bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerial Physical Interaction in Grabbing Conditions with Lightweight and Compliant Dual Arms
Authors: Suarez Alejandro , Sanchez-Cuevas Pedro J. , Heredia Guillermo , Ollero Anibal
Published: December 2020

This paper considers the problem of performing bimanual aerial manipulation tasks in grabbing conditions, with one of the arms grabbed to a fixed point (grabbing arm) while the other conducts the task (operation arm). The goal was to evaluate the positioning accuracy of the aerial platform and the end effector when the grabbing arm is used as position sensor, as well as to analyze the behavior of the robot during the aerial physical interaction on flight. The paper proposed a control scheme that exploits the information provided by the joint sensors of the grabbing arm for estimating the relative position of the aerial platform w.r.t. (with respect to) the grabbing point. A deflection-based Cartesian impedance control was designed for the compliant arm, allowing the generation of forces that help the aerial platform to maintain the reference position when it is disturbed due to external forces. The proposed methods were validated in an indoor testbed with a lightweight and compliant dual arm aerial manipulation robot.
Exact Soliton Solutions for Nonlinear Perturbed Schrödinger Equations with Nonlinear Optical Media
Authors: Gepreel Khaled A.
Published: December 2020

The nonlinear perturbed Schrödinger equations (NPSEs) with nonlinear terms as Kerr law, power law, quadratic-cubic law, and dual-power law nonlinearity media play an important role in optical fibers. In this article we implement the rational solitary wave method to study the NPSEs when nonlinear terms take some different forms. Additionally, we use the q-deformed hyperbolic function and q-deformed trigonometric function methods to study the exact solutions to NPSEs. Different kind of soliton solutions are obtained such as bright, dark, and singular periodic solutions to the NPSEs.
A Study on the Development of Tourist Support System Using ICT and Psychological Effects
Authors: Sasaki Akira , Xiang Fu , Hayashi Rina , Hiramatsu Yuko , Ueda Kazutaka , Harada Yasunari , Hatano Hiroyuki , Hasegawa Hiroshi , Ito Atsushi
Published: December 2020

We have been studying a sightseeing support application using Bluetooth Low Energy (BLE) beacons and mobile phones since 2014 to support sightseeing in Nikko, one of Japan’s World Heritage sites. Travelers can receive information relating to their position by using this application. We tried to use some psychological effects to increase travelers’ satisfaction when they receive such information. Moreover, we tried to emphasize travel memories of the place (scenery, culture, food, etc.) to encourage them to revisit or inspire their friends to visit it. Our tests prove the usefulness of our sightseeing support application for enhancing the travel experience. However, we had not yet developed a function to provide information that met the travelers’ intentions or needs. Moreover, it is hazardous to use a smartphone during walking, especially in an unfamiliar place. If a traveler uses a smartphone during walking, they might miss the beautiful scenery, historic buildings, and exotic atmosphere. We tried to adapt our sightseeing support application for use with a wearable device (smartwatch) to avoid using a smartphone during walking and introduced a prospect theory to evaluate information according to personal interest and behavior. Our experiments proved that our application provided the most appropriate sightseeing information to travelers and prevented danger during walking.
The Enhanced Mechanism of 0.05 wt. % Nd Addition on High Temperature Reliability of Sn-3.8Ag-0.7Cu/Cu Solder Joint
Authors: Xue Peng , Tao Jianzhi , He Peng , Long Weimin , Zhong Sujuan
Published: December 2020

In this study, the effect of appropriate Nd addition on improving the high-temperature reliability of Sn-3.8Ag-0.7Cu (SAC387)/Cu solder joint after aging treatment was investigated. The interfacial microstructure of solder joint was refined with proper addition of Nd. This phenomenon could be explained as the adsorbing-hindering effect of surface-active Nd atoms which blocked the growth of brittle intermetallic compounds (IMCs) in the solder joint. Theoretical analysis indicated that 0.05 wt. % addition of Nd could distinctly decrease the growth constant of Cu6Sn5 IMCs and slightly decrease the growth constant of Cu3Sn IMCs respectively. The shear force of SAC387-0.05Nd/Cu solder joint was evidently improved compared with the origin solder joint. In addition, SAC387-0.05Nd/Cu solder joint maintained excellent mechanical property compared with SAC387/Cu solder joint even after 1440 h aging treatment.
Intermediate Band Studies of Substitutional V2+, Cr2+, and Mn2+ Defects in ZnTe Alloys
Authors: Tung Jen-Chuan , Lin Bang-Wun , Liu Po-Liang
Published: December 2020

