bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Machining Induced Residual Shear and Normal Stresses on Fatigue Life and Stress Intensity Factor of Inconel 718
Authors: Hua Yang , Liu Zhanqiang
Published: November 2019

Residual shear stresses and normal stresses induced by machining affect the fatigue performance of components. Thus, residual shear and normal stresses should be considered simultaneously when evaluating the influence of residual stress on fatigue performance. In the present paper, the influences of residual shear and normal stresses on the fatigue life and stress intensity factor (SIF) of turned Inconel 718 were investigated. Firstly, the cos α measurement method was utilized to calculate the residual shear stress and residual normal stress of turned Inconel 718. Then, the combined effects of residual shear and normal stresses on fatigue life were evaluated through uniaxial tension–tension fatigue tests. Thirdly, a prediction model for the SIF was proposed by taking the residual shear and normal stresses into account. Finally, the predicted SIF was validated by the published experimental data from the literature. The predicted results of the proposed model generally agreed well with the available experimental data.
A Comprehensive Study of the Use of LoRa in the Development of Smart Cities
Authors: Andrade Roberto Omar , Yoo Sang Guun
Published: November 2019

The New Urban Agenda (Agenda 2030) adopted at the United Nations Conference related to Sustainable Urban Development (Habitat III) in the year 2016 has the goal of prompting cities to achieve the identified Sustainable Development Goals by the year 2030. In this context, cities can experiment strategies of circular economy for the optimization of resources, waste reduction, reuse, and recycling. The data generated by the components of an Internet of Things (IoT) ecosystem can contribute in two relevant ways to a smart city model: (1) by the generation of a circular economy and (2) by the creation of intelligence to improve the decision-making processes by citizens or city managers. In this context, it is in our interest to understand the most relevant axes of the research related to IoT, particularly those based on the LoRa technology. LoRa has attracted the interest of researchers because it is an open standard and contributes to the development of sustainable smart cities, since they are linked to the concepts of a circular economy. Additionally, the intention of this work is to identify the technological or practical barriers that hamper the development of solutions, find possible future trends that could exist in the context of smart cities and IoT, and understand how they could be exploited by the industry and academy.
Landslide Susceptibility Mapping Combining Information Gain Ratio and Support Vector Machines: A Case Study from Wushan Segment in the Three Gorges Reservoir Area, China
Authors: Yu Lanbing , Cao Ying , Zhou Chao , Wang Yang , Huo Zhitao
Published: November 2019

Landslides are destructive geological hazards that occur all over the world. Due to the periodic regulation of reservoir water level, a large number of landslides occur in the Three Gorges Reservoir area (TGRA). The main objective of this study was to explore the preference of machine learning models for landslide susceptibility mapping in the TGRA. The Wushan segment of TGRA was selected as a case study. At first, 165 landslides were identified and a total of 14 landslide causal factors were constructed from different data sources. Multicollinearity analysis and information gain ratio (IGR) model were applied to select landslide causal factors. Subsequently, the landslide susceptibility mapping using the calculated results of four models, namely, support vector machines (SVM), artificial neural networks (ANN), classification and regression tree (CART), and logistic regression (LR). The accuracy of these four maps were evaluated using the receive operating characteristic (ROC) and the accuracy statistic. Results revealed that eliminating the inconsequential factors can perhaps improve the accuracy of landslide susceptibility modelling, and the SVM model had the best performance in this study, providing strong technical support for landslide susceptibility modelling in TGRA.
Reliable Classification of FAQs with Spelling Errors Using an Encoder-Decoder Neural Network in Korean
Authors: Jang Youngjin , Kim Harksoo
Published: November 2019

To resolve lexical disagreement problems between queries and frequently asked questions (FAQs), we propose a reliable sentence classification model based on an encoder-decoder neural network. The proposed model uses three types of word embeddings; fixed word embeddings for representing domain-independent meanings of words, fined-tuned word embeddings for representing domain-specific meanings of words, and character-level word embeddings for bridging lexical gaps caused by spelling errors. It also uses class embeddings to represent domain knowledge associated with each category. In the experiments with an FAQ dataset about online banking, the proposed embedding methods contributed to an improved performance of the sentence classification. In addition, the proposed model showed better performance (with an accuracy of 0.810 in the classification of 411 categories) than that of the comparison model.
Evaluating Passenger Demand for Development of the Urban Transport System by an AHP Model with the Real-World Application of Amman
Authors: Alkharabsheh Ahmad , Moslem Sarbast , Duleba Szabolcs
Published: November 2019

