bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving data-limited stock assessment with sporadic stock index information in stock reduction analysis
Authors: Guan Lisha , Chen Yong , Boenish Robert , Jin Xianshi , Shan Xiujuan
Published: December 2019

As most exploited fisheries lack a coherent time series of biomass index, development of data-limited stock assessment methods such as stock reduction analysis (SRA), is critical for fishery stock assessment due to their modest data requirements for estimating stock status and overfishing catch limits. In this study, we propose that sporadic time series of biomass indices, if available, may be fully utilized to inform priors of recent relative biomass (BT/B1) for data-limited stocks. We evaluated the performance of SRA incorporating this index-based prior by comparing two other common SRA priors (a deterministic prior set at 40% of the unfished biomass and a catch-based prior) with estimates from the likelihood-based assessments of 91 fish stocks from the RAM Legacy database. We extended our analysis by evaluating performance based on life history attributes and two depletion levels with BT/BMSY equaling 1 as the breakpoint. Results suggest index-based priors enhance accuracy for fish stocks at both depletion levels. We demonstrate that performance of SRA can be affected by three factors: the reliability of priors for BT/B1, recent depletion level, and life history.
Therapeutic potential of selanyl amide derivatives in the in vitro anticholinesterase activity and in in vivo antiamnesic action
Authors: Wilhelm Ethel A. , Torres Marina Laura C.P. , Pereira Caroline F. , Vogt Ane G. , Cervo Rodrigo , dos Santos Brenda G.T. , Cargnelutti Roberta , Luchese Cristiane
Published: December 2019

The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of mice. In conclusion, the present study evidenced the in vitro anticholinesterase effect of two new selanyl amide derivatives in the cerebral structures of mice. Moreover, compound 1, a selanyl amide derivative containing a furan ring, demonstrated antiamnesic action due to its antioxidant and anticholinesterase activities in cerebral structures.
Simulation-Based Algorithms for Markov Decision Processes: Monte Carlo Tree Search from AlphaGo to AlphaZero
Authors: Fu Michael C.
Published: December 2019

AlphaGo and its successors AlphaGo Zero and AlphaZero made international headlines with their incredible successes in game playing, which have been touted as further evidence of the immense potential of artificial intelligence, and in particular, machine learning. AlphaGo defeated the reigning human world champion Go player Lee Sedol 4 games to 1, in March 2016 in Seoul, Korea, an achievement that surpassed previous computer game-playing program milestones by IBM’s Deep Blue in chess and by IBM’s Watson in the U.S. TV game show Jeopardy. AlphaGo then followed this up by defeating the world’s number one Go player Ke Jie 3-0 at the Future of Go Summit in Wuzhen, China in May 2017. Then, in December 2017, AlphaZero stunned the chess world by dominating the top computer chess program Stockfish (which has a far higher rating than any human) in a 100-game match by winning 28 games and losing none (72 draws) after training from scratch for just four hours! The deep neural networks of AlphaGo, AlphaZero, and all their incarnations are trained using a technique called Monte Carlo tree search (MCTS), whose roots can be traced back to an adaptive multistage sampling (AMS) simulation-based algorithm for Markov decision processes (MDPs) published in Operations Research back in 2005 [Chang, HS, MC Fu, J Hu and SI Marcus (2005). An adaptive sampling algorithm for solving Markov decision processes. Operations Research, 53, 126–139.] (and introduced even earlier in 2002). After reviewing the history and background of AlphaGo through AlphaZero, the origins of MCTS are traced back to simulation-based algorithms for MDPs, and its role in training the neural networks that essentially carry out the value/policy function approximation used in approximate dynamic programming, reinforcement learning, and neuro-dynamic programming is discussed, including some recently proposed enhancements building on statistical ranking & selection research in the operations research simulation community.
Flight Schedule Recovery: A Simulation-Based Approach
Authors: Wang Derui , Wu Yanfeng , Hu Jian-Qiang , Liu Miaomiao , Yu Peiwen , Zhang Cheng , Wu Yan
Published: December 2019

In this paper, we report our work on the flight recovery problem for China Eastern Airlines. Traditionally, the flight recovery problem is often modeled as an integer or mixed integer linear programming problem. However, such a model cannot take many complex constraints and uncertainties in real applications. Furthermore, we have found solutions obtained based on such a model difficult to implement in their existing operations, as in the case of CEA. Therefore, we propose a simulation-based approach, which works well with their existing operations. Our work demonstrates the potentials of simulation based methods in the study of the flight recovery problem, and possibly other similar problems.
Cardiac Alternans Suppression Under T ± 𝜖 Feedback Control: Nonlinear Dynamics Analysis
Authors: Liang Shiuan-Ni , Le Duy-Manh , Lai Pik-Yin
Published: December 2019

