bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification, Isolation, and Characterization of Melanocyte Precursor Cells in the Human Limbal Stroma
Authors: Li Shen , Zenkel Matthias , Kruse Friedrich E. , Gießl Andreas , Schlötzer-Schrehardt Ursula
Published: March 2022

Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes originating from the limbal epithelium, using magnetic-activated cell sorting (MACS) with positive (CD117/c-Kit microbeads) or negative (CD326/EpCAM or anti-fibroblast microbeads) selection approaches. Both approaches enabled fast and easy isolation and cultivation of pure limbal epithelial and stromal melanocyte populations, which differed in phenotype and gene expression, but exhibited similar functional properties regarding proliferative potential, pigmentation, and support of clonal growth of limbal epithelial stem/progenitor cells (LEPCs). In both melanocyte populations, limbus-specific matrix (laminin 511-E8) and soluble factors (LEPC-derived conditioned medium) stimulated melanocyte adhesion, dendrite formation, melanogenesis, and expression of genes involved in UV protection and immune regulation. The findings provided not only a novel protocol for the enrichment of pure melanocyte populations from limbal tissue applying easy-to-use MACS technology, but also identified a population of stromal melanocyte precursors, which may serve as a reservoir for the replacement of damaged epithelial melanocytes and an alternative resource for tissue engineering applications.
Future Challenges and Opportunities of Extracellular Matrix Hydrogels in Female Reproductive Medicine
Authors: Francés-Herrero Emilio , Rodríguez-Eguren Adolfo , Gómez-Álvarez María , de Miguel-Gómez Lucía , Ferrero Hortensia , Cervelló Irene
Published: March 2022

Bioengineering and reproductive medicine have progressed shoulder to shoulder for several decades. A key point of overlap is the development and clinical translation of technologies to support reproductive health, e.g., scaffold-free constructs, polymeric scaffolds, bioprinting or microfluidics, and hydrogels. Hydrogels are the focus of intense study, and those that are derived from the extracellular matrix (ECM) of reproductive tissues and organs are emerging as promising new players given their results in pre-clinical models. This literature review addresses the recent advances in the use of organ-specific ECM hydrogels in reproductive medicine, considering the entire female reproductive tract. We discuss in-depth papers describing the development of ECM hydrogels, their use in in vitro models, and their in vivo application in preclinical studies. We also summarize the functions of hydrogels, including as grafts, carriers for cell transplantation, or drug depots, and present the potential and possible scope for use of ECM hydrogels in the near future based on recent scientific advances.
Store-Operated Ca2+ Entry in Skeletal Muscle Contributes to the Increase in Body Temperature during Exertional Stress
Authors: Girolami Barbara , Serano Matteo , Michelucci Antonio , Pietrangelo Laura , Protasi Feliciano
Published: March 2022

Exertional heat stroke (HS) is a hyperthermic crisis triggered by an excessive accumulation of Ca2+ in skeletal muscle fibers. We demonstrated that exercise leads to the formation of calcium entry units (CEUs), which are intracellular junctions that reduce muscle fatigue by promoting the recovery of extracellular Ca2+ via store-operated Ca2+ entry (SOCE). Here, we tested the hypothesis that exercise-induced assembly of CEUs may increase the risk of HS when physical activity is performed in adverse environmental conditions (high temperature and humidity). Adult mice were: (a) first, divided into three experimental groups: control, trained-1 month (voluntary running in wheel cages), and acutely exercised-1 h (incremental treadmill run); and (b) then subjected to an exertional stress (ES) protocol, a treadmill run in an environmental chamber at 34 °C and 40% humidity. The internal temperature of the mice at the end of the ES was higher in both pre-exercised groups. During an ES ex-vivo protocol, extensor digitorum longus(EDL) muscles from the trained-1 month and exercised-1 h mice generated greater basal tension than in the control and were those that contained a greater number of CEUs, assessed by electron microscopy. The data collected suggest that the entry of Ca2+ from extracellular space via CEUs could contribute to exertional HS when exercise is performed in adverse environmental conditions.
Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
Authors: Vadana Mihaela , Cecoltan Sergiu , Ciortan Letitia , Macarie Razvan D. , Mihaila Andreea C. , Tucureanu Monica M. , Gan Ana-Maria , Simionescu Maya , Manduteanu Ileana , Droc Ionel , Butoi Elena
Published: March 2022

Parathyroid hormone (PTH) is a key regulator of calcium, phosphate and vitamin D metabolism. Although it has been reported that aortic valve calcification was positively associated with PTH, the pathophysiological mechanisms and the direct effects of PTH on human valvular cells remain unclear. Here we investigated if PTH induces human valvular endothelial cells (VEC) dysfunction that in turn could impact the switch of valvular interstitial cells (VIC) to an osteoblastic phenotype. Human VEC exposed to PTH were analyzed by qPCR, western blot, Seahorse, ELISA and immunofluorescence. Our results showed that exposure of VEC to PTH affects VEC metabolism and functions, modifications that were accompanied by the activation of p38MAPK and ERK1/2 signaling pathways and by an increased expression of osteogenic molecules (BMP-2, BSP, osteocalcin and Runx2). The impact of dysfunctional VEC on VIC was investigated by exposure of VIC to VEC secretome, and the results showed that VIC upregulate molecules associated with osteogenesis (BMP-2/4, osteocalcin and TGF-β1) and downregulate collagen I and III. In summary, our data show that PTH induces VEC dysfunction, which further stimulates VIC to differentiate into a pro-osteogenic pathological phenotype related to the calcification process. These findings shed light on the mechanisms by which PTH participates in valve calcification pathology and suggests that PTH and the treatment of hyperparathyroidism represent a therapeutic strategy to reduce valvular calcification.
Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options
Authors: Sas Zuzanna , Cendrowicz Ewa , Weinhäuser Isabel , Rygiel Tomasz P.
Published: March 2022

