bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple Lossless Inductive Snubbers-Assisted Series Load Resonant Inverter Operating under ZCS-PDM Scheme for High-Frequency Induction Heating Fixed Roller
Authors: Ogura Koki , Chandhaket Srawouth , Kolhe Mohan Lal , Sakphrom Siraporn , Mekhilef Saad
Published: January 2022

This paper presents a high-frequency pulse-density-modulated (PDM) soft-switching series load resonant inverter for use in induction heating (IH) fixed roller applications, which is used in copy and printing machines. The proposed simple high-frequency resonant inverter uses an asymmetrical pulse pattern PDM control scheme to achieve complete zero-current soft-switching commutations over a wide output range of input power regulation. Additionally, when the printer toner requires operation in very light load conditions, this causes difficulty in achieving zero-voltage or zero-current soft-switching operations in the IH high-frequency resonant inverters with pulse frequency modulation or pulse width modulation control schemes. The proposed resonant inverter demonstrates the capability to accomplish highly efficient power conversions. In this work, a fixed roller for printing machines is developed for doing experiments to verify the efficiency of the proposed circuit topology and its PDM control schemes. The inverter’s steady-state and transient operating principles are analyzed based on the proposed control strategy at a high-frequency PDM. Operating conditions such as power loss analysis, power conversion efficiency and temperature rise characteristics of the proposed inverter are presented and analyzed through experimental results. Finally, from a practical viewpoint, a comparative study of a conventional halogen lamp heater and the proposed IH fixed roller is deliberated.
Complete Genome Sequence and Benzophenone-3 Mineralisation Potential of Rhodococcus sp. USK10, A Bacterium Isolated from Riverbank Sediment
Authors: Martin Joseph Donald , Krüger Urse Scheel , Zervas Athanasios , Schostag Morten Dencker , Nielsen Tue Kjærgaard , Aamand Jens , Hansen Lars Hestbjerg , Ellegaard-Jensen Lea
Published: January 2022

Benzophenone-3 (BP3) is an organic UV filter whose presence in the aquatic environment has been linked to detrimental developmental impacts in aquatic organisms such as coral and fish. The genus Rhodococcus has been extensively studied and is known for possessing large genomes housing genes for biodegradation of a wide range of compounds, including aromatic carbons. Here, we present the genome sequence of Rhodococcus sp. USK10, which was isolated from Chinese riverbank sediment and is capable of utilising BP3 as the sole carbon source, resulting in full BP3 mineralisation. The genome consisted of 9,870,030 bp in 3 replicons, a G+C content of 67.2%, and 9722 coding DNA sequences (CDSs). Annotation of the genome revealed that 179 of these CDSs are involved in the metabolism of aromatic carbons. The complete genome of Rhodococcus sp. USK10 is the first complete, annotated genome sequence of a Benzophenone-3-degrading bacterium. Through radiolabelling, it is also the first bacterium proven to mineralise Benzophenone-3. Due to the widespread environmental prevalence of Benzophenone-3, coupled with its adverse impact on aquatic organisms, this characterisation provides an integral first step in better understanding the environmentally relevant degradation pathway of the commonly used UV filter. Given USK10′s ability to completely mineralise Benzophenone-3, it could prove to be a suitable candidate for bioremediation application.
Evapotranspiration of Irrigated Crops under Warming and Elevated Atmospheric CO2: What Is the Direction of Change?
Authors: Scarpare Fabio V. , Rajagopalan Kirti , Liu Mingliang , Nelson Roger L. , Stöckle Claudio O.
Published: January 2022

Future changes in crop evapotranspiration (ETc) are of interest to water management stakeholders. However, long-term projections are complex and merit further investigation due to uncertainties in climate data, differential responses of crops to climate and elevated atmospheric CO2, and adaptive agricultural management. We conducted factor-control simulation experiments using the process-based CropSyst model and investigated the contribution of each of these factors. Five major irrigated crops in the Columbia Basin Project area of the USA Pacific Northwest were selected as a case study and fifteen general circulation models (GCM) under two representative concentration pathways (RCP) were used as the climate forcing. Results indicated a wide range in ETc change, depending on the time frame, crop type, planting dates, and CO2 assumptions. Under the 2090s RCP8.5 scenario, ETc changes were crop-specific: +14.3% (alfalfa), +8.1% (potato), −5.1% (dry bean), −8.1% (corn), and −12.5% (spring wheat). Future elevated CO2 concentrations decreased ETc for all crops while earlier planting increased ETc for all crops except spring wheat. Changes in reference ET (ETo) only partially explains changes in ETc because crop responses are an important modulating factor; therefore, caution must be exercised in interpreting ETo changes as a proxy for ETc changes.
Impacts of Sea–Land Breeze Circulation on the Formation and Development of Coastal Sea Fog along the Shandong Peninsula: A Case Study
Authors: Jin Guoqi , Gao Shanhong , Shi Hao , Lu Xue , Yang Yue , Zheng Qing
Published: January 2022

