bluuebunny/crossref_metadata_2025 huggingface dataset:
Signals of Surface Deformation Areas in Central Chile, Related to Seismic Activity—Using the Persistent Scatterer Method and GIS
Authors: da Silva Luciana das Dores de Jesus , Montecino Castro Henry , Aguayo Arias Mauricio Ivan , González-Rodríguez Lisdelys , Rodríguez-López Lien , Cotias Simões Luiz Mateus
Published: March 2022

Interferometric synthetic aperture radar is an effective means of measuring changes in the altitude of the Earth’s surface. In this research, the areas of surface deformation associated with low- and medium-intensity seismic events in Central Chile were analyzed using SENTINEL 1 satellite radar interferograms and geographical information system (GIS) tools. The persistent scatterer method was used to reduce noise from conventional InSAR methods. The results revealed that the coastal zone of Central Chile has a high density of daily earthquakes with a prevalence (93.03%) of low- and medium-intensity earthquakes. Monthly deformation maps were developed for the coast of the Biobio region in Central Chile. A clear deformation pattern is defined along the coast, being greater in the Arauco, Lota and Lebu areas. It was also shown that there was a slight upward trend in the north and northeast zone (i.e., δup ~3 mm/year), while there was an obvious accentuated upward trend (i.e., δup ~24 mm/year) in the southern part. This movement increases as latitude increases. This pattern is related to the daily seismic activity, the product of the movement between plates, and the geological faults located in the area. The deformation and trend maps provide certainty in terms of where hotspots are located, e.g., the most hazardous areas in the study zone, which can be applied to urban planning and/or safety assessment.
Revisiting the Cu-Zn Disorder in Kesterite Type Cu2ZnSnSe4 Employing a Novel Approach to Hybrid Functional Calculations
Authors: Fritsch Daniel
Published: March 2022

In recent years, the search for more efficient and environmentally friendly materials to be employed in the next generation of thin film solar cell devices has seen a shift towards hybrid halide perovskites and chalcogenide materials crystallising in the kesterite crystal structure. Prime examples for the latter are Cu2ZnSnS4, Cu2ZnSnSe4, and their solid solution Cu2ZnSn(SxSe1−x)4, where actual devices already demonstrated power conversion efficiencies of about 13 %. However, in their naturally occurring kesterite crystal structure, the so-called Cu-Zn disorder plays an important role and impacts the structural, electronic, and optical properties. To understand the influence of Cu-Zn disorder, we perform first-principles calculations based on density functional theory combined with special quasirandom structures to accurately model the cation disorder. Since the electronic band gaps and derived optical properties are severely underestimated by (semi)local exchange and correlation functionals, supplementary hybrid functional calculations have been performed. Concerning the latter, we additionally employ a recently devised technique to speed up structural relaxations for hybrid functional calculations. Our calculations show that the Cu-Zn disorder leads to a slight increase in the unit cell volume compared to the conventional kesterite structure showing full cation order, and that the band gap gets reduced by about 0.2 eV, which is in very good agreement with earlier experimental and theoretical findings. Our detailed results on structural, electronic, and optical properties will be discussed with respect to available experimental data, and will provide further insights into the atomistic origin of the disorder-induced band gap lowering in these promising kesterite type materials.
Successful Second Autologous Stem Cell Transplantation for Late Disease Progression after the First Procedure in POEMS Syndrome
Authors: Autore Francesco , Innocenti Idanna , Sora Federica , Chiusolo Patrizia , Piccirillo Nicola , Bacigalupo Andrea , Sica Simona , Laurenti Luca
Published: March 2022

Autologous stem cell transplantation (ASCT) is a good option in fit young patients affected by POEMS syndrome. Few data are published on how to treat these patients in case of relapse. In this paper we described our two patients who underwent a second ASCT. From our experience, we can confirm that a second transplant is a real treatment option with good results and limited side effects. It provided excellent response and long-term disease-free survival in POEMS patients who relapsed after a first transplant, including late relapses.
Simulation Study of Vertical p–n Junction Photodiodes’ Optical Performance According to CMOS Technology
Authors: Ferreira Gabriel M. , Silva Vítor , Minas Graça , Catarino Susana O.
Published: March 2022

CMOS photodiodes have been widely reported in microsystem applications. This article presents the design and numerical simulation of p–n junction photodiodes, using COMSOL Multiphysics, for three CMOS technologies (0.18 μm, 0.35 μm and 0.7 μm) and three different p–n junction structures: n+/p-substrate, p+/n-well and n-well/p-substrate. For these simulations, the depth junctions and dopant concentrations were set according to the different technologies. Then, each photodiode was spectrophotometrically characterized regarding the current, responsivity and quantum efficiency. The obtained numerical results show that the 0.18 and 0.35 μm CMOS technologies are those with the highest peak of efficiency when visible spectral ranges are needed, comparative to the 0.7 µm technology. Furthermore, the three most common p–n vertical junction photodiode structures were compared. The n+/p-substrate junction photodiode appears to be the one with the highest quantum efficiency in the visible range, which is in agreement with the literature. It can be concluded that the photodiodes’ characteristic curves and dark current values are consistent with reports in the literature. Therefore, this numerical approach allows to predict the photodiodes’ performance, helping to select the best structural design for each required application, before their microfabrication.
Coffee Roasting and Extraction as a Factor in Cold Brew Coffee Quality
Authors: Maksimowski Damian , Pachura Natalia , Oziembłowski Maciej , Nawirska-Olszańska Agnieszka , Szumny Antoni
Published: March 2022