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease. In many cases, HCC is an effect of chronic liver inflammation, which leads to the formation of a complex tumor microenvironment (TME) composed of immune and stromal cells. The TME of HCC patients is a challenge for therapies, as it is involved in metastasis and the development of resistance. However, given that the TME is an intricate system of immune and stromal cells interacting with cancer cells, new immune-based therapies are being developed to target the TME of HCC. Therefore, understanding the complexity of the TME in HCC will provide new possibilities to design novel and more effective immunotherapeutics and combinatorial therapies to overcome resistance to treatment. In this review, we describe the role of inflammation during the development and progression of HCC by focusing on TME. We also describe the most recent therapeutic advances for HCC and possible combinatorial treatment options.
Editorial for Special Issue “Perspectives and Challenges in Doctoral Research—Selected Papers from the 9th Edition of the Scientific Conference of the Doctoral Schools from the “Dunărea de Jos”
Authors: Rusu Eugen , Rapeanu Gabriela
Published: March 2022

This Editorial is dedicated to the 9th edition of the Scientific Conference organized by the Doctoral Schools of “Dunărea de Jos” University of Galati (SCDS-UDJG), which was organized in June 2021 in Galati (Romania) [...]
Intravascular Lithotripsy for the Treatment of Stent Underexpansion: The Multicenter IVL-DRAGON Registry
Authors: Wańha Wojciech , Tomaniak Mariusz , Wańczura Piotr , Bil Jacek , Januszek Rafał , Wolny Rafał , Opolski Maksymilian P. , Kuźma Łukasz , Janas Adam , Figatowski Tomasz , Gąsior Paweł , Milewski Marek , Roleder-Dylewska Magda , Lewicki Łukasz , Kulczycki Jan , Włodarczak Adrian , Tomasiewicz Brunon , Iwańczyk Sylwia , Sacha Jerzy , Koltowski Łukasz , Dziarmaga Miłosz , Jaguszewski Miłosz , Kralisz Paweł , Olajossy Bartosz , Sobieszek Grzegorz , Dyrbuś Krzysztof , Łebek Mariusz , Smolka Grzegorz , Reczuch Krzysztof , Gil Robert J. , Dobrzycki Sławomir , Kwiatkowski Piotr , Rogala Marcin , Gąsior Mariusz , Ochała Andrzej , Kochman Janusz , Witkowski Adam , Lesiak Maciej , D’Ascenzo Fabrizio , Bartuś Stanisław , Wojakowski Wojciech
Published: March 2022

Background: Whereas the efficacy and safety of intravascular lithotripsy (IVL) have been confirmed in de novo calcified coronary lesions, little is known about its utility in treating stent underexpansion. This study aimed to investigate the impact of IVL in treating stent underexpansion. Methods and Results: Consecutive patients with stent underexpansion treated with IVL entered the multicenter IVL-Dragon Registry. The procedural success (primary efficacy endpoint) was defined as a relative stent expansion >80%. Thirty days device-oriented composite endpoint (DOCE) (defined as a composite of cardiac death, target lesion revascularization, or target vessel myocardial infarction) was the secondary endpoint. A total of 62 patients were enrolled. The primary efficacy endpoint was achieved in 72.6% of patients. Both stent underexpansion 58.5% (47.5–69.7) vs. 11.4% (5.8–20.7), p < 0.001, and the stenotic area 82.6% (72.4–90.8) vs. 21.5% (11.1–37.2), p < 0.001, measured by quantitative coronary angiography improved significantly after IVL. Intravascular imaging confirmed increased stent expansion following IVL from 37.5% (16.0–66.0) to 86.0% (69.2–90.7), p < 0.001, by optical coherence tomography and from 57.0% (31.5–77.2) to 89.0% (85.0–92.0), p = 0.002, by intravascular ultrasound. Secondary endpoint occurred in one (1.6%) patient caused by cardiac death. There was no target lesion revascularization or target vessel myocardial infarction during the 30-day follow-up. Conclusions: In this real-life, largest-to-date analysis of IVL use to manage underexpanded stent, IVL proved to be an effective and safe method for facilitating stent expansion and increasing luminal gain.
Augmented Reality Games and Presence: A Systematic Review
Authors: Marto Anabela , Gonçalves Alexandrino
Published: March 2022

The sense of presence in augmented reality (AR) has been studied by multiple researchers through diverse applications and strategies. In addition to the valuable information provided to the scientific community, new questions keep being raised. These approaches vary from following the standards from virtual reality to ascertaining the presence of users’ experiences and new proposals for evaluating presence that specifically target AR environments. It is undeniable that the idea of evaluating presence across AR may be overwhelming due to the different scenarios that may be possible, whether this regards technological devices—from immersive AR headsets to the small screens of smartphones—or the amount of virtual information that is being added to the real scenario. Taking into account the recent literature that has addressed the sense of presence in AR as a true challenge given the diversity of ways that AR can be experienced, this study proposes a specific scope to address presence and other related forms of dimensions such as immersion, engagement, embodiment, or telepresence, when AR is used in games. This systematic review was conducted following the PRISMA methodology, carefully analysing all studies that reported visual games that include AR activities and somehow included presence data—or related dimensions that may be referred to as immersion-related feelings, analysis or results. This study clarifies what dimensions of presence are being considered and evaluated in AR games, how presence-related variables have been evaluated, and what the major research findings are. For a better understanding of these approaches, this study takes note of what devices are being used for the AR experience when immersion-related feelings are one of the behaviours that are considered in their evaluations, and discusses to what extent these feelings in AR games affect the player’s other behaviours.
Numerical Study of Local Scour around Tripod Foundation in Random Waves
Authors: Hu Ruigeng , Wang Xiuhai , Liu Hongjun , Chen Da
Published: March 2022