The demand for a service includes generally two major components; quality elements and the reasonable and affordable price. Public transport can be considered as a special service, there is no direct market competition for the provider, but the use of private transport modes substitutes the usage of public vehicles. The dominating competitor, the usage of private cars, causes higher CO2 emission and has a serious impact on the environment. Thus, it is important to analyze from market and sustainability point of view which are the preferences of the public for the improvement of the urban transport system. This paper aims to conduct this analysis by including quality criteria and transport fare criteria related to the current service of a city and by setting up and testing a generally applicable model for decision support. Since the acquisition of public preference was the primary objective, and the problem can be considered as decision making, the Analytic Hierarchy Process was selected as methodology. There are previous research results of applying this method on public transport, however, not in an integrated model, in which quality and cost considerations are pairwise compared. Thus, the conventional Analytic Hierarchy Process (AHP) technique was used and the well-proven requisites of consistency and sensitivity check were analyzed. The new model was tested in a case study: surveying the public transport demand in the capital of Jordan, Amman.
Design of Novel Fiber Optical Flexible Routing System
Authors: Wu Po-Tsung , Liang Tsair-Chun
Published: November 2019

In this paper, we propose a new versatile routing device that utilizes arrayed waveguide gratings (AWGs), optical switches, and optical circulators to implement reconfigurable optical add/drop multiplexers (ROADMs), optical interleavers, and optical cross-connect (OXC). With the development of dense wavelength division multiplexing (DWDM) technology, ROADM and OXC technologies have also been put into practical use. Thus, the optical signal can be routed directly in the optical network according to its wavelength without the need for optical-electrical-optical (OEO) conversion. Although different optical network units (ONUs) have different bandwidth requirements, the use of optical interleavers has successfully solved the connection problem between old and new systems. According to the numerical experiments of static characteristics, the proposed routing device can effectively implement three different functionalities, thereby providing greater flexibility for fiber optic network applications.
Parallel Comparison of Major Sudden Stratospheric Warming Events in CESM1-WACCM and CESM2-WACCM
Authors: Liu Si-Ming , Chen Yuan-Hao , Rao Jian , Cao Can , Li Si-Yu , Ma Mu-Han , Wang Yao-Bin
Published: November 2019

After the recent release of the historical runs by community Earth system model version 2–the whole atmosphere community climate model (CESM2-WACCM), the major sudden stratospheric warming (SSW) events in this model and in its previous version (CESM1-WACCM) are compared based on a modern reanalysis (JRA55). Using the World Meteorological Organization (WMO) definition of SSWs and a threshold-based classification method that can describe the polar vortex morphology, SSWs in models and the reanalysis are further classified into two types, vortex displacement SSWs and vortex split SSWs. The general statistical characteristics of the two types of SSW events in the two model versions are evaluated. Both CESM1-WACCM and CESM2-WACCM models are shown to reproduce the SSW frequency successfully, although the circulations differences between vortex displacement SSWs and vortex split SSWs in CESM2-WACCM are smaller than in CESM1-WACCM. Composite polar temperature, geopotential height, wind, and eddy heat flux anomalies in both the two models and the reanalysis show similar evolutions. In addition, positive Pacific–North America and negative Western Pacific patterns in the troposphere preceding vortex displacement and split SSWs are observed in both observations and the models. The strong negative North Atlantic oscillation-like pattern, especially after vortex split SSW onset, is also identified in models. The near-surface cold Eurasia–warm North America pattern before both types of SSW onset, the warm Eurasia–cold North America pattern after displacement SSW onset, and the cold Eurasia–cold North America pattern after split SSW onset are consistently identified in JRA55, CESM1-WACCM, and CESM2-WACCM, although the temperature anomalies after the split SSW onset in CESM2-WACCM are somewhat underestimated.
A 5 km Resolution Regional Climate Simulation for Central Europe: Performance in High Mountain Areas and Seasonal, Regional and Elevation-Dependent Variations
Authors: Warscher Michael , Wagner Sven , Marke Thomas , Laux Patrick , Smiatek Gerhard , Strasser Ulrich , Kunstmann Harald
Published: November 2019

Mountain regions with complex orography are a particular challenge for regional climate simulations. High spatial resolution is required to account for the high spatial variability in meteorological conditions. This study presents a very high-resolution regional climate simulation (5 km) using the Weather Research and Forecasting Model (WRF) for the central part of Europe including the Alps. Global boundaries are dynamically downscaled for the historical period 1980–2009 (ERA-Interim and MPI-ESM), and for the near future period 2020–2049 (MPI-ESM, scenario RCP4.5). Model results are compared to gridded observation datasets and to data from a dense meteorological station network in the Berchtesgaden Alps (Germany). Averaged for the Alps, the mean bias in temperature is about −0.3 °C, whereas precipitation is overestimated by +14% to +19%. R 2 values for hourly, daily and monthly temperature range between 0.71 and 0.99. Temporal precipitation dynamics are well reproduced at daily and monthly scales (R 2 between 0.36 and 0.85), but are not well captured at hourly scale. The spatial patterns, seasonal distributions, and elevation-dependencies of the climate change signals are investigated. Mean warming in Central Europe exhibits a temperature increase between 0.44 °C and 1.59 °C and is strongest in winter and spring. An elevation-dependent warming is found for different specific regions and seasons, but is absent in others. Annual precipitation changes between −4% and +25% in Central Europe. The change signals for humidity, wind speed, and incoming short-wave radiation are small, but they show distinct spatial and elevation-dependent patterns. On large-scale spatial and temporal averages, the presented 5 km RCM setup has in general similar biases as EURO-CORDEX simulations, but it shows very good model performance at the regional and local scale for daily meteorology, and, apart from wind-speed and precipitation, even for hourly values.
Numerical Simulation of Turbulent Flow and Pollutant Dispersion in Urban Street Canyons
Authors: Nguyen Van Thinh , Nguyen Thanh Chuyen , Nguyen John
Published: November 2019