Due to the dynamic growth of the cold brew coffee market, the aim of this study was to identify and characterize main bioactive and aromatic compounds that may be helpful for quality control during the production of popular beverages. Using headspace solid-phase microextraction and GC-MS and LC-MS analysis, prepared cold brew coffee extracts were investigated and compared with different green bean roasting profiles and varying extraction temperature and time parameters. In terms of quantitative composition, the study showed that cold brew coffees are an exceptional source of chlorogenic acid. Therefore, they may change consumers purchasing decisions on the beverage market and establish a new and natural substitute for controversial energy drinks. The analyses confirm the possibility of producing a beverage with increased chlorogenic acid content above 900 mg/L or at a similar level of 400–500 mg/L with caffeine, which may be important on an industrial scale due to the possibility of diversifying beverage production. Furthermore, aroma compounds were presented as markers responsible for fruity or caramel–roasted-almond notes and changes in their concentrations according to the recipe were also presented. The best option for cold brew coffee production appears to be beans roasted in the 210–220 °C temperature range.
The Effect of Hot Water Extract of Tilapia on Exercise Capacity in Mice
Authors: Tsai Hui-Yun , Yang Jia-Fang , Chen Hua-Han , You Fu-Nian , Zhao Yu-Jie , Lin Yi-Hsien , Hsu Jue-Liang , Chang Chi-I , Chen Yu-Kuo
Published: March 2022

Tilapia (Oreochromis mossambicus) has become one of the main aquatic products of Taiwan. The aim of this study was to evaluate the efficacy of a hot water extract of tilapia (HWET) in relieving fatigue and enhancing exercise performance in mice in a swimming endurance test. Male ICR mice were randomly divided into four groups (n = 10 per group) and treated with either a vehicle (control group) or different doses of HWET, which were designated as HWET-L (800 mg/kg/day), HWET-M (1600 mg/kg/day), and HWET-H (4000 mg/kg/day). The results of the swimming endurance test showed that HWET treatment significantly improved exercise-induced fatigue as the swimming time of the mice increased (p < 0.05). One hour after the test, blood samples were collected from each mouse and serum biochemical parameters were measured. The serum levels of lactate, creatine kinase (CK), and blood urea nitrogen (BUN) were lower in mice treated with HWET compared to the control group. Moreover, HWET treatment increased serum glucose levels and glycogen content in the liver. Enhanced glutathione (GSH) content in the liver and muscle was also found in the HWET-M and HWET-H groups. Western blot results showed that the expression of tumor necrosis factor-α (TNF-α) in the liver tissue was downregulated by HWET treatment. Taken together, our results demonstrate that HWET supplementation could enhance exercise performance and alleviate fatigue via biochemical profile improvements. This suggests that HWET has the potential for future development into functional foods or nutritional supplements to relieve fatigue.
Factors Influencing PM2.5 Concentrations in the Beijing–Tianjin–Hebei Urban Agglomeration Using a Geographical and Temporal Weighted Regression Model
Authors: Li Qiuying , Li Xiaochun , Li Hongtao
Published: March 2022

Air pollution is the environmental issue of greatest concern in China, especially the PM2.5 pollution in the Beijing–Tianjin–Hebei urban agglomeration (BTHUA). Based on sustainable development, it is of interest to study the spatiotemporal distribution of PM2.5 and its influencing mechanisms. This study reveals the temporal evolution and spatial clustering characteristic of PM2.5 pollution from 2015 to 2019, and quantifies the drivers of its natural and socioeconomic factors on it by using a geographical temporal weighted regression model. Results show that PM2.5 concentrations reached their highest level in 2015 before decreasing in the following years. The monthly averages all present a U-shaped change trend. Relative to the traditional high concentrations in the northern part of the BTHUA domain in 2015, the gap in pollution between the north and south has reduced since 2018. The obvious spatial heterogeneity was demonstrated in both the strength and direction of the variables. This study may help identify reasons for high PM2.5 concentrations and suggest appropriate targeted control and prevention measures.
Data Filling of Micrometeorological Variables in Complex Terrain for High-Resolution Nowcasting
Authors: Gunawardena Nipun , Durand Pierre , Hedde Thierry , Dupuy Florian , Pardyjak Eric
Published: March 2022

