bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Multi-Axis Crank Linkage Motion System for Synchronized Flight Simulation with VR Immersion
Authors: Pan Cheng-Tang , Sun Pei-Yuan , Li Hao-Jan , Hsieh Cheng-Hsuan , Hoe Zheng-Yu , Shiue Yow-Ling
Published: April 2021

This paper developed a rotatable multi-axis motion platform combined with virtual reality (VR) immersion for flight simulation purposes. The system could simulate the state of the flight operation. The platform was mainly comprised of three crank linkage mechanisms to replace an expensive six degrees of freedom (DoF) Stewart platform. Then, an independent subsystem which could rotate ±180° was installed at the center of the platform. Therefore, this platform exhibited 4-DoF movement, such as heave, roll, pitch, and yaw. In the servo motor control unit, Visual Studio C# was applied as the software to establish a motion control system to interact with the motion controller and four sets of servo motors. Ethernet Control Automation Technology (EtherCAT) was utilized to communicate the commands and orders between a PC and each servo motor. The optimum controller parameters of this system were obtained using Simulink simulation and verified by experiment. The multiple sets of servo motors and crank linkage mechanisms were synchronized with flight VR imagery. For VR imagery, the software Unity was used to design the flying digital content. The controller was used to transmit the platform’s spatial information to meet the direction of the pilot commands and to compensate the direction of the deviation in spatial coordinates. To achieve synchronized response and motion with respect to the three crank linkage mechanism platform and VR imagery on the tester’s goggle view, the relation of the spatial coordinate of VR imagery and three crank linkage mechanisms was transformed to angular displacement, speed and acceleration which were used to command the motor drive system. As soon as the position of the VR imagery changed, the computer instantly synchronized the VR imagery information to the multi-axis platform and performed multi-axis dynamic motion synchronously according to its commanded information. The testers can thus immerse in the VR image environment by watching the VR content, and obtain a flying experience.
Automatic Identification of Different Types of Consumer Configurations by Using Harmonic Current Measurements
Authors: Domagk Max , Gu Irene Yu-Hua , Meyer Jan , Schegner Peter
Published: April 2021

Power quality (PQ) is an increasing concern in the distribution networks of modern industrialized countries. The PQ monitoring activities of distribution system operators (DSO), and consequently the amount of PQ measurement data, continuously increase, and consequently new and automated tools are required for efficient PQ analysis. Time characteristics of PQ parameters (e.g., harmonics) usually show characteristic daily and weekly cycles, mainly caused by the usage behaviour of electric devices. In this paper, methods are proposed for the classification of harmonic emission profiles for typical consumer configurations in public low voltage (LV) networks using a binary decision tree in combination with support vector machines. The performance of the classification was evaluated based on 40 different measurement sites in German public LV grids. This method can support network operators in the identification of consumer configurations and the early detection of fundamental changes in harmonic emission behaviour. This enables, for example, assistance in resolving customer complaints or supporting network planning by managing PQ levels using typical harmonic emission profiles.
Investigation of Magnetic Anisotropy and Barkhausen Noise Asymmetry Resulting from Uniaxial Plastic Deformation of Steel S235
Authors: Pitoňák Martin , Neslušan Miroslav , Minárik Peter , Čapek Jiří , Zgútová Katarína , Jurkovič Martin , Kalina Tomáš
Published: April 2021

This study investigates alterations in magnetic anisotropy and the marked asymmetry in Barkhausen noise (MBN) signals after the uniaxial plastic straining of steel S235 obtained from a shipyard and used as standard structural steel in shipbuilding. It was found that the initial easy axis of magnetisation in the direction of previous rolling, and also in the direction of loading, becomes the hard axis of magnetisation as soon as the plastic strain attains the critical threshold. This behaviour is due to the preferential matrix orientation and the corresponding realignment of the magneto-crystalline anisotropy. Apart from the angular dependence of MBN, the asymmetry in the consecutive MBN bursts at the lower plastic strains is also analysed and explained as a result of magnetic coupling between the grains plastically strained and those unaffected by the tensile test. It was found that, by increasing the degree of plastic strain, the marked asymmetry in MBN tends to vanish. Moreover, the asymmetry in MBN bursts occurs in the direction of uniaxial tension and disappears in the perpendicular direction. Besides the MBN technique, XRD and EBSD techniques were also employed in order to provide a deeper insight into the investigated aspects.
A Deep Neural Network Model for Speaker Identification
Authors: Ye Feng , Yang Jun
Published: April 2021

