and survival outcomes in patients with colorectal cancer. MALAT1 rs664589 CG/GG genotypes significantly increased the associated risk and decreased overall survival of patients with colorectal cancer compared with the CC genotype. In vitro and in vivo experiments showed that the rs664589 C to G mutation facilitated carcinogenesis and metastasis of colorectal cancer. Mechanistically, the miRNA miR-194-5p targeted MALAT1 for degradation in the nucleus in an Ago2-dependent manner; the rs664589 G allele altered the binding of MALAT1 to miR-194-5p, resulting in increased expression of MALAT1. Colorectal cancer cells and human tissues with the rs664589 CG/GG genotype expressed significantly higher MALAT1 than those with the rs664589 CC genotype. Multivariate Cox regression analysis showed that MALAT1 was a poor prognostic factor of colorectal cancer. In summary, MALAT1 with the rs664589 G allele demonstrates altered binding to miR-194-5p in the nucleus, leading to increased MALAT1 expression and enhanced colorectal cancer development.

Significance:

These findings highlight the functional role of MALAT1 polymorphism in colorectal cancer metastasis and survival as well as the underlying mechanism.
Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation
Authors: Burslem George M. , Schultz Anna Reister , Bondeson Daniel P. , Eide Christopher A. , Savage Stevens Samantha L. , Druker Brian J. , Crews Craig M.
Published: July 2019

Although the use of ATP-competitive tyrosine kinase inhibitors of oncoprotein BCR-ABL1 has enabled durable responses in patients with chronic myeloid leukemia (CML), issues of drug resistance and residual leukemic stem cells remain. To test whether the degradation of BCR-ABL1 kinase could offer improved response, we developed a series of proteolysis-targeting chimera (PROTAC) that allosterically target BCR-ABL1 protein and recruit the E3 ligase Von Hippel-Lindau, resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein. In both human CML K562 cells and murine Ba/F3 cells expressing BCR-ABL1, lead compound GMB-475 induced rapid proteasomal degradation and inhibition of downstream biomarkers, such as STAT5, and showed increased sensitivity compared with diastereomeric controls lacking degradation activity. Notably, GMB-475 inhibited the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants and further sensitized Ba/F3 BCR-ABL1 cells to inhibition by imatinib, while demonstrating no toxicity toward Ba/F3 parental cells. Reverse phase protein array analysis suggested additional differences in levels of phosphorylated SHP2, GAB2, and SHC associated with BCR-ABL1 degradation. Importantly, GMB-475 reduced viability and increased apoptosis in primary CML CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations. GMB-475 degraded BCR-ABL1 and reduced cell viability in primary CML stem cells. Together, these findings suggest that combined BCR-ABL1 kinase inhibition and protein degradation may represent a strategy to address BCR-ABL1–dependent drug resistance, and warrant further investigation into the eradication of persistent leukemic stem cells, which rely on neither the presence nor the activity of the BCR-ABL1 protein for survival.

Significance:

Small-molecule–induced degradation of BCR-ABL1 in CML provides an advantage over inhibition and provides insights into CML stem cell biology.