In this paper, two different computationally inexpensive methods for nowcasting/data filling spatially varying meteorological variables (wind velocity components, specific humidity, and virtual potential temperature) covering scales ranging from 100 m to 5 km in regions marked by complex terrain are compared. Multivariable linear regression and artificial neural networks are used to predict micrometeorological variables at eight locations using the measurements from three nearby weather stations. The models are trained using data gathered from a system of eleven low-cost automated weather stations that were deployed in the Cadarache Valley of southeastern France from December 2016 to June 2017. The models are tested on two held-out periods of measurements of thermally-driven flow and synoptically forced flow. It is found that the models have statistically significant performance differences for the wind components during the synoptically driven flow period (p = 6.6 × 10−3 and p = 2.0 × 10−2 for U and V, respectively), but perform the same otherwise. These methods can be used to spatially fill gaps in micrometeorological datasets. Recommended future work should include statistically interpreting the predictive models and testing their capabilities on meteorological datasets from different locations.
Rectangular Gb-Metric Spaces and Some Fixed Point Theorems
Authors: Li Chaobo , Cui Yunan
Published: March 2022

In this paper, we first introduce the concept of rectangular Gb-metric space which generalizes the notion of rectangular metric space and Gb-metric space. Then, some fixed point results connected with certain contractions are obtained in the setting of rectangular Gb-metric spaces. Additionally, we also introduce the concept of convex rectangular Gb-metric space by means of the convex structure and study the fixed points of enriched type contractions in this space.
Multi-Point Boundary Value Problems for (k, ϕ)-Hilfer Fractional Differential Equations and Inclusions
Authors: Tariboon Jessada , Samadi Ayub , Ntouyas Sotiris K.
Published: March 2022

In this paper we initiate the study of boundary value problems for fractional differential equations and inclusions involving (k,ϕ)-Hilfer fractional derivative of order in (1,2]. In the single-valued case the existence and uniqueness results are established by using classical fixed-point theorems, such as Banach, Krasnoselskiĭ and Leray-Schauder. In the multivalued case we consider both cases, when the right-hand side has convex or non-convex values. In the first case, we apply the Leray–Schauder nonlinear alternative for multivalued maps, and in the second, the Covit–Nadler fixed-point theorem for multivalued contractions. All results are well illustrated by numerical examples.
Biological Response of Irisin Induced by Different Types of Exercise in Obese Subjects: A Non-Inferiority Controlled Randomized Study
Authors: D’Amuri Andrea , Raparelli Valeria , Sanz Juana Maria , Capatti Eleonora , Di Vece Francesca , Vaccari Filippo , Lazzer Stefano , Zuliani Giovanni , Dalla Nora Edoardo , Neri Luca Maria , Passaro Angelina
Published: March 2022

Background: Weight loss through physical exercise is warranted among obese individuals. Recently, a greater benefit in cardiorespiratory fitness was achievable with high-intensity interval training (HIIT) as compared with moderate intensity continuous training. The beneficial effect of training on CV health might be related to a specific modulation of circulating irisin, an adypo-myokine implicated in the regulation of energy expenditure. Methods: The present study investigates the circulating plasma levels of irisin at baseline and in response to 12-week of training program either with HIIT or moderate-intensity continuous training (MICT) among young female and male obese subjects. Clinical, anthropometric, and training characteristics for each participant were available. A sex-disaggregated data for circulating plasma levels of irisin pre- and post-training are provided as well as an adjusted multivariate linear regression model to identify the determinants of post-training irisin levels. Results: Data from a total of 32 obese healthy individuals (47% female, mean age 38.7 years, mean BMI 35.6 kg/m2), randomized in a 1:1 manner to HIIT or MICT were analyzed. Circulating plasma levels of irisin similarly and significantly decreased in both MICT and HIIT interventional groups. Females had higher post-exercise irisin levels than males (6.32 [5.51–6.75] vs. 4.97 [4.57–5.72] μg/mL, p = 0.001). When stratified by an interventional group, a statistically significant difference was observed only for the MICT group (male, 4.76 [4.20–5.45] μg/mL vs. female 6.48 [4.88–6.84] μg/mL p = 0.03). The circulating post-training level of irisin was independently associated with post-training fat-free mass (β −0.34, 95% confidence interval, CI −0.062, −0.006, p = 0.019) in a model adjusted confounders. When female sex was added into the adjusted model, it was retained as the only factor independently associated with irisin levels (β 1.22, 95% CI, 0.50, 1.93, p = 0.002). Conclusions: In obese healthy subjects, circulating irisin levels were reduced in response to 12-weeks of exercise involving either HIIT or MICT. A sex-specific differences in circulating irisin levels at baseline and as biological response to chronic exercise was described. Sex-specific biological response of irisin to exercise should be further explored to tailor sex-specific training approaches for improving the cardiovascular health of obese healthy subjects.
Amino Acid Signaling for TOR in Eukaryotes: Sensors, Transducers, and a Sustainable Agricultural fuTORe
Authors: Lutt Nanticha , Brunkard Jacob O.
Published: March 2022