The nonlinear dynamical properties of the recently proposed [Formula: see text] feedback control for suppressing cardiac alternans is investigated in detail for the discrete cardiac restitution map model and the continuous Luo–Rudy I ionic model. It is shown that cardiac alternans, induced by fast pacing, can be dramatically reduced by small changes of fixed magnitude ([Formula: see text]) under feedback control when [Formula: see text] exceeds a critical threshold. Remarkably, the suppression is achieved by utilizing the induced chaotic dynamics. Detailed information on the nature and mechanism of the control, and properties of the attractors are analyzed and discussed in the light of nonlinear dynamics.
Li–Yorke Chaos in Globally Coupled Map Lattice with Delays
Authors: Nag Mayurakshi , Poria Swarup
Published: December 2019

Delay coupled smooth maps over a ring network with global coupling have been considered. Proof of the existence of chaos in the sense of Li–Yorke in the globally coupled smooth maps with homogeneous unit delay has been given by defining a suitable matrix norm. Conditions for the existence of Li–Yorke chaos depending on the coupling strength, map parameter and lattice size have been derived analytically. Chaotic regions in the parameter space are plotted numerically for delay coupled logistic maps.
Planar pure braids on six strands
Authors: Mostovoy Jacob , Roque-Márquez Christopher
Published: December 2019

The group of planar (or flat) pure braids on [Formula: see text] strands, also known as the pure twin group, is the fundamental group of the configuration space [Formula: see text] of [Formula: see text] labeled points in [Formula: see text] no three of which coincide. The planar pure braid groups on 3, 4 and 5 strands are free. In this note, we describe the planar pure braid group on 6 strands: it is a free product of the free group on 71 generators and 20 copies of the free abelian group of rank two.
A Graph and Clustering-Based Framework for Efficient XACML Policy Evaluation
Authors: Li Yanfei , Deng Fan
Published: December 2019

EXtensible Access Control Markup Language (XACML) is one of the standardized languages for specifying access control policies. Policies described by the XACML are used to express the security requirement in the network and information system when we study authorization access control. With the aim to improve the Policy Decision Point (PDP) evaluation performance, we put forward a Graph and Clustering-Based Framework, employing the aggregate function. First, we partition the rule set into subsets. For the single value, we select the best partition quantity based on the aggregate function. As for the interval value, we handle with the start point and the finish point, respectively, in the same way as single value. Second, the policy set is split according to the partition of rule set. In this way, not only single values, but also interval values are taken into consideration. After that, we explore the searching tree to obtain the possibly matched rules. Finally, we construct the combining tree and output the policy decision on the basis of it. The experimental results show that our approach is orders of magnitude better than the Sun PDP. A comparison in evaluation performance between the redundancy detecting and eliminating engine and the Sun PDP, as well as XEngine and SBA-XACML, is made. Experimental results show that the evaluation performance of the PDP can be prominently improved by eliminating redundancies.
LAMDA-HAD, an Extension to the LAMDA Classifier in the Context of Supervised Learning
Authors: Morales Luis , Aguilar José , Chávez Danilo , Isaza Claudia
Published: December 2019

This paper proposes a new approach to improve the performance of Learning Algorithm for Multivariable Data Analysis (LAMDA). This algorithm can be used for supervised and unsupervised learning, based on the calculation of the Global Adequacy Degree (GAD) of one individual to a class, through the contributions of all its descriptors. LAMDA has the capability of creating new classes after the training stage. If an individual does not have enough similarity to the preexisting classes, it is evaluated with respect to a threshold called the Non-Informative Class (NIC), this being the novelty of the algorithm. However, LAMDA has problems making good classifications, either because the NIC is constant for all classes, or because the GAD calculation is unreliable. In this work, its efficiency is improved by two strategies, the first one, by the calculation of adaptable NICs for each class, which prevents that correctly classified individuals create new classes; and the second one, by computing the Higher Adequacy Degree (HAD), which grants more robustness to the algorithm. LAMDA-HAD is validated by applying it in different benchmarks and comparing it with LAMDA and other classifiers, through a statistical analysis to determinate the cases in which our algorithm presents a better performance.
An Approach using Multicriteria Decision Methods to Barges Configuration for Pushed Convoys in the Amazon
Authors: Lameira Pedro Igor Dias , Filgueiras Tainã Carvalho Garcia Miranda , Botter Rui Carlos , dos Santos Saavedra Rodrigo
Published: December 2019

The Amazon region has the largest hydrographic basin in the world and a favorable geographical location as a strategic export point but does not satisfactorily exploit its potential for transport and cargo flow, mainly as a differential factor of logistic competitiveness. For the waterway mode, cargo transportation is predominantly carried out by pushed convoys. The objective of this research is to evaluate and select, the best river train for the outflow of iron ore on the Marabá – Vila do Conde stretch, through a multiple criteria decision-making approach. To meet the objectives, a methodological framework is proposed using a hybrid AHP-DEMATEL method, based on a statistical analysis and to guarantee the reliability of the results for the proposed alternatives and not only considering the preference function, the ELECTRE method was used and also a parametric comparison of the AHP results. The main goals of this work were achieved and it was possible to infer that the combination of these methods has, in addition to the evident efficacy, a high reliability in the water transport area, being able to be used with accuracy of diverse forms in the academic area, as well as in industrial applications. Therefore, it can be affirmed that the best-pushed convoy configuration for the iron ore runoff in the Marabá – Vila do Conde stretch is composed by six barges in the arrangement of two columns and three rows with the measurements, by barge, with length of 60.96[Formula: see text]m; beam of 13.75[Formula: see text]m; and a 5[Formula: see text]m molded depth.
Theoretical Characterization of Thermodynamic, Magnetic and Electronic Proprieties of Full-Heusler Co2YGa (Y = V, Cr and Mn) Alloys
Authors: Mokhtari M. , Amari D. , Dahmane F. , Benabdellah G. , Zekri L. , Zekri N.
Published: December 2019

