bluuebunny/crossref_metadata_2025 huggingface dataset:
Evacuation Strategy Considering Path Capacity and Risk Level for Cruise Ship
Authors: Liu Yang , Zhang Huajun , Zhan Yu , Deng Kunxiang , Dong Liangzhi
Published: March 2022

Cruise ships are large and complex, and it is difficult to manually make a plan to evacuate people to safe areas in a short time. Evacuation time and personnel safety are both important for emergency evacuation. This paper proposes an evacuation strategy that considers the path capacity and risk level to guide evacuees in fire; it not only ensures the safety of people on dangerous paths but also reduces road congestion to shorten evacuation time. High crowd density means slow moving speed, an exponential function including straight path and stairs speed characteristics is proposed to illustrate the relationship between crowd density and moving speed. Path capacity constraints are used to avoid the congestion caused by the evacuees in a panic. In order to evacuate the evacuees in the risk areas as soon as possible, this paper divides the path into three risk levels according to carbon monoxide concentration, visibility, and temperature along the paths. The people on the higher-risk paths are given higher priority to enter evacuation paths than those on lower risk. The priority strategy evacuates the people on risk paths to safe areas in less time. This paper models the evacuation network topology of a cruise ship and simulates the evacuation process of some situations that have different numbers of evacuees and path capacity constraints. The evacuation strategies and simulation results are guidelines for the crews to guide the people to evacuate to safe areas when there is a fire accident on the cruise ship.
Flow Characteristics of Oblique Submerged Impinging Jet at Various Impinging Heights
Authors: Zhang Di , Wang Hongliang , Liu Jinhua , Wang Chuan , Ge Jie , Zhu Yong , Chen Xinxin , Hu Bo
Published: March 2022

To study the influence of impinging height H/D on the flow field characteristics of oblique submerged impinging jets, the numerical calculation of an oblique submerged impinging jet was carried out based on Wray–Agarwal (W–A) turbulence model. The jet flow field structure and pressure distribution under various impinging heights (1 ≤ H/D ≤ 8) when the impinging angle was θ = 45° were analyzed. The results show that with the increase in the impinging height, the diffusion degree of the jet gradually increased and the velocity decreased when the jet reached the impingement region, and the distance between the stagnation point (SP) and the geometric center (GC) gradually increased, the flow angle φ along the jet centerline remained constant in the free-jet region and rapidly decreased in the impingement region. The impingement plate pressure distribution at various heights was similar, and the impinging pressure concentration on the upstream side of the maximum pressure point was higher.
New Record of Hydrothermal Vent Squat Lobster (Munidopsis lauensis) Provides Evidence of a Dispersal Corridor between the Pacific and Indian Oceans
Authors: Hwang Hee-seung , Cho Boongho , Cho Jaemin , Park Beomseok , Kim Taewon
Published: March 2022

Hydrothermal vents are chemosynthetically driven ecosystems and one of the most extreme environments on Earth. Vent communities exhibit remarkable taxonomic novelty at the species and supra-species levels, and over 80% of vent species are endemic. Here, we used mitochondrial DNA to identify the biogeographic distribution of Munidopsis lauensis and the heme-binding regions of A1-type COX1 from six species (including M. lauensis) to investigate whether genetic variation in the protein structure affects oxygen-binding ability. We verified the identity of Indian Ocean specimens by comparing sequences from the barcoding gene mitochondrial cytochrome oxidase subunit 1 (COI) with known M. lauensis sequences from the NCBI database. The data show that these are the first recorded specimens of M. lauensis in the Indian Ocean; previously, this species had been reported only in the southwest Pacific. Our findings support the hypothesis that vent fauna in the Pacific and Indian Oceans can interact via active ridges. In the case of the mitochondrial DNA-binding site, the arrangement of heme-binding ligands and type A1 motif of M. lauensis was identical to that in other species. Moreover, our findings suggest that the mechanism of oxygen binding is well conserved among species from terrestrial organisms to hydrothermal extremophiles. Overall, dispersal of the same species to geologically separated hydrothermal vents and conserved heme-binding regions in mitochondrial proteins suggest that hydrothermal species might have evolved from shallow sea organisms and became distributed geographically using a dispersion corridor.
On the Interplay between Freshwater Content and Hydrographic Conditions in the Arctic Ocean in the 1990s–2010s
Authors: Pnyushkov Andrey V. , Alekseev Genrikh V. , Smirnov Alexander V.
Published: March 2022

