bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Twin and Reinforcement Learning-Based Resilient Production Control for Micro Smart Factory
Authors: Park Kyu Tae , Son Yoo Ho , Ko Sang Wook , Noh Sang Do
Published: March 2021

To achieve efficient personalized production at an affordable cost, a modular manufacturing system (MMS) can be utilized. MMS enables restructuring of its configuration to accommodate product changes and is thus an efficient solution to reduce the costs involved in personalized production. A micro smart factory (MSF) is an MMS with heterogeneous production processes to enable personalized production. Similar to MMS, MSF also enables the restructuring of production configuration; additionally, it comprises cyber-physical production systems (CPPSs) that help achieve resilience. However, MSFs need to overcome performance hurdles with respect to production control. Therefore, this paper proposes a digital twin (DT) and reinforcement learning (RL)-based production control method. This method replaces the existing dispatching rule in the type and instance phases of the MSF. In this method, the RL policy network is learned and evaluated by coordination between DT and RL. The DT provides virtual event logs that include states, actions, and rewards to support learning. These virtual event logs are returned based on vertical integration with the MSF. As a result, the proposed method provides a resilient solution to the CPPS architectural framework and achieves appropriate actions to the dynamic situation of MSF. Additionally, applying DT with RL helps decide what-next/where-next in the production cycle. Moreover, the proposed concept can be extended to various manufacturing domains because the priority rule concept is frequently applied.
Application of Spatial Time Domain Reflectometry for Investigating Moisture Content Dynamics in Unsaturated Loamy Sand for Gravitational Drainage
Authors: Yan Guanxi , Bore Thierry , Li Zi , Schlaeger Stefan , Scheuermann Alexander , Li Ling
Published: March 2021

The strength of unsaturated soil is defined by the soil water retention behavior and soil suction acting inside the soil matrix. In order to obtain the suction and moisture profile in the vadose zone, specific measuring techniques are needed. Time domain reflectometry (TDR) conventionally measures moisture at individual points only. Therefore, spatial time domain reflectometry (spatial TDR) was developed for characterizing the moisture content profile along the unsaturated soil strata. This paper introduces an experimental set-up used for measuring dynamic moisture profiles with high spatial and temporal resolution. The moisture measurement method is based on inverse modeling the telegraph equation with a capacitance model of soil/sensor environment using an optimization technique. With the addition of point-wise soil suction measurement using tensiometers, the soil water retention curve (SWRC) can be derived in the transient flow condition instead of the static or steady-state condition usually applied for conventional testing methodologies. The experiment was successfully set up and conducted with thorough validations to demonstrate the functionalities in terms of detecting dynamic moisture profiles, dynamic soil suction, and outflow seepage flux under transient flow condition. Furthermore, some TDR measurements are presented with a discussion referring to the inverse analysis of TDR traces for extracting the dielectric properties of soil. The detected static SWRC is finally compared to the static SWRC measured by the conventional method. The preliminary outcomes underpin the success of applying the spatial TDR technique and also demonstrate several advantages of this platform for investigating the unsaturated soil seepage issue under transient flow conditions.
Application Ranges of EPB Shield TBM in Weathered Granite Soil: A Laboratory Scale Study
Authors: Kim Tae-Hwan , Lee In-Mo , Chung Hee-Young , Park Jeong-Jun , Ryu Young-Moo
Published: March 2021

Soil conditioning is a key factor in increasing tunnel face stability and extraction efficiency of excavated soil when excavating tunnels using an earth pressure balance (EPB) shield tunnel boring machine (TBM). Weathered granite soil, which is abundant in the Korean Peninsula (also in Japan, Hong Kong, and Singapore), has different characteristics than sand and clay; it also has particle-crushing characteristics. Conditioning agents were mixed with weathered granite soils of different individual particle-size gradations, and three characteristics (workability, permeability, and compressibility) were evaluated to find an optimal conditioning method. The lower and upper bounds of the water content that are needed for a well-functioning EPB shield TBM were also proposed. Through a trial-and-error experimental analysis, it was confirmed that soil conditioning using foam only was possible when the water content was controlled within the allowable range, that is, between the upper and lower bounds; when water content exceeded the upper bound, soil conditioning with solidification agents was needed along with foam. By taking advantage of the particle-crushing characteristics of the weathered granite soil, it was feasible to adopt the EPB shield TBM even when the soil was extremely coarse and cohesionless by conditioning with polymer slurries along with foam. Finally, the application ranges of EPB shield TBM in weathered granite soil were proposed; the newly proposed ranges are wider and expanded to coarser zones compared with those proposed so far.
Network Analysis to Identify the Risk of Epidemic Spreading
Authors: Kim Kiseong , Yoo Sunyong , Lee Sangyeon , Lee Doheon , Lee Kwang-Hyung
Published: March 2021