In this study, we have developed a numerical model based on an open source Computational Fluid Dynamics (CFD) package OpenFOAM, in order to investigate the flow pattern and pollutant dispersion in urban street canyons with different geometry configurations. In the new model, the pollutant transport driven by airflow is modeled by the scalar transport equation coupling with the momentum equations for airflow, which are deduced from the Reynolds Averaged Navier-Stokes (RANS) equations. The turbulent flow calculation has been calibrated by various two-equation turbulence closure models to select a practical and efficient turbulence model to reasonably capture the flow pattern. Particularly, an appropriate value of the turbulent Schmidt number has been selected for the pollutant dispersion in urban street canyons, based upon previous studies and careful calibrations against experimental measurements. Eventually, the numerical model has been validated against different well-known laboratory experiments in regard to various aspect ratios (a relationship between the building height and the width of the street canyon), and different building roof shapes (flat, shed, gable and round). The comparisons between the numerical simulations and experimental measurements show a good agreement on the flow pattern and pollutant distribution. This indicates the ability of the new numerical model, which can be applied to investigate the wind flow and pollutant dispersion in urban street canyons.
Long-Term Trends in PAH Concentrations and Sources at Rural Background Site in Central Europe
Authors: Lhotka Radek , Pokorná Petra , Zíková Naděžda
Published: November 2019

An increased burden due to polycyclic aromatic hydrocarbons (PAH) is a long-term air quality problem in Central and Eastern Europe. Extensive PAH monitoring has been implemented at the National Atmospheric Observatory Košetice (NAOK), a rural background site in the Czech Republic, as a representative for Central Europe. Data from NAOK are used for evaluation of PAH concentration trends and source apportionment. In total, concentrations of 14 PAHs in particulate matter (PM10) and in the gas phase between 2006 and 2016 were evaluated. The highest concentrations were measured at the beginning of the study period in 2006. Mean annual concentrations of benzo(a)pyrene, for example, showed a weak, however statistically significant decreasing trend. The positive matrix factorization (PMF) was used to determine the sources of PAHs at NAOK, with three factors resolved. The probable origin areas of PMF factors were identified by the conditional bivariate probability function (CBPF) and the potential source contribution function (PSCF) methods. The NAOK is affected by local sources of PAHs, as well as by regional and long-range transport. The PAH concentrations correlate negatively with industrial production and traffic intensity. High PAH emissions have been linked to local heating, suggesting that the planned replacement of obsolete combustion sources in the households could improve the overall air quality situation, not only with respect to PAHs.
A Critical Review of Lithium-Ion Battery Recycling Processes from a Circular Economy Perspective
Authors: Velázquez-Martínez Omar , Valio Johanna , Santasalo-Aarnio Annukka , Reuter Markus , Serna-Guerrero Rodrigo
Published: November 2019

Lithium-ion batteries (LIBs) are currently one of the most important electrochemical energy storage devices, powering electronic mobile devices and electric vehicles alike. However, there is a remarkable difference between their rate of production and rate of recycling. At the end of their lifecycle, only a limited number of LIBs undergo any recycling treatment, with the majority go to landfills or being hoarded in households. Further losses of LIB components occur because the the state-of-the-art LIB recycling processes are limited to components with high economic value, e.g., Co, Cu, Fe, and Al. With the increasing popularity of concepts such as “circular economy” (CE), new LIB recycling systems have been proposed that target a wider spectrum of compounds, thus reducing the environmental impact associated with LIB production. This review work presents a discussion of the current practices and some of the most promising emerging technologies for recycling LIBs. While other authoritative reviews have focused on the description of recycling processes, the aim of the present was is to offer an analysis of recycling technologies from a CE perspective. Consequently, the discussion is based on the ability of each technology to recover every component in LIBs. The gathered data depicted a direct relationship between process complexity and the variety and usability of the recovered fractions. Indeed, only processes employing a combination of mechanical processing, and hydro- and pyrometallurgical steps seemed able to obtain materials suitable for LIB (re)manufacture. On the other hand, processes relying on pyrometallurgical steps are robust, but only capable of recovering metallic components.
2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase
Authors: Krátký Martin , Štěpánková Šárka , Houngbedji Neto-Honorius , Vosátka Rudolf , Vorčáková Katarína , Vinšová Jarmila
Published: November 2019