We investigated liquid freshwater content (FWC) in the upper 100 m layer of the Arctic Ocean using oceanographic observations covering the period from 1990 through 2018. Our analysis revealed two opposite tendencies in freshwater balance—the freshening in the Canada Basin at the mean rate of 2.04 ± 0.64 m/decade and the salinization of the eastern Eurasian Basin (EB) at the rate of 0.96 ± 0.86 m/decade. In line with this, we found that the Arctic Ocean gained an additional 19,000 ± 1000 km3 of freshwater over the 1990–2018 period. FWC changes in the EB since 1990 demonstrate an intermittent pattern with the most rapid decrease (from ~5.5 to 3.8 m) having occurred between 2000 and 2005. The 1990–2018 FWC changes in the upper ocean were concurrent with prominent changes of the thermohaline properties of the intermediate Atlantic Water (AW)—the main source of salt and heat for the Arctic Basin. In the eastern EB, we found a 50 m rise of the upper AW boundary accompanied by a ~0.5 °C increase in the AW core temperature. The close relationship (R > 0.7 ± 0.2) between available potential energy in the layer above the AW and FWC in the eastern EB suggests a positive feedback mechanism that links the amount of freshwater with the intensity of vertical heat and salt exchange in the halocline and upper AW layers. Together with other mechanisms of Atlantification, this feedback creates a complex picture of interactions behind the observed changes in the hydrological and ice regimes of the Eurasian sector of the Arctic Ocean.
Structural Analysis and Experimental Study on the Spherical Seal of a Subsea Connector Based on a Non-Standard O-Ring Seal
Authors: Liu Dong , Yun Feihong , Jiao Kefeng , Wang Liquan , Yan Zheping , Jia Peng , Wang Xiangyu , Liu Weifeng , Hao Xiaoquan , Xu Xiujun
Published: March 2022

Underwater oil and gas pipelines are prone to alignment differences and angle offsets during docking, and the spherical flange connector can address this problem. Its main function is to enable compensation of the different angles of the pipeline during docking and to apply a non-standard spherical sealing structure using O-rings to the connection. In this paper, the study of a spherical sealing structure using O-rings was based on a spherical structural model of the connector. The Mooney–Rivlin constitutive equation and material parameters of the O-ring were determined according to nonlinear theory. The structure of the non-standard spherical sealing groove was designed and analysed with reference to the standard sealing groove, the calculation expression of the spherical groove specific size was deduced, and the width and depth of the groove were determined. A finite element analysis of the non-standard O-ring sealing structure was carried out using ANSYS Workbench software; the effects of different pressures and compression ratios on the O-ring sealing performance were analysed and studied in terms of von Mises stress, contact pressure and contact width of different contact surfaces so as to determine a more reasonable compression ratio in the sealing structure. Finally, the theoretical analysis of the non-standard spherical sealing structure using O-rings was validated by testing, and it was proven that it could maintain a good seal under high pressure.
Novel Chromogenic Medium CHROMagarTM Candida Plus for Detection of Candida auris and Other Candida Species from Surveillance and Environmental Samples: A Multicenter Study
Authors: Mulet Bayona Juan Vicente , Salvador García Carme , Tormo Palop Nuria , Valentín Martín Amparo , González Padrón Carmelo , Colomina Rodríguez Javier , Pemán Javier , Gimeno Cardona Concepción
Published: March 2022

Epidemiological trends show a dramatic increase in the prevalence of fungal infections, and in the isolation of multidrug-resistant species, such as Candida auris. CHROMagarTM Candida (CC; CHROMagar, Paris, France) and other chromogenic media, which are widely used in the clinical laboratory because they allow a rapid identification of most Candida species. Recently, CHROMagarTM Candida Plus (CC-Plus; CHROMagar, Paris, France) was developed to detect and differentiate C. auris in addition to other major clinical Candida species, such as C. albicans, C. tropicalis, C. glabrata, or C. krusei. C. auris colonies display a differential light blue color with a blue halo. A multicentric study was designed to evaluate the performance of the CC-Plus medium in the detection of Candida species in patients’ surveillance and environmental samples from three Spanish hospitals with active C. auris outbreaks. A total of 364 patients’ surveillance samples and 212 environmental samples were tested. Samples were inoculated in CC and CC-Plus in parallel, and the plates were read at 24 and 48 h. All recovered colonies were presumptively identified according to colony color described by manufacturer, and the definitive identification was performed by mass spectrometry at 48 h. A total of 134 C. auris isolates were obtained (101 from patients’ surveillance samples, and 33 from environmental samples). Sensitivity, specificity, and predictive positive and negative values were 99.5%, 100%, 100%, and 99.1%, respectively, for the main clinical Candida species, showing that CC-Plus is comparable to CC, with the advantage of being able to differentiate C. auris from C. parapsilosis. Furthermore, CC-Plus was able to detect one C. albicans, one C. glabrata, and eight C. auris that did not grow in CC. Additionally, the yeast colonies were generally larger, suggesting that this novel medium could be a richer medium, and suitable for surveillance and environmental cultures of C. auris and other clinically relevant Candida species.
Corporate Failure Risk Assessment for Knowledge-Intensive Services Using the Evidential Reasoning Approach
Authors: Tan Meng-Meng , Xu Dong-Ling , Yang Jian-Bo
Published: March 2022

In this study, a new risk assessment model is developed and the evidence reasoning (ER) approach is applied to assess failure risk of knowledge-intensive services (KIS) corporates in the UK. General quantitative financial indicators alone (e.g., operational capability or profitability) cannot comprehensively evaluate the probability of company bankruptcy in the KIS sector. This new model combines quantitative financial indicators with macroeconomic variables, industrial factors and company non-financial criteria for robust and balanced risk analysis. It is based on the theory of enterprise risk management (ERM) and can be used to analyze company failure possibility as an important aspect of risk management. This study provides new insight into the selection of macro and industry factors based on statistical analysis. Another innovation is related to how marginal utility functions of variables are constructed and imperfect data can be handled in a distributed assessment framework. It is the first study to convert observed data into probability distributions using the likelihood analysis method instead of subjective judgement for data-driven risk analysis of company bankruptcy in the KIS sector within the ER framework, which makes the model more interpretable and informative. The model can be used to provide an early warning mechanism to assist stakeholders to make investment and other decisions.
Copulas and Portfolios in the Electric Vehicle Sector
Authors: Stenšin Andrej , Bloznelis Daumantas
Published: March 2022

