bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?
Authors: Hosseinkhani Negar , Derakhshani Afshin , Kooshkaki Omid , Abdoli Shadbad Mahdi , Hajiasgharzadeh Khalil , Baghbanzadeh Amir , Safarpour Hossein , Mokhtarzadeh Ahad , Brunetti Oronzo , Yue Simon , Silvestris Nicola , Baradaran Behzad
Published: November 2020

Although the ever-increasing number of cancer patients pose substantial challenges worldwide, finding a treatment with the highest response rate and the lowest number of side effects is still undergoing research. Compared to chemotherapy, the relatively low side effects of cancer immunotherapy have provided ample opportunity for immunotherapy to become a promising approach for patients with malignancy. However, the clinical translation of immune-based therapies requires robust anti-tumoral immune responses. Immune checkpoints have substantial roles in the induction of an immunosuppressive tumor microenvironment and tolerance against tumor antigens. Identifying and targeting these inhibitory axes, which can be established between tumor cells and tumor-infiltrating lymphocytes, can facilitate the development of anti-tumoral immune responses. Bispecific T-cell engagers, which can attract lymphocytes to the tumor microenvironment, have also paved the road for immunological-based tumor elimination. The development of CAR-T cells and their gene editing have brought ample opportunity to recognize tumor antigens, independent from immune checkpoints and the major histocompatibility complex (MHC). Indeed, there have been remarkable advances in developing various CAR-T cells to target tumoral cells. Knockout of immune checkpoints via gene editing in CAR-T cells might be designated for a breakthrough for patients with malignancy. In the midst of this fast progress in cancer immunotherapies, there is a need to provide up-to-date information regarding immune checkpoints, bispecific T-cell engagers, and CAR-T cells. Therefore, this review aims to provide recent findings of immune checkpoints, bispecific T-cell engagers, and CAR-T cells in cancer immunotherapy and discuss the pertained clinical trials.
The Potential Anticancer Activity of Phytoconstituents against Gastric Cancer—A Review on In Vitro, In Vivo, and Clinical Studies
Authors: Nakonieczna Sylwia , Grabarska Aneta , Kukula-Koch Wirginia
Published: November 2020

Gastric cancer belongs to the heterogeneous malignancies and, according to the World Health Organization, it is the fifth most commonly diagnosed cancer in men. The aim of this review is to provide an overview on the role of natural products of plant origin in the therapy of gastric cancer and to present the potentially active metabolites which can be used in the natural therapeutical strategies as the support to the conventional treatment. Many of the naturally spread secondary metabolites have been proved to exhibit chemopreventive properties when tested on the cell lines or in vivo. This manuscript aims to discuss the pharmacological significance of both the total extracts and the single isolated metabolites in the stomach cancer prevention and to focus on their mechanisms of action. A wide variety of plant-derived anticancer metabolites from different groups presented in the manuscript that include polyphenols, terpenes, alkaloids, or sulphur-containing compounds, underlines the multidirectional nature of natural products.
Vertebral Bone Marrow-Derived Mesenchymal Stromal Cells from Osteoporotic and Healthy Patients Possess Similar Differentiation Properties In Vitro
Authors: Haddouti El-Mustapha , Randau Thomas M. , Hilgers Cäcilia , Masson Werner , Pflugmacher Robert , Burger Christof , Gravius Sascha , Schildberg Frank A.
Published: November 2020

Osteoporosis is a disease characterized by low bone mass and an increased risk of fractures. Although several cellular players leading to osteoporosis have been identified, the role of mesenchymal stromal cells (MSC) is still not fully elaborated. The aim of this study was, therefore, to isolate and characterize MSCs from vertebral body of healthy non-osteoporotic and osteoporotic patients, with a particular focus on their osteogenic differentiation potential. Isolated MSCs were characterized by their osteogenic, adipogenic, and chondrogenic differentiation, as well as surface marker expression, proliferation behavior, and immunomodulatory capacity. The mineralization process was confirmed using Alizarin Red S and alkaline phosphatase (ALP) stains and further evaluated by determining ALP activity, mineral deposition, and free phosphate ion release. MSCs from both healthy and osteoporotic patients showed common fibroblast-like morphology and similar proliferation behavior. They expressed the typical MSC surface markers and possessed immunomodulatory capacity. Both groups demonstrated solid trilineage differentiation potential; osteogenic differentiation was further confirmed by increased ALP activity, deposition of inorganic crystals, phosphate ion release, and expression of osteoblast marker genes. Overall, MSCs from osteoporotic and non-osteoporotic patients showed neither a difference in general MSC features nor in the detailed analysis regarding osteogenic differentiation. These data suggest that vertebral body MSCs from osteoporotic patients were not impaired; rather, they possessed full osteogenic potential compared to MSCs from non-osteoporotic patients.
Urdu Documents Clustering with Unsupervised and Semi-Supervised Probabilistic Topic Modeling
Authors: Mustafa Mubashar , Zeng Feng , Ghulam Hussain , Muhammad Arslan Hafiz
Published: November 2020