The development of novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer’s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns and their esters with phosphorus-based acids were synthesized in yields of 72% to 92% and characterized. They were evaluated for in vitro inhibition of AChE from electric eel and BuChE from equine serum using modified Ellman’s spectrophotometric method. The benzamides exhibited a moderate inhibition of AChE with IC50 values in a narrow concentration range from 33.1 to 85.8 µM. IC50 values for BuChE were higher (53.5–228.4 µM). The majority of derivatives inhibit AChE more efficiently than BuChE and are comparable or superior to rivastigmine—an established cholinesterases inhibitor used in the treatment of Alzheimer’s disease. Phosphorus-based esters especially improved the activity against BuChE with 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 µM). This derivative was also the most selective inhibitor of BuChE. It caused a mixed inhibition of both cholinesterases and acted as a pseudo-irreversible inhibitor. Several structure-activity relationships were identified, e.g., favouring esters and benzamides obtained from 5-halogenosalicylic acids and polyhalogenated anilines. Both 2-hydroxy-N-phenylbenzamides and esters share convenient physicochemical properties for blood-brain-barrier penetration and thus central nervous system delivery.
Dithiocarbamate as a Valuable Scaffold for the Inhibition of Metallo-β-Lactmases
Authors: Ge Ying , Xu Li-Wei , Liu Ya , Sun Le-Yun , Gao Han , Li Jia-Qi , Yang Kewu
Published: November 2019

The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 < 26 μM. DC1 was found to be the best inhibitor of ImiS (IC50 < 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 µM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.
Molecular Characterization of a Novel Cold-Active Hormone-Sensitive Lipase (HaHSL) from Halocynthiibacter Arcticus
Authors: Le Ly Thi Huong Luu , Yoo Wanki , Lee Changwoo , Wang Ying , Jeon Sangeun , Kim Kyeong Kyu , Lee Jun Hyuck , Kim T. Doohun
Published: November 2019

Bacterial hormone-sensitive lipases (bHSLs), which are homologous to the catalytic domains of human HSLs, have received great interest due to their uses in the preparation of highly valuable biochemicals, such as drug intermediates or chiral building blocks. Here, a novel cold-active HSL from Halocynthiibacter arcticus (HaHSL) was examined and its enzymatic properties were investigated using several biochemical and biophysical methods. Interestingly, HaHSL acted on a large variety of substrates including tertiary alcohol esters and fish oils. Additionally, this enzyme was highly tolerant to high concentrations of salt, detergents, and glycerol. Furthermore, immobilized HaHSL retained its activity for up to six cycles of use. Homology modeling suggested that aromatic amino acids (Trp23, Tyr74, Phe78, Trp83, and Phe245) in close proximity to the substrate-binding pocket were important for enzyme activity. Mutational analysis revealed that Tyr74 played an important role in substrate specificity, thermostability, and enantioselectivity. In summary, the current study provides an invaluable insight into the novel cold-active HaHSL from H. arcticus, which can be efficiently and sustainably used in a wide range of biotechnological applications.
Conformation and Aggregation of Human Serum Albumin in the Presence of Green Tea Polyphenol (EGCg) and/or Palmitic Acid
Authors: Sun Xiaowei , Ferguson Haley N. , Hagerman Ann E.
Published: November 2019

Polyphenols such as epigallocatechin gallate (EGCg) may have roles in preventing some chronic diseases when they are ingested as components of plant-based foods and beverages. Human serum albumin (HSA) is a multi-domain protein that binds various ligands and aids in their transport, distribution, and metabolism in the circulatory system. In the present study, the HSA-EGCg interaction in the absence or presence of fatty acid has been investigated. Förster resonance energy transfer (FRET) was used to determine inter- and intra-domain distances in the protein with and without EGCg and palmitic acid (PA). By labeling Cys-34 with 7-(diethyl amino)-4-methylcoumarin 3-maleimide (CPM), the distance between Trp-214 at domain IIA and CPM-Cys-34 at domain IA could be established. A small amount of PA decreased the distance, while a large amount increased the distance up to 5.4 Å. EGCg increased the inter-domain distance in HSA and HSA-PA up to 2.8 and 7.6 Å, respectively. We concluded that PA affects protein conformation more significantly compared to EGCg. Circular dichroism (CD) established that EGCg affects protein secondary structure more significantly than PA. PA had little effect on the α-helix content of HSA, while EGCg decreased the α-helix content in a dose-dependent fashion. Moreover, EGCg decreased α-helix content in HSA and HSA-PA to the same level. Dynamic light scattering (DLS) data revealed that both PA and EGCg increased HSA aggregation. EGCg increased HSA aggregation more significantly and promoted formation of aggregates that were more heterogenous. Any of these effects could impact the ability of serum albumin to transport and stabilize ligands including EGCg and other polyphenols.
Shaping the Nascent Ribosome: AAA-ATPases in Eukaryotic Ribosome Biogenesis
Authors: Prattes Michael , Lo Yu-Hua , Bergler Helmut , Stanley Robin E.
Published: November 2019