Speaker identification is a classification task which aims to identify a subject from a given time-series sequential data. Since the speech signal is a continuous one-dimensional time series, most of the current research methods are based on convolutional neural network (CNN) or recurrent neural network (RNN). Indeed, these methods perform well in many tasks, but there is no attempt to combine these two network models to study the speaker identification task. Due to the spectrogram that a speech signal contains, the spatial features of voiceprint (which corresponds to the voice spectrum) and CNN are effective for spatial feature extraction (which corresponds to modeling spectral correlations in acoustic features). At the same time, the speech signal is in a time series, and deep RNN can better represent long utterances than shallow networks. Considering the advantage of gated recurrent unit (GRU) (compared with traditional RNN) in the segmentation of sequence data, we decide to use stacked GRU layers in our model for frame-level feature extraction. In this paper, we propose a deep neural network (DNN) model based on a two-dimensional convolutional neural network (2-D CNN) and gated recurrent unit (GRU) for speaker identification. In the network model design, the convolutional layer is used for voiceprint feature extraction and reduces dimensionality in both the time and frequency domains, allowing for faster GRU layer computation. In addition, the stacked GRU recurrent network layers can learn a speaker’s acoustic features. During this research, we tried to use various neural network structures, including 2-D CNN, deep RNN, and deep LSTM. The above network models were evaluated on the Aishell-1 speech dataset. The experimental results showed that our proposed DNN model, which we call deep GRU, achieved a high recognition accuracy of 98.96%. At the same time, the results also demonstrate the effectiveness of the proposed deep GRU network model versus other models for speaker identification. Through further optimization, this method could be applied to other research similar to the study of speaker identification.
How Do You Speak about Immigrants? Taxonomy and StereoImmigrants Dataset for Identifying Stereotypes about Immigrants
Authors: Sánchez-Junquera Javier , Chulvi Berta , Rosso Paolo , Ponzetto Simone Paolo
Published: April 2021

Stereotype is a type of social bias massively present in texts that computational models use. There are stereotypes that present special difficulties because they do not rely on personal attributes. This is the case of stereotypes about immigrants, a social category that is a preferred target of hate speech and discrimination. We propose a new approach to detect stereotypes about immigrants in texts focusing not on the personal attributes assigned to the minority but in the frames, that is, the narrative scenarios, in which the group is placed in public speeches. We have proposed a fine-grained social psychology grounded taxonomy with six categories to capture the different dimensions of the stereotype (positive vs. negative) and annotated a novel StereoImmigrants dataset with sentences that Spanish politicians have stated in the Congress of Deputies. We aggregate these categories in two supracategories: one is Victims that expresses the positive stereotypes about immigrants and the other is Threat that expresses the negative stereotype. We carried out two preliminary experiments: first, to evaluate the automatic detection of stereotypes; and second, to distinguish between the two supracategories of immigrants’ stereotypes. In these experiments, we employed state-of-the-art transformer models (monolingual and multilingual) and four classical machine learning classifiers. We achieve above 0.83 of accuracy with the BETO model in both experiments, showing that transformers can capture stereotypes about immigrants with a high level of accuracy.
Exploring the Thermal Microcosms at the Forest Floor—A Case Study of a Temperate Forest
Authors: Boehnke Denise
Published: April 2021

With the expected changes in summer weather due to global warming, knowledge of the microclimatic variability at the forest floor dramatically increased in importance for silviculture, wildfire management and biodiversity issues. Thus, during the warm season in 2014, thermal aspects within a heterogeneous forest were recorded at nine sites and compared to data from a nearby weather station. It was found that soil (−5 cm) and near-surface (0–2 cm) temperatures under shaded conditions stayed remarkably cooler than temporarily or fully radiated spots inside and outside the forest; largest differences occurred in maxima (July: 22.5 °C to 53.5 °C). Solar radiation was found to be the main driver for the strong heating of near-surface microhabitats, which could be reinforced by the vegetation type (moss). The weather station widely reflected the average condition on forest floor, but lacks the biological meaningful temperature extremes. The measurement system (internal versus external sensor) resulted in differences of up to 6 K. The findings underline the importance of old or dense stands for maintaining cool microrefugia. However, also the need for careful selection and analysis of microclimatic measurements in forests, representative for specific microhabitats, under consideration of ground vegetation modifications.
Changes in Air Quality Associated with Mobility Trends and Meteorological Conditions during COVID-19 Lockdown in Northern England, UK
Authors: Munir Said , Coskuner Gulnur , Jassim Majeed S. , Aina Yusuf A. , Ali Asad , Mayfield Martin
Published: April 2021