Document clustering is to group documents according to certain semantic features. Topic model has a richer semantic structure and considerable potential for helping users to know document corpora. Unfortunately, this potential is stymied on text documents which have overlapping nature, due to their purely unsupervised nature. To solve this problem, some semi-supervised models have been proposed for English language. However, no such work is available for poor resource language Urdu. Therefore, document clustering has become a challenging task in Urdu language, which has its own morphology, syntax and semantics. In this study, we proposed a semi-supervised framework for Urdu documents clustering to deal with the Urdu morphology challenges. The proposed model is a combination of pre-processing techniques, seeded-LDA model and Gibbs sampling, we named it seeded-Urdu Latent Dirichlet Allocation (seeded-ULDA). We apply the proposed model and other methods to Urdu news datasets for categorizing. For the datasets, two conditions are considered for document clustering, one is “Dataset without overlapping” in which all classes have distinct nature. The other is “Dataset with overlapping” in which the categories are overlapping and the classes are connected to each other. The aim of this study is threefold: it first shows that unsupervised models (Latent Dirichlet Allocation (LDA), Non-negative matrix factorization (NMF) and K-means) are giving satisfying results on the dataset without overlapping. Second, it shows that these unsupervised models are not performing well on the dataset with overlapping, because, on this dataset, these algorithms find some topics that are neither entirely meaningful nor effective in extrinsic tasks. Third, our proposed semi-supervised model Seeded-ULDA performs well on both datasets because this model is straightforward and effective to instruct topic models to find topics of specific interest. It is shown in this paper that the semi-supervised model, Seeded-ULDA, provides significant results as compared to unsupervised algorithms.
Muscularization of the Mesenchymal Outlet Septum during Cardiac Development
Authors: van den Hoff Maurice J. B. , Wessels Andy
Published: November 2020

After the formation of the linear heart tube, it becomes divided into right and left components by the process of septation. Relatively late during this process, within the developing outflow tract, the initially mesenchymal outlet septum becomes muscularized as the result of myocardialization. Myocardialization is defined as the process in which existing cardiomyocytes migrate into flanking mesenchyme. Studies using genetically modified mice, as well as experimental approaches using in vitro models, demonstrate that Wnt and TGFβ signaling play an essential role in the regulation of myocardialization. They also show the significance of the interaction between cardiomyocytes, endocardial derived cells, neural crest cells, and the extracellular matrix. Interestingly, Wnt-mediated non-canonical planar cell polarity signaling was found to be a crucial regulator of myocardialization in the outlet septum and Wnt-mediated canonical β-catenin signaling is an essential regulator of the expansion of mesenchymal cells populating the outflow tract cushions.
The Possibility of Intracranial Hypertension in Patients with Autism Spectrum Disorder Using Computed Tomography
Authors: Yamada Shuichi , Nakagawa Ichiro , Nishimura Fumihiko , Motoyama Yasushi , Park Young-Soo , Nakase Hiroyuki
Published: November 2020

Although intracranial pressure is considered to be normal in children with autism spectrum disorder (ASD), we aimed to assess whether such children may have increased intracranial pressure using noninvasive computed tomography (CT). Head CT scans of children with ASD (109 cases, male 91 and female 18, average age 4.3 years) and of children with typical development (60 cases, male 35 and female 25, average age 4.5 years) were acquired. The images were processed to map the shape of the inner skull surface. We predicted that a complex skull shape, based on a marked digital impression, would be indicative of chronically increased intracranial pressure. The data of the scans were extracted and processed to automatically establish inner and outer cranial circumferences. The circularity (reflecting inner skull shape and area) and C-ratio (ratio of inner/outer circumference) were determined and statistically analyzed. The circularity and C-ratio were significantly lower in children with ASD than in children with typical development. A lower circularity was associated with a more complex shape of the inner skull surface, which indicated the presence of intracranial hypertension. Our study suggests that children with ASD may be at a risk for chronic intracranial hypertension. Our technique incorporating the circularity and C-ratio is a useful noninvasive method for screening such patients and could impact future investigations of ASD.
Early Screening for Gestational Diabetes Using IADPSG Criteria May Be a Useful Predictor for Congenital Anomalies: Preliminary Data from a High-Risk Population
Authors: Zawiejska Agnieszka , Wróblewska-Seniuk Katarzyna , Gutaj Paweł , Mantaj Urszula , Gomulska Anna , Kippen Joanna , Wender-Ozegowska Ewa
Published: November 2020