Eukaryotic cells monitor and regulate metabolism through the atypical protein kinase target of rapamycin (TOR) regulatory hub. TOR is activated by amino acids in animals and fungi through molecular signaling pathways that have been extensively defined in the past ten years. Very recently, several studies revealed that TOR is also acutely responsive to amino acid metabolism in plants, but the mechanisms of amino acid sensing are not yet established. In this review, we summarize these discoveries, emphasizing the diversity of amino acid sensors in human cells and highlighting pathways that are indirectly sensitive to amino acids, i.e., how TOR monitors changes in amino acid availability without a bona fide amino acid sensor. We then discuss the relevance of these model discoveries to plant biology. As plants can synthesize all proteinogenic amino acids from inorganic precursors, we focus on the possibility that TOR senses both organic metabolites and inorganic nutrients. We conclude that an evolutionary perspective on nutrient sensing by TOR benefits both agricultural and biomedical science, contributing to ongoing efforts to generate crops for a sustainable agricultural future.
Ferroptosis in Cardiovascular Diseases: Current Status, Challenges, and Future Perspectives
Authors: Guo Yi , Lu Chanjun , Hu Ke , Cai Chuanqi , Wang Weici
Published: March 2022

Cardiovascular diseases (CVDs) are still a major cause of global mortality and disability, seriously affecting people’s lives. Due to the severity and complexity of these diseases, it is important to find new regulatory mechanisms to treat CVDs. Ferroptosis is a new kind of regulatory cell death currently being investigated. Increasing evidence showed that ferroptosis plays an important role in CVDs, such as in ischemia/reperfusion injury, heart failure, cardiomyopathy, and atherosclerosis. Protecting against CVDs by targeting ferroptosis is a promising approach; therefore, in this review, we summarized the latest regulatory mechanism of ferroptosis and the current studies related to each CVD, followed by critical perspectives on the ferroptotic treatment of CVDs and the future direction of this intriguing biology.
COL11A1-Driven Epithelial–Mesenchymal Transition and Stemness of Pancreatic Cancer Cells Induce Cell Migration and Invasion by Modulating the AKT/GSK-3β/Snail Pathway
Authors: Wang Hui , Zhou Huichao , Ni Hong , Shen Xiaohong
Published: March 2022

Background: Collagen type XI α1 (COL11A1) is associated with tumorigenesis and development in many human malignancies. Previous reports indicate that COL11A1 may be a significant diagnostic marker for pancreatic ductal adenocarcinoma (PDAC); however, its biological role in PDAC progression remains unclear. In this study, we investigated the influence of COL11A1 on the invasion and migration abilities of pancreatic cancer cells and explored its potential molecular mechanisms. Methods: Cell migration and invasion were assessed using Transwell assays in pancreatic cancer cells transfected with siCOL11A1 and pCNV3-COL11A1 plasmids. The protein and mRNA expression levels of N-cadherin, E-cadherin, Vimentin, cluster of differentiation (CD)-24, CD44, serine–threonine kinase (AKT), glycogen synthase kinase (GSK)-3β, phospho (p)-AKTSer473, p-GSK-3βSer9, and Snail were analyzed using Western blotting and real-time polymerase chain reaction (PCR). The effect of COL11A1 on cell stemness was tested using flow cytometry and clone formation assays. Results: These results demonstrated that COL11A1 significantly promoted the invasion and migration abilities of PDAC cells. Furthermore, COL11A1 facilitated the occurrence of epithelial–mesenchymal transition (EMT) and cell stemness by upregulating the expression levels of p-AKTSer473, p-GSK-3βSer9, and Snail. Conclusions: This study suggests that the activation of the AKT/GSK-3β/Snail signaling pathway induced by COL11A1 plays a major role in the progression of PDAC. Therefore, COL11A1 could serve as a potential target for PDAC treatment.
Therapeutic Approaches Targeting Proteins in Tumor-Associated Macrophages and Their Applications in Cancers
Authors: Wu Deyang , Liu Xiaowei , Mu Jingtian , Yang Jin , Wu Fanglong , Zhou Hongmei
Published: March 2022

Tumor-associated macrophages (TAMs) promote tumor proliferation, invasion, angiogenesis, stemness, therapeutic resistance, and immune tolerance in a protein-dependent manner. Therefore, the traditional target paradigms are often insufficient to exterminate tumor cells. These pro-tumoral functions are mediated by the subsets of macrophages that exhibit canonical protein markers, while simultaneously having unique transcriptional features, which makes the proteins expressed on TAMs promising targets during anti-tumor therapy. Herein, TAM-associated protein-dependent target strategies were developed with the aim of either reducing the numbers of TAMs or inhibiting the pro-tumoral functions of TAMs. Furthermore, the recent advances in TAMs associated with tumor metabolism and immunity were extensively exploited to repolarize these TAMs to become anti-tumor elements and reverse the immunosuppressive tumor microenvironment. In this review, we systematically summarize these current studies to fully illustrate the TAM-associated protein targets and their inhibitors, and we highlight the potential clinical applications of targeting the crosstalk among TAMs, tumor cells, and immune cells in anti-tumor therapy.
Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury
Authors: Ochoa Carmen A. , Nissen Claire G. , Mosley Deanna D. , Bauer Christopher D. , Jordan Destiny L. , Bailey Kristina L. , Wyatt Todd A.
Published: March 2022