Several epidemics, such as the Black Death and the Spanish flu, have threatened human life throughout history; however, it is unclear if humans will remain safe from the sudden and fast spread of epidemic diseases. Moreover, the transmission characteristics of epidemics remain undiscovered. In this study, we present the results of an epidemic simulation experiment revealing the relationship between epidemic parameters and pandemic risk. To analyze the time-dependent risk and impact of epidemics, we considered two parameters for infectious diseases: the recovery time from infection and the transmission rate of the disease. Based on the epidemic simulation, we identified two important aspects of human safety with regard to the threat of a pandemic. First, humans should be safe if the fatality rate is below 100%. Second, even when the fatality rate is 100%, humans would be safe if the average degree of human social networks is below a threshold value. Nevertheless, certain diseases can potentially infect all nodes in the human social networks, and these diseases cause a pandemic when the average degree is larger than the threshold value. These results indicated that certain infectious diseases lead to human extinction and can be prevented by minimizing human contact.
Thermal Characterizations of a Lithium Titanate Oxide-Based Lithium-Ion Battery Focused on Random and Periodic Charge-Discharge Pulses
Authors: Madani Seyed Saeed , Schaltz Erik , Kær Søren Knudsen
Published: March 2021

Thermal characterization of lithium-ion batteries is essential to improve an efficient thermal management system for lithium-ion batteries. Besides, it is needed for safe and optimum application. The investigated lithium-ion battery in the present research is a commercially available lithium titanate oxide-based lithium-ion battery, which can be used in different applications. Different experimental facilities were used to measure lithium-ion battery heat generation at different operating conditions and charge and discharge rates in this investigation. Isothermal battery calorimeter is the exclusive calorimeter globally, suitable for lithium-ion batteries’ accurate thermal measurements. Pulse charge and discharge in different increments of state of charge were applied to the lithium titanate oxide-based lithium-ion battery to designate the heat generation of the lithium-ion battery cell. Three different cases were studied. The precise effects of different state-of-charge levels and current-rates on lithium-ion battery total generated heat was investigated. The maximum heat generation during 13 A, 40 A, 50 A, 60 A and 100 A pulse discharges were 0.231 Wh, 0.77 Wh, 0.507 Wh, 0.590 Wh and 1.13 Wh correspondingly. It could be inferred that in the case of periodic charge and discharge pulses applied to the lithium titanate oxide-based lithium-ion battery, important parameters including state of charge, current rates, initial cycling, and temperature have a significant influence on total generated heat.
The Budapest Amyloid Predictor and Its Applications
Authors: Keresztes László , Szögi Evelin , Varga Bálint , Farkas Viktor , Perczel András , Grolmusz Vince
Published: March 2021

The amyloid state of proteins is widely studied with relevance to neurology, biochemistry, and biotechnology. In contrast with nearly amorphous aggregation, the amyloid state has a well-defined structure, consisting of parallel and antiparallel β-sheets in a periodically repeated formation. The understanding of the amyloid state is growing with the development of novel molecular imaging tools, like cryogenic electron microscopy. Sequence-based amyloid predictors were developed, mainly using artificial neural networks (ANNs) as the underlying computational technique. From a good neural-network-based predictor, it is a very difficult task to identify the attributes of the input amino acid sequence, which imply the decision of the network. Here, we present a linear Support Vector Machine (SVM)-based predictor for hexapeptides with correctness higher than 84%, i.e., it is at least as good as the best published ANN-based tools. Unlike artificial neural networks, the decisions of the linear SVMs are much easier to analyze and, from a good predictor, we can infer rich biochemical knowledge. In the Budapest Amyloid Predictor webserver the user needs to input a hexapeptide, and the server outputs a prediction for the input plus the 6 × 19 = 114 distance-1 neighbors of the input hexapeptide.
Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome
Authors: Morales Albert , Rojo Rello Silvia , Cristóbal Helena , Fiz-López Aida , Arribas Elisa , Marí Montserrat , Tutusaus Anna , de la Cal-Sabater Paloma , Nicolaes Gerry A.F. , Ortiz-Pérez José T. , Bernardo David , García de Frutos Pablo
Published: March 2021

Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.
Codisplay of Rhizopus oryzae and Candida rugosa Lipases for Biodiesel Production
Authors: Yang Xiaoxu , Zhang Yan , Pang Huimin , Yuan Sheng , Wang Xuxia , Hu Zhiming , Zhou Qinghua , He Yaojia , Yan Yunjun , Xu Li
Published: March 2021