Background: Our aim was to investigate whether the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) glycemic thresholds used for detecting hyperglycemia in pregnancy can be predictive for malformations in women with hyperglycemia detected in early pregnancy. Methods: a single-center, retrospective observational trial of 125 mother-infant pairs from singleton pregnancies with hyperglycemia according to the IADPSG criteria diagnosed at the gestational age below 16 weeks. Glucose values obtained from 75-g OGTT (oral glucose tolerance test) were investigated as predictors for congenital malformations in newborns. Results: Characteristics of the cohort: maternal age: 31.5 ± 5.2, pre-pregnancy body mass index (BMI) ≥ 30 kg/m2: 42.0%, gestational age at diagnosis (weeks): 12.0 ± 4.0, and newborns with congenital malformations: 8.8%. Fasting blood glycemia (FBG) and HbA1c (Haemoglobin A1c) at baseline significantly predicted the outcome (expB: 1.06 (1.02–1.1), p = 0.007 and expB: 2.05 (1.24–3.38), p = 0.005, respectively). Both the fasting blood glucose (FBG) value of 5.1 mmol/dL (diagnostic for gestational diabetes mellitus (GDM)) and 5.5 mmol/dL (upper limit for normoglycemia in the general population) significantly increased the likelihood ratio (LR) for fetal malformations: 1.3 (1.1; 1.4) and 1.5 (1.0; 2.4), respectively. Conclusions: (1) Fasting glycemia diagnostic for GDM measured in early pregnancy is associated with a significantly elevated risk for congenital malformations. (2) Our data suggest that women at elevated risks of GDM/diabetes in pregnancy (DiP) should have their fasting blood glucose assessed before becoming pregnant, and the optimization of glycemic control should be considered if the FBG exceeds 5.1 mmol/dL.
Three Drug Combinations in the Treatment of Fit Elderly Multiple Myeloma Patients
Authors: Gardeney Hélène , Bobin Arthur , Gruchet Cécile , Sabirou Florence , Lévy Anthony , Nsiala Laly , Cailly Laura , Tomowiak Cécile , Torregrosa Jose , Moya Niels , Hulin Cyrille , Leleu Xavier , Guidez Stéphanie
Published: November 2020

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.
Impact of COVID-19 Lockdown Measures on Spanish People with Chronic Pain: An Online Study Survey
Authors: Nieto Rubén , Pardo Rebeca , Sora Beatriz , Feliu-Soler Albert , Luciano Juan V.
Published: November 2020

The corona virus disease 2019 (COVID-19) pandemic is one of the most important healthcare and societal challenges to have emerged in the last century. It may have effects on both physical and psychosocial health, but studies considering the impact on vulnerable populations, such as people with chronic pain, are needed. In this cross-sectional study, an online survey of relevant chronic pain domains, coping strategies, triggers and potential related variables was answered by 502 Spanish individuals with chronic pain. Participants were mainly women (88%) with longstanding chronic pain and moderate to high pain intensity and disability. The perception of pain aggravation and the most pain-related outcomes were observed. Contextual variables such as job insecurity, worries about the future, people cohabiting, being close to someone who had passed away, or being potentially infected with COVID-19 were related to worse outcomes. More than half the participants altered their pain management style (e.g., increased medication intake) and several changes occurred with respect to pain triggers (cognitions, feelings of insecurity and loneliness, and sleeping problems were more frequently reported as triggers during lockdown). Our preliminary results highlight the negative effects of lockdown on patients with chronic pain as well as the need to make available cost-effective and remotely accessible healthcare resources for counteracting them.
Exploration of Functional Connectivity Changes Previously Reported in Fibromyalgia and Their Relation to Psychological Distress and Pain Measures
Authors: van Ettinger-Veenstra Helene , Boehme Rebecca , Ghafouri Bijar , Olausson Håkan , Wicksell Rikard K. , Gerdle Björn
Published: November 2020

Neural functional connectivity changes in the default mode network (DMN), Central executive network (CEN), and insula have been implicated in fibromyalgia (FM) but stem from a sparse set of small-scale studies with limited power for the investigation of confounding effects. We investigated whether anxiety, depression, pain sensitivity, and pain intensity modulated functional connectivity related to DMN nodes, CEN nodes, and insula. Resting-state functional magnetic resonance imaging data were collected from 31 females with FM and 28 age-matched healthy controls. Connectivity was analysed with a region-based connectivity analysis between DMN nodes in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex, CEN nodes in the intraparietal sulcus (IPS), and bilateral insula. FM patients displayed significantly higher levels of anxiety and depressive symptoms than controls. The right IPS node of the CEN showed a higher level of connectivity strength with right insula in FM with higher pain intensity compared to controls. More anxiety symptoms in FM correlated with higher levels of connectivity strength between the vmPFC DMN node and right sensorimotor cortex. These findings support the theory of altered insular connectivity in FM and also suggest altered IPS connectivity in FM. Interestingly, no change in insular connectivity with DMN was observed.
Preclinical Studies of a Rare CF-Causing Mutation in the Second Nucleotide Binding Domain (c.3700A>G) Show Robust Functional Rescue in Primary Nasal Cultures by Novel CFTR Modulators
Authors: Laselva Onofrio , McCormack Jacqueline , Bartlett Claire , Ip Wan , Gunawardena Tarini N. A. , Ouyang Hong , Eckford Paul D. W. , Gonska Tanja , Moraes Theo J. , Bear Christine E.
Published: November 2020