Most individuals diagnosed with alcohol use disorders smoke cigarettes. Large concentrations of malondialdehyde and acetaldehyde are found in lungs co-exposed to cigarette smoke and alcohol. Aldehydes directly injure lungs and form aldehyde protein adducts, impacting epithelial functions. Recently, 2-(3-Amino-6-chloroquinolin-2-yl)propan-2-ol (ADX-102) was developed as an aldehyde-trapping drug. We hypothesized that aldehyde-trapping compounds are protective against lung injury derived from cigarette smoke and alcohol co-exposure. To test this hypothesis, we pretreated mouse ciliated tracheal epithelial cells with 0–100 µM of ADX-102 followed by co-exposure to 5% cigarette smoke extract and 50 mM of ethanol. Pretreatment with ADX-102 dose-dependently protected against smoke and alcohol induced cilia-slowing, decreases in bronchial epithelial cell wound repair, decreases in epithelial monolayer resistance, and the formation of MAA adducts. ADX-102 concentrations up to 100 µM showed no cellular toxicity. As protein kinase C (PKC) activation is a known mechanism for slowing cilia and wound repair, we examined the effects of ADX-102 on smoke and alcohol induced PKC epsilon activity. ADX-102 prevented early (3 h) activation and late (24 h) autodownregulation of PKC epsilon in response to smoke and alcohol. These data suggest that reactive aldehydes generated from cigarette smoke and alcohol metabolism may be potential targets for therapeutic intervention to reduce lung injury.
ABCA1 Expression Is Upregulated in an EMT in Breast Cancer Cell Lines via MYC-Mediated De-Repression of Its Proximal Ebox Element
Authors: Prijic Sara , Chang Jeffrey T.
Published: March 2022

The ATP-Binding Cassette transporter A1 (ABCA1) reverse cholesterol transport channel has been associated with a number of phenotypes in breast cancer, including reduced proliferation and increased metastatic capacity. It is induced in an epithelial–mesenchymal transition (EMT), but little is known about how this occurs, and whether it is sufficient to promote metastatic phenotypes. To address these questions, we have deciphered the transcriptional regulation of ABCA1 across EMT states and found that it is repressed by MYC via an E-box element in its P1 alternative promoter. De-repression of the promoter by MYC knockdown leads to induction of ABCA1 expression. This indicates that ABCA1 expression is regulated in an EMT, revealing another link between ABCA1 and malignant phenotypes.
Genetics and Clinical Neuroscience in Intellectual Disability
Authors: Romano Corrado
Published: March 2022

This editorial summarizes the main information leading to a Special Issue on intellectual disability [...]
Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder
Authors: Gupta Ria , Mehan Sidharth , Sethi Pranshul , Prajapati Aradhana , Alshammari Abdulrahman , Alharbi Metab , Al-Mazroua Haneen A. , Narula Acharan S.
Published: March 2022

Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug’s effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD.
Study of Internal Drainage Systems for Steel Bridge Deck Pavements
Authors: Nie Wen , Wang Duanyi , Huang Jian , Jiang Caifeng , Yan Junjian
Published: March 2022

As large span steel bridges develop rapidly, the type of steel deck paving is also diversifying. However, the current steel deck paving layer is a dense-graded mixture of both upper and lower layers. This makes it difficult for water to drain out of the dense deck when it enters the interior of the deck, and the deck is easily damaged by the traffic load. This paper aims to prolong the service life of the pavement and solve the problem that the pavement is prone to water damage under the existing pavement system. In this paper, a new steel bridge deck paving system is formed by developing a new type of waterproofing binder layer material and developing an open-graded paving layer underlayment. Through indoor tests and finite element software analysis, the effect of the environment on the pull-out strength of the waterproofing binder layer material under different permaculture conditions is investigated; a suitable void ratio control range for the paving layer is explored through paving layer seepage analysis and indoor tests. The study revealed that the new epoxy resin waterproofing bonding layer was able to maintain a large pull-out strength value in a 60 °C water bath for 2 weeks. The paving with void ratios of 18, 20, and 22% were all able to drain 50% of the water inside the paving within 2 h, with excellent drainage capacity. Based on the modeling analysis and indoor test results, the target void ratio of the asphalt mix under the pavement is recommended to be controlled at 20–22%, with a void ratio in this range to solve the problem of water entering the steel bridge deck pavement and causing pavement distress.
Major Barriers and Best Solutions to the Adoption of Ethics and Compliance Program in Chinese International Construction Companies: A Sustainable Development Perspective
Authors: Luo Min , Hwang Bon-Gang , Deng Xiaopeng , Zhang Na , Chang Tengyuan
Published: March 2022