We present first-principles total-energy density functional calculations to study the intermediate band states of substitutional V2+, Cr2+, and Mn2+ ions in ZnTe alloys. The intermediate band states of substitutional transition metal defects of TM2+xZn1−xTe (TM = V, Cr, Mn) alloys are examined as their atomic, structural, and electronic analysis. Our findings show that the scissor-corrected transitions due to Jahn-Teller effects lead to the wavelengths 2530 nm and 2695 nm in the emission spectra. Our findings agree with previously reported experimental results.
Analysis of Surface Roughness Influence in Non-Destructive Magnetic Measurements Applied to Reactor Pressure Vessel Steels
Authors: Vértesy Gábor , Gasparics Antal , Griffin James M. , Mathew Jino , Fitzpatrick Michael E. , Uytdenhouwen Inge
Published: December 2020

The influence of surface roughness on magnetic measurements of Reactor Pressure Vessel Steels was investigated by applying two types of magnetic, non-destructive measurement on nuclear reactor pressure vessel steel samples: magnetic adaptive testing (MAT) and magnetic Barkhausen noise measurement (MBN). The surface roughness was modified by primary and secondary machine cutting forces. Different settings of machine cutting produced different surface conditions. It was found that for both measurements a monotonic correlation was found to exist between magnetic parameters and surface roughness. Results of the MAT measurements found that the correlation depends on the speed (i.e., on the applied slew rate) of the magnetizing current. In a similar fashion, results from the MBN method show good agreement with MAT, where the response diminishes with an increase in surface roughness. The results show the importance of accounting for surface condition in the interpretation of results of non-destructive magnetic testing.
Expected Impacts of the Massive Increase in Electric Vehicles in Slovakia
Authors: Živčák Jozef , Kádárová Jaroslava , Puškár Michal , Kočišová Michaela , Lachvajderová Laura
Published: December 2020

Society and the government perceive alternative propulsions as a way out of a world of high emissions. For several years now, European countries have been trying to enforce various strategic plans in which they give maximum support to electromobility. Subsidies and emission limits for car manufacturers or strategic plans for the development of electromobility in each European country are only a small part of the enormous support for the development of this new alternative drive. However, questions arise in the energy and ecology sectors: Is Slovakia ready to increase the number of electric vehicles? Will Slovakia have enough energy sources? Are electric cars really as clean as they are presented? The article focuses on these issues and, through detailed analysis, based on individual annual reports of each sector, refutes or confirms the fact that electromobility is a promising alternative and a replacement for internal combustion engines.
Condition Rating Prediction Using an Interactive Deterioration Model Development Package
Authors: Chang Minwoo , Maguire Marc
Published: December 2020

This paper presents an advanced method to determine explanatory variables required for developing deterioration models without the interference of human bias. Although a stationary set of explanatory variables is ideal for long-term monitoring and asset management, the penalty regression results vary annually due to the innate bias in the inspection data. In this study, weighting factors were introduced to consider the inspection data collected for several years, and the most stationary set was identified. To manage the substantial amount of inspection data effectively, we proposed a software package referred to as the Deterioration Model Development Package (DMDP). The objective of the DMDP is to provide a convenient platform for users to process and investigate bridge inspection data. Using the standardized data interpretation, the user can update an initial dataset for the deterioration model development when new inspection data are archived. The deterministic method and several stochastic approaches were included for the development of the deterioration models. The performances of the investigated methods were evaluated by estimating the error between the predicted and inspected condition ratings; further, this error was used for estimating the most effective number of explanatory variables for a given number of bridges.
Constructing a Reliable Health Indicator for Bearings Using Convolutional Autoencoder and Continuous Wavelet Transform
Authors: Kaji Mohammadreza , Parvizian Jamshid , van de Venn Hans Wernher
Published: December 2020

Estimating the remaining useful life (RUL) of components is a crucial task to enhance reliability, safety, productivity, and to reduce maintenance cost. In general, predicting the RUL of a component includes constructing a health indicator (HI) to infer the current condition of the component, and modelling the degradation process in order to estimate the future behavior. Although many signal processing and data-driven methods have been proposed to construct the HI, most of the existing methods are based on manual feature extraction techniques and require the prior knowledge of experts, or rely on a large amount of failure data. Therefore, in this study, a new data-driven method based on the convolutional autoencoder (CAE) is presented to construct the HI. For this purpose, the continuous wavelet transform (CWT) technique was used to convert the raw acquired vibrational signals into a two-dimensional image; then, the CAE model was trained by the healthy operation dataset. Finally, the Mahalanobis distance (MD) between the healthy and failure stages was measured as the HI. The proposed method was tested on a benchmark bearing dataset and compared with several other traditional HI construction models. Experimental results indicate that the constructed HI exhibited a monotonically increasing degradation trend and had good performance in terms of detecting incipient faults.
A Gravity Search for Oil and Gas and Groundwater in Egypt Using the Strike Angles Derived from EIGEN 6C4
Authors: Klokočník Jaroslav , Kostelecký Jan , Varadzinová Lenka , Bezděk Aleš , Kletetschka Gunther
Published: December 2020