How can investors unlock the returns on the electric vehicle industry? Available investment choices range from individual stocks to exchange traded funds. We select six representative assets and characterize the time-varying joint distribution of their returns by copula-GARCH models. They facilitate portfolio optimization targeted at a chosen combination of risk and reward. With daily data from 2012 to 2020, we illustrate the models’ applicability by building a minimum expected shortfall portfolio and comparing its performance to that of an equally weighted benchmark. Our results should be of interest to investors and risk managers seeking or facing exposure to the electric vehicle sector.
Acceleration and Relocation of Abandonment in a Mediterranean Mountainous Landscape: Drivers, Consequences, and Management Implications
Authors: Kiziridis Diogenis A. , Mastrogianni Anna , Pleniou Magdalini , Karadimou Elpida , Tsiftsis Spyros , Xystrakis Fotios , Tsiripidis Ioannis
Published: March 2022

Land abandonment in European mountains threatens habitats shaped for centuries by low-intensity agriculture and grazing. Hence, it is important to identify spatiotemporal patterns in rural abandonment, and relate them to biophysical and socioeconomic drivers. We pursued these goals in the theoretical context of transitions from traditional to productivist and then to post-productivist agriculture. We conducted a case study in a representative of southern Europe sub-mountainous marginal area that was once traditionally exploited (Pindus range, Epirus, Greece). Land cover was mapped from the outset of abandonment (years 1945, 1970, 1996 and 2015), and we subsequently calculated landscape metrics. An Intensity Analysis facilitated the comparison of rates of land cover change between time periods. By employing random forest modelling, we related socioeconomic, physiographic, geological and climatic predictors to land type occurrence and succession intensity. We found that farmland decreased from 30% to 3% during the 70 years of the study period, and that forest increased from 22% to 63%. The landscape’s heterogeneity, ecotone diversity, and spatial aggregation decreased. Abandonment and succession accelerated and relocated to lower elevation, especially during the latest time period, which was related to a second depopulation wave and livestock decrease. The remaining lowland farmlands were of productivist agriculture, and no widespread post-productivist regime was found. Thus, our study supports the view that policies, which have been mainly based on the linear transition of agricultural regimes in northern Europe, must take into account southern European mountains, where widespread abandonment can coexist with limited intensification and extensification.
Diversifying Forest Landscape Management—A Case Study of a Shift from Native Forest Logging to Plantations in Australian Wet Forests
Authors: Lindenmayer David , Taylor Chris
Published: March 2022

Natural forests have many ecological, economic and other values, and sustaining them is a challenge for policy makers and forest managers. Conventional approaches to forest management such as those based on maximum sustained yield principles disregard fundamental tenets of ecological sustainability and often fail. Here we describe the failure of a highly regulated approach to forest management focused on intensive wood production in the mountain ash forests of Victoria, Australia. Poor past management led to overcutting with timber yields too high to be sustainable and failing to account for uncertainties. Ongoing logging will have negative impacts on biodiversity and water production, alter fire regimes, and generate economic losses. This means there are few options to diversify forest management. The only ecologically and economically viable option is to cease logging mountain ash forests altogether and transition wood production to plantations located elsewhere in the state of Victoria. We outline general lessons for diversifying land management from our case study.
Public School Food Supply Chain during the COVID-19 Pandemic: A Case Study of the City of Vitória (Brazil)
Authors: Coelho Taniellen Miranda , Moscon Julianna Zambon , de Brito Junior Irineu , Alebrant Mendes Angélica , Yoshizaki Hugo Tsugunobu Yoshida
Published: March 2022

Background: Due to the COVID-19 pandemic, Brazilian public schools closed in 2020. This lockdown stopped the provision of school meals to public school students, most of whom belonged to low-income families facing food insecurity. To guarantee the students’ food security during this period, food items previously provided through school meals were converted into food kits and delivered to the students’ families. Methods: This case study analyzes the logistical impacts of this change in the school food supply chain concerning the legislation, procurement, assembly, and distribution of food kits in the city of Vitória, Brazil. We interviewed suppliers and workers of the Municipal Secretariat of Education and distributed a survey to professionals and beneficiaries. Results: One of the findings was that federal procurement regulations for the acquisition of food for public schools led to difficult choices for school officials during this period. These regulations determined that at least 30% of the budget must be used in local purchases from smallholder family farmers. However, almost all products generated by family farming in the region of Vitória are perishable and require distribution and consumption on the same day, which represents a challenge for the logistic process of assembling and distributing food kits. The solution was the selection of eggs as the primary protein item in the kits. Conclusions: The lessons learned through this study suggest potential actions that would make this supply chain more resilient in future emergencies.
Cesarean Scar Thickness Decreases during Pregnancy: A Prospective Longitudinal Study
Authors: Savukyne Egle , Machtejeviene Egle , Kliucinskas Mindaugas , Paskauskas Saulius
Published: March 2022

