bluuebunny/crossref_metadata_2025 huggingface dataset:
Modal Strain Energy-Based Structural Damage Detection Using Convolutional Neural Networks
Authors: Teng Shuai , Chen Gongfa , Liu Gen , Lv Jianbin , Cui Fangsen
Published: August 2019

In this paper, a convolutional neural network (CNN) was used to extract the damage features of a steel frame structure. As structural damage could induce changes of the modal parameters of the structure, the convolution operation was used to extract the features of modal parameters, and a classification algorithm was used to judge the damage state of the structure. The finite element method was applied to analyze the free vibration of the steel frame and obtain the first-order modal strain energy for various damage scenarios, which was used as the CNN training sample. Then vibration experiments were carried out, and modal parameters were obtained from the modal analysis of the vibration signals. The experimental data were inputted into the CNN to verify its damage detection capability. The result showed that the CNN was effective in detecting the intact structure, single damage, and multi damages with an accuracy of 100%. For comparison, the same samples were also applied to the traditional back propagation (BP) neural network, which failed to detect the intact structure and multiple-damage cases. It was found that: (1) The proposed CNN could be trained from finite element simulation data and used in real frame structure damage detection, and it performed better in structural damage detection than BP neural networks; (2) the measured data of a real structure could be supplemented by numerical simulation data, and satisfactory results have been demonstrated.
Feasibility of a Quasi-Static Approach in Assessing Side-Wind Hazards for Running Vehicles
Authors: Kim Se-Jin , Kim Ho-Kyung
Published: August 2019

This study is an examination into the feasibility of a quasi-static approach to evaluating the reaction forces that impact tires. This information could lend valuable insight into efforts to limit overturning and side-slip accidents of vehicles exposed to strong side winds. The performance of the quasi-static approach was evaluated by comparing the calculated tire forces with those created using TruckSim, which is a dynamic vehicle analysis software. Governing equations were formulated for two types of vehicles that are susceptible to the force of wind, vans, and trailers, by considering a force equilibrium, a compatibility condition, and several assumptions. The quasi-static approach for trailers is a novel expansion of the conventional approach to a two-axle vehicle. Proposed enhancements to the quasi-static approach reflect the additional rolling moment of a trailer. The curvature and the cant of a curved road were accounted for via centrifugal forces. Both uniform and turbulent wind conditions were considered in questioning the feasibility of this novel approach.
The Zerotrope, a Dynamic Holographic Display: Design and Implementation
Authors: Gentet Philippe , Joung Jinbeom , Gentet Yves , Kim Kwang-Jib , Lee Seung-Hyun
Published: August 2019

This paper presents the Zerotrope, an improved version of the classic phenakistiscope and zoetrope devices. This device is used to create a new 360-degree dynamic 3D display by the inclusion of a single ultra-realistic full-color hologram. The Zerotrope is built with a zero-degree transplane hologram mounted on a disk rotating at a constant speed. When a stroboscopic lamp synchronized with the rotation illuminates this hologram, the recorded characters, arranged radially around the center of the disk, are animated as in a stop-motion movie. The operation of the Zerotrope is successful and shows the effect of a 3D display without the need for special viewing aids.
Second-Harmonic Generation in Mie-Resonant GaAs Nanowires
Authors: de Ceglia Domenico , Carletti Luca , Vincenti Maria Antonietta , De Angelis Costantino , Scalora Michael
Published: August 2019

We investigate the enhancement of second-harmonic generation in cylindrical GaAs nanowires. Although these nanostructures confine light in two dimensions, power conversion efficiencies on the order of 10 − 5 with a pump peak intensity of ~ 1   GW / cm 2 are possible if the pump and the second-harmonic fields are coupled to the Mie-type resonances of the nanowire. We identify a large range of nanowire radii in which a double-resonance condition, i.e., both the pump and the second-harmonic fields excite normal modes of the nanowire, induces a high-quality-factor peak of conversion efficiency. We show that second-harmonic light can be scattered with large efficiency even if the second-harmonic photon energy is larger than 1.42 eV, i.e., the electronic bandgap of GaAs, above which the material is considered opaque. Finally, we evaluate the efficiency of one-photon absorption of second-harmonic light and find that resonant GaAs nanowires absorb second-harmonic light in the near-field region almost at the same rate at which they radiate second-harmonic light in the far-field region.
The Hay Inclined Plane in Coalbrookdale (Shropshire, England): Analysis through Computer-Aided Engineering
Authors: Rojas-Sola José , De la Morena-De la Fuente Eduardo
Published: August 2019