In this study, the local scour around tripods in random waves is numerically investigated. The seabed-tripod-fluid numerical model with an RNG k−ε turbulence model is built and validated. Following that, the scour characteristics and flow velocity distribution are analyzed using the present numerical model. Finally, a revised stochastic model is proposed to predict the equilibrium scour depth, Seq, around tripods in random waves. The results indicate that the present seabed-tripod-fluid numerical model is capable of depicting the scour process and of capturing the flow field around tripods with high accuracy. Due to the blockage effects of the main column and structural elements, there is enhanced flow acceleration underneath the main column and the lower diagonal braces, which increases the turbulence intensity and seabed shear stress, causing more particles to be mobilized and transported, resulting in more severe scour at the site. The revised stochastic model shows the best agreement with the numerical and experimental results when n = 20, but more experimental data and numerical results are still needed to verify the adaptation of the revised stochastic model for larger Keulegan–Carpenter (KC) number conditions (KCrms,a > 4).
Grazing Effects of Soil Fauna on White-Rot Fungi: Biomass, Enzyme Production and Litter Decomposition Ability
Authors: Chen Yunru , Cao Tingting , Lv Meiqi , Fang You , Liu Run , Luo Yunchao , Xu Chi , Tian Xingjun
Published: March 2022

Soil invertebrates and microorganisms are two major drivers of litter decomposition. Even though the importance of invertebrates and microorganisms in biogeochemical soil cycles and soil food webs has been studied, the effects of invertebrates on fungi are not well understood compared to other organisms. In this work, we investigated the effects of soil invertebrates on fungi as a factor that cannot be ignored in the study of nutrient cycling. The result showed the grazing of isopods on white-rot fungi was transitive and persistent. The grazed fungi appeared “compensatory” growing. The biomass of fungi increased after grazing. The activities of enzymes associated with nutrient cycling were increased under grazing. The zymography images showed the enzyme hotspots and activities also increased significantly in the grazing area. The results suggest that invertebrate grazing can significantly increase the fungal biomass and enzyme activity, accelerating litter decomposition in the unreached grazer area. The grazing effects of invertebrate plays an important role in promoting the nutrient cycling of the forest ecosystem. We believe that this study will be a good reference related to showing the relationship between soil invertebrates, fungi and soil biogeochemical cycles.
In Vitro and In Vivo Activity of Luliconazole (NND-502) against Planktonic Cells and Biofilms of Azole Resistant Aspergillus fumigatus
Authors: Furnica Dan-Tiberiu , Dittmer Silke , Sanders Maike Isabell , Steinmann Joerg , Rath Peter-Michael , Kirchhoff Lisa
Published: March 2022

Aspergillus fumigatus has become a significant threat in clinical settings. Cases of invasive infections with azole-resistant A. fumigatus isolates (ARAF) increased recently. Developing strategies for dealing with ARAF has become crucial. We here investigated the in-vitro and in-vivo activity of the imidazole luliconazole (LLCZ) against clinical ARAF. In total, the LLCZ minimum inhibitory concentrations (MICs) were tested for 101 A. fumigatus isolates (84 ARAF and 17 azole-susceptible A. fumigatus as wild-type controls) according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Additionally, antifungal activity was assessed in vitro, including an XTT planktonic growth kinetics assay and biofilm assays (crystal violet and XTT assay). Further, a single-dose LLCZ treatment (152 mg/L) was tested for seven days in vivo in a Galleria mellonella infection model. LLCZ showed an MIC50 of 0.002 mg/L and no significant difference was found between triazole-resistant and wild-type isolates. Growth inhibition took place between 6 and 12 h after the start of incubation. LLCZ inhibited biofilm formation when added in the pre-adhesion stages. In vivo, single-dose LLCZ-treated larvae show a significantly higher survival percentage than the control group (20%). In conclusion, LLCZ has activity against planktonic cells and early biofilms of ARAF.
High-Sensitivity Troponin T: A Potential Safety Predictive Biomarker for Discharge from the Emergency Department of Patients with Confirmed Influenza
Authors: Tazón-Varela Manuel Antonio , Ortiz de Salido-Menchaca Jon , Muñoz-Cacho Pedro , Iriondo-Bernabeu Enara , Martos-Almagro María Josefa , Lavín-López Emma , Vega-Zubiaur Ander , Escalona-Canal Edgar José , Alcalde-Díez Iratxe , Gómez-Vildosola Carmen , Belzunegui-Gárate Ainhoa , Espinoza-Cuba Fabiola , López-Cejuela José Antonio , García-García Alba , Torrejón-Cereceda Alejandro , Nisa-Martínez Elena Sabina , Moreira Nieto Diana , Hellín-Mercadal Cintia , García-Caballero Ander , Alonso-Valle Héctor
Published: March 2022