Background and Objectives: The aim of this study is to evaluate changes in uterine scar thickness after previous cesarean delivery longitudinally during pregnancy, and to correlate cesarean section (CS) scar myometrial thickness in the first trimester in two participants groups (CS scar with a niche and CS scar without a niche) with the low uterine segment (LUS) myometrial thickness changes between the second and third trimesters. Materials and Methods: In this prospective longitudinal study, pregnant women aged 18–41 years after at least one previous CS were included. Transvaginal sonography (TVS) was used to examine uterine scars after CS at 11–14 weeks. The CS scar niche (“defect”) was defined as an indentation at the site of the CS scar with a depth of at least 2 mm in the sagittal plane. Scar myometrial thickness was measured, and scars were classified subjectively as a scar with a niche (niche group) or without a niche (non-niche group). In the CS scar niche group, RMT (distance from the serosal surface of the uterus to the apex of the niche) was measured and presented as CS scar myometrial thickness in the first trimester. The myometrial thickness at the internal cervical os was measured in the non-niche group. The full LUS and myometrial LUS thickness at 18–20 and 32–35 weeks of gestation were measured in the thinnest part of the scar area using TVS. Friedman’s ANOVA test was used to analyse scar thickness during pregnancy and Mann–Whitney test to compare scar changes between CS scar niche and non-niche women groups. For a pairwise comparison in CS scar thickness measurements in the second and third trimesters, we used Wilcoxon Signed Ranks test. Results: A total of 122 eligible participants were recruited to the study during the first trimester of pregnancy. The scar niche was visible in 40.2% of cases. Uterine scar myometrial thickness decreases during pregnancy from 9.9 (IQR, 5.0–12.9) at the first trimester to 2.1 (IQR, 1.7–2.7) at the third trimester of pregnancy in the study population (p = 0.001). The myometrial CS scar thickness in the first trimester (over the niche) was thinner in the women’s group with CS scar niche compared with the non-niche group (at internal cervical os) (p < 0.001). The median difference between measurements in the CS scar niche group and non-niche group between the second and third trimester was 2.4 (IQR, 0.8–3.4) and 1.1 (IQR, 0.2–2.6) (p = 0.019), respectively. Myometrial LUS thickness as percentage decreases significantly between the second and third trimester in the CS scar niche group compared to the non-niche group (U = 1225; z = −2.438; p = 0.015). Conclusions: CS scar myometrial thickness changes throughout pregnancy and the appearance of the CS scar niche was associated with a more significant decrease in LUS myometrial thickness between the second and third trimesters.
Recent Progress in Organic Solar Cells: A Review on Materials from Acceptor to Donor
Authors: Li Yang , Huang Wei , Zhao Dejiang , Wang Lu , Jiao Zhiqiang , Huang Qingyu , Wang Peng , Sun Mengna , Yuan Guangcai
Published: March 2022

In the last few decades, organic solar cells (OSCs) have drawn broad interest owing to their advantages such as being low cost, flexible, semitransparent, non-toxic, and ideal for roll-to-roll large-scale processing. Significant advances have been made in the field of OSCs containing high-performance active layer materials, electrodes, and interlayers, as well as novel device structures. Particularly, the innovation of active layer materials, including novel acceptors and donors, has contributed significantly to the power conversion efficiency (PCE) improvement in OSCs. In this review, high-performance acceptors, containing fullerene derivatives, small molecular, and polymeric non-fullerene acceptors (NFAs), are discussed in detail. Meanwhile, highly efficient donor materials designed for fullerene- and NFA-based OSCs are also presented. Additionally, motivated by the incessant developments of donor and acceptor materials, recent advances in the field of ternary and tandem OSCs are reviewed as well.
The Role of Diet and Interventions on Multiple Sclerosis: A Review
Authors: Stoiloudis Panagiotis , Kesidou Evangelia , Bakirtzis Christos , Sintila Styliani-Aggeliki , Konstantinidou Natalia , Boziki Marina , Grigoriadis Nikolaos
Published: March 2022

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent clinical features include visual loss and sensorimotor symptoms and mainly affects those of young age. Some of the factors affecting its pathogenesis are genetic and/or environmental including viruses, smoking, obesity, and nutrition. Current research provides evidence that diet may influence MS onset, course, and quality of life of the patients. In this review, we address the role of nutrition on MS pathogenesis as well as dietary interventions that show promising beneficial results with respect to MS activity and progression. Investigation with large prospective clinical studies is required in order to thoroughly evaluate the role of diet in MS.
Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review
Authors: Gheorghe Adelina Silvana , Negru Șerban Mircea , Preda Mădălina , Mihăilă Raluca Ioana , Komporaly Isabela Anda , Dumitrescu Elena Adriana , Lungulescu Cristian Virgil , Kajanto Lidia Anca , Georgescu Bogdan , Radu Emanuel Alin , Stănculeanu Dana Lucia
Published: March 2022