AAA-ATPases are molecular engines evolutionarily optimized for the remodeling of proteins and macromolecular assemblies. Three AAA-ATPases are currently known to be involved in the remodeling of the eukaryotic ribosome, a megadalton range ribonucleoprotein complex responsible for the translation of mRNAs into proteins. The correct assembly of the ribosome is performed by a plethora of additional and transiently acting pre-ribosome maturation factors that act in a timely and spatially orchestrated manner. Minimal disorder of the assembly cascade prohibits the formation of functional ribosomes and results in defects in proliferation and growth. Rix7, Rea1, and Drg1, which are well conserved across eukaryotes, are involved in different maturation steps of pre-60S ribosomal particles. These AAA-ATPases provide energy for the efficient removal of specific assembly factors from pre-60S particles after they have fulfilled their function in the maturation cascade. Recent structural and functional insights have provided the first glimpse into the molecular mechanism of target recognition and remodeling by Rix7, Rea1, and Drg1. Here we summarize current knowledge on the AAA-ATPases involved in eukaryotic ribosome biogenesis. We highlight the latest insights into their mechanism of mechano-chemical complex remodeling driven by advanced cryo-EM structures and the use of highly specific AAA inhibitors.
Impact of Polymorphisms in the Serotonin Transporter Gene on Oscillatory Dynamics during Inhibition of Planned Movement in Children
Authors: Bocharov Andrey , Savostyanov Alexander , Tamozhnikov Sergey , Saprigyn Alexander , Proshina Ekaterina , Astakhova Tatiana , Knyazev Gennady
Published: November 2019

The serotonin transporter plays an important role in serotonergic neuromodulation. It is known that polymorphisms in the serotonin transporter gene are linked to the dysregulation of emotions. In the current study, we aimed to investigate the impact of variation in the gene encoding serotonin transporter polymorphism on oscillatory dynamics during inhibition of planned movement in the stop signal paradigm. During performance the stop signal paradigm, electroencephalograms (EEGs) were recorded in 90 healthy Caucasian children (39 girls) from 7 to 12 years. Buccal epithelium probes were taken from all participants. The La, Lg, and S alleles of serotonin transporter-linked polymorphic region (5-HTTLPR) polymorphism were detected in the DNA samples using PCR. LaLa genotype carriers did not differ from LaS\LgS and LgS\LgLg\SS carriers in a number of successful inhibitions of a prepotent response. Carriers of LaLa exhibit higher alpha and beta event-related spectral perturbations (ERSP) in parietal and occipital cortices after the presentation of signal of inhibition of movement than LaS\LgS and LgS\LgLg\SS carriers. Results are consistent with current literature and confirm that S allele carriers are more predisposed to disturbances in cognitive control.
Neurophysiological Characterization of Thalamic Nuclei in Epileptic Anaesthetized Patients
Authors: Vega-Zelaya Lorena , Torres Cristina V. , Navas Marta , Pastor Jesús
Published: November 2019

Deep brain stimulation (DBS) requires precise localization, which is especially difficult at the thalamus, and even more difficult in anesthetized patients. We aimed to characterize the neurophysiological properties of the ventral intermediate (V.im), ventral caudal (V.c), and centromedian parvo (Ce.pc) and the magnocellular (Ce.mc) thalamic nuclei. We obtained microelectrode recordings from five patients with refractory epilepsy under general anesthesia. Somatosensory evoked potentials recorded by microelectrodes were used to identify the V.c nucleus. Trajectories were reconstructed off-line to identify the nucleus recorded, and the amplitude of the action potential (AP) and the tonic (i.e., mean frequency, density, probability of interspike interval) and phasic (i.e., burst index, pause index, and pause ratio) properties of the pattern discharges were analyzed. The Mahalanobis metric was used to evaluate the similarity of the patterns. The mean AP amplitude was higher for the V.im nucleus (172.7 ± 7.6 µV) than for the other nuclei, and the mean frequency was lower for the Ce.pc nucleus (7.2 ± 0.8 Hz) and higher for the V.c nucleus (11.9 ± 0.8 Hz) than for the other nuclei. The phasic properties showed a bursting pattern for the V.c nucleus and a tonic pattern for the centromedian and V.im nuclei. The Mahalanobis distance was the shortest for the V.im/V.c and Ce.mp/Ce.pc pairs. Therefore, the different properties of the thalamic nuclei, even for patients under general anesthesia, can be used to positively define the recorded structure, improving the exactness of electrode placement in DBS.
Obsessive Compulsive Symptoms and Psychopathological Profile in Children and Adolescents with KBG Syndrome
Authors: Alfieri Paolo , Demaria Francesco , Licchelli Serena , Santonastaso Ornella , Caciolo Cristina , Digilio Maria , Sinibaldi Lorenzo , Leoni Chiara , Gnazzo Maria , Tartaglia Marco , Pasqualetti Patrizio , Vicari Stefano
Published: November 2019