The purpose of the study was to analyze the relationship between the high-sensitivity troponin T levels in patients with confirmed influenza virus infection and its severity determined by mortality during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow us to a safe discharge from the emergency department. An analytical retrospective observational study was designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed until the resolution of the clinical picture, and the frequency of mortality is analyzed. We included patients ≥ 16 years old with confirmed influenza virus infection and determination of high-sensitivity troponin T. One hundred twenty-eight patients were included (96.9% survivors, 3.1% deceased). Mean and median blood levels of high-sensitivity troponin T of survivors were 26.2 ± 58.3 ng/L and 14.5 ng/L (IQR 16 ng/L), respectively, and were statistically different when compared with those of the deceased patients, 120.5 ± 170.1 ng/L and 40.5 ng/L (IQR 266.5 ng/L), respectively, p = 0.012. The Youden index using mortality as the reference method was 0.76, and the cut-off value associated with this index was 24 ng/L (sensitivity 100%, specificity 76%, NPV 100%, PPV 4%) with AUC of 88,8% (95% CI: 79.8–92.2%), p < 0.001. We conclude that high-sensitivity troponin T levels in confirmed virus influenza infection are a good predictor of mortality in our population, and this predictor is useful for safely discharging patients from the emergency department.
Urban Gardening and Wellbeing in Pandemic Era: Preliminary Results from a Socio-Environmental Factors Approach
Authors: Harding Diana , Lukman Kevin Muhamad , Jingga Matheus , Uchiyama Yuta , Quevedo Jay Mar D. , Kohsaka Ryo
Published: March 2022

The nature and impacts of living in urban settings are gaining their saliences in developed and developing countries alike, particularly during the crisis of the COVID-19 pandemic. During the crisis, the wellbeing of urban society became intertwined with a so-called “new lifestyle”, which involved quarantine and working in a home environment. Facing such challenges, urban gardening is deemed as an alternative intervention to enhance residents’ wellbeing and the environmental sustainability of urban areas, including Indonesian cities. A preliminary study was conducted to monitor the wellbeing of urban gardening practitioners, as well as investigate the motivation and any association between gardening and wellbeing with the COVID-19 pandemic situation by analysing data from Indonesian metropolitan areas. The study utilized instruments of “satisfaction with life scale (SWLS)” and “scale of positive and negative experience (SPANE)” to investigate the subjective wellbeing of 67 respondents. Amongst others, we identified that urban gardening practitioners tend to be in positive moods and have better overall wellbeing; 52.24% of the respondents were highly satisfied with their life. Furthermore, we observed a variety of motivations to start gardening, with hobby and utilization of free space as prominent reasons, followed by other motivations such as environmental benefit and aesthetic. Integrating the environmental benefits of urban gardening and the implications for an individual’s wellbeing can be reflected for sustainable urban development and policies during the COVID-19 pandemic.
Variability of Permafrost and Landscape Conditions Following Forest Fires in the Central Yakutian Taiga Zone
Authors: Petrov Marat I. , Fedorov Alexander N. , Konstantinov Pavel Y. , Argunov Radomir N.
Published: March 2022

In the last two decades in Central Yakutia, there has been a significant change in cryogenic landscapes related to climate warming and anthropogenic disturbances. This period is characterized by the activity of forest fires, which significantly impact permafrost landscapes. We observed the dynamics of cryogenic landscapes after a forest fire in 2001 at the Neleger station in Central Yakutia, 35 km northwest of Yakutsk. The observations included ground temperature and active layer thickness monitoring and statements of changes in the soil moisture content of the active layer. Increases in ground temperature, the active layer thickness, and soil moisture content on the burnt site after a forest fire in Neleger station were noted in the first six to seven years after the disturbance. We found that, following forest fires, permafrost progressively restabilizes as forest cover redevelops over time. The results of the studies will become the basis for planning restoration work after forest fires in permafrost landscapes of Central Yakutia.
Fatty Acid-Binding Proteins 4 and 5 Are Involved in the Pathogenesis of Retinal Vascular Diseases in Different Manners
Authors: Higashide Megumi , Furuhashi Masato , Watanabe Megumi , Itoh Kaku , Suzuki Soma , Umetsu Araya , Tsugeno Yuri , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: March 2022

This study reports on the pathological significance of the vitreous fatty acid-binding protein (Vt-FABP) 4 and 5, and vascular endothelial growth factor A (Vt-VEGFA) in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO). Subjects with PDR (n = 20), RVO (n = 10), and controls (epiretinal membrane, n = 18) who had undergone vitrectomies were enrolled in this study. The levels of Vt-FABP4, Vt-FABP5, and Vt-VEGFA were evaluated by enzyme-linked immunosorbent assays (ELISA). Retinal circulation levels were measured by a laser-speckle flow analyzer (LSFA) and other relevant data were collected. The Vt-FABP5 levels were significantly (p < 0.05) elevated in patients with RVDs compared to control patients. This elevation was more evident in patients with RVO than with PDR. Log Vt-FABP5 was significantly correlated negatively or positively with all the LSFA retinal circulation indexes or Log triglycerides (r = 0.31, p = 0.031), respectively. However, the elevations in the Vt-FABP4 and Vt-VEGFA levels were more evident in the PDR group (p < 0.05) and these factors were correlated positively with Log fasting glucose and negatively with some of the LSFA retinal circulation indexes. Multivariable regression analyses indicated that the LSFA blood flows of the optic disc at baseline was an independent effector with Log Vt-FABP5 other than several possible factors including age, gender, Log triglycerides, Log Vt-FABP4 and Log Vt-VEGFA. These current findings suggest that Vt-FABP5 is involved in the pathogenesis of RVD in a manner that is different from that for Vt-FABP4 and Vt-VEGFA, presumably by regulating retinal circulation.
Study of Microstructure and Fatigue in Aluminum/Steel Butt Joints Made by CMT Fusion-Brazing Technology
Authors: Fang Yu , Yang Shanglei , Huang Yubao , Meng Xuan
Published: March 2022