We correlate the gravity aspects (descriptors), namely the strike angles, derived from a recent gravity field model, with the known oil, gas and groundwater deposits/reservoirs and hypothetical paleolakes with the locations of archaeological sites. This allows us to extrapolate the investigation, by analogy, to unknown regions. The gravity aspects, derived from the EIGEN 6C4 gravity field model, are used, together with EMAG 2 magnetic anomalies and ETOPO 1 topography model, for the investigation of oil, gas and water deposits in Egypt. One of the gravity aspects, s/c strike angle, is significantly combed (oriented in one direction locally) in places where the known deposits exist. However, they are combed also in some other places. This may be used as a guide as to where to seek new and promising deposits. Accounting for the combed strike angles and the relationship between gravity anomalies and height differences, we reconstructed potential paleolakes under thick sand layers in the Great Sand Sea, Western Egypt (our previous work), and between Kharga and Toshka, Southern Egypt (this work), consistent with the known archaeological sites.
Forecasting Warping Deformation Using Multivariate Thermal Time Series and K-Nearest Neighbors in Fused Deposition Modeling
Authors: Song Donghwan , Chung Baek Adrian Matias , Koo Jageon , Busogi Moise , Kim Namhun
Published: December 2020

Over the past decades, additive manufacturing has rapidly advanced due to its advantages in enabling diverse material usage and complex design production. Nevertheless, the technology has limitations in terms of quality, as printed products are sometimes different from their desired designs or are inconsistent due to defects. Warping deformation, a defect involving layer shrinkage induced by the thermal residual stress generated during manufacturing processes, is a major factor in lowering the quality and raising the cost of printed products. This study utilized a variety of thermal time series data and the K-nearest neighbors (KNN) algorithm with dynamic time warping (DTW) to detect and predict the warping deformation in the printed parts using fused deposition modeling (FDM) printers. Multivariate thermal time series data extracted from thermocouples were trained using DTW-based KNN to classify warping deformation. The results showed that the proposed approach can predict warping deformation with an accuracy of over 80% by only using thermal time series data corresponding to 20% of the whole printing process. Additionally, the classification accuracy exhibited the promising potential of the proposed approach in warping prediction and in actual manufacturing processes, so the additional time and cost resulting from defective processes can be reduced.
Air Pollution Measurements and Land-Use Regression in Urban Sub-Saharan Africa Using Low-Cost Sensors—Possibilities and Pitfalls
Authors: Abera Asmamaw , Mattisson Kristoffer , Eriksson Axel , Ahlberg Erik , Sahilu Geremew , Mengistie Bezatu , Bayih Abebe Genetu , Aseffaa Abraham , Malmqvist Ebba , Isaxon Christina
Published: December 2020

Air pollution is recognized as the most important environmental factor that adversely affects human and societal wellbeing. Due to rapid urbanization, air pollution levels are increasing in the Sub-Saharan region, but there is a shortage of air pollution monitoring. Hence, exposure data to use as a base for exposure modelling and health effect assessments is also lacking. In this study, low-cost sensors were used to assess PM2.5 (particulate matter) levels in the city of Adama, Ethiopia. The measurements were conducted during two separate 1-week periods. The measurements were used to develop a land-use regression (LUR) model. The developed LUR model explained 33.4% of the variance in the concentrations of PM2.5. Two predictor variables were included in the final model, of which both were related to emissions from traffic sources. Some concern regarding influential observations remained in the final model. Long-term PM2.5 and wind direction data were obtained from the city’s meteorological station, which should be used to validate the representativeness of our sensor measurements. The PM2.5 long-term data were however not reliable. Means of obtaining good reference data combined with longer sensor measurements would be a good way forward to develop a stronger LUR model which, together with improved knowledge, can be applied towards improving the quality of health. A health impact assessment, based on the mean level of PM2.5 (23 µg/m3), presented the attributable burden of disease and showed the importance of addressing causes of these high ambient levels in the area.
Radiation in the Atmosphere—A Hazard to Aviation Safety?
Authors: Meier Matthias M. , Copeland Kyle , Klöble Klara E. J. , Matthiä Daniel , Plettenberg Mona C. , Schennetten Kai , Wirtz Michael , Hellweg Christine E.
Published: December 2020