This article analyzes the ‘Hay inclined plane’ designed by the English engineer and entrepreneur William Reynolds and put into operation in 1792 to facilitate the transport of vessels between channels at different levels using an inclined plane. To this end, a study of computer-aided engineering (CAE) was carried out using the parametric software Autodesk Inventor Professional, consisting of a static analysis using the finite-element method (FEM) of the 3D model of the invention under real operating conditions. The results obtained after subjecting the mechanism to the two most unfavorable situations (blockage situation of the inertia flywheel and emergency braking situation) indicate that, with the exception of the braking bar, the rest of the assembly is perfectly designed and dimensioned. In particular, for the blockage situation, the point with the greatest stress is at the junction between the inertia flywheel and the axle to which it is attached, the maximum value of von Mises stress being at that point (186.9 MPa) lower than the elastic limit of the cast iron. Also, at this point the deformation is very low (0.13% of its length), as well as the maximum displacement that takes place in the inertia flywheel itself (22.98 mm), and the lowest safety factor has a value of 3.51 (located on the wooden shaft support), which indicates that the mechanism is clearly oversized. On the other hand, the emergency braking situation, which is technically impossible with a manual operation, indicates that the braking bar supports a maximum von Mises stress of 1025 MPa, above the elastic limit of the material, so it would break. However, other than that element, the rest of the elements have lower stresses, with a maximum value of 390.7 MPa, and with safety factors higher than 1.7, which indicates that the mechanism was well dimensioned.
Pricing Personal Data Based on Data Provenance
Authors: Shen Yuncheng , Guo Bing , Shen Yan , Wu Fan , Zhang Hong , Duan Xuliang , Dong Xiangqian
Published: August 2019

Data have become an important asset. Mining the value contained in personal data, making personal data an exchangeable commodity, has become a hot spot of industry research. Then, how to price personal data reasonably becomes a problem we have to face. Based on previous research on data provenance, this paper proposes a novel minimum provenance pricing method, which is to price the minimum source tuple set that contributes to the query. Our pricing model first sets prices for source tuples according to their importance and then makes query pricing based on data provenance, which considers both the importance of the data itself and the relationships between the data. We design an exact algorithm that can calculate the exact price of a query in exponential complexity. Furthermore, we design an easy approximate algorithm, which can calculate the approximate price of the query in polynomial time. We instantiated our model with a select-joint query and a complex query and extensively evaluated its performances on two practical datasets. The experimental results show that our pricing model is feasible.
LCF: A Local Context Focus Mechanism for Aspect-Based Sentiment Classification
Authors: Zeng Biqing , Yang Heng , Xu Ruyang , Zhou Wu , Han Xuli
Published: August 2019

Aspect-based sentiment classification (ABSC) aims to predict sentiment polarities of different aspects within sentences or documents. Many previous studies have been conducted to solve this problem, but previous works fail to notice the correlation between the aspect’s sentiment polarity and the local context. In this paper, a Local Context Focus (LCF) mechanism is proposed for aspect-based sentiment classification based on Multi-head Self-Attention (MHSA). This mechanism is called LCF design, and utilizes the Context features Dynamic Mask (CDM) and Context Features Dynamic Weighted (CDW) layers to pay more attention to the local context words. Moreover, a BERT-shared layer is adopted to LCF design to capture internal long-term dependencies of local context and global context. Experiments are conducted on three common ABSC datasets: the laptop and restaurant datasets of SemEval-2014 and the ACL twitter dataset. Experimental results demonstrate that the LCF baseline model achieves considerable performance. In addition, we conduct ablation experiments to prove the significance and effectiveness of LCF design. Especially, by incorporating with BERT-shared layer, the LCF-BERT model refreshes state-of-the-art performance on all three benchmark datasets.
Exploring Efficient Neural Architectures for Linguistic–Acoustic Mapping in Text-To-Speech
Authors: Pascual Santiago , Serrà Joan , Bonafonte Antonio
Published: August 2019

Conversion from text to speech relies on the accurate mapping from linguistic to acoustic symbol sequences, for which current practice employs recurrent statistical models such as recurrent neural networks. Despite the good performance of such models (in terms of low distortion in the generated speech), their recursive structure with intermediate affine transformations tends to make them slow to train and to sample from. In this work, we explore two different mechanisms that enhance the operational efficiency of recurrent neural networks, and study their performance–speed trade-off. The first mechanism is based on the quasi-recurrent neural network, where expensive affine transformations are removed from temporal connections and placed only on feed-forward computational directions. The second mechanism includes a module based on the transformer decoder network, designed without recurrent connections but emulating them with attention and positioning codes. Our results show that the proposed decoder networks are competitive in terms of distortion when compared to a recurrent baseline, whilst being significantly faster in terms of CPU and GPU inference time. The best performing model is the one based on the quasi-recurrent mechanism, reaching the same level of naturalness as the recurrent neural network based model with a speedup of 11.2 on CPU and 3.3 on GPU.
Evaluation of High-Speed Handpiece Cutting Efficiency According to Bur Eccentricity: An In Vitro Study
Authors: Kim Duk-Yeon , Son Keunbada , Lee Kyu-bok
Published: August 2019