Cold metal transfer (CMT) fusion brazing technology was used to weld 6061 aluminum alloy and Q235 galvanized steel with ER4043 welding wire. The microstructure, hardness, tensile performance, and fatigue performance of the welded joint were observed and analyzed. The results show that the tensile strength of the welded joint is 110.83 MPa and the fatigue strength limit is 170 MPa. In the fatigue process, the coupon first undergoes cyclic hardening and then cyclic softening and a ratchet effect occurs. The coupon was broken at the interface layer or weld zone where the fatigue strength limit is the lowest. The fatigue crack initiation is mainly caused by: (1) inclusions and second-phase particles; and (2) porosity and incomplete fusion. When cracks encounter holes during expansion, the expansion direction will change. The fatigued coupon displays a toughness fracture in the instantaneous fracture zone.
The Ordering Optimization Model for Bounded Rational Retailer with Inventory Transshipment
Authors: He Qingren , Shi Taiwei , Liu Botao , Qiu Wanhua
Published: March 2022

In order to study retailers’ ordering behavior deviating from the standard theoretical optimal decision, which is caused by retailers’ information asymmetry, cognitive ability, insufficient computing ability, and other factors, we construct a bounded-rationality choice model with quantal response equilibrium. First, the existence and uniqueness of quantal response equilibrium of transshipment game have been proved with the transshipment price satisfying certain conditions. Then, the numerical example demonstrates that with the increase of bounded-rationality parameters, retailers’ quantal response equilibrium will converge to Nash equilibrium due to the learning effect, and their profits will converge to the profits predicted by standard theory. Finally, the results show that retailers are more averse to the explicit loss of shortage than to the implicit loss of inventory surplus caused by the increase of order quantity. Hence, retailers tend to overorder to avoid loss of shortage.
Reliability-Based Topology Optimization of Thermo-Elastic Structures with Stress Constraint
Authors: Zhang Liang , Zhao Qinghai , Chen Jianliang
Published: March 2022

Traditional topology optimization of thermo-elastic structures is based on deterministic conditions, without considering the influence of uncertainty factors. To address the impact uncertainty on structural strength, a reliability-based topology optimization of thermo-elastic structure with stress constraint is proposed. The probabilistic uncertainty quantities are associated with the structural material property, mechanical loads and the thermal stress coefficient with the topology optimization formulation considering volume minimization and stress constraint. The relaxation stress method combined with normalized p-norm function is adopted to condense whole element stresses into the global stress measurement that approximates the maximum stress. The adjoint variable method is utilized to derive the sensitivity of the stress constraint and the optimization problem is solved by the method of moving asymptote (MMA). Finally, several numerical examples are presented to demonstrate the effectiveness and validity of the proposed approach. Compared with the deterministic design, the reliability design has distinct topological configurations and the optimized structures maintain a higher reliability level.
Diversity of Bivariate Concordance Measures
Authors: Manstavičius Martynas
Published: March 2022

We revisit the axioms of Scarsini, defining bivariate concordance measures for a pair of continuous random variables (X,Y); such measures can be understood as functions of the bivariate copula C associated with (X,Y). Two constructions, investigated in the works of Edwards, Mikusiński, Taylor, and Fuchs, are generalized, yielding, in particular, examples of higher than degree-two polynomial-type concordance measures, along with examples of non-polynomial-type concordance measures, and providing an incentive to investigate possible further characterizations of such concordance measures, as was achieved by Edwards and Taylor for the degree-one case.
IFS-Based Image Reconstruction of Binary Images with Functional Networks
Authors: Gálvez Akemi , Fister Iztok , Iglesias Andrés , Fister Iztok , Gómez-Jauregui Valentín , Manchado Cristina , Otero César
Published: March 2022

This work addresses the IFS-based image reconstruction problem for binary images. Given a binary image as the input, the goal is to obtain all the parameters of an iterated function system whose attractor approximates the input image accurately; the quality of this approximation is measured according to a similarity function between the original and the reconstructed images. This paper introduces a new method to tackle this issue. The method is based on functional networks, a powerful extension of neural networks that uses functions instead of the scalar weights typically found in standard neural networks. The method relies on an artificial network comprised of several functional networks, one for each of the contractive affine maps forming the IFS. The method is applied to an illustrative and challenging example of a fractal binary image exhibiting a complicated shape. The graphical and numerical results show that the method performs very well and is able to reconstruct the input image using IFS with high accuracy. The results also show that the method is not yet optimal and offers room for further improvement.
Antibacterial Molecules from Marine Microorganisms against Aquatic Pathogens: A Concise Review
Authors: Guo Siya , Zhang Zongyi , Guo Lei
Published: March 2022

Antibiotic resistance and residues in aquaculture are a growing concern worldwide and consequently identifying favorable antibacterial compounds against aquatic pathogenic bacteria are gained more attention. Active compounds derived from marine microorganisms have shown great promise in this area. This review is aimed to make a comprehensive survey of anti-aquatic pathogenic bacterial compounds that were produced by marine microorganisms. A total of 79 compounds have been reported, covering literature from 1997 to 2021. The compounds are included in different structural classes such as polyketides, terpenoids, nitrogen compounds and others, and some of them present the potential to be developed into agents for the treatment of aquatic pathogenic bacteria.
5-O-(N-Boc-l-Alanine)-Renieramycin T Induces Cancer Stem Cell Apoptosis via Targeting Akt Signaling
Authors: Suksamai Darinthip , Racha Satapat , Sriratanasak Nicharat , Chaotham Chatchai , Aphicho Kanokpol , Lin Aye Chan Khine , Chansriniyom Chaisak , Suwanborirux Khanit , Chamni Supakarn , Chanvorachote Pithi
Published: March 2022