The COVID-19 pandemic triggered catastrophic impacts on human life, but at the same time demonstrated positive impacts on air quality. In this study, the impact of COVID-19 lockdown interventions on five major air pollutants during the pre-lockdown, lockdown, and post-lockdown periods is analysed in three urban areas in Northern England: Leeds, Sheffield, and Manchester. A Generalised Additive Model (GAM) was implemented to eliminate the effects of meteorological factors from air quality to understand the variations in air pollutant levels exclusively caused by reductions in emissions. Comparison of lockdown with pre-lockdown period exhibited noticeable reductions in concentrations of NO (56.68–74.16%), NO2 (18.06–47.15%), and NOx (35.81–56.52%) for measured data. However, PM10 and PM2.5 levels demonstrated positive gain during lockdown ranging from 21.96–62.00% and 36.24–80.31%, respectively. Comparison of lockdown period with the equivalent period in 2019 also showed reductions in air pollutant concentrations, ranging 43.31–69.75% for NO, 41.52–62.99% for NOx, 37.13–55.54% for NO2, 2.36–19.02% for PM10, and 29.93–40.26% for PM2.5. Back trajectory analysis was performed to show the air mass origin during the pre-lockdown and lockdown periods. Further, the analysis showed a positive association of mobility data with gaseous pollutants and a negative correlation with particulate matter.
Adult Users of the Oticon Medical Neuro Cochlear Implant System Benefit from Beamforming in the High Frequencies
Authors: Bastos Cordeiro Bianca , Banhara Marcos Roberto , Cardeal Mendes Carlos Maurício , Danieli Fabiana , Laplante-Lévesque Ariane , Karoui Chadlia , Hoen Michel , Ardoint Marine , Gauvrit Fanny , Demullier Romane , Vincent Christophe
Published: April 2021

The Oticon Medical Neuro cochlear implant system includes the modes Opti Omni and Speech Omni, the latter providing beamforming (i.e., directional selectivity) in the high frequencies. Two studies compared sentence identification scores of adult cochlear implant users with Opti Omni and Speech Omni. In Study 1, a double-blind longitudinal crossover study, 12 new users trialed Opti Omni or Speech Omni (random allocation) for three months, and their sentence identification in quiet and noise (+10 dB signal-to-noise ratio) with the trialed mode were measured. The same procedure was repeated for the second mode. In Study 2, a single-blind study, 11 experienced users performed a speech identification task in quiet and at relative signal-to-noise ratios ranging from −3 to +18 dB with Opti Omni and Speech Omni. The Study 1 scores in quiet and in noise were significantly better with Speech Omni than with Opti Omni. Study 2 scores were significantly better with Speech Omni than with Opti Omni at +6 and +9 dB signal-to-noise ratios. Beamforming in the high frequencies, as implemented in Speech Omni, leads to improved speech identification in medium levels of background noise, where cochlear implant users spend most of their day.
Identification of the Critical Factors for Global Supply Chain Management under the COVID-19 Outbreak via a Fusion Intelligent Decision Support System
Authors: Hu Kuang-Hua , Chen Fu-Hsiang , Hsu Ming-Fu , Yao Shuyi , Hung Ming-Chin
Published: April 2021

Under the ravages of COVID-19, global supply chains have encountered unprecedented disruptions. Past experiences cannot fully explain the situations nor provide any suitable responses to these fatal shocks on supply chain management (SCM), especially in todays’ highly intertwined/globalized business environment. This research thus revisits and rechecks the crucial components for global SCM during such special periods, and the basic essence of such management covers numerous perspectives that can be categorized into a multiple criteria decision making (MCDM) approach. To handle this complex issue appropriately, one can introduce a fusion intelligent system that involves data envelopment analysis (DEA), rough set theory (RST), and MCDM to understand the reality of the analyzed problem in a faster and better manner. Based on the empirical results, we rank the priorities in order as cash management and information (D), raw material supply (B), global management strategy (C), and productivity and logistics (A) for improvement in SCM. This finding is confirmed by companies now undergoing a downsizing strategy in order to survive in this harsh business environment.
Radu–Miheţ Method for the Existence, Uniqueness, and Approximation of the ψ-Hilfer Fractional Equations by Matrix-Valued Fuzzy Controllers
Authors: Eidinejad Zahra , Saadati Reza , de la Sen Manuel
Published: April 2021

We apply the Radu–Miheţ method derived from an alternative fixed-point theorem with a class of matrix-valued fuzzy controllers to approximate a fractional Volterra integro-differential equation with the ψ-Hilfer fractional derivative in matrix-valued fuzzy k-normed spaces to obtain an approximation for this type of fractional equation.
Fractional Coupled Hybrid Sturm–Liouville Differential Equation with Multi-Point Boundary Coupled Hybrid Condition
Authors: Paknazar Mohadeseh , De La Sen Manuel
Published: April 2021

The Sturm–Liouville differential equation is an important tool for physics, applied mathematics, and other fields of engineering and science and has wide applications in quantum mechanics, classical mechanics, and wave phenomena. In this paper, we investigate the coupled hybrid version of the Sturm–Liouville differential equation. Indeed, we study the existence of solutions for the coupled hybrid Sturm–Liouville differential equation with multi-point boundary coupled hybrid condition. Furthermore, we study the existence of solutions for the coupled hybrid Sturm–Liouville differential equation with an integral boundary coupled hybrid condition. We give an application and some examples to illustrate our results.
A Preliminary Study on the Effect of Psyllium Husk Ethanolic Extract on Hyperlipidemia, Hyperglycemia, and Oxidative Stress Induced by Triton X-100 Injection in Rats
Authors: Hashem Mohamed A. , Abd-Allah Noura A. , Mahmoud Essam A. , Amer Shimaa A. , Alkafafy Mohamed
Published: April 2021