KBG syndrome is a rare multisystem developmental disorder caused by ankyrin repeat domain-containing protein 11 (ANKRD11) gene haploinsufficiency, resulting from either intragenic loss-of-function mutations or microdeletions encompassing the gene. Concerning the behavioral phenotype, a limited amount of research has been focused on attention deficit and hyperactivity disorder, autistic-like features, anxiety and impairments in emotion regulation, and no study has provided a systematic assessment. The aim of the present work is to investigate the psychopathological profile in children, adolescents, and young adults with KBG syndrome. Seventeen subjects with molecularly confirmed diagnoses were evaluated to investigate cognitive abilities and psychopathological features. Parametric and nonparametric indexes were used to describe the patient cohort according to type and distribution of specific measures. The KBG subjects were characterized by a low mean IQ score, with a distribution characterized by a variability similar to that occurring in the general population. Prevalence of neuropsychiatric disorders were computed as well as the corresponding confidence intervals to compare their prevalence to that reported for the general population. The KBG subjects were characterized by higher prevalence of obsessive-compulsive, tic, depressive and attention deficit and hyperactivity disorders. Obsessive-compulsive disorder is a peculiar aspect characterizing the psychopathological profile of KBG patients, which does not seem to be related to the cognitive level. The present study provides new relevant information towards the definition of a psychopathological phenotype of KBG syndromes useful to plan a better treatment for patients.
An Optimal Seismic Force Pattern for Uniform Drift Distribution
Authors: Montuori Rosario , Nastri Elide , Tagliafierro Bonaventura
Published: November 2019

The force distribution proposed by codes, which in many cases is framed in the equivalent static force procedure, likely leads to design structures with non-uniform drift distribution in terms of inter-storey drift and ductility demands. This can lead to an unbalanced drift demand at certain storeys. This phenomenon may also amass cyclic damage to the dissipative elements at this very storey, therefore increasing the probability of premature failure for low-cycle fatigue. This work proposes a new force design distribution that accounts for higher mode effects and limits the displacement concentration at any storey thus improving the dissipative capacity of the whole structures. The main advantage of the proposed method stands in its formulation, which allows to spare any previous set up with structural analyses. The proposed force distribution has been applied to multi-degree-of-freedom systems to check its effectiveness, and the results have been compared with other proposals. In addition, in order to obtain a further validation of the proposed force distribution, the results obtained by using a genetic algorithm have been evaluated and compared. Additionally, the results provided in this work validate the proposed procedure to develop a more efficient lateral load pattern.
Carcinogenesis and Metastasis in Liver: Cell Physiological Basis
Authors: Rossetto Anna , De Re Valli , Steffan Agostino , Ravaioli Matteo , Miolo Gianmaria , Leone Patrizia , Racanelli Vito , Uzzau Alessandro , Baccarani Umberto , Cescon Matteo
Published: November 2019

Hepatocellular carcinoma (HCC) incidence is rising. This paper summarises the current state of knowledge and recent discoveries in the cellular and physiological mechanisms leading to the development of liver cancer, especially HCC, and liver metastases. After reviewing normal hepatic cytoarchitecture and immunological characteristics, the paper addresses the pathophysiological factors that cause liver damage and predispose to neoplasia. Particular attention is given to chronic liver diseases, metabolic syndrome and the impact of altered gut microbiota, disrupted circadian rhythm and psychological stress. Improved knowledge of the multifactorial aetiology of HCC has important implications for the prevention and treatment of this cancer and of liver metastases in general.
Treatment with a Combination of Metformin and 2-Deoxyglucose Upregulates Thrombospondin-1 in Microvascular Endothelial Cells: Implications in Anti-Angiogenic Cancer Therapy
Authors: Mathews Samuel Samson , Satheesh Noothan Jyothi , Ghosh Suparna , Büsselberg Dietrich , Majeed Yasser , Ding Hong , Triggle Chris R.
Published: November 2019

Metformin, the most widely used anti-diabetic drug, also exhibits anti-cancer properties; however, the true potential of metformin as an anticancer drug remains largely unknown. In this study using mouse microvascular endothelial cells (MMECs), we investigated the effects of metformin alone or in combination with the glycolytic inhibitor, 2-deoxyglucose (2DG), on angiogenesis-a process known to be an integral part of tumor growth, cancer cell survival and metastasis. MMECs were exposed to 2DG (1–10 mM) for 48 h in the absence or presence of metformin (2 mM). The status of angiogenic and anti-angiogenic marker proteins, proteins of the mTOR pathway and cell-cycle-related proteins were quantified by Western blot analysis. Assays for cell proliferation, migration and tubulogenesis were also performed. We observed robust up-regulation of anti-angiogenic thrombospondin-1 (TSP1) and increased TSP1-CD36 co-localization with a marked decrease in the levels of phosphorylated vascular endothelial growth factor receptor-2 (pVEGFR2; Y1175) in 2DG (5 mM) exposed cells treated with metformin (2 mM). Additionally, treatment with metformin and 2DG (5 mM) inhibited the Akt/mTOR pathway and down-regulated the cell-cycle-related proteins such as p-cyclin B1 (S147) and cyclins D1 and D2 when compared to cells that were treated with either 2DG or metformin alone. Treatment with a combination of 2DG (5 mM) and metformin (2 mM) also significantly decreased cell proliferation, migration and tubulogenic capacity when compared to cells that were treated with either 2DG or metformin alone. The up-regulation of TSP1, inhibition of cell proliferation, migration and tubulogenesis provides support to the argument that the combination of metformin and 2DG may prove to be an appropriate anti-proliferative and anti-angiogenic therapeutic strategy for the treatment of some cancers.
Phosphodiesterase 5 (PDE5) Is Highly Expressed in Cancer-Associated Fibroblasts and Enhances Breast Tumor Progression
Authors: Catalano Stefania , Panza Salvatore , Augimeri Giuseppina , Giordano Cinzia , Malivindi Rocco , Gelsomino Luca , Marsico Stefania , Giordano Francesca , Győrffy Balázs , Bonofiglio Daniela , Andò Sebastiano , Barone Ines
Published: November 2019