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.
DIetary ASSessment (DIASS) Study: Design of an Evaluation Study to Assess Validity, Usability and Perceived Burden of an Innovative Dietary Assessment Methodology
Authors: Lucassen Desiree A. , Brouwer-Brolsma Elske M. , Slotegraaf Anne I. , Kok Esther , Feskens Edith J. M.
Published: March 2022

During recent years, the integration of technology has substantially improved self-reported dietary assessment methods, such as food frequency questionnaires (FFQ), food records, and 24-h recalls. To further reduce measurement error, additional innovations are urgently needed. Memory-related measurement error is one of the aspects that warrants attention, which is where new smartphone technologies and ecological momentary assessment (EMA) approaches provide a unique opportunity. In this article, we describe the DIASS study, which was designed to evaluate an innovative 2-h recall (2hR) smartphone-based methodology, against traditional 24-h recalls, FFQ, and biomarkers, to assess both actual and habitual dietary intake. It is hypothesized that a 2-h reporting window decreases reliance on memory and reporting burden, and increases data accuracy. We included 215 men (28%) and women (72%), with a mean ± SD age of 39 ± 19 years and a mean ± SD BMI of 23.8 ± 4.0. Most participants were highly educated (58%). Response rates for the various dietary assessment methods were >90%. Besides the evaluation of the accuracy, usability, and perceived burden of the 2hR methodology, the study set-up also allows for (further) evaluation of the other administrated dietary assessment tools.
Predictors of Mortality Following Aortic Valve Replacement in Aortic Stenosis Patients
Authors: Shvartz Vladimir , Sokolskaya Maria , Petrosyan Andrey , Ispiryan Artak , Donakanyan Sergey , Bockeria Leo , Bockeria Olga
Published: March 2022

Background: Understanding of the risk factors for the development of adverse outcomes after aortic valve replacement is necessary to develop timely preventive measures and to improve the results of surgical treatment. Methods: We analyzed patients with aortic stenosis (n = 742) who underwent surgical treatment in the period 2014–2020. The average age was 63 (57;69) years—men 58%, women 42%. Results: The hospital mortality rate was 3% (22 patients). The following statistically significant threshold values (cut-off points) were obtained in the ROC analysis: aortic cross-clamp time > 93 min AUC (CI) 0.676 (0.640–0.710), p = 0.010; cardiopulmonary bypass time > 144 min AUC (CI) 0.809 (0.778–0.837), p < 0.0001, hemoglobin before op <120 g/L. AUC (CI) 0.762 (0.728–0.793), p < 0.0001, hematocrit before op <39% AUC (CI) 0.755 (0.721–0.786), p < 0.001, end-diastolic dimension index >2.39 AUC (CI) 0.647 (0.607–0.686), p = 0.014, end-systolic dimension index > 1.68 AUC (CI) 0.657 (0.617–0.695), p = 0.009. Statistically significant independent predictors of hospital mortality were identified: BMI > 30 kg/m2 (OR 2.84; CI 1.15–7.01), ischemic heart disease (OR 3.65; CI 1.01–13.2), diabetes (OR 3.88; CI 1.38–10.9), frequent ventricular ectopy before operation (OR 9.78; CI 1.91–50.2), mitral valve repair (OR 4.47; CI 1.76–11.3), tricuspid valve repair (OR 3.06; CI 1.09–8.58), 3 and more procedures (OR 4.44; CI 1.67–11.8). Conclusions: The hospital mortality rate was 3%. The main indicators associated with the risk of death were: diabetes, overweight (body mass index more than 30 kg/m2), frequent ventricular ectopy before surgery, hemoglobin level below 120 g/L, hematocrit level below 39%, longer cardiopulmonary bypass time and aortic cross-clamp time, additional mitral and tricuspid valve interventions.
Design, Green Synthesis and Tailoring of Vitamin E TPGS Augmented Niosomal Nano-Carrier of Pyrazolopyrimidines as Potential Anti-Liver and Breast Cancer Agents with Accentuated Oral Bioavailability
Authors: Anwer Kurls E. , El-Sattar Nour E. A. Abd , Shamaa Marium M. , Zakaria Mohamed Y. , Beshay Botros Y.
Published: March 2022