Exposure of aircrew to cosmic radiation has been recognized as an occupational health risk for several decades. Based on the recommendations by the International Commission on Radiological Protection (ICRP), many countries and their aviation authorities, respectively have either stipulated legal radiation protection regulations, e.g., in the European Union or issued corresponding advisory circulars, e.g., in the United States of America. Additional sources of ionizing and non-ionizing radiation, e.g., due to weather phenomena have been identified and discussed in the scientific literature in recent years. This article gives an overview of the different generally recognized sources due to weather as well as space weather phenomena that contribute to radiation exposure in the atmosphere and the associated radiation effects that might pose a risk to aviation safety at large, including effects on human health and avionics. Furthermore, potential mitigation measures for several radiation sources and the prerequisites for their use are discussed.
Actinomycetes Enrich Soil Rhizosphere and Improve Seed Quality as well as Productivity of Legumes by Boosting Nitrogen Availability and Metabolism
Authors: AbdElgawad Hamada , Abuelsoud Walid , Madany Mahmoud M. Y. , Selim Samy , Zinta Gaurav , Mousa Ahmed S. M. , Hozzein Wael N.
Published: December 2020

The use of actinomycetes for improving soil fertility and plant production is an attractive strategy for developing sustainable agricultural systems due to their effectiveness, eco-friendliness, and low production cost. Out of 17 species isolated from the soil rhizosphere of legume crops, 4 bioactive isolates were selected and their impact on 5 legumes: soybean, kidney bean, chickpea, lentil, and pea were evaluated. According to the morphological and molecular identification, these isolates belong to the genus Streptomyces. Here, we showed that these isolates increased soil nutrients and organic matter content and improved soil microbial populations. At the plant level, soil enrichment with actinomycetes increased photosynthetic reactions and eventually increased legume yield. Actinomycetes also increased nitrogen availability in soil and legume tissue and seeds, which induced the activity of key nitrogen metabolizing enzymes, e.g., glutamine synthetase, glutamate synthase, and nitrate reductase. In addition to increased nitrogen-containing amino acids levels, we also report high sugar, organic acids, and fatty acids as well as antioxidant phenolics, mineral, and vitamins levels in actinomycete treated legume seeds, which in turn improved their seed quality. Overall, this study shed the light on the impact of actinomycetes on enhancing the quality and productivity of legume crops by boosting the bioactive primary and secondary metabolites. Moreover, our findings emphasize the positive role of actinomycetes in improving the soil by enriching its microbial population. Therefore, our data reinforce the usage of actinomycetes as biofertilizers to provide sustainable food production and achieve biosafety.
Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions
Authors: Kovynev Igor B. , Titov Sergei E. , Ruzankin Pavel S. , Agakishiev Mechti M. , Veryaskina Yuliya A. , Nedel’ko Viktor M. , Pospelova Tatiana I. , Zhimulev Igor F.
Published: December 2020

Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA expression profiles in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and hematopoietic conditions induced by non-tumor pathologies (NTP). Methods: A total of 114 cytological samples obtained by sternal puncture and aspiration biopsy of bone marrow (22 ALLs, 44 AMLs, and 48 NTPs) were analyzed by real-time PCR regarding preselected 25 miRNAs. For the classification of the samples, logistic regression was used with balancing of comparison group weights. Results: Our results indicated potential feasibility of (i) differentiating ALL+AML from a nontumor hematopoietic pathology with 93% sensitivity and 92% specificity using miR-150:miR-21, miR-20a:miR-221, and miR-24:nf3 (where nf3 is a normalization factor calculated from threshold cycle values of miR-103a, miR-191, and miR-378); (ii) diagnosing ALL with 81% sensitivity and 81% specificity using miR-181b:miR-100, miR-223:miR-124, and miR-24:nf3; and (iii) diagnosing AML with 81% sensitivity and 84% specificity using miR-150:miR-221, miR-100:miR-24, and miR-181a:miR-191. Conclusion: The results presented herein allow the miRNA expression profile to de used for differentiation between AL and NTP, no matter what AL subtype.
Examination of Oral Squamous Cell Carcinoma and Precancerous Lesions Using Proximity Extension Assay and Salivary RNA Quantification
Authors: Scholtz Beáta , Vo Minh Doan , Kiss Csongor , Tar Ildikó , Kumar Ajneesh , Tőzsér József , Csősz Éva , Márton Ildikó
Published: December 2020

Saliva is an easy-to access body fluid with high diagnostic potential. The utilization of saliva for oral cancer diagnosis can be an attractive possibility. Besides the oral cancer, it is important to better understand the precancerous lesions such as oral lichen planus (OLP) and leukoplakia (OLK). In order to examine the changes of salivary proteins in controls, patients with oral cancer, and patients with precancerous conditions, proximity extension assay was utilized. Some proteins and functions were characteristic to the examined groups and can serve as a starting point for further biomarker studies. The different nature of OLK and OLP was demonstrated, showing the malignant transformation and the inflammation as the prominent biological processes in the OLK and OLP, respectively. The salivary level of IL6 was verified using quantitative ELISA and the mRNA level was also studied. Elevated IL6 levels could be detected in precancerous groups compared to controls.
Anti-c-myc RNAi-Based Onconanotherapeutics
Authors: Habib Saffiya , Ariatti Mario , Singh Moganavelli
Published: December 2020