The overexpression of phosphodiesterase (PDE) 5 is frequently found in various human cancers, such as those of the breast. However, PDE5’s role in the tumor microenvironment is still unknown. As PDE5 represents a high-value therapeutic target, we investigated whether the expression and function of PDE5 in breast cancer-associated fibroblasts (CAFs) may be clinically relevant to malignant progression. PDE5 expression was increased in human breast cancer stroma compared with normal stroma and was correlated to a shorter overall survival. Treatment of CAFs, isolated from breast tumor biopsies, with selective PDE5 inhibitors inhibited their proliferation, motility, and invasiveness, and negatively controlled tumor–stroma interactions in both ‘in vitro’ and ‘in vivo’ models. PDE5 stable overexpression transformed immortalized mouse embryonic fibroblasts (MEFs) towards an activated fibroblast phenotype, impacting their intrinsic characteristics and paracrine effects on breast cancer cell growth and migration through an enhanced production of the C-X-C motif chemokine 16 (CXCL16). On the other hand, CAF exposure to PDE5 inhibitors was associated with reduced CXCL16 expression and secretion. Importantly, CXCL16 levels in breast cancer stroma showed a strong correlation with PDE5 levels and poor patient outcomes. In conclusion, PDE5 is overexpressed in breast cancer stroma, enhances the tumor-stimulatory activities of fibroblasts, and impacts clinical outcomes; thus, we propose this enzyme as an attractive candidate for prognosis and a potential target for treatments in breast cancer patients.
Streptomyces sp. MUM256: A Source for Apoptosis Inducing and Cell Cycle-Arresting Bioactive Compounds against Colon Cancer Cells
Authors: Tan Loh Teng-Hern , Chan Chim-Kei , Chan Kok-Gan , Pusparajah Priyia , Khan Tahir Mehmood , Ser Hooi-Leng , Lee Learn-Han , Goh Bey-Hing
Published: November 2019

New and effective anticancer compounds are much needed as the incidence of cancer continues to rise. Microorganisms from a variety of environments are promising sources of new drugs; Streptomyces sp. MUM256, which was isolated from mangrove soil in Malaysia as part of our ongoing efforts to study mangrove resources, was shown to produce bioactive metabolites with chemopreventive potential. This present study is a continuation of our previous efforts and aimed to investigate the underlying mechanisms of the ethyl acetate fraction of MUM256 crude extract (MUM256 EA) in inhibiting the proliferation of HCT116 cells. Our data showed that MUM256 EA reduced proliferation of HCT116 cells via induction of cell-cycle arrest. Molecular studies revealed that MUM256 EA regulated the expression level of several important cell-cycle regulatory proteins. The results also demonstrated that MUM256 EA induced apoptosis in HCT116 cells mediated through the intrinsic pathway. Gas chromatography-mass spectrometry (GC-MS) analysis detected several chemical compounds present in MUM256 EA, including cyclic dipeptides which previous literature has reported to demonstrate various pharmacological properties. The cyclic dipeptides were further shown to inhibit HCT116 cells while exerting little to no toxicity on normal colon cells in this study. Taken together, the findings of this project highlight the important role of exploring the mangrove microorganisms as a bioresource which hold tremendous promise for the development of chemopreventive drugs against colorectal cancer.
Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer
Authors: Lin Kun-I , Yang Jia-Lian , Lin Yu-Chao , Chou Che-Yi , Chen Jin-Hua , Hung Chin-Chuan
Published: November 2019

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.
HDAC4 Levels Control Sensibility toward Cisplatin in Gastric Cancer via the p53-p73/BIK Pathway
Authors: Spaety Marie-Elodie , Gries Alexandre , Badie Amandine , Venkatasamy Aina , Romain Benoit , Orvain Christophe , Yanagihara Kazuyoshi , Okamoto Koji , Jung Alain C. , Mellitzer Georg , Pfeffer Sébastien , Gaiddon Christian
Published: November 2019