In this study, we overcame the limitations of single-enzyme system catalysis by codisplaying Candida rugosa lipase 1 (CRL1) and Rhizopus oryzae lipase (ROL) on the cell surfaces of the whole-cell catalyst Pichia pastoris to produce biodiesel from tallow seed oil. We screened double antibiotic-resistant strains on tributyrin plates, performed second electroporation based on single-displayed ROL on GS115/KpRS recombinants and single-displayed CRL1 on GS115/ZCS recombinants and obtained an ROL/CRL1 codisplay on P. pastoris GS115 surfaces. The maximum activity of the codisplaying GS115/pRCS recombinant was 470.59 U/g dried cells, which was 3.9-fold and 1.3-fold higher than that of single-displayed ROL and CRL1, respectively. When self-immobilized lipases were used as whole-cell catalysts, the rate of methyl ester production from GS115/pRCS harboring ROL and CRL1 was 1.4-fold higher than that obtained with single-displayed ROL. Therefore, biodiesel catalysis by synergetic codisplayed enzymes is an alternative biodiesel production strategy.
Getting Ahead of the Arms Race: Hothousing the Coevolution of VirusTotal with a Packer
Authors: Menéndez Héctor D. , Clark David , T. Barr Earl
Published: March 2021

Malware detection is in a coevolutionary arms race where the attackers and defenders are constantly seeking advantage. This arms race is asymmetric: detection is harder and more expensive than evasion. White hats must be conservative to avoid false positives when searching for malicious behaviour. We seek to redress this imbalance. Most of the time, black hats need only make incremental changes to evade them. On occasion, white hats make a disruptive move and find a new technique that forces black hats to work harder. Examples include system calls, signatures and machine learning. We present a method, called Hothouse, that combines simulation and search to accelerate the white hat’s ability to counter the black hat’s incremental moves, thereby forcing black hats to perform disruptive moves more often. To realise Hothouse, we evolve EEE, an entropy-based polymorphic packer for Windows executables. Playing the role of a black hat, EEE uses evolutionary computation to disrupt the creation of malware signatures. We enter EEE into the detection arms race with VirusTotal, the most prominent cloud service for running anti-virus tools on software. During our 6 month study, we continually improved EEE in response to VirusTotal, eventually learning a packer that produces packed malware whose evasiveness goes from an initial 51.8% median to 19.6%. We report both how well VirusTotal learns to detect EEE-packed binaries and how well VirusTotal forgets in order to reduce false positives. VirusTotal’s tools learn and forget fast, actually in about 3 days. We also show where VirusTotal focuses its detection efforts, by analysing EEE’s variants.
Ubiquitous Vehicular Ad-Hoc Network Computing Using Deep Neural Network with IoT-Based Bat Agents for Traffic Management
Authors: Kannan Srihari , Dhiman Gaurav , Natarajan Yuvaraj , Sharma Ashutosh , Mohanty Sachi Nandan , Soni Mukesh , Easwaran Udayakumar , Ghorbani Hamidreza , Asheralieva Alia , Gheisari Mehdi
Published: March 2021

In this paper, Deep Neural Networks (DNN) with Bat Algorithms (BA) offer a dynamic form of traffic control in Vehicular Adhoc Networks (VANETs). The former is used to route vehicles across highly congested paths to enhance efficiency, with a lower average latency. The latter is combined with the Internet of Things (IoT) and it moves across the VANETs to analyze the traffic congestion status between the network nodes. The experimental analysis tests the effectiveness of DNN-IoT-BA in various machine or deep learning algorithms in VANETs. DNN-IoT-BA is validated through various network metrics, like packet delivery ratio, latency and packet error rate. The simulation results show that the proposed method provides lower energy consumption and latency than conventional methods to support real-time traffic conditions.
Design of Power-Efficient Training Accelerator for Convolution Neural Networks
Authors: Hong JiUn , Arslan Saad , Lee TaeGeon , Kim HyungWon
Published: March 2021

To realize deep learning techniques, a type of deep neural network (DNN) called a convolutional neural networks (CNN) is among the most widely used models aimed at image recognition applications. However, there is growing demand for light-weight and low-power neural network accelerators, not only for inference but also for training process. In this paper, we propose a training accelerator that provides low power and compact chip size targeted for mobile and edge computing applications. It accelerates to achieve the real-time processing of both inference and training using concurrent floating-point data paths. The proposed accelerator can be externally controlled and employs resource sharing and an integrated convolution-pooling block to achieve low area and low energy consumption. We implemented the proposed training accelerator in an FPGA (Field Programmable Gate Array) and evaluated its training performance using an MNIST CNN example in comparison with a PC with GPU (Graphics Processing Unit). While both methods achieved a similar training accuracy of 95.1%, the proposed accelerator, when implemented in a silicon chip, reduced the energy consumption by 480 times compared to the counterpart. Additionally, when implemented on an FPGA, an energy reduction of over 4.5 times was achieved compared to the existing FPGA training accelerator for the MNIST dataset. Therefore, the proposed accelerator is more suitable for deployment in mobile/edge nodes compared to the existing software and hardware accelerators.
Participatory Impetus for and Forms of Citizens’ Co-Owned Power Plants: Cases from Higashi-Ohmi, Japan
Authors: Huang Hui-Tzu , Glaser Rüdiger
Published: March 2021