VEGF plays a crucial role in cancer development, angiogenesis and progression, principally liver and breast cancer. It is vital to uncover novel chemical candidates of VEGFR inhibitors to develop more potent anti-breast and anti-liver cancer agents than the currently available candidates, sorafenib and regorafenib, that face resistance obstacles and severe side effects. Herein, nine pyrazolopyrimidine derivatives were designed, synthesized as sorafenib and regorafenib analogues and screened for their in vitro cytotoxic and growth inhibition activities against four human cancer cell lines, namely breast cancer (Michigan Cancer Foundation-7 (MCF-7), hepatocellular carcinoma (HCC) type (HepG2), lung carcinoma (A-549) and human colorectal carcinoma-116 (HCT-116)). Among the tested compounds, compounds 1, 2a, 4b and 7 showed the uppermost cytotoxic activities against all aforementioned cell lines with IC50 estimates varying from 6 to 50 µM, among which compound 7 showed the best inhibitory activity on all tested compounds. Stunningly, compound 7 showed the best significant inhibition of the VEGFR-2 protein expression level (72.3%) as compared to the control and even higher than that produced with sorafenib and regorafenib (70.4% and 55.6%, respectively). Modeling studies provided evidence for the possible interactions of the synthesized compounds with the key residues of the ATP binding sites on the hinge region and the “DFG out” motif of VEGFR-2 kinase. Collectively, our present study suggests that pyrazolopyrimidine derivatives are a novel class of anti-cancer drug candidates to inhibit VEGF-VEGFR function. Aspiring to promote constrained aqueous solubility, hence poor oral bioavailability of the developed lead molecule, 7 and 2a-charged D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) surface-coated niosomes were successfully constructed, adopting a thin film hydration technique striving to overcome these pitfalls. A 23 full factorial design was involved in order to investigate the influence of formulation variables: type of surfactant, either Span 60 or Span 40; surfactant:cholesterol ratio (8:2 or 5:5) along with the amount of TPGS (25 mg or 50 mg) on the characteristics of the nanosystem. F2 and S2 were picked as the optimum formula for compounds 2a and 7 with desirability values of 0.907 and 0.903, respectively. In addition, a distinguished improvement was observed in the compound’s oral bioavailability and cytotoxic activity after being included in the nano-TPGS-coated niosomal system relative to the unformulated compound. The nano-TPGS-coated niosomal system increased the hepatocellular inhibitory activity four times fold of compound 7a (1.6 µM) and two-fold of 2a (3 µM) relative to the unformulated compounds (6 µM and 6.2 µM, respectively).
Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs
Authors: von Bredow Lukas , Schäfer Thomas Martin , Hogenkamp Julian , Tretbar Maik , Stopper Daniel , Kraft Fabian B. , Schliehe-Diecks Julian , Schöler Andrea , Borkhardt Arndt , Bhatia Sanil , Held Jana , Hansen Finn K.
Published: March 2022

Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads.
Revolutionization in Cancer Therapeutics via Targeting Major Immune Checkpoints PD-1, PD-L1 and CTLA-4
Authors: Pandey Pratibha , Khan Fahad , Qari Huda A. , Upadhyay Tarun Kumar , Alkhateeb Abdulhameed F. , Oves Mohammad
Published: March 2022

Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged as a viable strategy for developing anticancer immunity. Through the development of effective immune checkpoint inhibitors (ICIs) in multiple carcinomas, advances in cancer immunity have expedited a major breakthrough in cancer therapy. Blocking a variety of ICIs, such as PD-1 (programmed cell death-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved the immune system’s efficacy in combating cancer cells. Recent studies also supported the fact that ICIs combined with other potent antitumor candidates, such as angiogenic agents, could be a solid promising chemopreventive therapeutic approach in improving the effectiveness of immune checkpoint inhibitors. Immune checkpoint blockade has aided antiangiogenesis by lowering vascular endothelial growth factor expression and alleviating hypoxia. Our review summarized recent advances and clinical improvements in immune checkpoint blocking tactics, including combinatorial treatment of immunogenic cell death (ICD) inducers with ICIs, which may aid future researchers in creating more effective cancer-fighting strategies.
A pH- and Bioreducible Cationic Copolymer with Amino Acids and Piperazines for Adenovirus Delivery
Authors: Thambi Thavasyappan , Lee Jeongmin , Yoon A-Rum , Kasala Dayananda , Yun Chae-Ok
Published: March 2022

Adenoviruses (Ads) are attractive nonviral vectors and show great potential in cancer gene therapy. However, inherent properties of Ads, including immunogenicity, nonspecific toxicity, and coxsackie and adenovirus receptor (CAR)-dependent cell uptake, limit their clinical use. To surmount these issues, we developed a pH- and glutathione-responsive poly(ethylene glycol)-poly(ꞵ-aminoester)-polyethyleneimine (PPA) for conjugation with Ad. The pH sensitivity of the PPA copolymer was elegantly tuned by substitution with different amino acids (arginine, histidine, and tryptophan), piperazines (Pip1, Pip2, and Pip3), and guanidine residues in the backbone of the PPA conjugate. PPA copolymer was further functionalized with short-chain cross-linker succinimidyl 3-(2-pyridyldithio)propionate) (SPDP) to obtain PPA-SPDP for facile conjugation with Ad. The PPA-conjugated Ad (PPA-Ad) conjugate was obtained by reacting PPA-SPDP conjugate with thiolated Ad (Ad-SH). Ad-SH was prepared by reacting Ad with 2-iminothiolane. The size distribution and zeta potential results of PPA-Ad conjugate showed an increasing trend with an increase in copolymer dose. From in vitro test, it was found that the transduction efficiency of PPA-Ad conjugate in CAR-positive cells (A549 and H460 cells) was remarkably increased at the acidic pH condition (pH 6.2) when compared with PPA-Ad conjugate incubated under the physiological condition (pH 7.4). Interestingly, the increase in transduction efficiency was evidenced in CAR-negative cells (MDA-MB-231 and T24 cells). These results demonstrated that biocompatible and biodegradable PPA copolymers can efficiently cover the surface of Ad and can increase the transduction efficiency, and hence PPA copolymers can be a useful nanomaterial for viral vector delivery in cancer therapy.
Optical Phase Conjugation Conversion through a Nonlinear Bidirectional Semiconductor Optical Amplifier Configuration
Authors: Sun Fan , Wen Feng , Wu Baojian , Ling Yun , Qiu Kun
Published: March 2022