The combination therapies ORKAMBITM and TRIKAFTATM are approved for people who have the F508del mutation on at least one allele. In this study we examine the effects of potentiator and corrector combinations on the rare mutation c.3700A>G. This mutation produces a cryptic splice site that deletes six amino acids in NBD2 (I1234-R1239del). Like F508del it causes protein misprocessing and reduced chloride channel function. We show that a novel cystic fibrosis transmembrane conductance regulator CFTR modulator triple combination (AC1, corrector, AC2-2, co-potentiator and AP2, potentiator), rescued I1234-R1239del-CFTR activity to WT-CFTR level in HEK293 cells. Moreover, we show that although the response to ORKAMBI was modest in nasal epithelial cells from two individuals homozygous for I1234-R1239del-CFTR, a substantial functional rescue was achieved with the novel triple combination. Interestingly, while both the novel CFTR triple combination and TRIKAFTATM treatment showed functional rescue in gene-edited I1234-R1239del-CFTR-expressing HBE cells and in nasal cells from two CF patients heterozygous for I1234-R1239del/W1282X, nasal cells homozygous for I1234-R1239del-CFTR showed no significant response to the TRIKAFTATM combination. These data suggest a potential benefit of CFTR modulators on the functional rescue of I1234-R1239del -CFTR, which arises from the rare CF-causing mutation c.3700A>G, and highlight that patient tissues are crucial to our full understanding of functional rescue in rare CFTR mutations.
Activation of Rubber-Seed Shell Waste by Malic Acid as Potential CO2 Removal: Isotherm and Kinetics Studies
Authors: Borhan Azry , Yusuf Suzana
Published: November 2020

Carbon dioxide (CO2) has been deemed a significant contributor to the climate crisis and has an impact on environmental systems. Adsorption is widely used among other technologies for carbon capture because of its many benefits. As a starting material for the production of activated carbon (AC) by chemical activation using malic acid due to its biodegradable and non-toxic properties, rubber seed shell (RSS) was used as agricultural waste from rubber farming. Sample A6, which was carbonized for 120 min at a temperature of 600 °C and impregnated at a ratio of 1:2, was identified to achieve the highest surface area of 938.61 m2/g with micropore diameter of 1.368 nm, respectively. Using the fixed volumetric approach measured at 25, 50, and 100 °C, the maximum CO2 adsorption capability reported is 59.73 cm3/g of adsorbent. Using the pseudo-first order of Lagergren, the pseudo-second order and the Elovich model, experimental data is modeled. It appears that, based on the correlation coefficient, the pseudo-first order model is aligned with the experimental findings. Furthermore, the activation energy of under 40 kJ/mol indicated a physical adsorption occurs, indicating that the RSS chemically activated with malic acid is a fascinating source of CO2 removal requirements.
Biochars from Post-Production Biomass and Waste from Wood Management: Analysis of Carbonization Products
Authors: Kosakowski Wojciech , Bryszewska Malgorzata Anita , Dziugan Piotr
Published: November 2020

Waste biomass can be used as an alternative source of energy. However, such use requires prior treatment of the material. This paper describes the physicochemical characteristics of biochar obtained by the thermochemical decomposition of six types of agricultural waste biomass: residues from the production of flavored spirits (a pulp of lime, grapefruit and lemon), beetroot pulp, apple pomace, brewer’s spent grain, bark and municipal solid waste (bark, sawdust, off-cuts and wood chips). The biomass conversion process was studied under conditions of limited oxygen access in a reactor. The temperature was raised from 450 to 850 °C over 30 min, followed by a residence time of 60 min. The solid products were characterized in terms of their elemental compositions, mass, energy yield and ash content. The gaseous products from pyrolysis of the biomass were also analyzed and their compositions were characterized by GCMS (Gas Chromatography–Mass Spectrometry). The carbonization process increased the carbon content by, on average, 1.7 times, from an average percentage of 46.09% ± 3.65% for biomass to an average percentage of 74.72% ± 5.36% for biochars. After carbonization, the biochars were found to have a net calorific value of between 27 and 32 MJ/kg, which is comparable or even higher than good-quality coal (eco pea coal 24–26 MJ/kg). The net calorific values show that the volatile products can also be considered as a valuable source of energy.
Mechanical Assessment and Hyperelastic Modeling of Polyurethanes for the Early Stages of Vascular Graft Design
Authors: Said Arévalo-Alquichire , Carlos Dominguez-paz , Manuel F. Valero
Published: November 2020