The electronic structure, magnetism and thermal proprieties of the full-Heusler alloys Co2YGa (Y [Formula: see text] V, Cr and Mn) have been investigated by first-principles calculations based on density functional theory with the generalized gradient approximation (GGA). Our obtained results of lattice parameters show reasonable agreement to the previously reported experimental and other theoretical studies. The calculations show that all Co2YGa (Y [Formula: see text] V, Cr and Mn) alloys belong to half-metallic compound with a magnetic moment of 2.00, 3.00 and 4.00 [Formula: see text] at their respective equilibrium lattice constants which is in good agreement with the Slater–Pauling rule and perfect 100% spin polarization at the Fermi level. The thermal effect on the macroscopic properties of these alloys is presented such as the thermal expansion coefficient, heat capacity and Debye temperature, based on the quasi-harmonic Debye model.
Comparison and Modelling of Country-level Microblog User and Activity in Cyber-physical-social Systems Using Weibo and Twitter Data
Authors: Yang Po , Liu Jing , Qi Jun , Yang Yun , Wang Xulong , Lv Zhihan
Published: December 2019

As the rapid growth of social media technologies continues, Cyber-Physical-Social System (CPSS) has been a hot topic in many industrial applications. The use of “microblogging” services, such as Twitter, has rapidly become an influential way to share information. While recent studies have revealed that understanding and modelling microblog user behaviour with massive users’ data in social media are keen to success of many practical applications in CPSS, a key challenge in literatures is that diversity of geography and cultures in social media technologies strongly affect user behaviour and activity. The motivation of this article is to understand differences and similarities between microblogging users from different countries using social media technologies, and to attempt to design a Country-Level Micro-Blog User (CLMB) behaviour and activity model for supporting CPSS applications. We proposed a CLMB model for analysing microblogging user behaviour and their activity across different countries in the CPSS applications. The model has considered three important characteristics of user behaviour in microblogging data, including content of microblogging messages, user emotion index, and user relationship network. We evaluated CLBM model under the collected microblog dataset from 16 countries with the largest number of representative and active users in the world. Experimental results show that (1) for some countries with small population and strong cohesiveness, users pay more attention to social functionalities of microblogging service; (2) for some countries containing mostly large loose social groups, users use microblogging services as a news dissemination platform; (3) users in countries whose social network structure exhibits reciprocity rather than hierarchy will use more linguistic elements to express happiness in microblogging services.
Strategic Attack & Defense in Security Diffusion Games
Authors: Waniek Marcin , Michalak Tomasz P. , Alshamsi Aamena
Published: December 2019

Security games model the confrontation between a defender protecting a set of targets and an attacker who tries to capture them. A variant of these games assumes security interdependence between targets, facilitating contagion of an attack. So far, only stochastic spread of an attack has been considered. In this work, we introduce a version of security games, where the attacker strategically drives the entire spread of attack and where interconnections between nodes affect their susceptibility to be captured.

We find that the strategies effective in the settings without contagion or with stochastic contagion are no longer feasible when spread of attack is strategic. While in the former settings it was possible to efficiently find optimal strategies of the attacker, doing so in the latter setting turns out to be an NP-complete problem for an arbitrary network. However, for some simpler network structures, such as cliques, stars, and trees, we show that it is possible to efficiently find optimal strategies of both players. For arbitrary networks, we study and compare the efficiency of various heuristic strategies. As opposed to previous works with no or stochastic contagion, we find that centrality-based defense is often effective when spread of attack is strategic, particularly for centrality measures based on the Shapley value.
A Systematic Review on Literature-based Discovery
Authors: Thilakaratne Menasha , Falkner Katrina , Atapattu Thushari
Published: December 2019