This study aimed to evaluate the correlation between the cutting efficiency and bur eccentricity of high-speed handpieces. The prepared lithium disilicate samples were digitized using a 3D model scanner (reference model, RM) (n = 45), and the lithium disilicate samples were cut using three high-speed handpieces. To evaluate the cutting efficiency, the cut lithium disilicate sample was digitized (cutting model, CM), and the RM and CM were superimposed using a 3D analysis software. Bur eccentricity of the high-speed handpieces was measured using dedicated equipment. Statistical analyses were performed using an analysis software. The statistical differences in pairwise comparisons (α = 0.05) were analyzed using the Kruskal–Wallis and post hoc tests. The S-max M600 obtained a cutting efficiency of 6.13 mm3. TG-98 and TRAUS ATN-400 showed similar efficiencies of 2.914 and 3.05 mm3, respectively. There was a significant difference in the cutting efficiency of the S-max M600 compared with TG-98 and TRAUS ATN-400 (p < 0.001). S-max M600 had an eccentricity of 3.507 µm. TG-98 and TRAUS ATN-400 had eccentricities of 5.99 and 7.767 µm, respectively. There were statistically significant differences in the eccentricity among all the high-speed handpieces (p < 0.001).
Simulation of a Solar-Assisted Air-Conditioning System Applied to a Remote School
Authors: Aguilar-Jiménez Jesús Armando , Velázquez Nicolás , López-Zavala Ricardo , González-Uribe Luis A. , Beltrán Ricardo , Hernández-Callejo Luis
Published: August 2019

In this work, we present an absorption cooling system with 35 kW capacity driven by solar thermal energy, installed in the school of Puertecitos, Mexico, an off-grid community with a high level of social marginalization. The cooling system provides thermal comfort to the school’s classrooms through four 8.75-kW cooling coils, while a 110-m2 field of evacuated tube solar collectors delivers the thermal energy needed to activate the cooling machine. The characteristics of the equipment installed in the school were used for simulation and operative analysis of the system under the influence of typical factors of an isolated coastal community, such as the influence of climate, thermal load, and water consumption in the cooling tower, among others. The aim of this simulation study was to determine the best operating conditions prior to system start-up, to establish the requirements for external heating and cooling services, and to quantify the freshwater requirements for the proper functioning of the system. The results show that, with the simulated strategies implemented, with a maximum load operation, the system can maintain thermal comfort in the classrooms for five days of classes. This is feasible as long as weekends are dedicated to raising the water temperature in the thermal storage tank. As the total capacity of the system is distributed in the four cooling coils, it is possible to control the cooling demand in order to extend the operation periods. Utilizing 75% or less of the cooling capacity, the system can operate continuously, taking advantage of stored energy. The cooling tower requires about 750 kg of water per day, which becomes critical given the scarcity of this resource in the community.
Deformation Analysis of Large-Scale Rock Slopes Considering the Effect of Microseismic Events
Authors: Dong Linlu , Yang Ying , Qian Bo , Tan Yaosheng , Sun Hailong , Xu Nuwen
Published: August 2019

To research the macroscopic deformation of rock microseismic damage, a high-precision microseismic monitoring system was established on the left bank slope of the Baihetan hydropower station in Southwestern China. Based on the microseismic monitoring and field deformation data, the seismic source radius was applied to characterize the rock fracture scale. Numerical simulations introduced the rock micro-fracture information into the three-dimensional numerical model of the left bank slope and established the damage constitutive model. The unloading deformation process of the left bank abutment rock mass is described by numerical calculations. The feedback analysis method considering the effect of microseismic damage is preliminary exploratory research, which provides a new idea for the stability analysis of similar high rock slopes.
Battery Surface and Edge Defect Inspection Based on Sub-Regional Gaussian and Moving Average Filter
Authors: Hu Haibing , Zhang Bo , Xu Dongjian , Xia Guo
Published: August 2019

Detecting the defects of a battery on the surface and edge has always been difficult, especially for concave and convex ones, thereby seriously affecting its quality. Thus, sub-regional Gaussian and moving average filtering are innovatively proposed in this study considering the effect of the nonuniform background illumination of the battery edge and the difference between the edge background and the internal surface defects of the battery. The battery surface image is divided into two areas, namely, edge area W 1 and inner area W 2 . Gaussian and moving average filtering are carried out row-by-row and column-by-column in the inner area W 2 and the edge area W 1 , respectively. The algorithm is tested on 600 battery samples that mainly possess concave and convex defects. The proposed method has higher detection accuracy and lower omission detection rate than the traditional unpartitioned processing method, especially in detecting the accuracy of edge defects. The accuracy rates were approximately 20% higher than that obtained by the traditional processing algorithm. The proposed method has remarkable real-time performance that can process four 8192 × 10,240 pixel battery images per second, thereby meeting the industrial production line speed requirements while satisfying accuracy. The proposed method has been applied in actual production for defect inspection.
Novel Hand Gesture Alert System
Authors: Mambou Sebastien , Krejcar Ondrej , Maresova Petra , Selamat Ali , Kuca Kamil
Published: August 2019