Among the China Seas, the Yellow Sea has the highest occurrence frequency of sea fog that can be categorized into widespread sea fog and coastal sea fog. In this paper, we study a typical coastal sea fog along the Shandong Peninsula that is accompanied by sea-land breezes. Based on a series of numerical experiments conducted by the Weather Research and Forecasting model with high spatial resolution, the impacts of the sea–land breezes on the formation and development of sea fog are investigated in detail. The land breeze can act as an accelerator that enhances humidification and cooling near the coast which promotes sea fog formation during the nighttime, resulting from nearshore vapor convergence and offshore cool-air transportation jointly by the descending branch and low-level breeze of the land breeze circulation. During the daytime, the sea breeze acts as a reducer that inhibits sea fog development, including the contraction of fog area caused by onshore advection of the sea breeze on cloud liquid water, and the restraint of fog vertical growth due to warming and drying by the descending branch of the sea breeze circulation.
Radiation Exposure in the Lower Atmosphere during Different Periods of Solar Activity
Authors: Tezari Anastasia , Paschalis Pavlos , Stassinakis Argyris , Mavromichalaki Helen , Karaiskos Pantelis , Gerontidou Maria , Alexandridis Dimitris , Kanellakopoulos Anastasios , Crosby Norma , Dierckxsens Mark
Published: January 2022

In recent years, there has been a huge increase in air travel, both for business and leisure. For this reason, entities such as the European Commission and the International Committee on Radiological Protection have provided several recommendations for the radiation protection of aviation crews and frequent flyers, as well as highlighted the need for accurate tools for radiation assessment in the atmosphere. With a focus on the most frequent commercial flying altitudes, this work has performed dosimetry calculations in the lower atmosphere of Earth for different values of cut-off rigidity, covering the recent solar cycles 23 and 24. Results are based on Monte Carlo simulations performed with the validated Geant4 software application Dynamic Atmospheric Shower Tracking Interactive Model Application (DYASTIMA) and its extension, DYASTIMA-R.
Characteristics of PM2.5 Pollution in Osorno, Chile: Ion Chromatography and Meteorological Data Analyses
Authors: Nakamura Ayane , Nakatani Nobutake , Maruyama Fumito , Fujiyoshi So , Márquez-Reyes Rodrigo , Fernández Ricardo , Noda Jun
Published: January 2022

Over the decades, air pollution has become a serious problem in Osorno, Chile. This study aims to clarify the source of PM2.5 by comprehensively analyzing its chemical composition and comparing it with meteorological conditions. The PM2.5 and filter samples were collected during April 2019–August 2019 using a continuous particulate monitor. The analyses were conducted using Image J software, ion chromatography, and backward trajectory. The ion composition and the PM2.5 were compared. The results on the PM2.5 and potassium (K+) concentrations indicated a correlation factor of 0.93, indicating that biomass combustion, such as wood burning, is the dominant source of PM2.5 in Osorno. High PM2.5 concentrations of over 170 to 1124 µg/m3 were observed in low temperature, low precipitation, and low wind speed periods—meteorological conditions contributed to the development of a thermal inversion layer. In addition, correlations of 0.61 to 0.67 were found among the detected ions that are often found in seawater. The backward trajectory analyses showed dominant air mass transport from the South Pacific Ocean, suggesting that part of the detected PM2.5 was derived from the marine environment. Continuous monitoring and mitigation strategies focusing on wood combustion activities are necessary to alleviate the current air pollution problem in Osorno city.
Characterisation of Thunderstorms with Multiple Lightning Jumps
Authors: Rigo Tomeu , Farnell Carme
Published: January 2022

Several works have shown that lightning jumps are precursors of severe weather in deep-convective thunderstorms. Since 2017, the Meteorological Service of Catalonia has operationally run an algorithm that identifies lightning jumps (LJs) in real time. It has resulted in being an effective tool for nowcasting severe weather with a lead time between 15 min and 120 min in advance. This time can be of high value for managing emergencies caused by severe phenomena or heavy rains. The present research focused on the events’ analysis in which more than one lightning jump occurred, searching for those elements that differentiate single warning cases. Thunderstorms producing LJs were divided into two main categories, depending on the number of jumps triggered during the life cycle. Besides, both classes were split into two main sub-types, based on the level of the LJ that occurred. Multiple LJ thunderstorms produce more Level 2—related to severe weather—jumps than Level 1—small hail or intense precipitation—while in the case of a single LJ, the opposite behaviour occurs. In general, multiple LJ thunderstorms with at least one Level 2 jump are the more intense and have a higher vertical development. Finally, lineal and well-organised thunderstorms are the more common modes in those intenser cases.
Study on the Agricultural Air Pollution Aggravated by the Rural Labor Migration
Authors: Liu Ying , You Shibing , Li Nan , Fang Junsheng , Jia Jie , Li Xuesong , Ren Jingru
Published: January 2022