The aim of this study is to assess the efficiency of psyllium husk ethanolic extract (PHEE) on Triton X-100 induced hyperlipidemic rats by studying the changes in hepatic and pancreatic function and histopathology. Forty male albino rats (bodyweight 175–188 g) were grouped randomly into four sets with ten rats. The experimental groups included: (1) control group (CON); (2) Triton X-100 induced hyperlipidemic group—rats were intraperitoneally injected with a single dose of Triton X-100 (100 mg/kg body weight) on the 21st day of Trial onset; (3) PHEE group—PHEE was orally administered (100 mg/kg body weight dissolved in 1 mL of distilled water) by gastric tube from the first day of the experiment until the fortieth day, once daily, (PHEE); (4) PHEE +Triton group, which received PHEE orally with the induction of hyperlipidemia. Treating hyperlipidemic rats with PHEE showed a decrease in the total serum lipids, triglyceride (TG), total cholesterol (TC), atherogenic index (AI), and malondialdehyde (MDA) with an increase in superoxide dismutase (SOD) and catalase (CAT) activities. PHEE administration alleviated the negative impact of Triton on the serum levels of glucose, insulin, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA IR index), leptin hormone, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-Glutamyl Transferase (GGT) and proteinogram. The Triton-induced hyperlipidemic rats showed extensive histopathological changes in the liver and pancreas, which were alleviated with PHEE administration. It could be concluded that PHEE has potent effects against hyperlipidemia, hyperglycemia, and oxidative stress due to its biologically active constituents detected by GC-MS analysis. This study’s findings may help develop a novel trial against the effects of hyperlipidemia in the future.
Biochemical Characterization of the Amylase Activity from the New Haloarchaeal Strain Haloarcula sp. HS Isolated in the Odiel Marshlands
Authors: Gómez-Villegas Patricia , Vigara Javier , Romero Luis , Gotor Cecilia , Raposo Sara , Gonçalves Brígida , Léon Rosa
Published: April 2021

Alpha-amylases are a large family of α,1-4-endo-glycosyl hydrolases distributed in all kingdoms of life. The need for poly-extremotolerant amylases encouraged their search in extreme environments, where archaea become ideal candidates to provide new enzymes that are able to work in the harsh conditions demanded in many industrial applications. In this study, a collection of haloarchaea isolated from Odiel saltern ponds in the southwest of Spain was screened for their amylase activity. The strain that exhibited the highest activity was selected and identified as Haloarcula sp. HS. We demonstrated the existence in both, cellular and extracellular extracts of the new strain, of functional α-amylase activities, which showed to be moderately thermotolerant (optimum around 60 °C), extremely halotolerant (optimum over 25% NaCl), and calcium-dependent. The tryptic digestion followed by HPLC-MS/MS analysis of the partially purified cellular and extracellular extracts allowed to identify the sequence of three alpha-amylases, which despite sharing a low sequence identity, exhibited high three-dimensional structure homology, conserving the typical domains and most of the key consensus residues of α-amylases. Moreover, we proved the potential of the extracellular α-amylase from Haloarcula sp. HS to treat bakery wastes under high salinity conditions.
GPCR-Based Bioactive Peptide Screening Using Phage-Displayed Peptides and an Insect Cell System for Insecticide Discovery
Authors: Choi Man-Yeon , Vander Meer Robert K.
Published: April 2021

The discovery of new insecticides improves integrated pest management (IPM), but is usually a long high-risk process with a low probability of success. For over two decades, insect neuropeptides (NPs) and their G-protein coupled receptors (GPCRs) have been considered as biological targets for insect pest control, because they are involved in almost all physiological processes associated with insect life stages. A key roadblock to success has been the question of how large volume chemical libraries can be efficiently screened for active compounds. New genomic and proteomic tools have advanced and facilitated the development of new approaches to insecticide discovery. In this study, we report a novel GPCR-based screening technology that uses millions of short peptides randomly generated by bacteriophages, and a method using an insect Sf9 cell expression system. The fire ant is a good model system, since bioactive peptides have been identified for a specific GPCR. The novel small peptides could interfere with the target GPCR-ligand functions. Therefore, we refer to this new mechanism as “receptor interference” (RECEPTORi). The GPCR-based bioactive peptide screening method offers multiple advantages. Libraries of phage-displayed peptides (~109 peptides) are inexpensive. An insect cell-based screening system rapidly leads to target specific GPCR agonists or antagonists in weeks. Delivery of bioactive peptides to target pests can be flexible, such as topical, ingestion, and plant-incorporated protectants. A variety of GPCR targets are available, thus minimizing the development of potential insecticide resistance. This report provides the first proof-of-concept for the development of novel arthropod pest management strategies using neuropeptides, and GPCRs.
Multi-Enzymatic Cascades in the Synthesis of Modified Nucleosides: Comparison of the Thermophilic and Mesophilic Pathways
Authors: Fateev Ilja V. , Kostromina Maria A. , Abramchik Yuliya A. , Eletskaya Barbara Z. , Mikheeva Olga O. , Lukoshin Dmitry D. , Zayats Evgeniy A. , Berzina Maria Ya. , Dorofeeva Elena V. , Paramonov Alexander S. , Kayushin Alexey L. , Konstantinova Irina D. , Esipov Roman S.
Published: April 2021