Unethical behavior is one of the grand challenges facing international construction companies (ICCs) to move toward sustainable development when operating on an international basis. The ethics and compliance program (ECP) has played a significant role in addressing illegal and unethical behavior and avoiding liability in multinational companies. However, there have been few studies on the current status, major barriers, and best solutions to ECP adoption in ICCs. To fill this gap, an international questionnaire was conducted; 87 valid samples of Chinese ICCs located in 44 countries were filtered out for in-depth analysis. The survey results showed that only 36.8% of responding ICCs exercised compliance functions through the compliance department. The top five recognized barriers hampering ECP adoption were “lack of related laws and regulations”, “insufficient support from the government”, “lack of authorization to the compliance department”, “shortage of compliance professionals”, and “lack of case studies”. There was no disagreement about the barriers’ rankings among organizations of different firm ownerships, sizes, and locations, except the variable “great institutional distance”. Results also revealed the top five best solutions to help ICCs overcome the identified barriers. The findings would enhance the understanding of industry practitioners and policymakers, hence helping them address corresponding solutions to boost ECP adoption and promote the sustainable development of ICCs.
Building and Health: Mapping the Knowledge Development of Sick Building Syndrome
Authors: Wang Mengmeng , Li Lili , Hou Caixia , Guo Xiaotong , Fu Hanliang
Published: March 2022

At present, with more and more attention paid to the impact of buildings on the health and well-being of occupants, sick building syndrome (SBS) has become a global concern. Since the introduction of SBS by the World Health Organization (WHO) in 1983, thousands of research literatures have been published in this field. This paper systematically arranges knowledge development of SBS through bibliometric analysis, exploring the most influential countries, institutions, journals and scholars, as well as the main subject categories and keywords. Main path analysis (MPA) was used to list development trajectory under inheritance relationship of SBS knowledge, including symptom analysis, risk factors of SBS and the improved impact of ventilation on SBS and productivity. Furthermore, it is an emerging research trend to propose SBS solution in the building design stage.
Data-Driven Approach to Forecast Heat Consumption of Buildings with High-Priority Weather Data
Authors: Golmohamadi Hessam
Published: March 2022

By increasing the penetration of renewable energies in district heating (DH), the intermittency of the supply-side increases for heating service providers. Therefore, forecasting the energy consumption of buildings is needed in order to hedge against renewable power intermittency. This paper investigates the application of data-driven approaches to forecast the heat consumption of buildings in the winter, using high-priority weather data. The residential buildings are connected to mixing loops of DH to supply space heating and hot water. The heating consumption of the building is calculated using sensor data, including inflow/outflow temperature and mass flow. Principal component analysis (PCA) is applied to determine the key weather data affecting heat energy consumption. Then, the study compares the competences of artificial neural networks (ANNs), linear regression models (LRM), and k-nearest neighbors (k-NN) in forecasting heat consumption, using informative data. Based on the PCA analysis, ambient temperature and solar irradiation are shown to be the highest priority weather data, contributing to 40.6% and 29.2% of heat energy forecasting, respectively. Furthermore, the ANN exhibits a forecasting accuracy of more than 50% higher than LRM and k-NN.
Patchless Multi-Stage Transfer Learning for Improved Mammographic Breast Mass Classification
Authors: Ayana Gelan , Park Jinhyung , Choe Se-woon
Published: March 2022

Despite great achievements in classifying mammographic breast-mass images via deep-learning (DL), obtaining large amounts of training data and ensuring generalizations across different datasets with robust and well-optimized algorithms remain a challenge. ImageNet-based transfer learning (TL) and patch classifiers have been utilized to address these challenges. However, researchers have been unable to achieve the desired performance for DL to be used as a standalone tool. In this study, we propose a novel multi-stage TL from ImageNet and cancer cell line image pre-trained models to classify mammographic breast masses as either benign or malignant. We trained our model on three public datasets: Digital Database for Screening Mammography (DDSM), INbreast, and Mammographic Image Analysis Society (MIAS). In addition, a mixed dataset of the images from these three datasets was used to train the model. We obtained an average five-fold cross validation AUC of 1, 0.9994, 0.9993, and 0.9998 for DDSM, INbreast, MIAS, and mixed datasets, respectively. Moreover, the observed performance improvement using our method against the patch-based method was statistically significant, with a p-value of 0.0029. Furthermore, our patchless approach performed better than patch- and whole image-based methods, improving test accuracy by 8% (91.41% vs. 99.34%), tested on the INbreast dataset. The proposed method is of significant importance in solving the need for a large training dataset as well as reducing the computational burden in training and implementing the mammography-based deep-learning models for early diagnosis of breast cancer.
Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development
Authors: Manara Francesca , Jay Antonin , Odongo Grace , Mure Fabrice , Maroui Mohamed , Diederichs Audrey , Sirand Cecilia , Cuenin Cyrille , Granai Massimo , Mundo Lucia , Hernandez-Vargas Hector , Lazzi Stefano , Khoueiry Rita , Gruffat Henri , Herceg Zdenko , Accardi Rosita
Published: March 2022

Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein–Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV–AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-κB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies.
Molecular Landscape of Small Bowel Adenocarcinoma
Authors: Pandya Karan , Overman Michael J. , Gulhati Pat
Published: March 2022

Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and poor overall prognosis compared to other cancers of the gastrointestinal tract. Owing to the rarity of the disease along with the paucity of high-quality tissue samples and preclinical models, little is known about the molecular alterations characteristic of SBA. This is reflected by the fact that the clinical management of SBA is primarily extrapolated from colorectal cancer (CRC). Recent advances in genomic profiling have highlighted key differences between these tumors, establishing SBA as a molecularly unique intestinal cancer. Moreover, comprehensive molecular analysis has identified a relatively high incidence of potentially targetable genomic alterations in SBA, predictive of response to targeted and immunotherapies. Further advances in our knowledge of the mutational and transcriptomic landscape of SBA, guided by an increased understanding of the molecular drivers of SBA, will provide opportunities to develop novel diagnostic tools and personalized therapeutic strategies.
Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study
Authors: Kao Sung-Shuo , Li Chia-Jung , Wei James Cheng-Chung , Lin Cheng-Li , Chang Renin , Hung Yao-Min
Published: March 2022

Background: Hepatitis C virus (HCV) has been shown to be associated with human papillomavirus (HPV)-positive head and neck cancers. However, studies regarding HPV infection and the risk of new-onset hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients are limited. We examined the risk of HCC in CHC patients with or without HPV infection. Methods: In total, 9905 CHC patients from 2000 to 2016 constituted the whole cohort. HPV was defined as being diagnosed after HCV. The CHC cohort with HPV (N = 1981) and age-, sex-, inception point-, comorbidity-, and medication-matched non-HPV (N = 7924) were followed up until HCC, death, or 2018. HCC patients were extracted from the Taiwan Registry for Catastrophic Illness Database. We adopted the propensity score match and inverse probability of treatment weighting (IPTW) to eliminate bias. Cox proportional hazard regression analyses were performed to calculate HCC risk. Results: After a full adjustment, HPV was not associated with HCC risk (aHR, 0.74; 95% CI, 0.58–0.96 in the main model, and aHR, 0.76; 95% CI, 0.66–0.87 in IPTW, respectively). Almost all subgroup analyses verified this finding (HRs < 1.0). Conclusions: Among CHC patients older than 18 years old, those with HPV infection were associated with a lower risk of subsequent HCC.
Kinetic Model of Catalytic Steam Gasification of 2-Methoxy-4-methylphenol Using 5% Ni–0.25% Ru/γAl2O3 in a CREC-Riser Simulator
Authors: Calzada Hernandez Alán Rubén , Serrano Rosales Benito , de Lasa Hugo
Published: March 2022

Hydrogen is an energy vector with a great potential due its ample range of applications and clean combustion cycle. Hydrogen can be produced through biomass steam gasification, with novel catalysts being of significant value to implement this process. With this goal in mind, in the present study, 5 wt % Ni/γAl2O3 promoted with 0.25 wt % Ru was synthesized and characterized. It is assumed that ruthenium facilitates hydrogen transfer to nickel oxide sites, promoting a hydrogen spillover effect, with the H2 adsorbed on Ru being transported to Ni sites. To describe chemical changes, the present study considers a kinetic model involving Langmuir–Hinshelwood-based rate equations, as a sum of independent reactions, with this being applied to the steam gasification of 2-methoxy-4-methylphenol (2M4MP). This tar biomass surrogate was studied in a fluidized CREC (Chemical Reactor Engineering Centre) Riser Simulator reactor, at different reaction times (5, 20 and 30 s.) and temperatures (550 °C, 600 °C and 650 °C). The proposed kinetics model was fitted to the experimentally observed H2, CO2, CO, CH4 and H2O concentrations, with the estimated pre-exponential factors and activation energies being in accordance with the reported literature data. It is anticipated that the postulated model could be of significant value for the modeling of other biomass conversion processes for hydrogen production using other supported catalysts.
Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo
Authors: Goeritzer Madeleine , Schlager Stefanie , Kuentzel Katharina B. , Vujić Nemanja , Korbelius Melanie , Rainer Silvia , Kolb Dagmar , Mussbacher Marion , Salzmann Manuel , Schrottmaier Waltraud C. , Assinger Alice , Schlagenhauf Axel , Madreiter-Sokolowski Corina T. , Blass Sandra , Eichmann Thomas O. , Graier Wolfgang F. , Kratky Dagmar
Published: March 2022