Overexpression of the c-myc proto-oncogene features prominently in most human cancers. Early studies established that inhibiting the expression of oncogenic c-myc, produced potent anti-cancer effects. This gave rise to the notion that an appropriate c-myc silencing agent might provide a broadly applicable and more effective form of cancer treatment than is currently available. The endogenous mechanism of RNA interference (RNAi), through which small RNA molecules induce gene silencing by binding to complementary mRNA transcripts, represents an attractive avenue for c-myc inhibition. However, the development of a clinically viable, anti-c-myc RNAi-based platform is largely dependent upon the design of an appropriate carrier of the effector nucleic acids. To date, organic and inorganic nanoparticles were assessed both in vitro and in vivo, as carriers of small interfering RNA (siRNA), DICER-substrate siRNA (DsiRNA), and short hairpin RNA (shRNA) expression plasmids, directed against the c-myc oncogene. We review here the various anti-c-myc RNAi-based nanosystems that have come to the fore, especially between 2005 and 2020.
Exercise: A Gate That Primes the Brain to Perform
Authors: Perrey Stéphane
Published: December 2020

The improvement of exercise performance encountered in sports not only represents the enhancement of physical strength but also includes the development of psychological and cognitive functions [...]
One Multilocus Genomic Variation Is Responsible for a Severe Charcot–Marie–Tooth Axonal Form
Authors: Miressi Federica , Magdelaine Corinne , Cintas Pascal , Bourthoumieux Sylvie , Nizou Angélique , Derouault Paco , Favreau Frédéric , Sturtz Franck , Faye Pierre-Antoine , Lia Anne-Sophie
Published: December 2020

Charcot–Marie–Tooth (CMT) disease is a heterogeneous group of inherited disorders affecting the peripheral nervous system, with a prevalence of 1/2500. So far, mutations in more than 80 genes have been identified causing either demyelinating forms (CMT1) or axonal forms (CMT2). Consequentially, the genotype–phenotype correlation is not always easy to assess. Diagnosis could require multiple analysis before the correct causative mutation is detected. Moreover, it seems that approximately 5% of overall diagnoses for genetic diseases involves multiple genomic loci, although they are often underestimated or underreported. In particular, the combination of multiple variants is rarely described in CMT pathology and often neglected during the diagnostic process. Here, we present the complex genetic analysis of a family including two CMT cases with various severities. Interestingly, next generation sequencing (NGS) associated with Cov’Cop analysis, allowing structural variants (SV) detection, highlighted variations in MORC2 (microrchidia family CW-type zinc-finger 2) and AARS1 (alanyl-tRNA-synthetase) genes for one patient and an additional mutation in MFN2 (Mitofusin 2) in the more affected patient.
The Impacts of the Presence of an Unfamiliar Dog on Emerging Adults’ Physiological and Behavioral Responses Following Social Exclusion
Authors: Papousek Ilona , Reiter-Scheidl Katharina , Lackner Helmut K. , Weiss Elisabeth M. , Perchtold-Stefan Corinna M. , Aydin Nilüfer
Published: December 2020

Research indicates that non-human attachment figures may mitigate the negative consequences of social exclusion. In the current experiment, we examined how the presence of an unfamiliar companion dog in the laboratory effects physiological and behavioral reactions in female emerging adults after social exclusion compared to inclusion. Results revealed the beneficial effects of the dog: Socially excluded participants in the company of a dog showed less aggressive behavior in response to the hot sauce paradigm compared to excluded participants in the control condition. Furthermore, cardiac responses indicated mitigated perception of threat in a subsequent insult episode when a dog was present. The presence of a dog did not impact the most instantaneous, “reflexive” response to the social exclusion as revealed by characteristic cardiac changes. Together, the findings indicate that the presence of a companion dog takes effect in a later, reflective period following a social exclusion experience, which implicates relevant social elaboration and appraisal processes.
Suitability of Seismic Isolation for Buildings Founded on Soft Soil. Case Study of a RC Building in Shanghai
Authors: Almansa Francisco López , Weng Dagen , Li Tao , Alfarah Bashar
Published: December 2020