The vast nature of scientific publications brings out the importance ofLiterature-Based Discovery (LBD)research that is highly beneficial to accelerate knowledge acquisition and the research development process. LBD is a knowledge discovery workflow that automatically detects significant, implicit knowledge associations hidden in fragmented knowledge areas by analysing existing scientific literature. Therefore, the LBD output not only assists in formulating scientifically sensible, novel research hypotheses but also encourages the development of cross-disciplinary research. In this systematic review, we provide an in-depth analysis of the computational techniques used in the LBD process using a novel, up-to-date, and detailed classification. Moreover, we also summarise the key milestones of the discipline through a timeline of topics. To provide a general overview of the discipline, the review outlines LBD validation checks, major LBD tools, application areas, domains, and generalisability of LBD methodologies. We also outline the insights gathered through our statistical analysis that capture the trends in LBD literature. To conclude, we discuss the prevailing research deficiencies in the discipline by highlighting the challenges and opportunities of future LBD research.
Multi-level Steiner Trees
Authors: Ahmed Reyan , Angelini Patrizio , Sahneh Faryad Darabi , Efrat Alon , Glickenstein David , Gronemann Martin , Heinsohn Niklas , Kobourov Stephen G. , Spence Richard , Watkins Joseph , Wolff Alexander
Published: December 2019

In the classical Steiner tree problem, given an undirected, connected graph
G
=(
V
,
E
) with non-negative edge costs and a set of
terminals
T
⊆
V
, the objective is to find a minimum-cost tree
E
&prime
⊆
E
that spans the terminals. The problem is APX-hard; the best-known approximation algorithm has a ratio of ρ = ln (4)+ε < 1.39. In this article, we study a natural generalization, the
multi-level Steiner tree
(MLST) problem: Given a nested sequence of terminals
T
ℓ
⊂ … ⊂
T
1
⊆
V
, compute nested trees
E
ℓ
⊆ … ⊆
E
1
⊆
E
that span the corresponding terminal sets with minimum total cost.

The MLST problem and variants thereof have been studied under various names, including Multi-level Network Design, Quality-of-Service Multicast tree, Grade-of-Service Steiner tree, and Multi-tier tree. Several approximation results are known. We first present two simple
O
(ℓ)-approximation heuristics. Based on these, we introduce a rudimentary composite algorithm that generalizes the above heuristics, and determine its approximation ratio by solving a linear program. We then present a method that guarantees the same approximation ratio using at most 2ℓ Steiner tree computations. We compare these heuristics experimentally on various instances of up to 500 vertices using three different network generation models. We also present several integer linear programming formulations for the MLST problem and compare their running times on these instances. To our knowledge, the composite algorithm achieves the best approximation ratio for up to ℓ = 100 levels, which is sufficient for most applications, such as network visualization or designing multi-level infrastructure.
Behavioral Conceptualization and Treatment of Chronic Pain
Authors: Vlaeyen Johan W.S. , Crombez Geert
Published: December 2019

Pain is considered a hardwired signal of bodily disturbance belonging to a basic motivational system that urges the individual to act and to restore the body's integrity, rather than just a sensory and emotional experience. Given its eminent survival value, pain is a strong motivator for learning. Response to repeated pain increases when harm risks are high (sensitization) and decreases in the absence of such risks (habituation). Discovering relations between pain and other events provides the possibility to predict (Pavlovian conditioning) and control (operant conditioning) harmful events. Avoidance is adaptive in the short term but paradoxically may have detrimental long-term effects. Pain and pain-related responses compete with other demands in the environment. Exposure-based treatments share the aim of facilitating or restoring the pursuit of individual valued life goals in the face of persistent pain, and further improvements in pain treatment may require a paradigm shift toward more personalized approaches.
Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism
Authors: Lu Zhongyang , Li Yanchun , Syn Wing-Kin , Wang Zhewu , Lopes-Virella Maria F. , Lyons Timothy J. , Huang Yan
Published: December 2019

We reported previously that increased acid sphingomyelinase (ASMase)-catalyzed hydrolysis of sphingomyelin, which leads to increases in ceramide and sphingosine 1 phosphate (S1P), played a key role in the synergistic upregulation of proinflammatory cytokines by palmitic acid (PA), a major saturated fatty acid, and lipopolysaccharide (LPS) in macrophages. Since macrophages are vital players in nonalcoholic steatohepatitis (NASH) and atherosclerosis, we assessed the effect of ASMase inhibition on NASH and atherosclerosis cooperatively induced by high-PA-containing high-fat diet (HP-HFD) and LPS in LDL receptor-deficient (LDLR−/−) mice. LDLR−/− mice were fed HP-HFD, injected with low dose of LPS and treated with or without the ASMase inhibitor amitriptyline. The neutral sphingomyelinase inhibitor GW4869 was used as control. Metabolic study showed that both amitriptyline and GW4869 reduced glucose, lipids, and insulin resistance. Histological analysis and Oil Red O staining showed that amitriptyline robustly reduced hepatic steatosis while GW4869 had modest effects. Interestingly, immunohistochemical study showed that amitriptyline, but not GW4869, strongly reduced hepatic inflammation. Furthermore, results showed that both amitriptyline and GW4869 attenuated atherosclerosis. To elucidate the underlying mechanisms whereby amitriptyline inhibited both NASH and atherosclerosis, but GW4869 only inhibited atherosclerosis, we found that amitriptyline, but not GW4869, downregulated proinflammatory cytokines in macrophages. Finally, we found that inhibition of sphingosine 1 phosphate production is a potential mechanism whereby amitriptyline inhibited proinflammatory cytokines. Collectively, this study showed that amitriptyline inhibited NASH and atherosclerosis through modulation of sphingolipid metabolism in LDLR−/− mice, indicating that sphingolipid metabolism in macrophages plays a crucial role in the linkage of NASH and atherosclerosis.
Variable Speed Pump Storage for the Mitigation of SSR in Power System with Wind Generation
Authors: Fengchun Ye , Bitew Girmaw Teshager , Minxiao Han , Yao Sun , Hanhua Zhang
Published: December 2019