The optical phase conjugation (OPC) process is thoughtfully investigated in a nonlinear bidirectional semiconductor optical amplifier subsystem (SOA), demonstrating the conjugation conversion through the two ports of the SOA, simultaneously. The spectral responses, the nonlinear power curves and the quality optimization of the conjugated are discussed through the simulation in nonlinear bidirectional configuration. The experimental investigation of the polarization-insensitive SOA further confirms the OPC behavior in the bidirectional operation, achieving the error-free conjugation conversion with an output optical signal-to-noise ratio (OSNR) of up to 16 dB. The nonlinear bidirectional SOA configuration tested in the system relaxes the requirement of the conventional four-wave mixing (FWM), enabling the OPC conversion with the signal regeneration in only one unit.
Improved Search Algorithm of Digital Speckle Pattern Based on PSO and IC-GN
Authors: Chen Qiang , Tie Zhixin , Hong Liang , Qu Youtian , Wang Dengwen
Published: March 2022

Digital speckle correlation method has not only been widely used in a variety of photometric mechanical scenarios, but also integrated with multiple disciplines. In the future, it will even be inextricably linked to the Internet of Things, autonomous driving, deep learning and other fields. For a given hardware condition, it is of great significance to improve the efficiency of integer-pixel search and increase the accuracy and efficiency of the sub-pixel algorithm. In this paper, we propose an improved digital speckle correlation method, which consists of an integer-pixel search algorithm and a sub-pixel search algorithm. With respect to the integer-pixel search, aiming to address the two problems of uniqueness of maximum value and parameter setting of PSO-W algorithm, the algorithm PSO-1 is proposed, and the results of comparison experiments show that it has higher search efficiency. In terms of sub-pixels, based on IC-GN algorithm with the highest accuracy at present, the IV-ICGN algorithm is proposed, and the simulation experiment results show that the proposed algorithm has higher accuracy and higher efficiency than the comparison algorithm.
Enhancement of Ultraviolet Light Resistance of Colorless and Transparent Semi-Alicyclic Polyimide Nanocomposite Films via the Incorporation of Hindered Amine Light Stabilizers for Potential Applications in Flexible Optoelectronics
Authors: Wei Xin-Ying , He Zhi-Bin , Yuan Shun-Qi , Wu Hao , Zhi Xin-Xin , Zhang Yan , Chen Shu-Jing , Liu Jin-Gang
Published: March 2022

Optically transparent polymer films with excellent thermal and ultraviolet (UV) resistance have been highly desired in advanced optoelectronic fields, such as flexible substrates for photovoltaic devices. Colorless and transparent polyimide (CPI) films simultaneously possess the good thermal stability and optical transparency. However, conventional CPI films usually suffered from the UV exposure and have to face the deterioration of optical properties during the long-term service in UV environments. In the current work, the commercially available hindered amine light stabilizers (HALS) were tried to be incorporated into the semi-alicyclic CPI matrix with the aim of enhancing the UV exposure stability. For this target, a CPI-0 film was first prepared from hydrogenated pyromellitic dianhydride (HPMDA) and 2,2′-dimethylbenzidine (DMBZ) via a one-step polycondensation procedure. Then, the commercially available HALS were incorporated into the CPI-0 (HPMDA-DMBZ) film matrix to afford four series of CPI/HALS composite films. Experimental results indicated that the Tinuvin® 791 HALS showed the best miscibility with the CPI-0 film matrix and the derived CPI-D series of composite films exhibited the best optical transmittances. The CPI-D nanocomposite films showed apparently enhanced UV exposure stability via incorporation of the 791 additives. For the pristine CPI-0 film, after the UV exposure for 6 h, the optical properties, including the transmittance at the wavelength of 350 nm (T350), lightness (L*), yellow indices (b*), and haze obviously deteriorated with the T350 values from 55.7% to 17.5%, the L* values from 95.12 to 91.38, the b* values from 3.38 to 21.95, and the haze values from 1.46% to 9.33%. However, for the CPI-D-10 film (791: CPI-0 = 1.0 wt%, weight percent), the optical parameters were highly maintained with the T350 values from 61.4% to 53.8%, the L* values from 95.46 to 95.36, the b* values from 1.84 to 1.51, and the haze values from 0.69% to 3.34% under the same UV aging conditions.
Conductive Plastics from Al Platelets in a PBT-PET Polyester Blend Having Co-Continuous Morphology
Authors: Alhamidi Abdullah , Anis Arfat , Al-Zahrani Saeed M. , Bashir Zahir , Alrashed Maher M.
Published: March 2022