According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency in platelets are unknown, we used whole-body and platelet-specific (plat)Atgl-deficient (−/−) mice to investigate the loss of ATGL on platelet function. Our results showed that platelets accumulate only a few LD due to lack of ATGL. Stimulation with platelet-activating agonists resulted in comparable platelet activation in Atgl−/−, platAtgl−/−, and wild-type mice. Measurement of mitochondrial respiration revealed a decreased oxygen consumption rate in platelets from Atgl−/− but not from platAtgl−/− mice. Of note, global loss of ATGL was associated with an anti-thrombogenic phenotype, which was evident by reduced thrombus formation in collagen-coated channels in vitro despite unchanged bleeding and occlusion times in vivo. We conclude that genetic deletion of ATGL affects collagen-induced thrombosis without pathological bleeding and platelet activation.
Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress
Authors: Li Yanan , Li Shujing , Wu Huijian
Published: March 2022

In response to environmental stimuli, cells make a series of adaptive changes to combat the injury, repair the damage, and increase the tolerance to the stress. However, once the damage is too serious to repair, the cells will undergo apoptosis to protect the overall cells through suicidal behavior. Upon external stimulation, some intracellular proteins turn into unfolded or misfolded protein, exposing their hydrophobic regions to form protein aggregation, which may ultimately produce serious damage to the cells. Ubiquitin plays an important role in the degradation of these unnatural proteins by tagging with ubiquitin chains in the ubiquitin–proteasome or autophagy system. If the two processes fail to eliminate the abnormal protein aggregates, the cells will move to apoptosis and death. Dysregulation of ubiquitin–proteasome system (UPS) and autophagy may result in the development of numerous diseases. This review focuses on the molecular mechanisms of UPS and autophagy in clearance of intracellular protein aggregates, and the relationship between dysregulation of ubiquitin network and diseases.
RNAi-Mediated Screen of Primary AML Cells Nominates MDM4 as a Therapeutic Target in NK-AML with DNMT3A Mutations
Authors: Sidorova Olga Alexandra , Sayed Shady , Paszkowski-Rogacz Maciej , Seifert Michael , Camgöz Aylin , Roeder Ingo , Bornhäuser Martin , Thiede Christian , Buchholz Frank
Published: March 2022

DNA-methyltransferase 3A (DNMT3A) mutations belong to the most frequent genetic aberrations found in adult acute myeloid leukemia (AML). Recent evidence suggests that these mutations arise early in leukemogenesis, marking leukemic progenitors and stem cells, and persist through consolidation chemotherapy, providing a pool for AML relapse. Currently, there are no therapeutic approaches directed specifically against this cell population. To unravel therapeutically actionable targets in mutant DNMT3A-driven AML cells, we have performed a focused RNAi screen in a panel of 30 primary AML samples, all carrying a DNMT3A R882 mutation. As one of the strongest hits, we identified MDM4 as a gene essential for proliferation of primary DNMT3AWT/R882X AML cells. We analyzed a publicly available RNA-Seq dataset of primary normal karyotype (NK) AML samples and found a trend towards MDM4 transcript overexpression particularly in DNMT3A-mutant samples. Moreover, we found that the MDM2/4 inhibitor ALRN-6924 impairs growth of DNMT3AWT/R882X primary cells in vitro by inducing cell cycle arrest through upregulation of p53 target genes. Our results suggest that MDM4 inhibition is a potential target in NK-AML patients bearing DNMT3A R882X mutations.
Iron Supplementation Delays Aging and Extends Cellular Lifespan through Potentiation of Mitochondrial Function
Authors: Jing Jovian Lin , Ning Trishia Cheng Yi , Natali Federica , Eisenhaber Frank , Alfatah Mohammad
Published: March 2022

Aging is the greatest challenge to humankind worldwide. Aging is associated with a progressive loss of physiological integrity due to a decline in cellular metabolism and functions. Such metabolic changes lead to age-related diseases, thereby compromising human health for the remaining life. Thus, there is an urgent need to identify geroprotectors that regulate metabolic functions to target the aging biological processes. Nutrients are the major regulator of metabolic activities to coordinate cell growth and development. Iron is an important nutrient involved in several biological functions, including metabolism. In this study using yeast as an aging model organism, we show that iron supplementation delays aging and increases the cellular lifespan. To determine how iron supplementation increases lifespan, we performed a gene expression analysis of mitochondria, the main cellular hub of iron utilization. Quantitative analysis of gene expression data reveals that iron supplementation upregulates the expression of the mitochondrial tricarboxylic acid (TCA) cycle and electron transport chain (ETC) genes. Furthermore, in agreement with the expression profiles of mitochondrial genes, ATP level is elevated by iron supplementation, which is required for increasing the cellular lifespan. To confirm, we tested the role of iron supplementation in the AMPK knockout mutant. AMPK is a highly conserved controller of mitochondrial metabolism and energy homeostasis. Remarkably, iron supplementation rescued the short lifespan of the AMPK knockout mutant and confirmed its anti-aging role through the enhancement of mitochondrial functions. Thus, our results suggest a potential therapeutic use of iron supplementation to delay aging and prolong healthspan.