In recent years, air pollution has received serious concerns from researchers, media, and the public sectors, but air pollution from agricultural production activities has not received enough attention. This paper focuses on agricultural air pollution in central China, which is aggravated by the ongoing rural labor migration trend. With a set of panel data released from Hubei and Hunan provinces in China, we adopt the mediating effect model to explore the relationship between rural labor migration and air pollution caused by agricultural activity in China. First, we use the inventory analysis method and principal component analysis method to calculate the comprehensive index of the air pollution of agriculture in 152 counties and districts from Hubei and Hunan provinces, and we empirically test the impact of labor migration on air pollution with a mediating effect model as well as carry out regional heterogeneity analysis on the pollution effect of these two provinces mentioned above. The analysis above indicates that the increase of labor migration has intensified the comprehensive index of air pollution caused by agricultural activity by changing the supply of labor force in the agricultural sector, the budget line of rural residents, and the scale of agricultural production and crop planting structure, but there is a difference in the indirect total effect between the two provinces mentioned above according to our regional heterogeneity analysis. This study is a necessary extension to studies on alleviating and controlling air pollution in China.
Detecting the Causal Nexus between Particulate Matter (PM10) and Rainfall in the Caribbean Area
Authors: Plocoste Thomas
Published: January 2022

In this study, we investigate the interactions between particulate matter that have an aerodynamic diameter less than 10 μm diameter (PM10) and rainfall (RR) in entropy framework. Our results showed there is a bidirectional causality between PM10 concentrations and RR values. This means that PM10 concentrations influence RR values while RR induces the wet scavenging process. Rainfall seasonality has a significant impact on the wet scavenging process while African dust seasonality strongly influence RR behavior. Indeed, the wet scavenging process is 5 times higher during the wet season while PM10 impact on RR is 2.5 times higher during the first part of the high dust season. These results revealed two types of causality: a direct causality (RR to PM10) and an indirect causality (PM10 to RR). All these elements showed that entropy is an efficient way to quantify the behavior of atmospheric processes using ground-based measurements.
Effects of Recurring IPC vs. rIPC Maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: Special Consideration of Reflow Varieties
Authors: Grau Marijke , Seeger Benedikt , Mozigemba Lukas , Roth Roland , Baumgartner Luca , Predel Hans-Georg , Bloch Wilhelm , Tomschi Fabian
Published: January 2022

Beneficial effects of (remote) ischemia preconditioning ((r)IPC), short episodes of blood occlusion and reperfusion, are well-characterized, but there is no consensus regarding the effectiveness of (r)IPC on exercise performance. Additionally, direct comparisons of IPC and rIPC but also differences between reflow modes, low reflow (LR) and high reflow (HR) in particular, are lacking, which were thus the aims of this study. Thirty healthy males conducted a performance test before and after five consecutive days with either IPC or rIPC maneuvers (n = 15 per group). This procedure was repeated after a two-week wash-out phase to test for both reflow conditions in random order. Results revealed improved exercise parameters in the IPC LR and to a lesser extent in the rIPC LR intervention. RBC deformability increased during both rIPC LR and IPC LR, respectively. Pulse wave velocity (PWV) and blood pressures remained unaltered. In general, deformability and PWV positively correlated with performance parameters. In conclusion, occlusion of small areas seems insufficient to affect large remote muscle groups. The reflow condition might influence the effectiveness of the (r)IPC intervention, which might in part explain the inconsistent findings of previous investigations. Future studies should now focus on the underlying mechanisms to explain this finding.
The Seed and the Metabolism Regulation
Authors: El-Maarouf-Bouteau Hayat
Published: January 2022

The seed represents a critical stage in the life cycle of flowering plants. It corresponds to a dry structure carrying the plant embryo in dormant or quiescent state. Orthodox seeds possess a very low water content, preventing biochemical reactions, especially respiration. If the desiccation of living organisms leads to a loss of homeostasis, structure, and metabolism, the seeds go through it successfully thanks to their structure, cellular organization, and growth regulation. Seeds set up a certain number of sophisticated molecules to protect valuable macromolecules or organelles from dehydration/rehydration cycles. Moreover, dormancy takes place in a coordinated process with environmental cues in order to ensure embryo development at the most appropriate conditions for the establishment of the new plant. Moreover, repair processes are programmed to be ready to operate to maximize germination success and seed longevity. This review focuses on the physiology of the seed as related to hydration forces, respiration, and biochemical reactions in the transition from thermodynamically undefined dry state to self-sustained living system. Such processes are of importance for basic knowledge of the regulation of metabolism of living organisms, but also for the control of germination in the context of climate change due to global warming.
Variability of Bacterial Homopolysaccharide Production and Properties during Food Processing
Authors: Nabot Marion , Guérin Marie , Sivakumar Dharini , Remize Fabienne , Garcia Cyrielle
Published: January 2022