Subsynchronous resonance (SSR) can bring significant negative effects on the grid system like stability, security, and even generator shaft damage. This work presents a new method of using a doubly‐fed induction machine (DFIM) based system of variable speed pumped storage plant (VSPS) to mitigate SSR in the power system with high penetration of wind generation. The mitigation is reached based on the principle of balanced shaft mechanical input power and electromagnetic power. The fundamental concepts and phenomena of SSR with wind farm are discussed in brief in this work. For the sake of analysis and verification of performance of the proposed system, the network model including wind farm, VSPS, HVDC, and synchronous machine is built based on Ningxia grid for the SSR study using PSCAD platform. The result shows that VSPS brings significant effect to dampen the SSR in the power system with high penetration of wind generation.
Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study
Authors: Wang Zhe , Lian Le-jing , Dong Yan-yan , Cui Xiao , Qian Jian-chang , Huang Cheng-ke , Chen Rui-jie , Sun Wei
Published: December 2019

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1–50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.
Energy‐Saving Design of Building Envelope Based on Multiparameter Optimization
Authors: Gan Weinan , Cao Yunzhong , Jiang Wen , Li Liangqiang , Li Xiaolin
Published: December 2019

The contradiction between the indoor environment and building energy consumption has been controversial. The design of building envelope involves many parameters such as window size and exterior wall material. These parameters have significant influence on building energy‐saving design and indoor environment. In this paper, nondominant sorting genetic algorithm‐II (NSGA‐II) is utilized to calculate winter heat consumption, indoor total lighting energy consumption, and thermal comfort. The Pareto method is used to select the compromise solution and effective value of each building parameter. Different from other studies, we add more architectural design variables into the model calculation, which can bring architects more detailed energy‐saving design content.
Herpes Simplex Virus Pneumonia: Importance of Aspiration Etiology
Authors: Odani Kentaro , Tachibana Mitsuhiro , Tamashima Rintaro , Tsutsumi Yutaka
Published: December 2019

Herpes simplex virus (HSV) pneumonia caused by aspiration from the oropharyngeal exudates is described. An 89-year-old Japanese male in a poor performance state complained of appetite loss followed by difficulty in swallowing, and bilateral pulmonary infiltrates with interstitial reactions were radiologically pointed out. Antibiotics administration was ineffective, and he died on the 6th day of hospitalization. At autopsy, HSV-induced multiple mucosal erosions were observed on the tongue, pharynx, epiglottis, and trachea. In bilateral lower lobes of the lung, HSV infected bronchiolar and type-II alveolar cells in association with acute interstitial reactions. The infected cells with intranuclear inclusion bodies were immunoreactive with HSV antiserum. HSV-1 infection was confirmed by immunostaining with monospecific monoclonal antibodies and by type-specific real-time polymerase chain reaction. It is very likely that HSV pneumonia was provoked by aspiration of infected exudates from the upper airway (namely, sequential infection from the tongue, epiglottis, and trachea to lung). Oropharyngeal herpes might cause anorexia and difficulty in swallowing, probably accelerating aspiration. The medical staff did not recognize the oropharyngeal lesions of this aged patient. We must realize again the importance of oral care for hospitalized patients to avoid aspiration pneumonia, including herpetic pneumonia.
Head Loss in Thin-Walled Drip Tapes with Continuous Labyrinth
Authors: Melo Verônica G. M. L. , Araújo Ana C. S. , Camargo Antonio P. , Melo Leonardo L. , Frizzone José A. , Bombardelli Wagner W. A.
Published: December 2019