Base (seismic) isolation is a promising technology for seismic protection of buildings and other constructions. Nowadays, it is accepted that such a technique is efficient and reliable; however, it has two major limitations: soft foundation soil, and tall buildings. The first issue restrains the seismic isolation spreading, given that soft soil is frequent in densely populated areas, and usually such a soil type concentrates the highest seismicity levels. This paper aims to contribute to demonstrating that base isolation, if properly implemented, can be suitable for soft soil. A representative case study is analyzed: a 6-story reinforced concrete (RC) building with base isolation that has recently been built in Shanghai. Since the building is founded on soft soil, concern regarding base isolation suitability arose; even the Chinese design code does not recommend this solution for soft soil. To clarify this issue, non-linear time-history analyses are carried out for a number of natural and artificial seismic inputs that represent the site seismicity; the superstructure behavior is linear, while nonlinearities are concentrated in the isolation layer. The adequacy of base isolation is assessed in the superstructure (in terms of reduction of interstory drift, absolute acceleration and shear force) and in the isolation layer (in terms of axial force, torsion angle and shear strain). The relevance of soil–structure interaction is discussed. The behavior when the mechanical parameters of the isolation units have experienced important changes is also analyzed. The major conclusion is that base isolation of ordinary mid-height RC buildings founded on soft soil can perform satisfactorily in medium seismicity regions.
Seismic Acceleration and Displacement Demand Profiles of Non-Structural Elements in Hospital Buildings
Authors: Gabbianelli Giammaria , Perrone Daniele , Brunesi Emanuele , Monteiro Ricardo
Published: December 2020

The importance of non-structural elements in performance-based seismic design of buildings is presently widely recognized. These elements may significantly affect the functionality of buildings even for low seismic intensities, in particular for the case of critical facilities, such as hospital buildings. One of the most important issues to deal with in the seismic performance assessment of non-structural elements is the definition of the seismic demand. This paper investigates the seismic demand to which the non-structural elements of a case-study hospital building located in a medium–high seismicity region in Italy, are prone. The seismic demand is evaluated for two seismic intensities that correspond to the definition of serviceability limit states, according to Italian and European design and assessment guidelines. Peak floor accelerations, interstorey drifts, absolute acceleration, and relative displacement floor response spectra are estimated through nonlinear time–history analyses. The absolute acceleration floor response spectra are then compared with those obtained from simplified code formulations, highlighting the main shortcomings surrounding the practical application of performance-based seismic design of non-structural elements. The absolute acceleration floor response spectra are then compared with those obtained from simplified code formulations. The results, both in terms of absolute acceleration and relative displacement floor response spectra, highlighted the influence of the higher modes of the structure and the inaccuracy of the code provisions, pointing out the need for more accurate simplified methodologies for the practical application of performance-based seismic design of non-structural elements.
Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor
Authors: Umbreit Eric C. , Siddiqui Bilal A. , Hwang Michael J. , Joon Aron Y. , Maity Tapati , Westerman Mary E. , Merriman Kelly W. , Alhasson Hussam , Uthup Joma , Guo Tao , Moore Joseph A. , Ward John F. , Karam Jose A. , Wood Christopher G. , Pisters Louis L. , Zhang Miao , Tu Shi-Ming
Published: December 2020

Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease.
Prior PSMA PET-CT Imaging and Hounsfield Unit Impact on Tumor Yield and Success of Molecular Analyses from Bone Biopsies in Metastatic Prostate Cancer
Authors: Smits Minke , Ekici Kamer , Pamidimarri Naga Samhita , van Oort Inge M. , Sedelaar Michiel J. P. , Schalken Jack A. , Nagarajah James , Scheenen Tom W. J. , Gerritsen Winald R. , Fütterer Jurgen J. , Mehra Niven
Published: December 2020

Developing and optimizing targeted therapies in metastatic castration-resistant prostate cancer (mCRPC) necessitates molecular characterization. Obtaining sufficient tumor material for molecular characterization has been challenging. We aimed to identify clinical and imaging variables of imaging-guided bone biopsies in metastatic prostate cancer patients that associate with tumor yield and success in obtaining molecular results, and to design a predictive model: Clinical and imaging data were collected retrospectively from patients with prostate cancer who underwent a bone biopsy for histological and molecular characterization. Clinical characteristics, imaging modalities and imaging variables, were associated with successful biopsy results. In our study, we included a total of 110 bone biopsies. Histological conformation was possible in 84 of all biopsies, of which, in 73 of the 84, successful molecular characterization was performed. Prior use of PSMA PET-CT resulted in higher success rates in histological and molecular successful biopsies compared to CT or MRI. Evaluation of spine biopsies showed more often successful results compared to other locations for both histological and molecular biopsies (p = 0.027 and p = 0.012, respectively). Low Hounsfield units (HUs) and deviation (Dev), taken at CT-guidance, were associated with histological successful biopsies (p = 0.025 and p = 0.023, respectively) and with molecular successful biopsies (p = 0.010 and p = 0.006, respectively). A prediction tool combining low HUs and low Dev resulted in significantly more successful biopsies, histological and molecular (p = 0.023 and p = 0.007, respectively). Based on these results, we concluded that site selection for metastatic tissue biopsies with prior PSMA PET-CT imaging improves the chance of a successful biopsy. Further optimization can be achieved at CT-guidance, by selection of low HU and low Dev lesions. A prediction tool is provided to increase the success rate of bone biopsies in mCRPC patients, which can easily be implemented in daily practice.
HNC0014, a Multi-Targeted Small-Molecule, Inhibits Head and Neck Squamous Cell Carcinoma by Suppressing c-Met/STAT3/CD44/PD-L1 Oncoimmune Signature and Eliciting Antitumor Immune Responses
Authors: Lee Jih-Chin , Wu Alexander T.H. , Chen Jia-Hong , Huang Wen-Yen , Lawal Bashir , Mokgautsi Ntlotlang , Huang Hsu-Shan , Ho Ching-Liang
Published: December 2020