Various homopolysaccharides (HoPSs) can be produced by bacteria: α- and β-glucans, β-fructans and α-galactans, which are polymers of glucose, fructose and galactose, respectively. The synthesis of these compounds is catalyzed by glycosyltransferases (glycansucrases), which are able to transfer the monosaccharides in a specific substrate to the medium, which results in the growth of polysaccharide chains. The range of HoPS sizes is very large, from 104 to 109 Da, and mostly depends on the carbon source in the medium and the catalyzing enzyme. However, factors such as nitrogen nutrients, pH, water activity, temperature and duration of bacterial culture also impact the size and yield of production. The sequence of the enzyme influences the structure of the HoPS, by modulating the type of linkage between monomers, both for the linear chain and for the ramifications. HoPSs’ size and structure have an effect on rheological properties of some foods by their influence on viscosity index. As a consequence, the control of structural and environmental factors opens ways to guide the production of specific HoPS in foods by bacteria, either by in situ or ex situ production, but requires a better knowledge of HoPS production conditions.
Passive Immunization in Alpha-Synuclein Preclinical Animal Models
Authors: Folke Jonas , Ferreira Nelson , Brudek Tomasz , Borghammer Per , Van Den Berge Nathalie
Published: January 2022

Alpha-synucleinopathies include Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and multiple system atrophy. These are all progressive neurodegenerative diseases that are characterized by pathological misfolding and accumulation of the protein alpha-synuclein (αsyn) in neurons, axons or glial cells in the brain, but also in other organs. The abnormal accumulation and propagation of pathogenic αsyn across the autonomic connectome is associated with progressive loss of neurons in the brain and peripheral organs, resulting in motor and non-motor symptoms. To date, no cure is available for synucleinopathies, and therapy is limited to symptomatic treatment of motor and non-motor symptoms upon diagnosis. Recent advances using passive immunization that target different αsyn structures show great potential to block disease progression in rodent studies of synucleinopathies. However, passive immunotherapy in clinical trials has been proven safe but less effective than in preclinical conditions. Here we review current achievements of passive immunotherapy in animal models of synucleinopathies. Furthermore, we propose new research strategies to increase translational outcome in patient studies, (1) by using antibodies against immature conformations of pathogenic αsyn (monomers, post-translationally modified monomers, oligomers and protofibrils) and (2) by focusing treatment on body-first synucleinopathies where damage in the brain is still limited and effective immunization could potentially stop disease progression by blocking the spread of pathogenic αsyn from peripheral organs to the brain.
Determination of the Amino Acid Recruitment Order in Early Life by Genome-Wide Analysis of Amino Acid Usage Bias
Authors: Zhao Mingxiao , Ding Ruofan , Liu Yan , Ji Zhiliang , Zhao Yufen
Published: January 2022

The mechanisms shaping the amino acids recruitment pattern into the proteins in the early life history presently remains a huge mystery. In this study, we conducted genome-wide analyses of amino acids usage and genetic codons structure in 7270 species across three domains of life. The carried-out analyses evidenced ubiquitous usage bias of amino acids that were likely independent from codon usage bias. Taking advantage of codon usage bias, we performed pseudotime analysis to re-determine the chronological order of the species emergence, which inspired a new species relationship by tracing the imprint of codon usage evolution. Furthermore, the multidimensional data integration showed that the amino acids A, D, E, G, L, P, R, S, T and V might be the first recruited into the last universal common ancestry (LUCA) proteins. The data analysis also indicated that the remaining amino acids most probably were gradually incorporated into proteogenesis process in the course of two long-timescale parallel evolutionary routes: I→F→Y→C→M→W and K→N→Q→H. This study provides new insight into the origin of life, particularly in terms of the basic protein composition of early life. Our work provides crucial information that will help in a further understanding of protein structure and function in relation to their evolutionary history.
Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes
Authors: Salvatore Teresa , Galiero Raffaele , Caturano Alfredo , Vetrano Erica , Rinaldi Luca , Coviello Francesca , Di Martino Anna , Albanese Gaetana , Colantuoni Sara , Medicamento Giulia , Marfella Raffaele , Sardu Celestino , Sasso Ferdinando Carlo
Published: January 2022