The material design of vascular grafts is required for their application in the health sector. The use of polyurethanes (PUs) in vascular grafts intended for application in the body appears to be adequate due to the fact that native tissues have similar properties as PUs. However, the influence of chemical structure on the biomechanics of PUs remains poorly described. The use of constitutive models, together with numerical studies, is a powerful tool for evaluating the mechanical behavior of materials under specific physiological conditions. Therefore, the aim of this study was to assess the mechanical properties of different PU mixtures formed by polycaprolactone diol, polyethylene glycol, and pentaerythritol using uniaxial tensile, strain sweep, and multistep creep-recovery tests. Evaluations of the properties were also recorded after samples had been soaked in phosphate-buffer saline (PBS) to simulate physiological conditions. A hyperelastic model based on the Mooney–Rivlin strain density function was employed to model the performance of PUs under physiological pressure and geometry conditions. The results show that the inclusion of polyethylene glycol enhanced viscous flow, while polycaprolactone diol increased the elastic behavior. Furthermore, tensile tests revealed that hydration had an important effect on the softening phenomenon. Additionally, after the hydration of PUs, the ultimate strength was similar to those reported for other vascular conduits. Lastly, hyperelastic models revealed that the compliance of the PUs showed a cyclic behavior within the tested time and pressure conditions and is affected by the material composition. However, the compliance was not affected by the geometry of the materials. These tests demonstrate that the materials whose compositions are 5–90–5 and 46.3–46.3–7.5 could be employed in the designs of vascular grafts for medical applications since they present the largest value of compliance, ultimate strength, and elongation at break in the range of reported blood vessels, thus indicating their suitability. Moreover, the polyurethanes were revealed to undergo softening after hydration, which could reduce the risk of vascular trauma.
Multiple Pseudo-Plastic Appearance of the Dynamic Fracture in Quasi-Brittle Materials
Authors: Riganti Gianmario , Cadoni Ezio
Published: November 2020

Understanding and simulating the dynamic response of quasi-brittle materials still remains as one of the most challenging issues in structural engineering. This paper presents the damage propagation material model (DAMP) developed in order to obtain reliable results for use in structural engineering practice. A brief overview focuses on the differences between fracture mechanics studies, and engineering material modelling is presented to highlight possible guideline improvements. An experimental dynamic test performed on ultra-high-performance concrete specimens was used to obtain evidence of the physical behaviour of brittle materials with respect to specimen size variations and, consequently, to verify the reliability of the material equations proposed. Two widely used material models (RHT and M72R3), as representatives of the classical brittle material models for structural purposes, and the proposed material model are compared. Here, we show how: (i) the multiple structural strength of brittle materials arises from the damage propagation process, (ii) there is no contradiction between fracture mechanics and the engineering approach once the velocity of damage propagation is chosen as fundamental material property and (iii) classical dynamic material models are intrinsically not objective with related loss of predictive capability. Finally, the original material model equation and the experimental strategy, dedicated to its extended verification, will be shown in order to increase the design predictiveness in the dynamic range considering structure and specimen size variations. The dynamic stress increasing factor (DIF), experimentally observed and widely recognised in literature as a fundamental concept for quasi-brittle material modelling, has been reviewed and decomposed in its geometrical and material dependencies. The new material model defines its DIF starting from the physical quantities of the damage propagation velocity applied to the test case boundary conditions. The resultant material model predictiveness results improved greatly, demonstrating its ability to model several dynamic events considering size and dynamic load variations with a unique material property set without showing contradictions between numerical and experimental approaches.
UV-Cured Poly(Siloxane-Urethane)-Based Polymer Composite Materials for Lithium Ion Batteries—The Effect of Modification with Ionic Liquids
Authors: Kozakiewicz Janusz , Przybylski Jarosław , Hamankiewicz Bartosz , Sylwestrzak Krystyna , Trzaskowska Joanna , Krajewski Michal , Ratyński Maciej , Sarna Witold , Czerwiński Andrzej
Published: November 2020

The results of studies on the synthesis and characterization of conductive polymer composite materials designed as potential separators for lithium ion batteries are presented. The conductive polymer composites were prepared from UV-cured poly(siloxane-urethanes)s (PSURs) containing poly(ethylene oxide) (PEO) segments and modified with lithium salts and ionic liquids (ILs). The most encouraging results in terms of specific conductivity and mechanical properties of the composite were obtained when part of UV-curable PSUR prepolymer was replaced with a reactive UV-curable IL. Morphology of the composites modified with ILs or containing a standard ethylene carbonate/dimethyl carbonate mixture (EC/DMC) as solvent was compared. It was found that the composites showed a two-phase structure that did not change when non-reactive ILs were applied instead of EC/DMC but was much affected when reactive UV-curable ILs were used. The selected IL-modified UV-cured PSUR composite that did not contain flammable EC/DMC solvent was preliminarily tested as gel polymer electrolyte and separator for lithium ion batteries.
Dynamic Recrystallization Critical Conditions and a Physically–Based Constitutive Model of Al–4.8Mg Alloy Under Hot Working Conditions
Authors: Dai Qingsong , Deng Yunlai , Wang Yu , Huang Wenhui
Published: November 2020