Cancer stem cells (CSCs) drive aggressiveness and metastasis by utilizing stem cell-related signals. In this study, 5-O-(N-Boc-l-alanine)-renieramycin T (OBA-RT) was demonstrated to suppress CSC signals and induce apoptosis. OBA-RT exerted cytotoxic effects with a half-maximal inhibitory concentration of approximately 7 µM and mediated apoptosis as detected by annexin V/propidium iodide using flow cytometry and nuclear staining assays. Mechanistically, OBA-RT exerted dual roles, activating p53-dependent apoptosis and concomitantly suppressing CSC signals. A p53-dependent pathway was indicated by the induction of p53 and the depletion of anti-apoptotic Myeloid leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins. Cleaved poly (ADP-ribose) polymerase (Cleaved-PARP) was detected in OBA-RT-treated cells. Interestingly, OBA-RT exerted strong CSC-suppressing activity, reducing the ability to form tumor spheroids. In addition, OBA-RT could induce apoptosis in CSC-rich populations and tumor spheroid collapse. CSC markers, including prominin-1 (CD133), Octamer-binding transcription factor 4 (Oct4), and Nanog Homeobox (Nanog), were notably decreased after OBA-RT treatment. Upstream CSCs regulating active Akt and c-Myc were significantly decreased; indicating that Akt may be a potential target of action. Computational molecular modeling revealed a high-affinity interaction between OBA-RT and an Akt molecule. This study has revealed a novel CSC inhibitory effect of OBA-RT via Akt inhibition, which may improve cancer therapy.
The Interplay of Mycosporine-like Amino Acids between Phytoplankton Groups and Northern Krill (Thysanoessa sp.) in a High-Latitude Fjord (Kongsfjorden, Svalbard)
Authors: Kim Bo Kyung , Park Mi-Ok , Min Jun-Oh , Kang Sung-Ho , Shin Kyung-Hoon , Yang Eun Jin , Ha Sun-Yong
Published: March 2022

We investigated pigment and mycosporine-like amino acid (MAA) concentrations of phytoplankton and Northern krill (Thysanoessa sp.) in sub-Arctic Kongsfjorden. Chlorophyll a (Chl-a) concentrations in the surface and middle-layer water were 0.44 μg L−1 (±0.17 μg L−1) and 0.63 μg L−1 (±0.25 μg L−1), respectively. Alloxanthin (Allo, a marker of cryptophytes) was observed at all stations, and its mean values for surface and middle-layer water were 0.09 μg L−1 (±0.05 μg L−1) and 0.05 (±0.02 μg L−1), respectively. The mean MAA-to-Chl-a ratios at the surface (3.31 ± 2.58 μg (μg Chl-a)−1) were significantly higher than those in the middle-layer water (0.88 ± 0.49 μg (μg Chl-a)−1), suggesting that these compounds play an important role in reducing UV photodamage. In gut pigment levels of Northern krill, the most abundant accessory pigment was Allo (2.79 ± 0.33 μg g−1 dry weight; d.w.), as was the accumulation of Chl-a (8.29 ± 1.13 μg g−1 d.w.). The average concentration of MAAs was 1.87 mg g−1 d.w. (±0.88 mg g−1 d.w.) in krill eyes, which was higher than that in all other body parts (0.99 ± 0.41 mg g−1 d.w.), except for the gut. Thysanoessa sp. was found to contain five identified MAAs (shinorine, palythine, porphyra-334, mycosporine-glycine, and M-332) in the krill eye, whereas shinorine and porphyra-334 were only observed in the krill body, not the eyes and gut. These findings suggest that Northern krill accumulate MAAs of various compositions through the diet (mainly cryptophytes) and translocate them among their body parts as an adaptation for photoprotection and physiological demands.
Investigation of Applicability Flowdrill Technology for Joining Thin-Walled Metal Sheets
Authors: Guzanová Anna , Janoško Erik , Draganovská Dagmar , Vrabeľ Marek , Tomáš Miroslav , Horňak Peter , Vojtko Marek , Veligotskyi Nikita
Published: March 2022

The applicability of flowdrill technology to join steel and aluminum alloys is studied. When used to flowdrill two overlapped thin-walled materials, a joint is formed as a secondary effect. The quality of the resulting bushings forming the interference fit joint was investigated by metallography. The joints were formed using a combination of uncoated deep drawn steel, galvanized high-strength low alloy steel and aluminum alloy, in different positions in the joint. Subsequently, tensile shear testing of single joints was performed. The load-carrying capacity of the joints was also tested in combination with adhesive bonding. The combination of both technologies yields an increase in the dissipated energy of the joint at failure. The bonded connection provides a high maximum force at failure, the mechanical connection through bushings leads to an increase in the displacement value at failure, thereby increasing the area under the loading curve. The DC-Al joint showed the highest load-carrying capacity, up to 9 kN, as well as dissipative energy, up to 10.3 J. The joints were fractured by shearing of the inner bushing under tensile stress. The failure surfaces exhibited a typical ductile character with dimpled morphology. It was found that from the point of view of the load-carrying capacity of the joint, it is advisable to place a material with a higher melting temperature in the upper position in the joint. The combination of flowdrill technology with adhesive bonding results in a sealed joint with high load-bearing capacity, reduction in the risk of crevice and galvanic corrosion.
Antibiotic Isoflavonoids, Anthraquinones, and Pterocarpanoids from Pigeon Pea (Cajanus cajan L.) Seeds against Multidrug-Resistant Staphylococcus aureus
Authors: Balida Lex Aliko P. , Regalado Julia Theresa A. , Teodosio Jade Joshua R. , Dizon Kathryn Ann H. , Sun Zhe , Zhan Zhao Qi , Blancaflor Jenny Marie D. , Sollesta Jan Vincent N. , Villorente Zenith M. , Saludes Jonel P. , Dalisay Doralyn S.
Published: March 2022