Sexual assault can cause great societal damage, with negative socio-economic, mental, sexual, physical and reproductive consequences. According to the Eurostat, the number of crimes increased in the European Union between 2008 and 2016. However, despite the increase in security tools such as cameras, it is usually difficult to know if an individual is subject to an assault based on his or her posture. Hand gestures are seen by many as the natural means of nonverbal communication when interacting with a computer, and a considerable amount of research has been performed. In addition, the identifiable hand placement characteristics provided by modern inexpensive commercial depth cameras can be used in a variety of gesture recognition-based systems, particularly for human-machine interactions. This paper introduces a novel gesture alert system that uses a combination of Convolution Neural Networks (CNNs). The overall system can be subdivided into three main parts: firstly, the human detection in the image using a pretrained “You Only Look Once (YOLO)” method, which extracts the related bounding boxes containing his/her hands; secondly, the gesture detection/classification stage, which processes the bounding box images; and thirdly, we introduced a module called “counterGesture”, which triggers the alert.
Reflection, Ritual, and Memory in the Late Roman Painted Hypogea at Sardis
Authors: Rousseau Vanessa
Published: August 2019

Wall painting in the Sardis hypogea expresses a regional visual language situated within the context of Late Antique approaches to decorative surfaces and multivalent motifs of indeterminate religious affiliation. Iconographic ambivalence and a typically Late Antique absence of illusionism creates a supranatural world that is grounded in the familiar imagery of home and gardens but does not quite reflect the natural world. Ubiquitous and mundane motifs were thus elevated and potentially charged with polysemic allusions to funerary practice and belief. Twelve fourth century C.E. hypogea form a distinctive corpus with a largely homogenous decorative program of scattered flowers, garlands, baskets, and birds. Related imagery is common throughout the larger Roman world, but compositional parallels from Western Anatolia suggest a particularly local visual vocabulary. The chronologically, geographically, and typologically discrete nature of the Sardis corpus set it apart from the standard of Rome while underscoring commonalities in late Roman funerary decoration and ritual. The painted imagery evoked funerary processes and ongoing social negotiation between the living and the deceased.
On the ‘Divergence Problem’ in the Alatau Mountains, Central Asia: A Study of the Responses of Schrenk Spruce Tree-Ring Width to Climate under the Recent Warming and Wetting Trend
Authors: Zhang Tongwen , Zhang Ruibo , Jiang Shengxia , Bagila Maisupova , Ainur Utebekova , Yu Shulong
Published: August 2019

The divergence problem, which manifests as an unstable response relationship between tree-ring growth and climatic factors under the background of global warming, poses a challenge to both the traditional theory of dendroclimatology and the reliability of climatic reconstructions based on tree-ring data. Although Schrenk spruce, as the dominant tree species in the Tianshan Mountains, is frequently applied in the dendrochronological studies, the understanding of the divergence problem of this tree species is still limited. This study conducted correlation analysis between climatic factors and tree-ring width chronologies from 51 living and healthy specimens of Schrenk spruce at sites of high and low elevation in the Alatau Mountains to determine the stability of the response. The results revealed that the tree-ring width of the spruce specimens was correlated positively with precipitation and correlated negatively with temperature. Although the variations of the two tree-ring chronologies were similar, the radial growth of the spruce at the low elevation was found more sensitive to climatic factors. Furthermore, the sensitivity of tree growth to climate demonstrated an obvious increase after an abrupt change of climate under the background of the recent warming and wetting trend. Increased drought stress, calculated based on climatic data, was regarded as the main reason for this phenomenon. The results supply the gap of the stability of climatic response of tree growth in Central Asia to some extent.
The Dynamics of the Cell Wall Proteome of Developing Alfalfa Stems
Authors: Sergeant Kjell , Printz Bruno , Guerriero Gea , Renaut Jenny , Lutts Stanley , Hausman Jean-Francois
Published: August 2019