The microstructure evolution and the mechanical behavior of Al–4.8Mg alloy were investigated by means of isothermal compression tests at various temperatures (280–520 °C) and strain rates (0.01–10 s−1). The results shown that there are three main mechanisms of dynamic softening of samples within the range of selected process parameters: dynamic recovery, dynamic recovery + dynamic recrystallization, and dynamic recrystallization, and the equiaxed dynamic recrystallization grain tends to be formed under higher temperature and higher strain rate. In order to accurately describe the dynamic recrystallization condition of Al-4.8Mg alloy under a wide range of hot deformation parameters, an improved dynamic recrystallization critical conditions model is proposed based on deformation activation energy and work-hardening rate. Additionally, a two–stage physically constitutive model considering the influence of work hardening–dynamic recovery and dynamic recrystallization is established. Comparisons between the predicted and experimental data indicate that the proposed model can adequately predict the flow stress in the range of selected process parameters with the average absolute relative error of 4.02%.
To Google or Not: Differences on How Online Searches Predict Names and Faces
Authors: Moret-Tatay Carmen , Wester Abigail G. , Gamermann Daniel
Published: November 2020

Word and face recognition are processes of interest for a large number of fields, including both clinical psychology and computer calculations. The research examined here aims to evaluate the role of an online frequency’s ability to predict both face and word recognition by examining the stability of these processes in a given amount of time. The study will further examine the differences between traditional theories and current contextual frequency approaches. Reaction times were recorded through both a logarithmic transformation and through a Bayesian approach. The Bayes factor notation was employed as an additional test to support the evidence provided by the data. Although differences between face and name recognition were found, the results suggest that latencies for both face and name recognition are stable for a period of six months and online news frequencies better predict reaction time for both classical frequentist analyses. These findings support the use of the contextual diversity approach.
Dynamic Tension Deformation of Rare-Earth Containing Mg-1.9Mn-0.3Ce Alloy Sheet along the Rolling Direction at Various Temperatures
Authors: Wang Jin , Wang Yang , Li Ziran
Published: November 2020

The tensile properties of rare-earth containing Mg-1.9Mn-0.3Ce alloy sheet along the rolling direction were experimentally investigated within the strain rate and temperature ranges of 0.001–1300 s−1 and 213–488 K. The obtained stress-strain responses of the alloy sheet indicate that both yield strength and strain-hardening rate increase when the strain rate increases, whereas they decrease with increase of temperature. Microscopic examination results show that basal slip, prismatic slip, and {101¯2} tension twinning take place in the tensile plastic deformation, while the occurrence of twinning is not obviously affected by the rate and temperature. Tensile samples tend to fracture in a ductile mode with increasing strain rate and temperature.
The Weldability of Duplex Stainless-Steel in Structural Components to Withstand Corrosive Marine Environments
Authors: Calderon-Uriszar-Aldaca Iñigo , Briz Estibaliz , Garcia Harkaitz , Matanza Amaia
Published: November 2020

There is still a considerable gap in the definition of the weldability of Duplex Stainless Steel (DSS). A lack of clarity that is explained by the standard specification of the maximum content of equivalent carbon that defines a “weldable” steel coupled with the fact that the alloying elements of DSS exceed this defined limit of weldability. In this paper, welding quality in an inert environment and in presence of chlorides is analyzed with the aim of defining optimum welding conditions of 2001, 2304, and 2205 DSS. The same procedure is followed for a hybrid weld between DSS 2205 and a low carbon mild steel, S275JR. As main output, this study defined the optimal welding conditions with tungsten inert gas without filler for each type of DSS weld that showed excellent anti-corrosion performance, with the exception of the DSS 2205-S275JR weld where widespread corrosion was observed. Additionally, this study established a relationship between the thermal input during welding and the content of alloying elements in defect-free joints. Furthermore, it demonstrated that an increase in ferrite content did not lead to a worse corrosion resistance, as expected after passivation.
A Large-Scale Survey of the Bacterial Communities in Lakes of Western Mongolia with Varying Salinity Regimes
Authors: Tandon Kshitij , Baatar Bayanmunkh , Chiang Pei-Wen , Dashdondog Narangarvuu , Oyuntsetseg Bolormaa , Tang Sen-Lin
Published: November 2020

In recent years, climate change coupled with anthropogenic activities has led to monumental changes in saline lakes which are rapidly drying up across the globe and particularly in Central Asia. The landlocked country of Mongolia is rich in lakes which have remained primarily undisturbed by human impact, and many of these lakes have varying salinity regimes and are located across various geographical landscapes. In this study, we sampled 18 lakes with varying salinity regimes (hyperhaline, mesohaline, oligohaline, and polyhaline) covering 7000 km of western Mongolia and its various geographical landscapes (Gobi Desert, forests, and steppe). We identified that the bacterial communities that dominate these lakes are significantly influenced by salinity (p < 0.001) and geographical landscape (p < 0.001). Further, only five zOTUs were shared in all the lakes across the salinity regimes, providing evidence that both local and regional factors govern the community assembly and composition. Furthermore, the bacterial communities of hyperhaline lakes were significantly positively correlated with salinity (ANOVA, p < 0.001) and arsenic concentrations (ANOVA, p < 0.001), whereas bacterial communities of mesohaline and polyhaline lakes situated in forest and steppe landscapes were positively correlated with temperature (ANOVA, p < 0.001) and altitude (ANOVA, p < 0.001), respectively. Functional predictions based on the 16S rRNA gene indicated enrichment of KEGG Ontology terms related to transporters for osmoprotection and -regulation. Overall, our study provides a comprehensive view of the bacterial diversity and community composition present in these lakes, which might be lost in the future.
Aestipascuomyces dupliciliberans gen. nov, sp. nov., the First Cultured Representative of the Uncultured SK4 Clade from Aoudad Sheep and Alpaca
Authors: Stabel Marcus , Hanafy Radwa A. , Schweitzer Tabea , Greif Meike , Aliyu Habibu , Flad Veronika , Young Diana , Lebuhn Michael , Elshahed Mostafa S. , Ochsenreither Katrin , Youssef Noha H.
Published: November 2020