Citizen-led local participation is considered the key to a successful energy transition, and citizens’ co-owned power plants are an alternative and representative form of local participation. The extent to which citizens’ co-owned power plants can embody “locality, democracy, participation, energy autonomy, poverty reduction, and energy justice” has led to many controversial discussions. In response to these meaningful questions, this study argues for the focus to return to the impetus and driving forces of local participation in energy. This study proposes six possibilities for the impetus of local energy participation and the types of participation they may create. In the case analysis of the Higashi-Ohmi Model, in addition to the compound disaster of the 11 March 2011 earthquake and the transformation of the Japanese power grid, the driving factors depend on the self-consciousness of local promoters who insist on independence from policy influence. By linking local networks to discuss “local needs,” the residents form an integrated plan of “agricultural self-sufficiency, care system, and energy autonomy.” They promote the overall economic cycle of the region with energy regional energy currency, which inspired other rural forms of citizen energy participation. In addition, the simultaneous development of small-scale local enterprises and the ability of the local government to adjust policies centered on the needs of residents are important conditions for implementing the Higashi-Ohmi model.
Polystyrene Waste in Panels for Thermal Retrofitting of Historical Buildings: Experimental Study
Authors: Orlik-Kożdoń Bożena
Published: March 2021

The following article presents comprehensive research results for the insulation material based on polystyrene wastes. The presented product has the form of plates to be applied for thermal insulation of external envelopes from the inside. The laboratory tests were focused on the determination of basic technical parameters for this type of materials, i.e., thermal conductivity coefficient, diffusion resistance coefficient, reaction to fire, material sorption, and strength characteristics. For the recycling material, the obtained thermal conductivity value was 0.055 [W/mK]. The diffusion resistance coefficient was 5 [–], and therefore, this component has been qualified to a group of solutions that allow for interstitial condensation in the envelope. For the developed product, in situ tests were carried out on the actual wall system in a historical building. Based on the research, temperature and humidity profiles were obtained in the selected planes of the envelope. The performance of this material in real conditions was observed in relation to the reference product, i.e., lightweight cellular concrete (commonly used as thermal insulation from the inside). For the conducted in situ research, statistical inference was applied, which included the verification of the hypothesis-recycling panels in wall systems follow a trend of changes similar to that of slabs made of lightweight cellular concrete (a group of materials that allows for interstitial condensation). The proposed method of using secondary raw materials in insulation products allows us to obtain a product with high technical parameters that do not differ in quality from new components.
The RES in the Countries of the Commonwealth of Independent States: Potential and Production from 2015 to 2019
Authors: Chowaniak Maciej , Gródek-Szostak Zofia , Kotulewicz-Wisińska Karolina , Luc Małgorzata , Suder Marcin , Szeląg-Sikora Anna
Published: March 2021

Amidst the changes and adjustments of the international energy situation, the leading trend is to shift from fossil fuels to low-carbon fuels, and ultimately, to enter the era of sustainable energy, based mainly on renewable energy. The ongoing changes in global security of energy supply and the high volatility of fossil energy prices also stimulate investment in alternative energy sources, making renewable energy sources (RES) one of the rapidly growing elements in the global energy system. This article fills the research gap by analyzing the potential of using renewable energy in the countries of the Commonwealth of Independent States (CIS) in the years 2015–2018. The authors address the energy potential in the years 2015–2019, and energy consumption in the years 2015–2018 as the potential of RES in the CIS countries was not researched after 2014. Please note that the study covers the CIS countries, along with Georgia and Ukraine, which are no longer formal members of the Community, but have been included for cognitive and comparative purposes. Upon comparing the increase in energy production in the CIS countries to the average increase for the European Union (EU) countries, the value of this increase is observably higher than the average for the EU countries only in Ukraine. However, the average for the entire CIS is much lower than the EU average, therefore in CIS countries, the changes in the volume of RES energy production are varied. In some countries, there is a significant increase in the production of this type of energy (e.g., Ukraine, Kyrgyzstan, Belarus, Kazakhstan, Georgia). However, there are also countries in which the changes are negligible, or which noted significant drops in RES energy production (Uzbekistan, Moldova, Russia, Armenia). The findings contribute to the RES market debate and the international relations theory by comparing political factors with territorial and economic factors.
Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus
Authors: Dipla Konstantina , Zafeiridis Andreas , Mintziori Gesthimani , Boutou Afroditi K. , Goulis Dimitrios G. , Hackney Anthony C.
Published: March 2021