Cajanus cajan L. (pigeon pea, locally known in the Philippines as kadios) seed is a functional food with health benefits that extend beyond their nutritional value. C. cajan seeds contain highly diverse secondary metabolites with enriched beneficial properties, such as antibacterial, anticancer, and antioxidant activities. However, the antibacterial activities of secondary metabolites from Philippine-grown C. cajan, against multidrug-resistant Staphylococcus aureus have not been thoroughly described. Here, we investigated the in vitro antibacterial properties of C. cajan seed against multidrug-resistant S. aureus ATCC BAA-44 (MDRSA) and three other S. aureus strains (S. aureus ATCC 25923, S. aureus ATCC 6538, and coagulase-negative S. aureus) and, subsequently, identified the antibiotic markers against S. aureus strains using mass spectrometry. Secondary metabolites from C. cajan seeds were extracted using acetone, methanol, or 95% ethanol. Antibacterial screening revealed antibiotic activity for the C. cajan acetone extract. Bioassay-guided purification of the C. cajan acetone extract afforded three semi-pure high-performance liquid chromatography (HPLC) fractions exhibiting 32–64 µg/mL minimum inhibitory concentration (MIC) against MDRSA. Chemical profiling of these fractions using liquid chromatography mass spectrometry (LCMS) identified six compounds that are antibacterial against MDRSA. High-resolution mass spectrometry (HRMS), MS/MS, and dereplication using Global Natural Products Social Molecular Networking (GNPS)™, and National Institute of Standards and Technology (NIST) Library identified the metabolites as rhein, formononetin, laccaic acid D, crotafuran E, ayamenin A, and biochanin A. These isoflavonoids, anthraquinones, and pterocarpanoids from C. cajan seeds are potential bioactive compounds against S. aureus, including the multidrug-resistant strains.
Metabolic Responses of Dietary Fiber during Heat Stress: Effects on Reproductive Performance and Stress Level of Gestating Sows
Authors: Oh SeungMin , Hosseindoust Abdolreza , Ha SangHun , Moturi Joseph , Mun JunYoung , Tajudeen Habeeb , Kim JinSoo
Published: March 2022

Heat stress is an important issue, and the addition of fiber to the diet is an option in modifying intestinal health. This study evaluated the effect of acid detergent fiber (ADF) levels on reproductive performance, intestinal integrity, and metabolism of gestating sows, and its carry-over effect on the lactation period during heat stress. The diets included 4.3% (Low fiber; LF), 5.4% (Medium fiber; MF), and 6.5% (High fiber; HF) ADF. Sows fed the HF diet showed a lower respiratory rate, hair cortisol concentration, and farrowing duration compared with the LF treatment. The HF diet increased the pyruvate, citrate cycle, glyoxylate, dicarboxylate, and thiamine metabolism compared with the MF. The concentration of acetate and total short-chain fatty acids were increased in the sows fed the HF diet. The gene expression of glucose transporter 3 and glucose transporter 4 was increased in the HF treatment. The gene expression of heat shock protein 70 was decreased in the HF treatment. The HF diet during gestation increased feed intake, constipation index, piglet weight, and litter weight compared with the LF. Sows in the LF treatment showed the greatest digestibility of crude protein and the lowest digestibility of ADF. In conclusion, a 6.5% ADF level is recommended for gestating sows during heat stress.
Acinetobacter baumannii Isolates from COVID-19 Patients in a Hospital Intensive Care Unit: Molecular Typing and Risk Factors
Authors: Ceparano Mariateresa , Baccolini Valentina , Migliara Giuseppe , Isonne Claudia , Renzi Erika , Tufi Daniela , De Vito Corrado , De Giusti Maria , Trancassini Maria , Alessandri Francesco , Ceccarelli Giancarlo , Pugliese Francesco , Villari Paolo , Angiulli Maria , Battellito Stefania , Bellini Arianna , Bongiovanni Andrea , Caivano Lucilla , Castellani Marta , Coletti Monica , Cottarelli Alessia , D’Agostino Ludovica , De Giorgi Andrea , De Marchi Chiara , Germani Irma , Giannini Dara , Mazzeo Elisa , Orlandi Shadi , Piattoli Matteo , Ricci Eleonora , Siena Leonardo Maria , Territo Alessandro , Vrenna Gianluca , Zanni Stefano , Marzuillo Carolina
Published: March 2022