We report on the isolation of the previously-uncultured Neocallimastigomycota SK4 lineage, by two independent research groups, from a wild aoudad sheep rumen sample (Texas, USA) and an alpaca fecal sample (Baden-Württemberg, Germany). Isolates from both locations showed near-identical morphological and microscopic features, forming medium-sized (2–5 mm) white filamentous colonies with a white center of sporangia, on agar roll tubes and a heavy biofilm in liquid media. Microscopic analysis revealed monocentric thalli, and spherical polyflagellated zoospores with 7–20 flagella. Zoospore release occurred through an apical pore as well as by sporangial wall rupturing, a duality that is unique amongst described anaerobic gut fungal strains. Isolates were capable of growing on a wide range of mono-, oligo-, and polysaccharide substrates as the sole carbon source. Phylogenetic assessment based on the D1–D2 28S large rRNA gene subunit (D1–D2 LSU) and internal transcribed spacer-1 (ITS-1) regions demonstrated high sequence identity (minimum identity of 99.07% and 96.96%, respectively) between all isolates; but low sequence identity (92.4% and 86.7%, respectively) to their closest cultured relatives. D1–D2 LSU phylogenetic trees grouped the isolates as a new monophyletic clade within the Orpinomyces–Neocallimastix–Pecoramyces–Feramyces–Ghazallamyces supragenus group. D1–D2 LSU and ITS-1 sequences recovered from the obtained isolates were either identical or displayed extremely high sequence similarity to sequences recovered from the same aoudad sheep sample on which isolation was conducted, as well as several sequences recovered from domestic sheep and few other herbivores. Interestingly, members of the SK4 clade seem to be encountered preferably in animals grazing on summer pasture. We hence propose accommodating these novel isolates in a new genus, Aestipascuomyces (derived from the Latin word for “summer pasture”), and a new species, A. dupliciliberans. The type strain is Aestipascuomycesdupliciliberans strain R4.
Phase Relations in the FeO-Fe3C-Fe3N System at 7.8 GPa and 1350 °C: Implications for Oxidation of Native Iron at 250 km
Authors: Kruk Aleksei N. , Sokol Alexander G. , Seryotkin Yurii V. , Palyanov Yuri N.
Published: November 2020

Oxidation of native iron in the mantle at a depth about 250 km and its influence on the stability of main carbon and nitrogen hosts have been reconstructed from the isothermal section of the ternary phase diagram for the FeO-Fe3C-Fe3N system. The results of experiments at 7.8 GPa and 1350 °C show that oxygen increase in the system to > 0.5 wt % provides the stability of FeO and leads to changes in the phase diagram: the Fe3C, L, and Fe3N single-phase fields change to two-phase ones, while the Fe3C + L and Fe3N + L two-phase fields become three-phase. Сarbon in iron carbide (Fe3C, space group Pnma) is slightly below the ideal value and nitrogen is below the EMPA (Electron microprobe analysis) detection limit. Iron nitride (ε-Fe3N, space group P63/mmc) contains up to 2.7 wt % С and 4.4 wt % N in equilibrium with both melt and wüstite but 2.1 wt % С and 5.4 wt % N when equilibrated with wüstite alone. Impurities in wüstite (space group Fmm) are within the EMPA detection limit. The contents of oxygen, carbon, and nitrogen in the metal melt equilibrated with different iron compounds are within 0.5–0.8 wt % O even in FeO-rich samples; 3.8 wt % C and 1.2 wt % N for Fe3C + FeO; and 2.9 wt % C and 3.5 wt % N for Fe3N + FeO. Co-crystallization of Fe3C and Fe3N from the O-bearing metal melt is impossible because the fields of associated C- and N-rich compounds are separated by that of FeO + L. Additional experiments with excess oxygen added to the system show that metal melt, which is the main host of carbon and nitrogen in the metal-saturated (~0.1 wt %) mantle at a depth of ~250 km and a normal heat flux of 40 mW/m2, has the greatest oxygen affinity. Its partial oxidation produces FeO and causes crystallization of iron carbides (Fe3C and Fe7C3) and increases the nitrogen enrichment of the residual melt. Thus, the oxidation of metal melt in the mantle enriched in volatiles may lead to successive crystallization of iron carbides and nitrides. In these conditions, magnetite remains unstable till complete oxidation of iron carbide, iron nitride, and the melt. Iron carbides and nitrides discovered as inclusions in mantle diamonds may result from partial oxidation of metal melt which originally contained relatively low concentrations of carbon and nitrogen.
High-Sensitivity C-Reactive Protein and Carotid Intima Media Thickness as Markers of Subclinical Inflammation and Atherosclerosis in Pediatric Patients with Hypercholesterolemia
Authors: Blinc Lana , Mlinaric Matej , Battelino Tadej , Groselj Urh
Published: November 2020