Despite advancements in diagnostic and standard treatment modalities, including surgery, radiotherapy, and chemotherapy, overall survival rates of advanced-stage head and neck squamous cell carcinoma (HNSCC) patients have remained stagnant for over three decades. Failure of these treatment modalities, coupled with post-therapy complications, underscores the need for alternative interventions and an in-depth understanding of the complex signaling networks involved in developing treatment resistance. Using bioinformatics tools, we identified an increased expression of c-Met, STAT3, and CD44 corresponding to a poor prognosis and malignant phenotype of HNSCC. Subsequently, we showed that tumorsphere-derived exosomes promoted cisplatin (CDDP) resistance and colony and tumorsphere formation in parental HNSCC cells, accompanied by an increased level of oncogenic/immune evasive markers, namely, c-Met, STAT3, CD44, and PD-L1. We then evaluated the therapeutic potential of a new small molecule, HNC0014. The molecular docking analysis suggested strong interactions between HNC0014 and oncogenic molecules; c-Met, STAT3, CD44, and PD-L1. Subsequently, we demonstrated that HNC0014 treatment suppressed HNSCC tumorigenic and expression of stemness markers; HNC0014 also reduced cancer-associated fibroblast (CAF) transformation by Exosp- and CAF-induced tumorigenic properties. HNC0014 treatment alone suppressed tumor growth in a cisplatin-resistant (SAS tumorspheres) mouse xenograft model and with higher inhibitory efficacy when combined with CDDP. More importantly, HNC0014 treatment significantly delayed tumor growth in a syngeneic mouse HNSCC model, elicited an antitumor immune profile, and reduced the total c-Met, STAT3, and their phosphorylated forms, PD-L1 and CD44, contents in serum exosomes. Collectively, our findings provide supports for HNC0014 as a multi-targeted immunotherapeutic lead compound for further development.
Germline TP53 Testing in Breast Cancers: Why, When and How?
Authors: Evans D. Gareth , Woodward Emma R. , Bajalica-Lagercrantz Svetlana , Oliveira Carla , Frebourg Thierry
Published: December 2020

Germline TP53 variants represent a main genetic cause of breast cancers before 31 years of age. Development of cancer multi-gene panels has resulted in an exponential increase of germline TP53 testing in breast cancer patients. Interpretation of TP53 variants, which are mostly missense, is complex and requires excluding clonal haematopoiesis and circulating tumour DNA. In breast cancer patients harbouring germline disease-causing TP53 variants, radiotherapy contributing to the development of subsequent tumours should be, if possible, avoided and, within families, annual follow-up including whole-body MRI should be offered to carriers. We consider that, in breast cancer patients, germline TP53 testing should be performed before treatment and offered systematically only to patients with: (i) invasive breast carcinoma or ductal carcinoma in situ (DCIS) before 31; or (ii) bilateral or multifocal or HER2+ invasive breast carcinoma/DCIS or phyllode tumour before 36; or (iii) invasive breast carcinoma before 46 and another TP53 core tumour (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumour, adrenocortical carcinoma); or (iv) invasive breast carcinoma before 46 and one first- or second-degree relative with a TP53 core tumour before 56. In contrast, women presenting with breast cancer after 46, without suggestive personal or familial history, should not be tested for TP53.
Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond
Authors: Zhang Xiaoli , Powell Kimerly , Li Lang
Published: December 2020

Despite recent advances in diagnosis and treatment, breast cancer (BC) is still a major cause of cancer-related mortality in women. Breast cancer stem cells (BCSCs) are a small but significant subpopulation of heterogeneous breast cancer cells demonstrating strong self-renewal and proliferation properties. Accumulating evidence has proved that BCSCs are the driving force behind BC tumor initiation, progression, metastasis, drug resistance, and recurrence. As a heterogeneous disease, BC contains a full spectrum of different BC subtypes, and different subtypes of BC further exhibit distinct subtypes and proportions of BCSCs, which correspond to different treatment responses and disease-specific outcomes. This review summarized the current knowledge of BCSC biomarkers and their clinical relevance, the methods for the identification and isolation of BCSCs, and the mechanisms regulating BCSCs. We also discussed the cellular origin of BCSCs and the current advances in single-cell lineage tracing and transcriptomics and their potential in identifying the origin and lineage development of BCSCs.
Acute Conditioning of Antigen-Expanded CD8+ T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge
Authors: Taborska Pavla , Stakheev Dmitry , Svobodova Hana , Strizova Zuzana , Bartunkova Jirina , Smrz Daniel
Published: December 2020