Gastric cancer (GC) remains a health issue due to the low efficiency of therapies, such as cisplatin. This unsatisfactory situation highlights the necessity of finding factors impacting GC sensibility to therapies. We analyzed the cisplatin pangenomic response in cancer cells and found HDAC4 as a major epigenetic regulator being inhibited. HDAC4 mRNA repression was partly mediated by the cisplatin-induced expression of miR-140. At a functional level, HDAC4 inhibition favored cisplatin cytotoxicity and reduced tumor growth. Inversely, overexpression of HDAC4 inhibits cisplatin cytotoxicity. Importantly, HDAC4 expression was found to be elevated in gastric tumors compared to healthy tissues, and in particular in specific molecular subgroups. Furthermore, mutations in HDAC4 correlate with good prognosis. Pathway analysis of genes whose expression in patients correlated strongly with HDAC4 highlighted DNA damage, p53 stabilization, and apoptosis as processes downregulated by HDAC4. This was further confirmed by silencing of HDAC4, which favored cisplatin-induced apoptosis characterized by cleavage of caspase 3 and induction of proapoptotic genes, such as BIK, in part via a p53-dependent mechanism. Altogether, these results reveal HDAC4 as a resistance factor for cisplatin in GC cells that impacts on patients’ survival.
PAC-5 Gene Expression Signature for Predicting Prognosis of Patients with Pancreatic Adenocarcinoma
Authors: Kim Jieun , Jo Yong Hwa , Jang Miran , Nguyen Ngoc Ngo Yen , Yun Hyeong Rok , Ko Seok Hoon , Shin Yoonhwa , Lee Ju-Seog , Kang Insug , Ha Joohun , Choi Tae Gyu , Kim Sung Soo
Published: November 2019

Pancreatic adenocarcinoma (PAC) is one of the most aggressive malignancies. Intratumoural molecular heterogeneity impedes improvement of the overall survival rate. Current pathological staging system is not sufficient to accurately predict prognostic outcomes. Thus, accurate prognostic model for patient survival and treatment decision is demanded. Using differentially expressed gene analysis between normal pancreas and PAC tissues, the cancer-specific genes were identified. A prognostic gene expression model was computed by LASSO regression analysis. The PAC-5 signature (LAMA3, E2F7, IFI44, SLC12A2, and LRIG1) that had significant prognostic value in the overall dataset was established, independently of the pathological stage. We provided evidence that the PAC-5 signature further refined the selection of the PAC patients who might benefit from postoperative therapies. SLC12A2 and LRIG1 interacted with the proteins that were implicated in resistance of EGFR kinase inhibitor. DNA methylation was significantly involved in the gene regulations of the PAC-5 signature. The PAC-5 signature provides new possibilities for improving the personalised therapeutic strategies. We suggest that the PAC-5 genes might be potential drug targets for PAC.
First-Principles-Based Simulation of an Industrial Ethanol Dehydration Reactor
Authors: Van der Borght Kristof , Alexopoulos Konstantinos , Toch Kenneth , Thybaut Joris W. , Marin Guy B. , Galvita Vladimir V.
Published: November 2019

The achievement of new economically viable chemical processes often involves the translation of observed lab-scale phenomena into performance in an industrial reactor. In this work, the in silico design and optimization of an industrial ethanol dehydration reactor were performed, employing a multiscale model ranging from nano-, over micro-, to macroscale. The intrinsic kinetics of the elementary steps was quantified through ab initio obtained rate and equilibrium coefficients. Heat and mass transfer limitations for the industrial design case were assessed via literature correlations. The industrial reactor model developed indicated that it is not beneficial to utilize feeds with high ethanol content, as they result in lower ethanol conversion and ethene yield. Furthermore, a more pronounced temperature drop over the reactor was simulated. It is preferred to use a more H2O-diluted feed for the operation of an industrial ethanol dehydration reactor.
Gas Phase Catalytic Hydrogenation of C4 Alkynols over Pd/Al2O3
Authors: González-Fernández Alberto , Pischetola Chiara , Cárdenas-Lizana Fernando
Published: November 2019

Alkenols are commercially important chemicals employed in the pharmaceutical and agro-food industries. The conventional production route via liquid phase (batch) alkynol hydrogenation suffers from the requirement for separation/purification unit operations to extract the target product. We have examined, for the first time, the continuous gas phase hydrogenation (P = 1 atm; T = 373 K) of primary (3-butyn-1-ol), secondary (3-butyn-2-ol) and tertiary (2-methyl-3-butyn-2-ol) C4 alkynols using a 1.2% wt. Pd/Al2O3 catalyst. Post-TPR, the catalyst exhibited a narrow distribution of Pdδ- (based on XPS) nanoparticles in the size range 1-6 nm (mean size = 3 nm from STEM). Hydrogenation of the primary and secondary alkynols was observed to occur in a stepwise fashion (-C≡C- → -C=C- → -C-C-) while alkanol formation via direct -C≡C- → -C-C- bond transformation was in evidence in the conversion of 2-methyl-3-butyn-2-ol. Ketone formation via double bond migration was promoted to a greater extent in the transformation of secondary (vs. primary) alkynol. Hydrogenation rate increased in the order primary < secondary < tertiary. The selectivity and reactivity trends are accounted for in terms of electronic effects.
Catalyzed Mizoroki-Heck Reaction or C-H Activation
Authors: Berteina-Raboin Sabine
Published: November 2019

In the last few decade, research conducted on the development by catalytic processes of C-C bonds formation on the one hand and on the other hand on the activation of C-H bonds has grown considerably [...]