Hypercholesterolemia is a major cause of atherosclerosis development and premature cardiovascular disease (CVD). It leads to inflammation, which further accelerates atherosclerosis progression. Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated serum LDL-c from birth, due to a disease-causing variant in one of the causative genes (LDLR, APOB, PCSK9). In polygenic hypercholesterolemia (PH), the disease-causing genetic variant is absent; it is likely the cumulative result of multiple single nucleotide polymorphisms in LDL metabolism-related genes and other factors, such as lifestyle and environment. In high risk groups, such as patients with FH, an effective primary prevention of CVD must begin in childhood. High-sensitivity C-reactive protein (hsCRP) and carotid intima media thickness (cIMT) are two potential minimally invasive correlates of inflammation and subclinical atherosclerosis progression. hsCRP and cIMT have been shown to be significantly increased in patients with FH and PH relative to healthy controls, with some studies yielding conflicting results. In this review, we aim to summarize current knowledge and recent findings regarding the applicability of hsCRP and cIMT as markers of low-grade inflammation and subclinical atherosclerosis, focusing especially on children and adolescents with hypercholesterolemia.
Out of Sight, Out of Mind: The Effect of the Equilibration Protocol on the Structural Ensembles of Charged Glycolipid Bilayers
Authors: Messias Andresa , Santos Denys E. S. , Pontes Frederico J. S. , Lima Filipe S. , Soares Thereza A.
Published: November 2020

Molecular dynamics (MD) simulations represent an essential tool in the toolbox of modern chemistry, enabling the prediction of experimental observables for a variety of chemical systems and processes and majorly impacting the study of biological membranes. However, the chemical diversity of complex lipids beyond phospholipids brings new challenges to well-established protocols used in MD simulations of soft matter and requires continuous assessment to ensure simulation reproducibility and minimize unphysical behavior. Lipopolysaccharides (LPS) are highly charged glycolipids whose aggregation in a lamellar arrangement requires the binding of numerous cations to oppositely charged groups deep inside the membrane. The delicate balance between the fully hydrated carbohydrate region and the smaller hydrophobic core makes LPS membranes very sensitive to the choice of equilibration protocol. In this work, we show that the protocol successfully used to equilibrate phospholipid bilayers when applied to complex lipopolysaccharide membranes occasionally leads to a small expansion of the simulation box very early in the equilibration phase. Although the use of a barostat algorithm controls the system dimension and particle distances according to the target pressure, fluctuation in the fleeting pressure occasionally enables a few water molecules to trickle into the hydrophobic region of the membrane, with spurious solvent buildup. We show that this effect stems from the initial steps of NPT equilibration, where initial pressure can be fairly high. This can be solved with the use of a stepwise-thermalization NVT/NPT protocol, as demonstrated for atomistic MD simulations of LPS/DPPE and lipid-A membranes in the presence of different salts using an extension of the GROMOS forcefield within the GROMACS software. This equilibration protocol should be standard procedure for the generation of consistent structural ensembles of charged glycolipids starting from atomic coordinates not previously pre-equilibrated. Although different ways to deal with this issue can be envisioned, we investigated one alternative that could be readily available in major MD engines with general users in mind.
The New Dipeptide TSPO Ligands: Design, Synthesis and Structure–Anxiolytic Activity Relationship
Authors: Gudasheva Tatiana A. , Deeva Olga A. , Pantileev Andrey S. , Mokrov Grigory V. , Rybina Inna V. , Yarkova Milada A. , Seredenin Sergei B.
Published: November 2020

The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of N-acyl-tryptophanyl-containing dipeptides. These novel dipeptide TSPO ligands were designed with the original drug-based peptide design strategy using alpidem as non-peptide prototype. The anxiolytic activities were investigated in Balb/C mice using the illuminated open-field and elevated plus-maze tests in outbred laboratory mice ICR (CD-1). Dipeptide GD-102 (N-phenylpropionyl-l-tryptophanyl-l-leucine amide) in the dose range of 0.01–0.5 mg/kg intraperitoneally (i.p.) has a pronounced anxiolytic activity. The anxiolytic effect of GD-102 was abolished by PK11195, a specific TSPO antagonist. The structure–activity relationship study made it possible to identify a pharmacophore fragment for the dipeptide TSPO ligand. It was shown that l,d-diastereomer of GD-102 has no activity, and the d,l-isomer has less pronounced activity. The anxiolytic activity also disappears by replacing the C-amide group with the methyl ester, a free carboxyl group or methylamide. Consecutive replacement of each amino acid residue with glycine showed the importance of each of the amino acid residues in the structure of the ligand. The most active and technologically available compound GD-102, was selected for evaluation as a potential anxiolytic drug.