A comparative study of the possibilities of using ribokinase → phosphopentomutase → nucleoside phosphorylase cascades in the synthesis of modified nucleosides was carried out. Recombinant phosphopentomutase from Thermus thermophilus HB27 was obtained for the first time: a strain producing a soluble form of the enzyme was created, and a method for its isolation and chromatographic purification was developed. It was shown that cascade syntheses of modified nucleosides can be carried out both by the mesophilic and thermophilic routes from D-pentoses: ribose, 2-deoxyribose, arabinose, xylose, and 2-deoxy-2-fluoroarabinose. The efficiency of 2-chloradenine nucleoside synthesis decreases in the following order: Rib (92), dRib (74), Ara (66), F-Ara (8), and Xyl (2%) in 30 min for mesophilic enzymes. For thermophilic enzymes: Rib (76), dRib (62), Ara (32), F-Ara (<1), and Xyl (2%) in 30 min. Upon incubation of the reaction mixtures for a day, the amounts of 2-chloroadenine riboside (thermophilic cascade), 2-deoxyribosides (both cascades), and arabinoside (mesophilic cascade) decreased roughly by half. The conversion of the base to 2-fluoroarabinosides and xylosides continued to increase in both cases and reached 20-40%. Four nucleosides were quantitatively produced by a cascade of enzymes from D-ribose and D-arabinose. The ribosides of 8-azaguanine (thermophilic cascade) and allopurinol (mesophilic cascade) were synthesized. For the first time, D-arabinosides of 2-chloro-6-methoxypurine and 2-fluoro-6-methoxypurine were synthesized using the mesophilic cascade. Despite the relatively small difference in temperatures when performing the cascade reactions (50 and 80 °C), the rate of product formation in the reactions with Escherichia coli enzymes was significantly higher. E. coli enzymes also provided a higher content of the target products in the reaction mixture. Therefore, they are more appropriate for use in the polyenzymatic synthesis of modified nucleosides.
Impaired Audiovisual Representation of Phonemes in Children with Developmental Language Disorder
Authors: Kaganovich Natalya , Schumaker Jennifer , Christ Sharon
Published: April 2021

We examined whether children with developmental language disorder (DLD) differed from their peers with typical development (TD) in the degree to which they encode information about a talker’s mouth shape into long-term phonemic representations. Children watched a talker’s face and listened to rare changes from [i] to [u] or the reverse. In the neutral condition, the talker’s face had a closed mouth throughout. In the audiovisual violation condition, the mouth shape always matched the frequent vowel, even when the rare vowel was played. We hypothesized that in the neutral condition no long-term audiovisual memory traces for speech sounds would be activated. Therefore, the neural response elicited by deviants would reflect only a violation of the observed audiovisual sequence. In contrast, we expected that in the audiovisual violation condition, a long-term memory trace for the speech sound/lip configuration typical for the frequent vowel would be activated. In this condition then, the neural response elicited by rare sound changes would reflect a violation of not only observed audiovisual patterns but also of a long-term memory representation for how a given vowel looks when articulated. Children pressed a response button whenever they saw a talker’s face assume a silly expression. We found that in children with TD, rare auditory changes produced a significant mismatch negativity (MMN) event-related potential (ERP) component over the posterior scalp in the audiovisual violation condition but not in the neutral condition. In children with DLD, no MMN was present in either condition. Rare vowel changes elicited a significant P3 in both groups and conditions, indicating that all children noticed auditory changes. Our results suggest that children with TD, but not children with DLD, incorporate visual information into long-term phonemic representations and detect violations in audiovisual phonemic congruency even when they perform a task that is unrelated to phonemic processing.
Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses
Authors: Schaefer Michael , Hellmann-Regen Julian , Enge Sören
Published: April 2021

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.
New Housing Developments in the City Center of Guadalajara (Mexico): An Analysis from the Perspective of Collective and Sustainable Dwelling
Authors: Cireddu Alessandra
Published: April 2021