Gestational Diabetes Mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Regular exercise is important for a healthy pregnancy and can lower the risk of developing GDM. For women with GDM, exercise is safe and can affect the pregnancy outcomes beneficially. A single exercise bout increases skeletal muscle glucose uptake, minimizing hyperglycemia. Regular exercise training promotes mitochondrial biogenesis, improves oxidative capacity, enhances insulin sensitivity and vascular function, and reduces systemic inflammation. Exercise may also aid in lowering the insulin dose in insulin-treated pregnant women. Despite these benefits, women with GDM are usually inactive or have poor participation in exercise training. Attractive individualized exercise programs that will increase adherence and result in optimal maternal and offspring benefits are needed. However, as women with GDM have a unique physiology, more attention is required during exercise prescription. This review (i) summarizes the cardiovascular and metabolic adaptations due to pregnancy and outlines the mechanisms through which exercise can improve glycemic control and overall health in insulin resistance states, (ii) presents the pathophysiological alterations induced by GDM that affect exercise responses, and (iii) highlights cardinal points of an exercise program for women with GDM.
Antimicrobial Activity and Chemical Characterization of a Non-Polar Extract of Saffron Stamens in Food Matrix
Authors: Zara Severino , Petretto Giacomo L. , Mannu Alberto , Zara Giacomo , Budroni Marilena , Mannazzu Ilaria , Multineddu Chiara , Pintore Giorgio , Fancello Francesco
Published: March 2021

The production of saffron spice generates large quantities of plant by-products: over 90% of the plant material collected is discarded, and a consideration fraction of this waste is plant stamens. This work investigated the chemical composition and the antimicrobial activities of the non-polar fraction extracted from four different saffron flower stamens. The chemical composition of ethereal extracts of the saffron stamens was qualitatively assessed by means of gas–chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses. These analyses revealed ethereal extracts to possess a high polyunsaturated fatty acid content. In vitro antibacterial activity of stamen extracts showed no large differences between Gram-positive and Gram-negative bacteria in terms of minimal inhibitory concentration (MIC). In food matrix microbial analysis of the bacterial strains belonging to the main foodborne pathogen species, including Staphylococcus aureus DSM 20231, Escherichia coli DSM 30083, and Listeria monocytogenes DSM 20600, using low-fat UHT milk, revealed a statistically significant reduction in the number of cells (particularly for E. coli and S. aureus with a complete elimination of the population of the two target bacteria following incubation in diethyl ether extracts of saffron stamen (DES) at high concentrations tested, both at 37 °C and 6 °C (for 48 h and 7 days, respectively). A synergic effect was observed when the pathogens were incubated at 6 °C with DES. This work shows these by-products to be excellent sources of bioactive compounds, which could be exploited in high-added-value products, such as food, cosmetics, and drugs.
Biowaste as a Potential Source of Bioactive Compounds—A Case Study of Raspberry Fruit Pomace
Authors: Krivokapić Slađana , Vlaović Milorad , Damjanović Vratnica Biljana , Perović Andrej , Perović Svetlana
Published: March 2021

Raspberry fruit pomace, a byproduct of juice production, was studied as a potential source of antioxidant compounds. Target high-performance liquid chromatography analysis of important polyphenolic compounds (gallic, p-coumaric, caffeic, quercitrin, chlorogenic, and ellagic acid) was performed together with analysis of total phenolic content (TPC), total flavonoid content (TFC), total anthocyanins content (TAC), and antioxidant capacity (via ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays). The differences in polyphenolic content of Rubus idaeus L. pomace were evaluated following ultrasound-assisted extraction and conventional maceration with different organic solvents. Additionally, the yield of free phenolics was measured in hydrolyzed pomace extracts. The results obtained show that the ultrasound method maximizes the quantity of antioxidant compounds in terms of TPC (27.79 mg/L gallic acid equivalent (GAE)), TFC (8.02 mg/g quercetin equivalent (QE)), TAC (7.13 mg/L cyanidine-3-glucoside equivalent (C3G Eq)), caffeic (19.17 µg/g), chlorogenic (3.56 µg/g), ellagic (105.52 µg/g), and gallic acids (8.75 µg/g), as well as FRAP (1002.72 µmol/L) and DPPH assays (969.71 µmol/mL vitamin C equivalent (vit C Eq); 567.00 µmol/100 g Trolox equivalent (TE)). On the other hand, conventional maceration maximizes the yield of quercetin and p-coumaric acid. In terms of biowaste valorization, raspberry fruit pomace has a promising industrial potential and may prove to be useful in the development of antioxidant dietary supplements.
The Perspective of Croatian Old Apple Cultivars in Extensive Farming for the Production of Functional Foods
Authors: Duralija Boris , Putnik Predrag , Brdar Dora , Bebek Markovinović Anica , Zavadlav Sandra , Pateiro Mirian , Domínguez Rubén , Lorenzo José M. , Bursać Kovačević Danijela
Published: March 2021

The Republic of Croatia has a long tradition of fruit growing due to its geographical location, climatic conditions, and high quality of fruit crops, especially apple fruits. Apples can be used for the formulation of functional foods either in processed form (e.g., juice), or as a by-product (e.g., apple pomace). However, there is a growing demand for functional foods derived from ancient and traditional plant sources as they are recognized as a very valuable source of health-promoting bioactive ingredients. Similarly, old apple cultivars (Malus domestica Borkh.) are characterized by good morphological and pomological properties, less need for chemicals during cultivation and the higher share of biologically active compounds (BACs) with better sensory acceptability compared to commercial cultivars. However, their nutritional and biological potential is underestimated, as is their ability to be processed into functional food. The importance in preserving old apple cultivars can also be seen in their significance for improving the nutritional composition of other apple cultivars through innovative cultivation strategies, and therefore old local apple cultivars could be of great importance in future breeding programs.
S-PDR: SBAUPT-Based Pedestrian Dead Reckoning Algorithm for Free-Moving Handheld Devices
Authors: Khedr Maan , El-Sheimy Naser
Published: March 2021