CD8+ T cells protect against tumors and intracellular pathogens. The inflammatory cytokines IL-2, IL-15, and IL-7 are necessary for their expansion. However, elevated serum levels of these cytokines are often associated with cancer, poorer prognosis of cancer patients, and exhaustion of antigen-expanded CD8+ T cells. The impact of acute conditioning of antigen-expanded CD8+ T cells with these cytokines is unknown. Here, we generated antigen-expanded CD8+ T cells using dendritic cells and PC-3 cells. The cells were acutely (18–24 h) conditioned with IL-2 and either the GSK3β inhibitor TWS119, the mTORC1 inhibitor rapamycin, or the mTORC1/2 inhibitor Torin1, then their immediate and post-re-expansion (distal) cytokine responses after antigen rechallenge were evaluated. We found that acute IL-2 conditioning upregulated the immediate antigen-induced cytokine response of the tested cells. Following their re-expansion, however, the cells showed a decreased cytokine response. These IL-2 conditioning-mediated impacts were counteracted with TWS119 or rapamycin but not with Torin1. Our data revealed that the acute conditioning of antigen-expanded CD8+ T cells with IL-2 modulates the GSK3β-mTORC signaling axis. This modulation differentially affected the immediate and distal cytokine responses of the cells. The acute targeting of this signaling axis could, therefore, represent a novel strategy for the modulation of antigen-expanded CD8+ T cells.
Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release
Authors: Peñate Medina Tuula , Gerle Mirko , Humbert Jana , Chu Hanwen , Köpnick Anna-Lena , Barkmann Reinhard , Garamus Vasil M. , Sanz Beatriz , Purcz Nicolai , Will Olga , Appold Lia , Damm Timo , Suojanen Juho , Arnold Philipp , Lucius Ralph , Willumeit-Römer Regina , Açil Yahya , Wiltfang Joerg , Goya Gerardo F. , Glüer Claus C. , Peñate Medina Oula
Published: December 2020

Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.
Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer
Authors: Sunami Yoshiaki , Häußler Johanna , Kleeff Jörg
Published: December 2020

Pancreatic cancer is projected to become the second deadliest cancer by 2030 in the United States, and the overall five-year survival rate stands still at around 9%. The stroma compartment can make up more than 90% of the pancreatic tumor mass, contributing to the hypoxic tumor microenvironment. The dense stroma with extracellular matrix proteins can be a physical and metabolic barrier reducing therapeutic efficacy. Cancer-associated fibroblasts are a source of extracellular matrix proteins. Therefore, targeting these cells, or extracellular matrix proteins, have been considered as therapeutic strategies. However, several studies show that deletion of cancer-associated fibroblasts may have tumor-promoting effects. Cancer-associated fibroblasts are derived from a variety of different cell types, such as pancreatic stellate cells and mesenchymal stem cells, and constitute a diverse cell population consisting of several functionally heterogeneous subtypes. Several subtypes of cancer-associated fibroblasts exhibit a tumor-restraining function. This review article summarizes recent findings regarding origin and functional heterogeneity of tumor-promoting as well as tumor-restraining cancer-associated fibroblasts. A better understanding of cancer-associated fibroblast heterogeneity could provide more specific and personalized therapies for pancreatic cancer patients in the future.
Human Papillomavirus and Cancers
Authors: Tornesello Maria Lina , Buonaguro Franco M.
Published: December 2020

Persistent infection with oncogenic human papillomaviruses (HPVs) is the main cause of nearly all cervical cancers as well as of a significant proportion of other malignancies arising from the mucosal squamous epithelia of the anogenital tract as well as of the head and neck region [1]. [...]
Cancer Immunotherapy and Application of Nanoparticles in Cancers Immunotherapy as the Delivery of Immunotherapeutic Agents and as the Immunomodulators
Authors: Debele Tilahun Ayane , Yeh Cheng-Fa , Su Wen-Pin
Published: December 2020

In the last few decades, cancer immunotherapy becomes an important tactic for cancer treatment. However, some immunotherapy shows certain limitations including poor therapeutic targeting and unwanted side effects that hinder its use in clinics. Recently, several researchers are exploring an alternative methodology to overcome the above limitations. One of the emerging tracks in this field area is nano-immunotherapy which has gone through rapid progress and revealed considerable potentials to solve limitations related to immunotherapy. Targeted and stimuli-sensitive biocompatible nanoparticles (NPs) can be synthesized to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity and to enhance the survival rate of cancer patients. In this review, we have discussed cancer immunotherapy and the application of NPs in cancer immunotherapy, as a carrier of immunotherapeutic agents and as a direct immunomodulator.