New vertical housing developments in Guadalajara (Mexico) are reaching the city center as a response for redensification after many years of expansion of the urban area characterized by a suburban, low density and fragmented pattern. This horizontal growth, dominated by use of the automobile as prevailing mode of transport, has proven to be unsustainable not only from an environmental point of view, but also from a social perspective where the “human scale” of the city has been affected, same as the daily life of its inhabitants. On the other hand, vertical housing proposals are by their very nature associated with concepts of redensification, compact city and collective living; the aim of this article is to analyze some new housing developments in Guadalajara downtown in order to evaluate to what extent the new buildings embody a more sustainable, livable and collective dwelling, to discuss findings, successes and failures and thus be able to contribute some conclusions and open a broader reflection about contemporary housing, urban density and downtown redevelopment in Latin America cities through collective and sustainable dwelling.
Innovation in Sustainable Solar-Powered Net-Zero Energy Solar Decathlon Houses: A Review and Showcase
Authors: Baghi Yeganeh , Ma Zhenjun , Robinson Duane , Boehme Tillmann
Published: April 2021

Solar Decathlon is a showcase of cutting-edge residential buildings containing innovative solutions and technologies. This study reviewed, identified, and categorized technological innovations from past Solar Decathlon competitions. The review was based on publicly available data of the top five houses from each U.S. and international Solar Decathlon competition. The most prolific innovations identified were from building services systems and architectural design and construction. It was observed that most innovations within building services systems were in heating, ventilation, and air-conditioning, and home automation, while architectural design and construction innovations focused on building adaptability, façade, structure, and building materials. It was found that although there is no fixed relationship between the numbers of innovations in the houses and their overall competition points, there is a high probability for an innovative house to be placed within the top five houses. This study also provides information about technological innovations within Solar Decathlon houses and offers an innovation classification scheme to guide Solar Decathletes to understand what innovations could be implemented in their future entries.
Home-Based Aerobic and Resistance Exercise Interventions in Cancer Patients and Survivors: A Systematic Review
Authors: Batalik Ladislav , Winnige Petr , Dosbaba Filip , Vlazna Daniela , Janikova Andrea
Published: April 2021

Cancer is a chronic disease requiring long-term treatment. Exercise interventions are increasingly being recognized as an important part of treatment and supportive cancer care for patients and survivors. Previous reviews have evaluated the benefits of exercise interventions in populations of patients under supervision at a center, but none have explored the possibilities of a home-based (HB) approach in exercise during cancer rehabilitation and the period immediately following the end of cancer treatment. The aim of this descriptive systematic review was to identify the literature focusing on the health effects of HB exercise interventions in cancer survivors and to evaluate the methodological quality of the examined studies. Relevant studies were identified by a systematic search of PubMed and the Web of Science until January 2021. Nine randomized controlled trials were included. Most studies were on aerobic and resistance exercises, and the frequency, duration, intensity, and modality varied across the different interventions. Improvements in cardiorespiratory fitness (CRF), physical activity (PA) levels, fatigue, health-related quality of life (HRQOL), and body composition have been reported. However, all the studies were limited in methodology and the reporting of results. Nevertheless, the evidence in this new area, despite the methodological limitations of the studies, suggests that HB exercise interventions are feasible, and may provide physiological and psychological benefits for cancer survivors during the rehabilitation period. A methodologically rigorous design for future research is essential for making progress in this field of study.
Targeting Post-Translational Modifications of the p73 Protein: A Promising Therapeutic Strategy for Tumors
Authors: Omran Ziad , H. Dalhat Mahmood , Abdullah Omeima , Kaleem Mohammed , Hosawi Salman , A Al-Abbasi Fahd , Wu Wei , Choudhry Hani , Alhosin Mahmoud
Published: April 2021

The tumor suppressor p73 is a member of the p53 family and is expressed as different isoforms with opposing properties. The TAp73 isoforms act as tumor suppressors and have pro-apoptotic effects, whereas the ΔNp73 isoforms lack the N-terminus transactivation domain and behave as oncogenes. The TAp73 protein has a high degree of similarity with both p53 function and structure, and it induces the regulation of various genes involved in the cell cycle and apoptosis. Unlike those of the p53 gene, the mutations in the p73 gene are very rare in tumors. Cancer cells have developed several mechanisms to inhibit the activity and/or expression of p73, from the hypermethylation of its promoter to the modulation of the ratio between its pro- and anti-apoptotic isoforms. The p73 protein is also decorated by a panel of post-translational modifications, including phosphorylation, acetylation, ubiquitin proteasomal pathway modifications, and small ubiquitin-related modifier (SUMO)ylation, that regulate its transcriptional activity, subcellular localization, and stability. These modifications orchestrate the multiple anti-proliferative and pro-apoptotic functions of TAp73, thereby offering multiple promising candidates for targeted anti-cancer therapies. In this review, we summarize the current knowledge of the different pathways implicated in the regulation of TAp73 at the post-translational level. This review also highlights the growing importance of targeting the post-translational modifications of TAp73 as a promising antitumor strategy, regardless of p53 status.
Novel Nomograms-Based Prediction Models for Patients with Primary Undifferentiated Pleomorphic Sarcomas Resections
Authors: Lin Qiaowei , Huang Qiuyi , Wang Qifeng , Yan Wangjun , Sun Yangbai
Published: April 2021

Background: Undifferentiated pleomorphic sarcomas (UPS) were one of the most common soft tissue sarcomas. As UPS had relatively high potentials of recurrence and metastasis, we designed two nomograms to better predict the overall survival (OS) and time to recurrence (TTR) for patients who underwent primary surgery. Methods: The data of UPS patients who underwent primary surgery were extracted from Shanghai Cancer Center, Fudan University. Multivariate analyses were performed using Cox proportional hazards regression to identify independent prognostic factors. Kaplan–Meier analysis was used to compare differences for patients who underwent primary surgery in OS and TTR. Nomograms were designed with the help of R software and validated using calibration curves and receiver operating characteristic curves (ROC). Results: Kaplan–Meier curves showed that patients with older ages (p = 0.0024), deeper locations (p = 0.0422), necrosis (p < 0.0001), G3 French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification (p < 0.0001), higher Ki-67 (p < 0.0001), higher mitotic index (p < 0.0001), R1/R2 resections (p = 0.0002) and higher invasive depth (p = 0.0099) had shorter OS than the other patients while patients with older ages (p = 0.0108), necrosis (p = 0.0001), G3 FNCLCC classification (p < 0.0001), higher Ki-67 (p = 0.0006), higher mitotic index (p < 0.0001) and R1/R2 resections (p < 0.0001) had shorter TTR compared with those without. Multivariate analyses demonstrated that mitotic rates and surgical margin were independent factors for TTR while age and invasive depth were independent factors for OS. Three parameters were adopted to build the nomograms for 3- and 5-year OS and TTR. The Area Under Curve (AUC) of this nomogram at 3- and 5-year TTR reached 0.802, 0.814, respectively, while OS reached 0.718, 0.802, respectively. Calibration curves for the prediction of 3- and 5-year OS and TTR showed excellent agreement between the predicted and the actual survival outcomes. Conclusions: Some important parameters could be used to predict the outcome of individual UPS patients such as mitotic age, rates, surgical margin, and invasive depth. We developed two accurate and practicable nomograms that could predict 3- and 5-year OS and TTR for UPS patients, which could be involved in the modern medical decision-making process.
A Network Pharmacological Approach to Reveal the Pharmacological Targets and Its Associated Biological Mechanisms of Prunetin-5-O-Glucoside against Gastric Cancer
Authors: Vetrivel Preethi , Murugesan Rajeswari , Bhosale Pritam Bhagwan , Ha Sang Eun , Kim Hun Hwan , Heo Jeong Doo , Kim Gon Sup
Published: April 2021

Gastric cancer (GC) is an aggressive malignancy with increased mortality rate and low treatment options. Increasing evidence suggests that network pharmacology will be a novel method for identifying the systemic mechanism of therapeutic compounds in diseases like cancer. The current study aimed to use a network pharmacology approach to establish the predictive targets of prunetin-5-O-glucoside (PG) against gastric cancer and elucidate its biological mechanisms. Primarily, genes associated with the pathogenesis of GC was identified from the DiGeNET database and targets of PG was obtained from the Swiss target prediction database. In total, 65 correlative hits were identified as anti-gastric cancer targets of PG. Functional enrichment and pathway analysis revealed significant biological mechanisms of the targets. Interaction of protein network and cluster analysis using STRING resulted in three crucial interacting hub targets namely, HSP90AA1, CDK2, and MMP1. Additionally, the in vitro cytotoxic potential of PG was assessed on three gastric cancer cells (AGS, MKN-28, and SNU-484). Furthermore, the crucial targets were validated using molecular docking, followed by their expressions being evaluated by western blot and Human Protein Atlas. The findings indicate that the pharmacological action of PG against GC might be associated with the regulation of three core targets: HSP90AA1, CDK2, and MMP1. Thus, the network pharmacology undertaken in the current study established the core active targets of PG, which may be extensively applied with further validations for treatment in GC.
The Role of Rituximab in the Treatment of Primary Central Nervous System Lymphoma
Authors: Van Dijck Ruben , Doorduijn Jeanette K. , Bromberg Jacoline E.C.
Published: April 2021

Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin lymphoma limited to the central nervous system. It has a poor prognosis. Consensus has been reached on the treatment of newly diagnosed patients with high-dose methotrexate-based chemotherapy, but whether the addition of the monoclonal anti-CD20 antibody rituximab improves survival, as it does in systemic B-cell non-Hodgkin lymphoma, remains disputed. In this review, we reflect on the available evidence of the use of rituximab in PCNSL. Whether rituximab has any beneficial effect remains uncertain.
Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma
Authors: Peña-Asensio Julia , Calvo Henar , Torralba Miguel , Miquel Joaquín , Sanz-de-Villalobos Eduardo , Larrubia Juan-Ramón
Published: April 2021

Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8+ T cells is discussed in this review.
Using the R Package Spatstat to Assess Inhibitory Effects of Microregional Hypoxia on the Infiltration of Cancers of the Head and Neck Region by Cytotoxic T Lymphocytes
Authors: Kaufmann Justus , Biscio Christophe A. N. , Bankhead Peter , Zimmer Stefanie , Schmidberger Heinz , Rubak Ege , Mayer Arnulf
Published: April 2021

(1) Background: The immune system has physiological antitumor activity, which is partially mediated by cytotoxic T lymphocytes (CTL). Tumor hypoxia, which is highly prevalent in cancers of the head and neck region, has been hypothesized to inhibit the infiltration of tumors by CTL. In situ data validating this concept have so far been based solely upon the visual assessment of the distribution of CTL. Here, we have established a set of spatial statistical tools to address this problem mathematically and tested their performance. (2) Patients and Methods: We have analyzed regions of interest (ROI) of 22 specimens of cancers of the head and neck region after 4-plex immunofluorescence staining and whole-slide scanning. Single cell-based segmentation was carried out in QuPath. Specimens were analyzed with the endpoints clustering and interactions between CTL, normoxic, and hypoxic tumor areas, both visually and using spatial statistical tools implemented in the R package Spatstat. (3) Results: Visual assessment suggested clustering of CTL in all instances. The visual analysis also suggested an inhibitory effect between hypoxic tumor areas and CTL in a minority of the whole-slide scans (9 of 22, 41%). Conversely, the objective mathematical analysis in Spatstat demonstrated statistically significant inhibitory interactions between hypoxia and CTL accumulation in a substantially higher number of specimens (16 of 22, 73%). It showed a similar trend in all but one of the remaining samples. (4) Conclusion: Our findings provide non-obvious but statistically rigorous evidence of inhibition of CTL infiltration into hypoxic tumor subregions of cancers of the head and neck. Importantly, these shielded sites may be the origin of tumor recurrences. We provide the methodology for the transfer of our statistical approach to similar questions. We discuss why versions of the Kcross and pcf.cross functions may be the methods of choice among the repertoire of statistical tests in Spatstat for this type of analysis.
A Disintegrin and Metalloprotease 12 Promotes Tumor Progression by Inhibiting Apoptosis in Human Colorectal Cancer
Authors: Park Young-Lan , Park Sun-Young , Oh Hyung-Hoon , Chung Min-Woo , Hong Ji-Yun , Kim Ki-Hyun , Myung Dae-Seong , Cho Sung-Bum , Lee Wan-Sik , Kim Hyun-Soo , Joo Young-Eun
Published: April 2021

A disintegrin and metalloprotease 12 (ADAM12) has been implicated in cell growth, tumor formation, and metastasis. Therefore, we evaluated the role of ADAM12 in colorectal cancer (CRC) progression and prognosis, and elucidated whether targeted downregulation of ADAM12 could lead to therapeutic sensitization. The effect of ADAM12 on tumor cell behavior was assessed in CRC cell lines, CRC tissues, and a mouse xenograft model. ADAM12 overexpression enhanced proliferation, inhibited apoptosis, and acted as positive regulator of cell cycle progression in CRC cells. Phosphorylation of PTEN was decreased and that of Akt was increased by ADAM12 overexpression. These results were reversed upon ADAM12 knockdown. ADAM12 overexpression was significantly associated with the cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival in CRC patients. In a mouse xenograft model, tumor area, volume, and weight were significantly greater for the ADAM12-pcDNA6-myc-transfected group than for the empty-pcDNA6-myc-transfected group, and significantly lower for the ADAM12-pGFP-C-shLenti-transfected group than for the scrambled pGFP-C-shLenti-transfected group. In conclusion, ADAM12 overexpression is essential for the growth and progression of CRC. Furthermore, ADAM12 knockdown reveals potent anti-tumor activity in a mouse xenograft model. Thus, ADAM12 may serve as a promising biomarker and/or therapeutic target in CRC.
Assessment of Resistance Mechanisms and Clinical Implications in Patients with KRAS Mutated-Metastatic Breast Cancer and Resistance to CDK4/6 Inhibitors
Authors: Raimondi Lucrezia , Raimondi Filippo Maria , Pietranera Marta , Di Rocco Arianna , Di Benedetto Laura , Miele Evelina , Lazzeroni Rachele , Cimino Giuseppe , Spinelli Gian Paolo
Published: April 2021

Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life.