Thin-walled drip tapes with continuous labyrinth have been used for irrigation of vegetables and other short-cycle crops, especially due to their low cost. The continuous labyrinths welded into the pipe inner wall affect the head loss along such emitting pipes. In addition, the flow cross section of thin-walled pipes may change due to the effects of the operating pressure, which also has consequences for the head loss. The objective of this work was to investigate experimentally the friction factor and the head loss on thin-walled drip tapes with continuous labyrinths operated under various pressures. Two models of commercial thin-walled drip tapes with continuous labyrinths were evaluated. Nonperforated samples were used to determine the head-loss equations. The equations were adjusted as a function of flow rate and pressure head at the pipe inlet. Alternatively, the diameter in the Darcy–Weisbach equation was adjusted as a function of the pressure head by a power-law model. The possibility of using a mean diameter in the Darcy–Weisbach equation was also analyzed. Experimental investigation indicated that the friction factor in the Darcy–Weisbach equation can be accurately described using a power-law model, like the Blasius equation, but characterized by a coefficient a=0.3442 for the Turbo Tape and a=0.3225 for the Silver Tape. The obtained values of a are larger than those generally used and available in the literature. The influence of the operating pressure on the pipe diameter can be neglected for the purpose of calculating the head loss. The two approaches, considering the variation of the diameter with the pressure head and considering an optimum average diameter for the calculation of head loss by the Darcy–Weisbach equation, produce similar results, allowing accurate prediction of head loss. Evaluating the proposed mathematical models, 95% of predictions presented relative errors of head loss smaller than 5%. For the Turbo Tape, the optimum diameter for the purpose of calculating the head loss is 16.01 mm, which is very close to the value indicated by its manufacturer (15.9 mm). For the Silver Drip, the optimum diameter is 15.71 mm, while the manufacturer gives a value of 16.22 mm, which produces considerable error in the calculation of head loss.
Fluoride Release of Fresh and Aged Glass Ionomer Cements after Recharging with High-Fluoride Dentifrice
Authors: Rolim Fabiana Gouveia , de Araújo Lima Allan David , Lima Campos Islany Cardoso , de Sousa Ferreira Robson , da Cunha Oliveira-Júnior Carlos , Gomes Prado Vera Lúcia , Vale Glauber Campos
Published: December 2019

Objective. This study aimed to evaluate F release from GICs before and after recharging with F-dentifrices and after aging process. Methods. Fifteen specimens of GICs (conventional, resin modified, and high viscosity) and composite resin were stored individually in a polystyrene tube containing 2 ml of deionized water (DW), with water replacement every 24 hours. After 15 days, the specimens were treated with a dentifrice suspension (1 : 3 by volume) containing 0 μg F/g (n = 5), 1,100 μg F/g (n = 5), or 5,000 μg F/g (n = 5). After 3 min, the specimens were rinsed and replaced in new tubes with 2 ml of DW. This procedure was performed 2x/day for 2 days. The readings were taken on days 1, 5, 10, and 15 before and after the treatments. A second experiment was performed, using the same specimens of the previous study that were submitted to an aging process (specimens were kept in 2 ml of DW, remaining at 37°C for 36 weeks). Readings using specific electrode for F detection were taken on days 1, 5, 10, and 15 after treatment of the samples as described above. Data were analyzed by ANOVA and Tukey’s test with α fixed at 5%. Results. It was observed that the highest release of F for all the GICs occurred on the first day after the treatments, especially when using a high-fluoride dentifrice, with decreasing release over time. Also, although aged GICs still recharge with F treatments, the amount of F released was lower than fresh materials. Conclusion. GICs present a high F recharge and release capacity, especially in the first 24 hours and after the treatment with a high-fluoride dentifrice, even after material aging.
First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors
Authors: Falchook Gerald S. , Kurzrock Razelle , Amin Hesham M. , Xiong Wenyuan , Fu Siqing , Piha-Paul Sarina A. , Janku Filip , Eskandari Ghazaleh , Catenacci Daniel V. , Klevesath Manfred , Bruns Rolf , Stammberger Uz , Johne Andreas , Bladt Friedhelm , Friese-Hamim Manja , Girard Pascal , El Bawab Samer , Hong David S.
Published: December 2019

Purpose:

Tepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine the recommended phase II dose (RP2D).

Patients and Methods:

Patients received tepotinib orally according to one of three dose escalation regimens (R) on a 21-day cycle: R1, 30–400 mg once daily for 14 days; R2, 30–315 mg once daily 3 times/week; or R3, 300–1,400 mg once daily. After two cycles, treatment could continue in patients with stable disease until disease progression or unacceptable toxicity. The primary endpoint was incidence of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAE). Secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects.

Results:

One hundred and forty-nine patients received tepotinib (R1: n = 42; R2: n = 45; R3: n = 62). Although six patients reported DLTs [one patient in R1 (115 mg), three patients in R2 (60, 100, 130 mg), two patients in R3 (1,000, 1,400 mg)], the MTD was not reached at the highest tested dose of 1,400 mg daily. The RP2D of tepotinib was established as 500 mg once daily, supported by translational modeling data as sufficient to achieve ≥95% MET inhibition in ≥90% of patients. Treatment-related TEAEs were mostly grade 1 or 2 fatigue, peripheral edema, decreased appetite, nausea, vomiting, and lipase increase. The best overall response in R3 was partial response in two patients, both with MET overexpression.