Mobile location-based services (MLBS) are attracting attention for their potential public and personal use for a variety of applications such as location-based advertisement, smart shopping, smart cities, health applications, emergency response, and even gaming. Many of these applications rely on Inertial Navigation Systems (INS) due to the degraded GNSS services indoors. INS-based MLBS using smartphones is hindered by the quality of the MEMS sensors provided in smartphones which suffer from high noise and errors resulting in high drift in the navigation solution rapidly. Pedestrian dead reckoning (PDR) is an INS-based navigation technique that exploits human motion to reduce navigation solution errors, but the errors cannot be eliminated without aid from other techniques. The purpose of this study is to enhance and extend the short-term reliability of PDR systems for smartphones as a standalone system through an enhanced step detection algorithm, a periodic attitude correction technique, and a novel PCA-based motion direction estimation technique. Testing shows that the developed system (S-PDR) provides a reliable short-term navigation solution with a final positioning error that is up to 6 m after 3 min runtime. These results were compared to a PDR solution using an Xsens IMU which is known to be a high grade MEMS IMU and was found to be worse than S-PDR. The findings show that S-PDR can be used to aid GNSS in challenging environments and can be a viable option for short-term indoor navigation until aiding is provided by alternative means. Furthermore, the extended reliable solution of S-PDR can help reduce the operational complexity of aiding navigation systems such as RF-based indoor navigation and magnetic map matching as it reduces the frequency by which these aiding techniques are required and applied.
Technical Modifications for Ductal Stenting in Neonates with Duct-Dependent Pulmonary Circulation
Authors: Promphan Worakan , Qureshi Shakeel A.
Published: March 2021

The ductal stenting (DS) is currently an acceptable palliative treatment in newborns suffering with duct-dependent pulmonary circulation. However, this procedure remains technically a challenge in complex ductal morphology, which may eventually lead to detrimental outcomes. This review is mainly focused on pre-procedural planning, essential instruments and practical approaches for DS, and post-procedural care.
Ribosome-Profiling Reveals Restricted Post Transcriptional Expression of Antiviral Cytokines and Transcription Factors during SARS-CoV-2 Infection
Authors: Alexander Marina R. , Brice Aaron M. , Jansen van Vuren Petrus , Rootes Christina L. , Tribolet Leon , Cowled Christopher , Bean Andrew G. D. , Stewart Cameron R.
Published: March 2021

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here, we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.
Expression of AhATL1, an ABA Transport Factor Gene from Peanut, Is Affected by Altered Memory Gene Expression Patterns and Increased Tolerance to Drought Stress in Arabidopsis
Authors: Qin Ming , Li Xiaoyan , Tang Shaohua , Huang Yinglin , Li Ling , Hu Bo
Published: March 2021

Arachis hypogaea abscisic acid transporter like-1 (AhATL1) modulates abscisic acid (ABA) sensitivity by specifically influencing the importing of ABA into cells, and is a key player in plant stress responses. However, there is limited information on ABA transporters in crops. In this study, we found that the level of AhATL1 expression and AhATL1 distribution increased more rapidly in the second drought (D2) compared with in the first drought (D1). Compared with the first recovery (R1), the AhATL1 expression level and ABA content remained at a higher level during the second recovery (R2). The heterologous overexpression of AhATL1 in Arabidopsis changed the expression pattern of certain memory genes and changed the post response gene type into the memory gene type. Regarding the proline and water content of Col (Arabidopsis thaliana L. Heynh., Col-0), atabcg22, and AhATL1-OX during drought training, the second drought (D2) was more severe than the first drought (D1), which was more conducive to maintaining the cell osmotic balance and resisting drought. In summary, drought stress memory resulted in a rapid increase in the AhATL1 expression and AhATL1 distribution level, and then raised the endogenous ABA content and changed the post response gene type into the memory gene type, which enhanced the drought resistance and recovery ability.
Cruciform Formable Sequences within Pou5f1 Enhancer Are Indispensable for Mouse ES Cell Integrity
Authors: Yamamoto Yu , Miura Osamu , Ohyama Takashi
Published: March 2021