Conductive plastics are made by placing conductive fillers in polymer matrices. It is known that a conductive filler in a binary polymer blend with a co-continuous morphology is more effective than in a single polymer, because it aids the formation of a ‘segregated conductive network’. We embedded a relatively low-cost conductive filler, aluminium nano platelets, in a 60/40 PBT/PET polymer blend. While 25 vol.% of the Al nanoplatelets when placed in a single polymer (PET) gave a material with the resistivity of an insulator (1014 Ωcm), the same Al nano platelets in the 60/40 PBT/PET blend reduced the resistivity to 7.2 × 107 Ωcm, which is in the category of an electrostatic charge dissipation material. While PET tends to give amorphous articles, the 60/40 PBT/PET blends crystallised in the time scale of the injection moulding and hence the conductive articles had dimensional stability above the Tg of PET.
Rubber Material-Model Characterization for Coupled Thermo-Mechanical Vulcanization Foaming Processes
Authors: Alcalá Noelia , Castrillón Mariana , Viejo Ismael , Izquierdo Salvador , Gracia Leticia A.
Published: March 2022

A novel experimental methodology is developed for the characterization of the vulcanization and foaming processes of an ethylene propylene diene (EPDM) cellular rubber and for establishing the relationship of its physical and mechanical property evolution with vulcanization and foaming process temperature. To establish this relationship, the vulcanization and foaming reaction kinetics and their coupling have been determined, as well as important parameters in the behaviour of the material, such as conductivity, specific heat capacity and coefficients of expansion and foaming. This aforementioned strategy allows the setting of a material model that can be implemented into finite-element (FE) codes to reproduce the material changes during the vulcanization and foaming processes. The material model developed reproduces with enough accuracy the coupling of chemical kinetics of vulcanization and foaming reactions. The results provided by the numerical material model fit a similar trend, and values with an accuracy of 90–99% to those observed in the experiments conducted for the determination of the cellular rubber expansion in function of the temperature. Moreover, the cellular rubber expansion values agree with the structural analysis of vulcanized and foamed samples at different isothermal temperatures and with the proportional loss of mechanical properties in the function of the vulcanization and foaming degree.
Predicting the Solubility of Nonelectrolyte Solids Using a Combination of Molecular Simulation with the Solubility Parameter Method MOSCED: Application to the Wastewater Contaminants Monuron, Diuron, Atrazine and Atenolol
Authors: Ollier Rachel , Nguyen Thomas , Agarwal Hrithik , Phifer Jeremy , Ferreira da Silva Larissa , Gonçalves Nogueira Gabriel , Pereira Barbosa Ana , Ley Ryan , O’Loughlin Elizabeth , Rygelski Brett , Sabatino Spencer , Paluch Andrew
Published: March 2022

Methods to predict the equilibrium solubility of nonelectrolyte solids are indispensable for early-stage process development, design, and feasibility studies. Conventional analytic methods typically require reference data to regress parameters, which may not be available or limited for novel systems. Molecular simulation is a promising alternative, but is computationally intensive. Here, we demonstrate the ability to use a small number of molecular simulation free energy calculations to generate reference data to regress model parameters for the analytical MOSCED (modified separation of cohesive energy density) model. The result is an efficient analytical method to predict the equilibrium solubility of nonelectrolyte solids. The method is demonstrated for the wastewater contaminants monuron, diuron, atrazine and atenolol. Predictions for monuron, diuron and atrazine are in reasonable agreement with MOSCED parameters regressed using experimental solubility data. Predictions for atenolol are inferior, suggesting a potential limitation in the adopted molecular models, or the solvents selected to generate the necessary reference data.
The Impact of Climate Change on Hydrological Processes of the Glacierized Watershed and Projections
Authors: Liu Jing , Long Aihua , Deng Xiaoya , Yin Zhenliang , Deng Mingjiang , An Qiang , Gu Xinchen , Li Shuoyang , Liu Guihua
Published: March 2022

Under the influence of climate change, the hydrological processes of glaciers have undergone significant changes, a fact which is seriously affecting agricultural production in the downstream region of the Tianshan Mountains, China. In order to explore the intrinsic relationship between climate change and hydrological elements, we proposed an “evaluation-driving-prediction” system to study it. First, we constructed a glacier-enhanced soil and water assessment tool model (GE-SWAT) and used a two-stage calibration method to optimize the model parameters. Next, a scenario analysis was used to evaluate the driving factors of historical runoff changes. Finally, we projected future runoff changes using bias-corrected regional climate model (RCM) outputs. The results of the case study on the Jinghe River Basin in the Tianshan Mountains show that from 1963 to 2016, total runoff increased by 13.3%, 17.7% of which was due to increasing precipitation and 1.8% of which was negated by rising temperatures. The glacier runoff increased by 14.5%, mainly due to the rising temperatures. A 3.4% reduction in snowmelt was caused by a lower snowfall/precipitation ratio, which significantly reduced the snowfall from June to August. The RCM projection indicated that the warming and humidification phenomenon in the study area will continue at least through to the mid-21st century. A consistent increase in glacier runoff and total runoff is projected, but the contribution rate of the glacier runoff will have little to no change under the RCP4.5 and RCP8.5 emission scenarios. Our research demonstrates the simulation performance of the GE-SWAT model in a basin with moderate glacier cover. This method is shown to be efficient in quantifying the impact of climate change on glacier hydrological processes and predicting future streamflow changes, providing a good research reference for similar regions.