Conclusions:

Tepotinib was well tolerated with clinical activity in MET-dysregulated tumors. The RP2D of tepotinib was established as 500 mg once daily. MET abnormalities can drive tumorigenesis. This first-in-man trial demonstrated that the potent, highly selective MET inhibitor tepotinib can reduce or stabilize tumor burden and is well tolerated at doses up to 1,400 mg once daily. An RP2D of 500 mg once daily, as determined from translational modeling and simulation integrating human population pharmacokinetic and pharmacodynamic data in tumor biopsies, is being used in ongoing clinical trials.
Combined Targeting of G9a and Checkpoint Kinase 1 Synergistically Inhibits Pancreatic Cancer Cell Growth by Replication Fork Collapse
Authors: Urrutia Guillermo , Salmonson Ann , Toro-Zapata Jorge , de Assuncao Thiago M. , Mathison Angela , Dusetti Nelson , Iovanna Juan , Urrutia Raul , Lomberk Gwen
Published: December 2019

Because of its dismal outcome, pancreatic ductal adenocarcinoma (PDAC) remains a therapeutic challenge making the testing of new pharmacologic tools a goal of paramount importance. Here, we developed a rational approach for inhibiting PDAC growth based on leveraging cell-cycle arrest of malignant cells at a phase that shows increased sensitivity to distinct epigenomic inhibitors. Specifically, we simultaneously inhibited checkpoint kinase 1 (Chk1) by prexasertib and the G9a histone methyltransferase with BRD4770, thereby targeting two key pathways for replication fork stability. Methodologically, the antitumor effects and molecular mechanisms of the combination were assessed by an extensive battery of assays, utilizing cell lines and patient-derived cells as well as 3D spheroids and xenografts. We find that the prexasertib–BRD4770 combination displays a synergistic effect on replication-associated phenomena, including cell growth, DNA synthesis, cell-cycle progression at S phase, and DNA damage signaling, ultimately leading to a highly efficient induction of cell death. Moreover, cellular and molecular data reveal that the synergistic effect of these pathways can be explained, at least in large part, by the convergence of both Chk1 and G9a functions at the level of the ATR–RPA–checkpoint pathway, which is operational during replication stress. Thus, targeting the epigenetic regulator G9a, which is necessary for replication fork stability, combined with inhibition of the DNA damage checkpoint, offers a novel approach for controlling PDAC growth through replication catastrophe.

Implications:

This study offers an improved, context-dependent, paradigm for the use of epigenomic inhibitors and provides mechanistic insight into their potential therapeutic use against PDAC.
Galectin-3 Interacts with C/EBPβ and Upregulates Hyaluronan-Mediated Motility Receptor Expression in Gastric Cancer
Authors: Kang Hyeon-Gu , Kim Won-Jin , Kang Hyeok-Gu , Chun Kyung-Hee , Kim Seok-Jun
Published: December 2019

The hyaluronan-mediated motility receptor (HMMR) is overexpressed in gastric cancer; however, the apparent role of HMMR has not been well defined owing to lack of detailed studies on gastric tumorigenesis. Therefore, we elucidated the functional and regulatory mechanisms of HMMR in gastric cancer. Using publicly available data, we confirmed HMMR overexpression in patients with gastric cancer. HMMR silencing decreased proliferation, migration, and invasion of gastric cancer cells, whereas HMMR overexpression reversed these effects. A gastric cancer xenograft mouse model showed statistically significant inhibition of tumor growth upon HMMR depletion. Previous data from cDNA microarray showed reduced HMMR expression upon inhibition of galectin-3. However, overexpression of galectin-3 increased HMMR expression, cell proliferation, and motility in gastric cancer cells, whereas HMMR silencing blocked these effects. Interestingly, galectin-3 interacted directly with C/EBPβ and bound to HMMR promoter to drive its transcription, and gastric cancer cell proliferation and motility. Altogether, high expression of HMMR promoted gastric cancer cell proliferation and motility and could be a prognostic factor in gastric cancer. In addition, HMMR expression was regulated by the interaction between C/EBPβ and galectin-3. Therefore, targeting HMMR along with galectin-3 and C/EBPβ complex could be a potential treatment strategy for inhibiting gastric cancer progression and metastasis.

Implications:

This study provides evidence that galectin-3 interacts with C/EBPβ in gastric cancer, and galectin-3 and C/EBPβ complex promotes gastric cancer cell progression and motility through upregulating HMMR expression.
Lean Tissue Deficit in Preterm Infants Persists up to 4 Months of Age: Results from a Swedish Longitudinal Study
Authors: Chmielewska Anna , Farooqi Aijaz , Domellöf Magnus , Ohlund Inger
Published: December 2019