DNA can adopt various structures besides the B-form. Among them, cruciform structures are formed on inverted repeat (IR) sequences. While cruciform formable IRs (CFIRs) are sometimes found in regulatory regions of transcription, their function in transcription remains elusive, especially in eukaryotes. We found a cluster of CFIRs within the mouse Pou5f1 enhancer. Here, we demonstrate that this cluster or some member(s) plays an active role in the transcriptional regulation of not only Pou5f1, but also Sox2, Nanog, Klf4 and Esrrb. To clarify in vivo function of the cluster, we performed genome editing using mouse ES cells, in which each of the CFIRs was altered to the corresponding mirror repeat sequence. The alterations reduced the level of the Pou5f1 transcript in the genome-edited cell lines, and elevated those of Sox2, Nanog, Klf4 and Esrrb. Furthermore, transcription of non-coding RNAs (ncRNAs) within the enhancer was also upregulated in the genome-edited cell lines, in a similar manner to Sox2, Nanog, Klf4 and Esrrb. These ncRNAs are hypothesized to control the expression of these four pluripotency genes. The CFIRs present in the Pou5f1 enhancer seem to be important to maintain the integrity of ES cells.
Hyposialylation Must Be Considered to Develop Future Therapies in Autoimmune Diseases
Authors: Bordron Anne , Morel Marie , Bagacean Cristina , Dueymes Maryvonne , Pochard Pierre , Harduin-Lepers Anne , Jamin Christophe , Pers Jacques-Olivier
Published: March 2021

Autoimmune disease development depends on multiple factors, including genetic and environmental. Abnormalities such as sialylation levels and/or quality have been recently highlighted. The adjunction of sialic acid at the terminal end of glycoproteins and glycolipids is essential for distinguishing between self and non-self-antigens and the control of pro- or anti-inflammatory immune reactions. In autoimmunity, hyposialylation is responsible for chronic inflammation, the anarchic activation of the immune system and organ lesions. A detailed characterization of this mechanism is a key element for improving the understanding of these diseases and the development of innovative therapies. This review focuses on the impact of sialylation in autoimmunity in order to determine future treatments based on the regulation of hyposialylation.
Metalloproteinases in Ovarian Cancer
Authors: Carey Preston , Low Ethan , Harper Elizabeth , Stack M. Sharon
Published: March 2021

Proteases play a crucial role in the progression and metastasis of ovarian cancer. Pericellular protein degradation and fragmentation along with remodeling of the extracellular matrix (ECM) is accomplished by numerous proteases that are present in the ovarian tumor microenvironment. Several proteolytic processes have been linked to cancer progression, particularly those facilitated by the matrix metalloproteinase (MMP) family. These proteases have been linked to enhanced migratory ability, extracellular matrix breakdown, and development of support systems for tumors. Several studies have reported the direct involvement of MMPs with ovarian cancer, as well as their mechanisms of action in the tumor microenvironment. MMPs play a key role in upregulating transcription factors, as well as the breakdown of structural proteins like collagen. Proteolytic mechanisms have been shown to enhance the ability of ovarian cancer cells to migrate and adhere to secondary sites allowing for efficient metastasis. Furthermore, angiogenesis for tumor growth and development of metastatic implants is influenced by upregulation of certain proteases, including MMPs. While proteases are produced normally in vivo, they can be upregulated by cancer-associated mutations, tumor–microenvironment interaction, stress-induced catecholamine production, and age-related pathologies. This review outlines the important role of proteases throughout ovarian cancer progression and metastasis.
Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells
Authors: Luparello Claudio , Cruciata Ilenia , Joerger Andreas C. , Ocasio Cory A. , Jones Rhiannon , Tareque Raysa Khan , Bagley Mark C. , Spencer John , Walker Martin , Austin Carol , Ferrara Tiziana , D′Oca Pietro , Bellina Rossella , Branni Rossella , Caradonna Fabio
Published: March 2021

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily primed PCR to analyze their intrinsic DNA damage-inducing and DNA methylation-changing abilities. We demonstrate that small modifications in the substitution patterns of carbazoles can have profound effects on their intrinsic genotoxic and epigenetic properties, with PK9320 and PK9323 being eligible candidates as “anticancer compounds” and “anticancer epi-compounds” and PK083 a “damage-corrective” compound on human breast adenocarcinoma cells. Such different properties may be exploited for their use as anticancer agents and chemical probes.
5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
Authors: Opretzka Luiza Carolina França , Freitas Humberto Fonseca de , Espírito-Santo Renan Fernandes , Abreu Lucas Silva , Alves Iura Muniz , Tavares Josean Fechine , Velozo Eudes da Silva , Castilho Marcelo Santos , Villarreal Cristiane Flora
Published: March 2021