Cardiovascular (CV) disease and heart failure (HF) are the leading cause of mortality in type 2 diabetes (T2DM), a metabolic disease which represents a fast-growing health challenge worldwide. Specifically, T2DM induces a cluster of systemic metabolic and non-metabolic signaling which may promote myocardium derangements such as inflammation, fibrosis, and myocyte stiffness, which represent the hallmarks of heart failure with preserved ejection fraction (HFpEF). On the other hand, several observational studies have reported that patients with T2DM have an abnormally enlarged and biologically transformed epicardial adipose tissue (EAT) compared with non-diabetic controls. This expanded EAT not only causes a mechanical constriction of the diastolic filling but is also a source of pro-inflammatory mediators capable of causing inflammation, microcirculatory dysfunction and fibrosis of the underlying myocardium, thus impairing the relaxability of the left ventricle and increasing its filling pressure. In addition to representing a potential CV risk factor, emerging evidence shows that EAT may guide the therapeutic decision in diabetic patients as drugs such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 inhibitors (SGLT2-Is), have been associated with attenuation of EAT enlargement.
Sensory Processing Phenotypes in Phelan-McDermid Syndrome and SYNGAP1-Related Intellectual Disability
Authors: Lyons-Warren Ariel M. , McCormack Maria C. , Holder Jimmy L.
Published: January 2022

Sensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASDs). Significant work has been carried out to characterize and classify specific sensory profiles in non-syndromic autism. However, it is not known if syndromic autism disorders, such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID), have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding their underlying mechanisms. Our objective in this work was to determine the sensory processing abnormalities present in two syndromic ASDs: Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability. Using a standardized instrument, the Short Sensory Profile-2, we characterized sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID, and sub-scores were then calculated for seeking, avoiding, sensitivity and registration, as well as overall sensory and behavior scores. We found both patient groups exhibited atypical sensory features, including high scores in the areas of avoiding and seeking. Thus, we discovered significant sensory processing abnormalities are common in these syndromic ASDs. Measurements of sensory processing could serve as useful clinical endpoints for trials of novel therapeutics for these populations.
Evaluation of the Effect of the Dynamic Behavior and Topology Co-Learning of Neurons and Synapses on the Small-Sample Learning Ability of Spiking Neural Network
Authors: Yang Xu , Lei Yunlin , Wang Mengxing , Cai Jian , Wang Miao , Huan Ziyi , Lin Xialv
Published: January 2022

Small sample learning ability is one of the most significant characteristics of the human brain. However, its mechanism is yet to be fully unveiled. In recent years, brain-inspired artificial intelligence has become a very hot research domain. Researchers explored brain-inspired technologies or architectures to construct neural networks that could achieve human-alike intelligence. In this work, we presented our effort at evaluation of the effect of dynamic behavior and topology co-learning of neurons and synapses on the small sample learning ability of spiking neural network. Results show that the dynamic behavior and topology co-learning mechanism of neurons and synapses presented in our work could significantly reduce the number of required samples, while maintaining a reasonable performance on the MNIST data-set, resulting in a very lightweight neural network structure.
Localizing Spectral Interactions in the Resting State Network Using the Hilbert–Huang Transform
Authors: Hsu Ai-Ling , Li Chia-Wei , Qin Pengmin , Lo Men-Tzung , Wu Changwei W.
Published: January 2022

Brain synchronizations are orchestrated from neuronal oscillations through frequency interactions, such as the alpha rhythm during relaxation. Nevertheless, how the intrinsic interaction forges functional integrity across brain segregations remains elusive, thereby motivating recent studies to localize frequency interactions of resting-state fMRI (rs-fMRI). To this point, we aim to unveil the fMRI-based spectral interactions using the time-frequency (TF) analysis; however, Fourier-based TF analyses impose restrictions on revealing frequency interactions given the limited time points in fMRI signals. Instead of using the Fourier-based wavelet analysis to identify the fMRI frequency of interests, we employed the Hilbert–Huang transform (HHT) for probing the specific frequency contribution to the functional integration, called ensemble spectral interaction (ESI). By simulating data with time-variant frequency changes, we demonstrated the Hilbert TF maps with high spectro-temporal resolution and full accessibility in comparison with the wavelet TF maps. By detecting amplitude-to-amplitude frequency couplings (AAC) across brain regions, we elucidated the ESI disparity between the eye-closed (EC) and eye-open (EO) conditions in rs-fMRI. In the visual network, the strength of the spectral interaction within 0.03–0.04 Hz was amplified in EC compared with that in EO condition, whereas a canonical connectivity analysis did not present differences between conditions. Collectively, leveraging from the instantaneous frequency of HHT, we firstly addressed the ESI technique to map the fMRI-based functional connectivity in a brand-new AAC perspective. The ESI possesses potential in elucidating the functional connectivity at specific frequency bins, thereby providing additional diagnostic merits for future clinical neuroscience.
SmartRock-Based Research on Gyratory Locking Point for Stone Mastic Asphalt Mixture
Authors: Cheng Zhiqiang , Zhang De , Xie Shengjia , Polaczyk Pawel Andrzej , Wang Tao
Published: January 2022