Background: At term-equivalent age, infants born prematurely are shorter, lighter and have more adipose tissue compared to term counterparts. Little is known on whether the differences in body composition persist in later age. Methods: We prospectively recruited 33 preterm infants (<32 weeks gestational age, mean gestational age 28.1 weeks) and 69 term controls. Anthropometry and body composition (air displacement plethysmography) were monitored up to 4 months of age. Nutrient intakes from preterm infants were collected from clinical records. Results: At 4 months of age preterm infants were lighter and shorter than term controls (mean weight-for-age z-score: –0.73 vs. 0.06, p = 0.001; mean length-for-age z-score: –1.31 vs. 0.29, p < 0.0001). The significantly greater percentage of total body fat seen in preterm infants at term-equivalent age (20.2 vs. 11.7%, p < 0.0001) was no longer observed at 4 months. A deficit of fat-free mass persisted until 4 months of age (fat-free mass at term-equivalent age: 2.71 vs. 3.18 kg, p < 0.0001; at 4 months: 4.3 vs. 4.78 kg, p < 0.0001). The fat mass index and fat-free mass index (taking length into account) did not differ between the groups. Nutrition had little effect on body composition. Higher protein intake at week 2 was a negative predictor of fat-free mass at discharge. Conclusions: At 4 months corrected age, preterm infants were both lighter and shorter than term controls and the absolute fat-free mass deficit remained until this age. Little effect of nutrition on body composition was observed.
Jaw Elevator Muscle Coordination during Rhythmic Mastication in Primates: Are Triplets Units of Motor Control?
Authors: Ram Yashesvini , Ross Callum F.
Published: December 2019

The activity of mammal jaw elevator muscles during chewing has often been described using the concept of the triplet motor pattern, in which triplet I (balancing side superficial masseter and medial pterygoid; working side posterior temporalis) is consistently activated before triplet II (working side superficial masseter and medial pterygoid; balancing side posterior temporalis), and each triplet of muscles is recruited and modulated as a unit. Here, new measures of unison, synchrony, and coordination are used to determine whether in 5 primate species (Propithecus verreauxi, Eulemur fulvus, Papio anubis, Macaca fuscata,and Pan troglodytes)muscles in the same triplet are active more in unison, are more synchronized, and are more highly coordinated than muscles in different triplets. Results show that triplet I muscle pairs are active more in unison than other muscle pairs in Eulemur, Macaca, and Papio,buttriplet muscle pairs are mostly not more tightly synchronized than non-triplet pairs. Triplet muscles are more coordinated during triplet pattern cycles than non-triplet cycles, while non-triplet muscle pairs are more coordinated during non-triplet cycles than triplet cycles. These results suggest that the central nervous system alters patterns of coordination between cycles, recruiting triplet muscles as a coordinated unit during triplet cycles but employing a different pattern of muscle coordination during non-triplet cycles. The triplet motor pattern may simplify modulation of rhythmic mastication by being one possible unit of coordination that can be recruited on a cycle-to-cycle basis.
Body Composition Analysis of Computed Tomography Scans in Clinical Populations: The Role of Deep Learning
Authors: Paris Michael T.
Published: December 2019

Background: Body composition is increasingly being recognized as an important prognostic factor for health outcomes across cancer, liver cirrhosis, and critically ill patients. Computed tomography (CT) scans, when taken as part of routine care, provide an excellent opportunity to precisely measure the quantity and quality of skeletal muscle and adipose tissue. However, manual analysis of CT scans is costly and time-intensive, limiting the widespread adoption of CT-based measurements of body composition. Summary: Advances in deep learning have demonstrated excellent success in biomedical image analysis. Several recent publications have demonstrated excellent accuracy in comparison to human raters for the measurement of skeletal muscle, visceral adipose, and subcutaneous adipose tissue from the lumbar vertebrae region, indicating that analysis of body composition may be successfully automated using deep neural networks. Key Messages: The high accuracy and drastically improved speed of CT body composition analysis (<1 s/scan for neural networks vs. 15 min/scan for human analysis) suggest that neural networks may aid researchers and clinicians in better understanding the role of body composition in clinical populations by enabling cost-effective, large-scale research studies. As the role of body composition in clinical settings and the field of automated analysis advance, it will be critical to examine how clinicians interact with these systems and to evaluate whether these technologies are beneficial in improving treatment and health outcomes for patients.
Stuttering Impact: A Shared Perception for Parents and Children?
Authors: Rocha Mónica , Yaruss J. Scott , Rato Joana R.
Published: December 2019

Background/Aims: Previous research has provided information about how school-aged children perceive their own stuttering; however, less is known about how stuttering is perceived by their parents. The ways that parents view their children’s stuttering could influence how the children themselves react to it. This study proceeds to assess how parents’ perceptions of the impact of stuttering relate to the perceptions of children. Method: Participants were 50 children who stutter aged 7–12 years (mean = 9.10; SD = 1.7) and their parents, recruited from different cities in Portugal. The European Portuguese version of the Overall Assessment of the Speaker’s Experience of Stuttering was administered to the children, and an adapted version of the tool was administered to their parents. Results: Both parents and children showed generally similar overall impact ratings, typically falling in the mild and moderate ranges. Differences were observed in families with a history of stuttering: for those families, a comparison of parents’ and children’s scores revealed, in some domains, that parents perceived the impact of stuttering to be greater than the children did, especially related with children’s reactions to stuttering and their quality of life. Conclusion: Knowledge about how parents perceive the impact of stuttering on their children is important because families can play a key role in helping children cope with stuttering. These findings highlight the benefits of using an individualized treatment approach for each child that focuses on their perceptions, as well as on those of the parents, in order to address negative attitudes toward children’s stuttering.