The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromone scaffold have shown a variety of biological activities, including analgesic effects. This work presents for the first time the centrally mediated antinociceptive activity of 5-O-methylcneorumchromone K (5-CK). Cold plate and tail flick tests in mice showed that the 5-CK-induced antinociception was dose-dependent, longer-lasting, and more efficacious than that induced by morphine. The 5-CK-induced antinociception was not reversed by the opioid antagonist naloxone. Topological descriptors (fingerprints) were employed to narrow the antagonist selection to further investigate 5-CK’s mechanism of action. Next, based on the results of fingerprints analysis, functional antagonist assays were conducted on nociceptive tests. The effect of 5-CK was completely reversed in both cold plate and tail-flick tests by GABAA receptor antagonist bicuculline, but not by atropine or glibenclamide. Molecular docking studies suggest that 5-CK binds to the orthosteric binding site, with a similar binding profile to that observed for bicuculline and GABA. These results evidence that 5-CK has a centrally mediated antinociceptive effect, probably involving the activation of GABAergic pathways.
Intra-Articular Administration of Cramp into Mouse Knee Joint Exacerbates Experimental Osteoarthritis Progression
Authors: Choi Moon-Chang , Jo Jiwon , Lee Myeongjin , Park Jonggwan , Park Yoonkyung
Published: March 2021

Osteoarthritis (OA) is the most common type of arthritis and is associated with wear and tear, aging, and inflammation. Previous studies revealed that several antimicrobial peptides are up-regulated in the knee synovium of patients with OA or rheumatoid arthritis. Here, we investigated the functional effects of cathelicidin-related antimicrobial peptide (Cramp) on OA pathogenesis. We found that Cramp is highly induced by IL-1β via the NF-κB signaling pathway in mouse primary chondrocytes. Elevated Cramp was also detected in the cartilage and synovium of mice suffering from OA cartilage destruction. The treatment of chondrocytes with Cramp stimulated the expression of catabolic factors, and the knockdown of Cramp by small interfering RNA reduced chondrocyte catabolism mediated by IL-1β. Moreover, intra-articular injection of Cramp into mouse knee joints at a low dose accelerated traumatic OA progression. At high doses, Cramp affected meniscal ossification and tears, leading to cartilage degeneration. These findings demonstrate that Cramp is associated with OA pathophysiology.
Generation of a Novel Nkx6-1 Venus Fusion Reporter Mouse Line
Authors: Burtscher Ingo , Tarquis-Medina Marta , Salinno Ciro , Schirge Silvia , Beckenbauer Julia , Bakhti Mostafa , Lickert Heiko
Published: March 2021

Nkx6-1 is a member of the Nkx family of homeodomain transcription factors (TFs) that regulates motor neuron development, neuron specification and pancreatic endocrine and β-cell differentiation. To facilitate the isolation and tracking of Nkx6-1-expressing cells, we have generated a novel Nkx6-1 Venus fusion (Nkx6-1-VF) reporter allele. The Nkx6-1-VF knock-in reporter is regulated by endogenous cis-regulatory elements of Nkx6-1 and the fluorescent protein fusion does not interfere with the TF function, as homozygous mice are viable and fertile. The nuclear localization of Nkx6-1-VF protein reflects the endogenous Nkx6-1 protein distribution. During embryonic pancreas development, the reporter protein marks the pancreatic ductal progenitors and the endocrine lineage, but is absent in the exocrine compartment. As expected, the levels of Nkx6-1-VF reporter are upregulated upon β-cell differentiation during the major wave of endocrinogenesis. In the adult islets of Langerhans, the reporter protein is exclusively found in insulin-secreting β-cells. Importantly, the Venus reporter activities allow successful tracking of β-cells in live-cell imaging and their specific isolation by flow sorting. In summary, the generation of the Nkx6-1-VF reporter line reflects the expression pattern and dynamics of the endogenous protein and thus provides a unique tool to study the spatio-temporal expression pattern of this TF during organ development and enables isolation and tracking of Nkx6-1-expressing cells such as pancreatic β-cells, but also neurons and motor neurons in health and disease.
Genotyping by Sequencing Reveals Genetic Relatedness of Southwestern U.S. Blue Maize Landraces
Authors: Nankar Amol N. , Pratt Richard C.
Published: March 2021

Maize has played a key role in the sustenance and cultural traditions of the inhabitants of the southwestern USA for many centuries. Blue maize is an important component of the diverse landraces still cultivated in the region but the degree to which they are related is unknown. This research was designed to ascertain the genotypic, morphological, and phenotypic diversity of six representative southwestern blue maize landraces. Their genotypic diversity was examined using tunable genotyping-by-sequencing (tGBS™). A total of 81,038 high quality SNPs were identified and obtained through tGBS. A total of 45 morphological and biochemical traits were evaluated at two locations in New Mexico. The varieties Los Lunas High and Flor del Rio were genetically less related with other southwestern landraces whereas diffusion between Navajo Blue, Hopi Blue, Yoeme Blue, and Taos Blue demonstrated that these landraces were genetically related. Phenotypic variability was highest for kernel traits and least for plant traits. Plant, ear, and kernel traits were fairly consistent within and across locations. Principal component analysis and tGBS showed that Corn Belt variety ‘Ohio Blue’ was distinctly different from southwestern landraces. Genotypic analysis displayed that southwestern landraces are genetically closely related, but selection has resulted in differing phenotypes. This study has provided additional insight into the genetic relatedness of southwestern blue maize landraces.