For gyratory compaction, the concept of the locking point was initially developed to identify the compactability of asphalt mixes and to alleviate potential aggregate crushing in the mold. Most previous studies on the locking point were based on specimens’ height change. Recent studies have indicated that the gyratory locking point of cold mix asphalt mixtures could be determined by the rotation angle range indicator using SmartRock. However, height or rotation angle change ultimately reflects a change in volume. Additionally, there is no clear physical and mechanical connection between the volume change and the gyratory locking point. In this paper, a stone mastic asphalt mixture (SMA 13) was selected for gyratory compaction applying various compaction temperatures. The compaction data were recorded by a SmartRock embedded in different positions. Collected data included stress, rotation angle, and acceleration. The major findings are as follows: (1) the specimen’s locking point could be determined based on a representative stress value when the SmartRock was embedded in the specimen’s center, and the results are close to the traditional evaluation results (LP3 or LP2-2-3); (2) the representative rotation angle value reached a plateau earlier than the representative stress value; (3) the representative acceleration value is not suitable for characterizing the interlocking process during gyratory compaction.
Selecting Appropriate Risk Response Strategies Considering Utility Function and Budget Constraints: A Case Study of a Construction Company in Iran
Authors: Safaeian Mojgan , Fathollahi-Fard Amir M. , Kabirifar Kamyar , Yazdani Maziar , Shapouri Mohammad
Published: January 2022

Successful implementation of construction projects worldwide calls for a set of effective risk management plans in which uncertainties associated with risks and effective response strategies are addressed meticulously. Thus, this study aims to provide an optimization approach with which risk response strategies that maximize the utility function are selected. This selection is by opting for the most appropriate strategies with the highest impact on the project regarding the weight of each risk and budget constraints. Moreover, the risk assessment and response strategy of a construction project in Iran as a case study, based on the global standard of the project management body of knowledge (PMBOK) and related literature, is evaluated. To handle the complexity of the proposed model, different state of the art metaheuristic algorithms including the ant lion optimizer (ALO), dragonfly algorithm (DA), grasshopper optimization algorithm (GOA), Harris hawks optimization (HHO), moth-flame optimization algorithm (MFO), multi-verse optimizer (MVO), sine cosine algorithm (SCA), salp swarm algorithm (SSA), whale optimization algorithm (WOA), and grey wolf optimizer (GWO). These algorithms are validated by the exact solver from CPLEX software and compare with each other. One finding from this comparison is the high performance of MFO and HHO algorithms. Based on some sensitivity analyses, an extensive discussion is provided to suggest managerial insights for real-world construction projects.
Plant-Derived Terpenoids: A Promising Tool in the Fight against Melanoma
Authors: Kłos Patrycja , Chlubek Dariusz
Published: January 2022

Melanoma is responsible for the highest number of skin cancer-caused deaths worldwide. Despite the numerous melanoma-treating options, the fight against it remains challenging, mainly due to its great heterogeneity and plasticity, as well as the high toxicity of standard drugs. Plant-derived terpenoids are a group of plant defense molecules that have been proven effective in killing many different types of cancer cells, both in in vitro experiments and in vivo models. In this review, we focus on recent results in the search for plant terpenoids with anti-melanoma activity. We also report on the synergistic action of combining terpenoids with other plant-derived substances, MAP kinase inhibitors, or radiation. Additionally, we present examples of terpenoid-loaded nanoparticle carriers as anti-melanoma agents that have increased permeation through the cancer tissue.
Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective
Authors: Bleve Augusto , Consonni Francesca Maria , Porta Chiara , Garlatti Valentina , Sica Antonio
Published: January 2022