In this study, the cell-wall-enriched subproteomes at three different heights of alfalfa stems were compared. Since these three heights correspond to different states in stem development, a view on the dynamics of the cell wall proteome during cell maturation is obtained. This study of cell wall protein-enriched fractions forms the basis for a description of the development process of the cell wall and the linking cell wall localized proteins with the evolution of cell wall composition and structure. The sequential extraction of cell wall proteins with CaCl2, EGTA, and LiCl-complemented buffers was combined with a gel-based proteome approach and multivariate analysis. Although the highest similarities were observed between the apical and intermediate stem regions, the proteome patterns are characteristic for each region. Proteins that bind carbohydrates and have proteolytic activity, as well as enzymes involved in glycan remobilization, accumulate in the basal stem region. Beta-amylase and ferritin likewise accumulate more in the basal stem segment. Therefore, remobilization of nutrients appears to be an important process in the oldest stem segment. The intermediate and apical regions are sites of cell wall polymer remodeling, as suggested by the high abundance of proteins involved in the remodeling of the cell wall, such as xyloglucan endoglucosylase, beta-galactosidase, or the BURP-domain containing polygalacturonase non-catalytic subunit. However, the most striking change between the different stem parts is the strong accumulation of a DUF642-conserved domain containing protein in the apical region of the stem, which suggests a particular role of this protein during the early development of stem tissues.
Proteomic Insights into Phycobilisome Degradation, A Selective and Tightly Controlled Process in The Fast-Growing Cyanobacterium Synechococcus elongatus UTEX 2973
Authors: Nagarajan Aparna , Zhou Mowei , Nguyen Amelia Y. , Liberton Michelle , Kedia Komal , Shi Tujin , Piehowski Paul , Shukla Anil , Fillmore Thomas L. , Nicora Carrie , Smith Richard D. , Koppenaal David W. , Jacobs Jon M. , Pakrasi Himadri B.
Published: August 2019

Phycobilisomes (PBSs) are large (3–5 megadalton) pigment-protein complexes in cyanobacteria that associate with thylakoid membranes and harvest light primarily for photosystem II. PBSs consist of highly ordered assemblies of pigmented phycobiliproteins (PBPs) and linker proteins that can account for up to half of the soluble protein in cells. Cyanobacteria adjust to changing environmental conditions by modulating PBS size and number. In response to nutrient depletion such as nitrogen (N) deprivation, PBSs are degraded in an extensive, tightly controlled, and reversible process. In Synechococcus elongatus UTEX 2973, a fast-growing cyanobacterium with a doubling time of two hours, the process of PBS degradation is very rapid, with 80% of PBSs per cell degraded in six hours under optimal light and CO2 conditions. Proteomic analysis during PBS degradation and re-synthesis revealed multiple proteoforms of PBPs with partially degraded phycocyanobilin (PCB) pigments. NblA, a small proteolysis adaptor essential for PBS degradation, was characterized and validated with targeted mass spectrometry. NblA levels rose from essentially 0 to 25,000 copies per cell within 30 min of N depletion, and correlated with the rate of decrease in phycocyanin (PC). Implications of this correlation on the overall mechanism of PBS degradation during N deprivation are discussed.
Aortic Oxidative Stress, Inflammation and DNA Damage Following Pulmonary Exposure to Cerium Oxide Nanoparticles in a Rat Model of Vascular Injury
Authors: Nemmar Abderrahim , Al-Salam Suhail , Beegam Sumaya , Yuvaraju Priya , Ali Badreldin
Published: August 2019

Pulmonary exposure to cerium oxide nanoparticles (CeO2 NPs) can occur either at the workplace, or due to their release in the environment. Inhaled CeO2 NPs are known to cross the alveolar–capillary barrier and reach various parts of the body, including the vasculature. The anticancer drug cisplatin (CP) causes vascular damage. However, the effects CeO2 NPs on vascular homeostasis in a rat model of CP-induced vascular injury remain unclear. Here, we assessed the impact and underlying mechanism of pulmonary exposure to CeO2 NPs on aorta in rats given a single intraperitoneal injection of cisplatin (CP, 6 mg/kg) to induce vascular damage. Six days later, the rats were intratracheally instilled with either CeO2 NPs (1 mg/kg) or saline (control), and various variables were studied 24 h thereafter in the aortic tissue. The concentration of reduced glutathione and the activity of catalase were significantly increased in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. The activity of superoxide dismutase was significantly decreased in the CP + CeO2 NPs group compared with both the CP + saline and CeO2 NPs groups. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) by the nuclei of smooth muscles and endocardial cells assessed by immunohistochemistry was significantly augmented in CeO2 NPs versus saline, in CP + saline versus saline, and in CP + CeO2 NPs versus CeO2 NPs. Moreover, the concentrations of total nitric oxide, lipid peroxidation and 8-hydroxy-2-deoxyguanosine were significantly elevated in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. Similarly, compared with both the CP + saline and CeO2 NPs groups, the combination of CP and CeO2 NPs significantly elevated the concentrations of interleukin-6 and tumour necrosis factor-α. Additionally, aortic DNA damage assessed by Comet assay was significantly increased in CeO2 NPs compared with saline, and in CP + saline versus saline, and all these effects were significantly aggravated by the combination of CP and CeO2 NPs. We conclude that pulmonary exposure to CeO2 NPs aggravates vascular toxicity in animal model of vascular injury through mechanisms involving oxidative stress, Nrf2 expression, inflammation and DNA damage.
There Is Treasure Everywhere: Reductive Plastid Evolution in Apicomplexa in Light of Their Close Relatives
Authors: Salomaki Eric , Kolisko Martin
Published: August 2019

The phylum Apicomplexa (Alveolates) comprises a group of host-associated protists, predominately intracellular parasites, including devastating parasites like Plasmodium falciparum, the causative agent of malaria. One of the more fascinating characteristics of Apicomplexa is their highly reduced (and occasionally lost) remnant plastid, termed the apicoplast. Four core metabolic pathways are retained in the apicoplast: heme synthesis, iron–sulfur cluster synthesis, isoprenoid synthesis, and fatty acid synthesis. It has been suggested that one or more of these pathways are essential for plastid and plastid genome retention. The past decade has witnessed the discovery of several apicomplexan relatives, and next-generation sequencing efforts are revealing that they retain variable plastid metabolic capacities. These data are providing clues about the core genes and pathways of reduced plastids, while at the same time further confounding our view on the evolutionary history of the apicoplast. Here, we examine the evolutionary history of the apicoplast, explore plastid metabolism in Apicomplexa and their close relatives, and propose that the differences among reduced plastids result from a game of endosymbiotic roulette. Continued exploration of the Apicomplexa and their relatives is sure to provide new insights into the evolution of the apicoplast and apicomplexans as a whole.
Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization
Authors: dos Santos Nilton , Franco Roseane , Camarini Rosana , Munhoz Carolina , Eichler Rosangela , Gewehr Mayara , Reckziegel Patricia , Llanos Ricardo , Dale Camila , da Silva Victoria , Borges Vanessa , Lima Braulio , Cunha Fernando , Visniauskas Bruna , Chagas Jair , Tufik Sergio , Peres Fernanda , Abilio Vanessa , Florio Jorge , Iwai Leo , Rioli Vanessa , Presoto Benedito , Guimaraes Alessander , Pesquero Joao , Bader Michael , Castro Leandro , Ferro Emer
Published: August 2019

Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1−/−) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.
Effects of Sound-Pressure Change on the 40 Hz Auditory Steady-State Response and Change-Related Cerebral Response
Authors: Motomura Eishi , Inui Koji , Kawano Yasuhiro , Nishihara Makoto , Okada Motohiro
Published: August 2019

The auditory steady-state response (ASSR) elicited by a periodic sound stimulus is a neural oscillation recorded by magnetoencephalography (MEG), which is phase-locked to the repeated sound stimuli. This ASSR phase alternates after an abrupt change in the feature of a periodic sound stimulus and returns to its steady-state value. An abrupt change also elicits a MEG component peaking at approximately 100–180 ms (called “Change-N1m”). We investigated whether both the ASSR phase deviation and Change-N1m were affected by the magnitude of change in sound pressure. The ASSR and Change-N1m to 40 Hz click-trains (1000 ms duration, 70 dB), with and without an abrupt change (± 5, ± 10, or ± 15 dB) were recorded in ten healthy subjects. We used the source strength waveforms obtained by a two-dipole model for measurement of the ASSR phase deviation and Change-N1m values (peak amplitude and latency). As the magnitude of change increased, Change-N1m increased in amplitude and decreased in latency. Similarly, ASSR phase deviation depended on the magnitude of sound-pressure change. Thus, we suspect that both Change-N1m and the ASSR phase deviation reflect the sensitivity of the brain’s neural change-detection system.
Corticospinal-Evoked Responses from the Biceps Brachii during Arm Cycling across Multiple Power Outputs
Authors: Lockyer Evan J. , Hosel Katarina , Nippard Anna P. , Button Duane C. , Power Kevin E.
Published: August 2019

Background: We examined corticospinal and spinal excitability across multiple power outputs during arm cycling using a weak and strong stimulus intensity. Methods: We elicited motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) in the biceps brachii using magnetic stimulation over the motor cortex and electrical stimulation of corticospinal axons during arm cycling at six different power outputs (i.e., 25, 50, 100, 150, 200 and 250 W) and two stimulation intensities (i.e., weak vs. strong). Results: In general, biceps brachii MEP and CMEP amplitudes (normalized to maximal M-wave (Mmax)) followed a similar pattern of modulation with increases in cycling intensity at both stimulation strengths. Specifically, MEP and CMEP amplitudes increased up until ~150 W and ~100 W when the weak and strong stimulations were used, respectively. Further increases in cycling intensity revealed no changes on MEP or CMEP amplitudes for either stimulation strength. Conclusions: In general, MEPs and CMEPs changed in a similar manner, suggesting that increases and subsequent plateaus in overall excitability are likely mediated by spinal factors. Interestingly, however, MEP amplitudes were disproportionately larger than CMEP amplitudes as power output increased, despite being initially matched in amplitude, particularly with strong stimulation. This suggests that supraspinal excitability is enhanced to a larger degree than spinal excitability as the power output of arm cycling increases.
Epigenetic Dysregulation at the Crossroad of Women’s Cancer
Authors: Kumar Rakesh , Paul Aswathy Mary , Rameshwar Pranela , Pillai M. Radhakrishna
Published: August 2019

An increasingly number of women of all age groups are affected by cancer, despite substantial progress in our understanding of cancer pathobiology, the underlying genomic alterations and signaling cascades, and cellular-environmental interactions. Though our understanding of women’s cancer is far more complete than ever before, there is no comprehensive model to explain the reasons behind the increased incidents of certain reproductive cancer among older as well as younger women. It is generally suspected that environmental and life-style factors affecting hormonal and growth control pathways might help account for the rise of women’s cancers in younger age, as well, via epigenetic mechanisms. Epigenetic regulators play an important role in orchestrating an orderly coordination of cellular signals in gene activity in response to upstream signaling and/or epigenetic modifiers present in a dynamic extracellular milieu. Here we will discuss the broad principles of epigenetic regulation of DNA methylation and demethylation, histone acetylation and deacetylation, and RNA methylation in women’s cancers in the context of gene expression, hormonal action, and the EGFR family of cell surface receptor tyrosine kinases. We anticipate that a better understanding of the epigenetics of women’s cancers may provide new regulatory leads and further fuel the development of new epigenetic biomarkers and therapeutic approaches.
Clinical-Scale Production of CAR-T Cells for the Treatment of Melanoma Patients by mRNA Transfection of a CSPG4-Specific CAR under Full GMP Compliance
Authors: Wiesinger Manuel , März Johannes , Kummer Mirko , Schuler Gerold , Dörrie Jan , Schuler-Thurner Beatrice , Schaft Niels
Published: August 2019

Chimeric antigen receptor (CAR)-T cells already showed impressive clinical regressions in leukemia and lymphoma. However, the development of CAR-T cells against solid tumors lags behind. Here we present the clinical-scale production of CAR-T cells for the treatment of melanoma under full GMP compliance. In this approach a CAR, specific for chondroitin sulfate proteoglycan 4 (CSPG4) is intentionally transiently expressed by mRNA electroporation for safety reasons. The clinical-scale protocol was optimized for: (i) expansion of T cells, (ii) electroporation efficiency, (iii) viability, (iv) cryopreservation, and (v) potency. Four consistency runs resulted in CAR-T cells in clinically sufficient numbers, i.e., 2.4 × 109 CAR-expressing T cells, starting from 1.77x108 PBMCs, with an average expansion of 13.6x, an electroporation efficiency of 88.0% CAR-positive cells, a survival of 74.1% after electroporation, and a viability of 84% after cryopreservation. Purity was 98.7% CD3+ cells, with 78.1% CD3+/CD8+ T cells and with minor contaminations of 1.2% NK cells and 0.6% B cells. The resulting CAR-T cells were tested for cytolytic activity after cryopreservation and showed antigen-specific and very efficient lysis of tumor cells. Although our work is descriptive rather than investigative in nature, we expect that providing this clinically applicable protocol to generate sufficient numbers of mRNA-transfected CAR-T cells will help in moving the field of adoptive cell therapy of cancer forward.
Single-Cell Analysis of Multiple Steps of Dynamic NF-κB Regulation in Interleukin-1α-Triggered Tumor Cells Using Proximity Ligation Assays
Authors: Mayr-Buro Christin , Schlereth Eva , Beuerlein Knut , Tenekeci Ulas , Meier-Soelch Johanna , Schmitz M. Lienhard , Kracht Michael
Published: August 2019

The frequently occurring heterogeneity of cancer cells and their functional interaction with immune cells in the tumor microenvironment raises the need to study signaling pathways at the single cell level with high precision, sensitivity, and spatial resolution. As aberrant NF-κB activity has been implicated in almost all steps of cancer development, we analyzed the dynamic regulation and activation status of the canonical NF-κB pathway in control and IL-1α-stimulated individual cells using proximity ligation assays (PLAs). These systematic experiments allowed the visualization of the dynamic dissociation and re-formation of endogenous p65/IκBα complexes and the nuclear translocation of NF-κB p50/p65 dimers. PLA combined with immunostaining for p65 or with NFKBIA single molecule mRNA-FISH facilitated the analysis of (i) further levels of the NF-κB pathway, (i) its functionality for downstream gene expression, and (iii) the heterogeneity of the NF-κB response in individual cells. PLA also revealed the interaction between NF-κB p65 and the P-body component DCP1a, a new p65 interactor that contributes to efficient p65 NF-κB nuclear translocation. In summary, these data show that PLA technology faithfully mirrored all aspects of dynamic NF-κB regulation, thus allowing molecular diagnostics of this key pathway at the single cell level which will be required for future precision medicine.
Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation
Authors: Montalto Francesca Ida , Giordano Francesca , Chiodo Chiara , Marsico Stefania , Mauro Loredana , Sisci Diego , Aquila Saveria , Lanzino Marilena , Panno Maria Luisa , Andò Sebastiano , De Amicis Francesca
Published: August 2019

Progesterone-Receptor (PR) positivity is related with an enhanced response to breast cancer therapy, conversely cyclin D1 (CD1) is a retained marker of poor outcome. Herein, we demonstrate that hydroxyprogesterone (OHPg) through progesterone receptor B (PR-B) reduces breast cancer cell aggressiveness, by targeting the cytoplasmic CD1. Specifically, OHPg diminishes CD1 expression by a transcriptional regulation due to the recruitment of PR-B at a canonical half-PRE site of the CD1 promoter, together with HDAC1, determining a chromatin conformation less prone for gene transcription. CD1, together with its kinase partner Cdk4, regulates cell migration and metastasis, through the association with key components of focal adhesion, such as Paxillin (Pxn). Kaplan-Meier analysis shows that low Pxn expression was associated with increased distant metastasis-free survival in luminal A PR+ breast carcinomas. Interestingly, OHPg treatment reduced Pxn content in T47-D and MCF-7 cells; besides, the interaction between endogenous cytoplasmic CD1/Cdk4 with Pxn was reduced. This was consistent with the reduction of p-Ser83Pxn levels, crucially causing the delay in cell migration and a concomitant inhibition of Rac1 activity and p-PAK. Collectively, these findings support the role of PR-B in breast epithelial cell integrity and reinforce the importance in targeting PR-B as a potential strategy to restrict breast tumor cell invasion and metastasis.
Soluble HLA in the Aqueous Humour of Uveal Melanoma Is Associated with Unfavourable Tumour Characteristics
Authors: Wierenga Annemijn P. A. , Gezgin Gülçin , van Beelen Els , Eikmans Michael , Spruyt-Gerritse Marijke , Brouwer Niels J. , Versluis Mieke , Verdijk Robert M. , van Duinen Sjoerd G. , Marinkovic Marina , Luyten Gregorius P. M. , Jager Martine J.
Published: August 2019

A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tissue using a Fluidigm assay. In 19/108 UM-containing eyes, the sHLA level in the aqueous was above the detection limit. Tumours in sHLA-positive eyes were significantly larger, more frequently involved the ciliary body, and more often showed monosomy 3, gain of chromosome 8q and loss of BAP1 staining. Melanoma-related survival was worse in patients with sHLA-positive aqueous humour. sHLA in the aqueous did not represent the tumour’s HLA expression and did not relate to immune cell infiltration in the tumour. We conclude that UM-containing eyes may contain sHLA in the aqueous humour, where it is a prognostically-unfavourable sign and may influence local immune responses.
Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer
Authors: Jahanban-Esfahlan Rana , Seidi Khaled , Manjili Masoud H. , Jahanban-Esfahlan Ali , Javaheri Tahereh , Zare Peyman
Published: August 2019

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including angiogenic switch, immune escape, cancer stem cells, extracellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer and discuss the implications of such approaches in cancer treatment.
Influence of MoS2 on Activity and Stability of Carbon Nitride in Photocatalytic Hydrogen Production
Authors: Sivasankaran Ramesh P. , Rockstroh Nils , Kreyenschulte Carsten R. , Bartling Stephan , Lund Henrik , Acharjya Amitava , Junge Henrik , Thomas Arne , Brückner Angelika
Published: August 2019

MoS2/C3N4 (MS-CN) composite photocatalysts have been synthesized by three different methods, i.e., in situ-photodeposition, sonochemical, and thermal decomposition. The crystal structure, optical properties, chemical composition, microstructure, and electron transfer properties were investigated by X-ray diffraction, UV-vis diffuse reflectance spectroyscopy, X-ray photoelectron spectroscopy, electron microscopy, photoluminescence, and in situ electron paramagnetic resonance spectroscopy. During photodeposition, the 2H MoS2 phase was formed upon reduction of [MoS4]2− by photogenerated conduction band electrons and then deposited on the surface of CN. A thin crystalline layer of 2H MoS2 formed an intimate interfacial contact with CN that favors charge separation and enhances the photocatalytic activity. The 2H MS-CN phase showed the highest photocatalytic H2 evolution rate (2342 μmol h−1 g−1, 25 mg catalyst/reaction) under UV-vis light irradiation in the presence of lactic acid as sacrificial reagent and Pt as cocatalyst.
Rab GTPases: Switching to Human Diseases
Authors: Guadagno Noemi Antonella , Progida Cinzia
Published: August 2019

Rab proteins compose the largest family of small GTPases and control the different steps of intracellular membrane traffic. More recently, they have been shown to also regulate cell signaling, division, survival, and migration. The regulation of these processes generally occurs through recruitment of effectors and regulatory proteins, which control the association of Rab proteins to membranes and their activation state. Alterations in Rab proteins and their effectors are associated with multiple human diseases, including neurodegeneration, cancer, and infections. This review provides an overview of how the dysregulation of Rab-mediated functions and membrane trafficking contributes to these disorders. Understanding the altered dynamics of Rabs and intracellular transport defects might thus shed new light on potential therapeutic strategies.