Infections caused by Acinetobacter baumannii represent a major concern for intensive care unit (ICU) patients. However, the epidemiology of these infections among COVID-19 patients has not been fully explored. The aims of this study were (i) to characterize the clonal spread of A. baumannii among COVID-19 patients admitted to the ICU of the Umberto I hospital of Rome during the first year of the pandemic and (ii) to identify risk factors for its acquisition. Isolates were analysed by pulsed-field gel electrophoresis, and a multivariable regression model was constructed. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Overall, 193 patients were included, and 102 strains were analysed. All isolates had highly antibiotic-resistant profiles and derived from two genotypes. The cumulative incidence of A. baumannii acquisition (colonization or infection) was 36.8%. Patients with A. baumannii had higher mortality and length of stay. Multivariable analysis showed that previous carbapenem use was the only risk factor associated with A. baumannii acquisition (aOR: 4.15, 95% CI: 1.78–9.64). We documented substantial A. baumannii infections and colonization and high levels of clonal transmission. Given the limited treatment options, effective prevention and containment strategies to limit the spread of A. baumannii should be implemented.
Inability to Catabolize Rhamnose by Sinorhizobium meliloti Rm1021 Affects Competition for Nodule Occupancy
Authors: Rivers Damien M. R. , Kim Derek D. , Oresnik Ivan J.
Published: March 2022

Rhizobium leguminosarum strains unable to grow on rhamnose as a sole carbon source are less competitive for nodule occupancy. To determine if the ability to use rhamnose as a sole carbon source affects competition for nodule occupancy in Sinorhizobium meliloti, Tn5 mutants unable to use rhamnose as a sole carbon source were isolated. S. meliloti mutations affecting rhamnose utilization were found in two operons syntenous to those of R. leguminosarum. Although the S. meliloti Tn5 mutants were complemented using an R. leguminosarum cosmid that contains the entire wild-type rhamnose catabolic locus, complementation did not occur if the cosmids carried Tn5 insertions within the locus. Through a series of heterologous complementation experiments, enzyme assays, gene fusion, and transport experiments, we show that the S. meliloti regulator, RhaR, is dominant to its R. leguminosarum counterpart. In addition, the data support the hypothesis that the R. leguminosarum kinase is capable of directly phosphorylating rhamnose and rhamnulose, whereas the S. meliloti kinase does not possess rhamnose kinase activity. In nodule competition assays, S. meliloti mutants incapable of rhamnose transport were shown to be less competitive than the wild-type and had a decreased ability to bind plant roots in the presence of rhamnose. The data suggests that rhamnose catabolism is a general determinant in competition for nodule occupancy that spans across rhizobial species.
Beyond the ABCs—Discovery of Three New Plasmid Types in Rhodobacterales (RepQ, RepY, RepW)
Authors: Freese Heike M. , Ringel Victoria , Overmann Jörg , Petersen Jörn
Published: March 2022

Copiotrophic marine bacteria of the Roseobacter group (Rhodobacterales, Alphaproteobacteria) are characterized by a multipartite genome organization. We sequenced the genomes of Sulfitobacter indolifex DSM 14862T and four related plasmid-rich isolates in order to investigate the composition, distribution, and evolution of their extrachromosomal replicons (ECRs). A combination of long-read PacBio and short-read Illumina sequencing was required to establish complete closed genomes that comprised up to twelve ECRs. The ECRs were differentiated in stably evolving chromids and genuine plasmids. Among the chromids, a diagnostic RepABC-8 replicon was detected in four Sulfitobacter species that likely reflects an evolutionary innovation that originated in their common ancestor. Classification of the ECRs showed that the most abundant plasmid system is RepABC, followed by RepA, DnaA-like, and RepB. However, the strains also contained three novel plasmid types that were designated RepQ, RepY, and RepW. We confirmed the functionality of their replicases, investigated the genetic inventory of the mostly cryptic plasmids, and retraced their evolutionary origin. Remarkably, the RepY plasmid of S. pontiacus DSM 110277 is the first high copy-number plasmid discovered in Rhodobacterales.
Mineralogy, Geochemistry, and Geochronology of the Yehe-Shigna Ophiolitic Massif, Tuva-Mongolian Microcontinent, Southern Siberia: Evidence for a Back-Arc Origin and Geodynamic Implications
Authors: Zhmodik Sergey Mikhailovich , Buslov Mikhail Mikhailovich , Damdinov Bulat Batuevich , Mironov Anatoli Georgievich , Khubanov Valentin Borisovich , Buyantuyev Molon Gimitovich , Damdinova Ludmila Borisovna , Airiyants Evgeniya Vladimirovna , Kiseleva Olga Nikolaevna , Belyanin Dmitriy Konstantinovich
Published: March 2022

The new results have been represented of mineralogical–geochemical and geochronological studies of rocks of the Yehe-Shigna ophiolite massif located in the Tuva-Mongolian microcontinent in the northern part of the Central Asian orogenic belt (Eastern Sayan, Southern Siberia). The Yehe-Shigna ophiolite massif is part of the Belsk-Dugda ophiolite belt. The structural position, age, and geochemical characteristics of the belt indicate its formation in the setting of the back-arc basin of the Shishkhid intraoceanic island arc, developing in the period of 810–750 million years. It is assumed that together with the same-age formations of the Oka accretion wedge and the Sarkhoi active margin, it formed on the convergent margin of the Gondwana supercontinent. Its basement is represented by the Archean-Early Precambrian crystalline rocks and carbonate cover (“Gargan Glyba”). The gold-bearing Neoproterozoic deposits with dominant gold-telluride assemblages are localization in large ophiolites thrust zones along with the frame of the “Gargan Glyba”. They are allochthonous with respect to the Late Neoproterozoic-Cambrian Tuva-Mongolian island arc of the Siberian continent. A similar type of gold deposit is probably worth looking for ophiolites thrust zones in other Precambrian Gondwana-derived microcontinents.