In recent years, the immune system has emerged as a critical regulator of tumor development, progression and dissemination. Advanced therapeutic approaches targeting immune cells are currently under clinical use and improvement for the treatment of patients affected by advanced malignancies. Among these, anti-PD1/PD-L1 and anti-CTLA4 immune checkpoint inhibitors (ICIs) are the most effective immunotherapeutic drugs at present. In spite of these advances, great variability in responses to therapy exists among patients, probably due to the heterogeneity of both cancer cells and immune responses, which manifest in diverse forms in the tumor microenvironment (TME). The variability of the immune profile within TME and its prognostic significance largely depend on the frequency of the infiltrating myeloid cells, which often represent the predominant population, characterized by high phenotypic heterogeneity. The generation of heterogeneous myeloid populations endowed with tumor-promoting activities is typically promoted by growing tumors, indicating the sequential levels of myeloid reprogramming as possible antitumor targets. This work reviews the current knowledge on the events governing protumoral myelopoiesis, analyzing the mechanisms that drive the expansion of major myeloid subsets, as well as their functional properties, and highlighting recent translational strategies for clinical developments.
Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia
Authors: ten Kate Chantal A. , de Klein Annelies , de Graaf Bianca M. , Doukas Michail , Koivusalo Antti , Pakarinen Mikko P. , van der Helm Robert , Brands Tom , IJsselstijn Hanneke , van Bever Yolande , Wijnen René M.H. , Spaander Manon C.W. , Brosens Erwin
Published: January 2022

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.
Therapeutic Advancements in Metal and Metal Oxide Nanoparticle-Based Radiosensitization for Head and Neck Cancer Therapy
Authors: Dubey Poornima , Sertorio Mathieu , Takiar Vinita
Published: January 2022

Although radiation therapy (RT) is one of the mainstays of head and neck cancer (HNC) treatment, innovative approaches are needed to further improve treatment outcomes. A significant challenge has been to design delivery strategies that focus high doses of radiation on the tumor tissue while minimizing damage to surrounding structures. In the last decade, there has been increasing interest in harnessing high atomic number materials (Z-elements) as nanoparticle radiosensitizers that can also be specifically directed to the tumor bed. Metallic nanoparticles typically display chemical inertness in cellular and subcellular systems but serve as significant radioenhancers for synergistic tumor cell killing in the presence of ionizing radiation. In this review, we discuss the current research and therapeutic efficacy of metal nanoparticle (MNP)-based radiosensitizers, specifically in the treatment of HNC with an emphasis on gold- (AuNPs), gadolinium- (AGdIX), and silver- (Ag) based nanoparticles together with the metallic oxide-based hafnium (Hf), zinc (ZnO) and iron (SPION) nanoparticles. Both in vitro and in vivo systems for different ionizing radiations including photons and protons were reviewed. Finally, the current status of preclinical and clinical studies using MNP-enhanced radiation therapy is discussed.
CXCR2 Mediates Distinct Neutrophil Behavior in Brain Metastatic Breast Tumor
Authors: Safarulla Simrit , Madan Ankit , Xing Fei , Chandrasekaran Arvind
Published: January 2022

Brain metastasis is one of the main causes of mortality among breast cancer patients, but the origins and the mechanisms that drive this process remain poorly understood. Here, we report that the upregulation of certain CXCR2-associated ligands in the brain metastatic variants of the breast cancer cells (BrM) dynamically activate the corresponding CXCR2 receptors on the neutrophils, thereby resulting in the modulation of certain key functional neutrophil responses towards the BrM. Using established neutrophil-tumor biomimetic co-culture models, we show that the upregulation of CXCR2 increases the recruitment of Tumor-Associated Neutrophils (TANs) towards the BrM, to enable location-favored formation of Neutrophil Extracellular Traps (NETs). Inhibition of CXCR2 using small molecule antagonist AZD5069 reversed this behavior, limiting the neutrophil responses to the BrM and retarding the reciprocal tumor development. We further demonstrate that abrogation of NETs formation using Neutrophil Elastase Inhibitor (NEI) significantly decreases the influx of neutrophils towards BrM but not to their parental tumor, suggesting that CXCR2 activation could be used by the brain metastatic tumors as a mechanism to program the tumor-infiltrating TANs into a pro-NETotic state, so as to assume a unique spatial distribution that assists in the subsequent migration and invasion of the metastatic tumor cells. This new perspective indicates that CXCR2 is a critical target for suppressing neutrophilic inflammation in brain metastasis.
Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity
Authors: Koch Elias A. T. , Petzold Anne , Wessely Anja , Dippel Edgar , Gesierich Anja , Gutzmer Ralf , Hassel Jessica C. , Haferkamp Sebastian , Kähler Katharina C. , Knorr Harald , Kreuzberg Nicole , Leiter Ulrike , Loquai Carmen , Meier Friedegund , Meissner Markus , Mohr Peter , Pföhler Claudia , Rahimi Farnaz , Schadendorf Dirk , Schell Beatrice , Schlaak Max , Terheyden Patrick , Thoms Kai-Martin , Schuler-Thurner Beatrice , Ugurel Selma , Ulrich Jens , Utikal Jochen , Weichenthal Michael , Ziller Fabian , Berking Carola , Heppt Markus V.
Published: January 2022

Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1–23.8) versus 9.4 months (cohort B, 95% CI: 6.1–14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.
Bronchial Carcinoids: From Molecular Background to Treatment Approach
Authors: Araujo-Castro Marta , Pascual-Corrales Eider , Molina-Cerrillo Javier , Moreno Mata Nicolás , Alonso-Gordoa Teresa
Published: January 2022

A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.
NanoString Digital Molecular Profiling of Protein and microRNA in Rhabdomyosarcoma
Authors: Ahmed Atif A. , Farooqi Midhat S. , Habeebu Sultan S. , Gonzalez Elizabeth , Flatt Terrie G. , Wilson Ashley L. , Barr Frederic G.
Published: January 2022

Purpose: Rhabdomyosarcoma (RMS) exhibits a complex prognostic algorithm based on histologic, biologic and clinical parameters. The embryonal (ERMS) and spindle cell-sclerosing RMS (SRMS) histologic subtypes warrant further studies due to their heterogenous genetic background and variable clinical behavior. NanoString digital profiling methods have been previously highlighted as robust novel methods to detect protein and microRNA expression in several cancers but not in RMS. Methods/Patients: To identify prognostic biomarkers, we categorized 12 ERMS and SRMS tumor cases into adverse (n = 5) or favorable (n = 7) prognosis groups and analyzed their signaling pathways and microRNA profiles. The digital spatial profiling of protein and microRNA analysis was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue using NanoString technology. Results: The detectable expression of several component members of the PI3K/AKT, MAPK and apoptosis signaling pathways was highlighted in RMS, including INPP4B, Pan-AKT, MET, Pan-RAS, EGFR, phospho-p90 RSK, p44/42 ERK1/2, BAD, BCL-XL, cleaved caspase-9, NF1, PARP and p53. Compared to cases with favorable prognosis, the adverse-prognosis tumor samples had significantly increased expression of INPP4B, which was confirmed with traditional immunohistochemistry. The analysis of microRNA profiles revealed that, out of 798 microRNAs assessed, 228 were overexpressed and 134 downregulated in the adverse prognosis group. Significant over-expression of oncogenic/tumor suppressor miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548ar-5p and miR-548y (p < 0.05) was noted in the adverse prognosis group. Conclusion: This study highlights the utility of NanoString digital profiling methods in RMS, where it can detect distinct molecular signatures with the expression of signaling pathways and microRNAs from FFPE tumor tissue that may help identify prognostic biomarkers of interest. The overexpression of INPP4B and miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548y and miR-548ar-5p may be associated with worse overall survival in ERMS and SRMS.
Increased Activity of a NK-Specific CAR-NK Framework Targeting CD3 and CD5 for T-Cell Leukemias
Authors: Voynova Elisaveta , Hawk Nga , Flomerfelt Francis A. , Telford William G. , Gress Ronald E. , Kanakry Jennifer A. , Kovalovsky Damian
Published: January 2022

NK effector cells expressing a CAR construct may be used to target T-lineage markers. In this work, we compared the activity of a NK-specific CAR-NK and a CAR-T framework when expressed on NK effector cells to target CD3 and CD5 in T-cell malignancies. Our results show that CD3-CAR-T is more active than CD5-CAR-T to eliminate malignant T cells in vitro, however, CD3-CAR-T were less efficient to eliminate tumor cells in vivo, while CD5-CAR-T had antitumor activity in a diffuse xenograft model. Lack of in vivo efficacy correlated with downregulation of CD3 levels in target T cells after coculture with CD3-CAR effector cells. The CAR-NK framework greatly improved the efficacy of CARs leading to increased degranulation, cytokine secretion and elimination of the tumor xenograft by CD5-CAR-NK effector cells. Finally, all CAR constructs were similarly effective to eliminate malignant T cells in vitro. Our results show that the NK-CAR framework improves the activity of CARs in NK cells and that CD5 would be a better target than CD3 for T-cell malignancies, as dynamic downregulation of target expression may affect in vivo efficacy.
Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
Authors: Alig Annabel H. S. , Heinemann Volker , Geissler Michael , Fischer von Weikersthal Ludwig , Decker Thomas , Heinrich Kathrin , Held Swantje , Weiss Lena , Fischer Laura E. , Moosmann Nicolas , Stahler Arndt , Jelas Ivan , Kurreck Annika , von Einem Jobst C. , Reinacher-Schick Anke C. , Tannapfel Andrea , Giessen-Jung Clemens , Stintzing Sebastian , Modest Dominik P.
Published: January 2022

Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the relevance of primary tumor location (PTL) in RAS/BRAF wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan–Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver (p = 0.001), lung (p = 0.047), peritoneal (p < 0.001) and lymph nodes (p = 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in RAS/BRAF wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered.