bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Study of Security and Privacy of Emerging Non-Volatile Memories
Authors: Khan Mohammad Nasim Imtiaz , Ghosh Swaroop
Published: September 2021

Several promising non-volatile memories (NVMs) such as magnetic RAM (MRAM), spin-transfer torque RAM (STTRAM), ferroelectric RAM (FeRAM), resistive RAM (RRAM), and phase-change memory (PCM) are being investigated to keep the static leakage within a tolerable limit. These new technologies offer high density and consume zero leakage power and can bridge the gap between processor and memory. The desirable properties of emerging NVMs make them suitable candidates for several applications including replacement of conventional memories. However, their unique characteristics introduce new data privacy and security issues. Some of them are already available in the market as discrete chips or a part of full system implementation. They are considered to become ubiquitous in future computing devices. Therefore, it is important to ensure their security/privacy issues. Note that these NVMs can be considered for cache, main memory, or storage application. They are also suitable to implement in-memory computation which increases system throughput and eliminates von Neumann bottleneck. Compute-capable NVMs impose new security and privacy challenges that are fundamentally different than their storage counterpart. This work identifies NVM vulnerabilities and attack vectors originating from the device level all the way to circuits and systems, considering both storage and compute applications. We also summarize the circuit/system-level countermeasures to make the NVMs robust against security and privacy issues.
Effect of Sheets’ Thickness and Rivet Geometry on Mechanical Properties of Orbital Riveted Aluminium Joints: Experimental and Numerical Analysis
Authors: Di Bella Guido , Calabrese Luigi , Borsellino Chiara , Alderucci Tiziana
Published: September 2021

Orbital riveting is an innovative joining technology used in various industrial fields. Despite its diffusion in recent years, it has not been accompanied by an equivalent interest from the scientific community, which has neglected the aspects of process optimization and joint performance. In this experimental/numerical study, six different configurations of orbital riveted joints were realised and tested to determine the effects of sheet thickness and rivet geometry on the mechanical properties of the joints and their failure modes. The results showed that the configuration of the joint significantly affects both its resistance and fracture mechanism. Moreover, it was possible to identify a transition between different failure modes by changing the rivet diameter. A non-optimal joint geometry favours a premature fracture at very low load (i.e., S9A21 batch with net tension fracture). The highest mechanical resistance was found in the S8A15 batch, which experienced unbuttoning failure. In order to better correlate the joint geometry with the mechanical behaviour and the relative stress distribution, a simplified numerical FEM was validated with the experimental results.
Towards Material-Batch-Aware Tool Condition Monitoring
Authors: Lutz Benjamin , Howell Philip , Regulin Daniel , Engelmann Bastian , Franke Jörg
Published: September 2021

In subtractive manufacturing, process monitoring systems are used to observe the manufacturing process, to predict maintenance actions and to suggest process optimizations. One challenge, however, is that the observable signals are influenced not only by the degradation of the cutting tool, but also by deviations in machinability among material batches. Thus it is necessary to first predict the respective material batch before making maintenance decisions. In this study, an approach is shown for batch-aware tool condition monitoring using feature extraction and unsupervised learning to analyze high-frequency control data in order to detect clusters of materials with different machinability, and subsequently optimize the respective manufacturing process. This approach is validated using cutting experiments and implemented as an edge framework.
5-[4-(tert-Butyl)cyclohexylidene]-2-thioxothiazolidin-4-one
Authors: Holota Serhii , Lozynskyi Andrii , Konechnyi Yulian , Shepeta Yulia , Lesyk Roman
Published: September 2021

The Knoevenagel reaction is an essential synthetic tool in the organic and medicinal chemistry of thiazolidin-4-one derivatives. In the present work, the application of ethylenediamine diacetate (EDDA) as an effective catalyst for the interaction of 2-thioxothiazolidin-4-one with 4-(tert-butyl)cyclohexanone is proposed. The structure of novel synthesized 5-[4-(tert-butyl)cyclohexylidene]-2-thioxothiazolidin-4-one (yield 61%) was confirmed by 1H-, 13C-NMR, LC-MS, IR, and UV spectra. Drug-like properties of the synthesized compound were evaluated in silico using the SwissAdme, and their potential antimicrobial activity against 15 strains of Gram-positive and Gram-negative bacteria as well as yeasts was evaluated in vitro. The synthesized compound possesses satisfactory drug-like parameters and promising antimicrobial properties and presents interest as a prospective intermediate for the forthcoming design of biologically active small molecules.
Multivariate Correlation Analysis of the Electroconductive Textiles Obtained Using Functionalization by Radio-Frequency Oxygen Plasma Treatments
Authors: Aileni Raluca Maria , Chiriac Laura , Toma Doina , Sandulache Irina
Published: September 2021

This paper presents a study concerning the preliminary treatments in radiofrequency (RF)oxygen (O2) plasma used to obtain a hydrophilic effect on raw cotton fabrics followed by electroconductive thin film deposition to obtain electroconductive textile surfaces. In addition, this study presents a multivariate correlation analysis of experimental parameters. The treatment using RF plasma O2 aimed to increase the hydrophilic character of the raw fabric and adherence of paste-based polymeric on polyvinyl alcohol (PVA) matrix and nickel (Ni), silver (Ag) or copper (Cu) microparticles. The purpose of the research was to develop electroconductive textiles for flexible electrodes, smart materials using a clean technology such as radiofrequency (RF) plasma O2 to obtain a hydrophilic surface with zero wastewater and reduced chemicals and carbon footprint. To achieve the foreseen results, we used advanced functionalization technologies such as RF plasma O2, followed by scraping a thin film of conductive paste-based Ni, Ag or Cu microparticles, and multivariate correlation methods to observe the dependence between parameters involved (dependent and independent variables). Overall, the fabrics treated in plasma with O2 using a kHz or MHz generator and power 100–200 W present an excellent hydrophilic character obtained in 3 min. After RF O2 plasma functionalization, a thin film based on polymeric matrix PVA and Ni microparticles have been deposited on the fabric surface to obtain electroconductive materials.
Temperature-Sensing Inks Using Electrohydrodynamic Inkjet Printing Technology
Authors: Ahn Ju-Hun , Hong Hee-Ju , Lee Chang-Yull
Published: September 2021

Temperature measurement is very important for thermal control, which is required for the advancement of mechanical and electronic devices. However, current temperature sensors are limited by their inability to measure curved surfaces. To overcome this problem, several methods for printing flexible substrates were proposed. Among them, electrohydrodynamic (EHD) inkjet printing technology was adopted because it has the highest resolution. Since EHD inkjet printing technology is limited by the type of ink used, an ink with temperature-sensing properties was manufactured for use in this printer. To confirm the applicability of the prepared ink, its resistance characteristics were investigated, and the arrangement and characteristics of the particles were observed. Then, the ink was printed using the EHD inkjet approach. In addition, studies of the meniscus shapes and line widths of the printed results under various conditions confirmed the applicability of the ink to the EHD inkjet printing technology and the change in its resistance with temperature.
The Influence of CNC Turning with VBMT, RCMX, 3ER, and MGMN Type Indexable Inserts on West African Ebony/Diospyros crassiflora, San Domingo Boxwood/Phyllostylon brasiliense, Rio Rosewood/Dalbergia nigra, Beechwood/Fagus sylvatica, Oakwood/Quercus robur, and Pinewood/Pinus silvestris Surface Roughness
Authors: Bembenek Michał , Kudelski Rafał , Pawlik Jan , Kowalski Łukasz
Published: September 2021

The current scientific literature lacks an adequate description of hardware used to machine timber. Traditional woodworking and metals fabrication consists of tungsten carbide (TC) inserts. In this work, the authors investigate the influence of cutting tool geometry on the resulting surface roughness of timber samples. A variety of wood types were used in these studies to provide broad information on the correlation between the cutting tools used and resulting surface morphology. The cutting tools were prepared on a computer numerical control (CNC) lathe and roughness average (Ra) and average maximum peak to valley height of the profile (Rz) parameters were measured by contact stylus. The tip radius of the TC inserts used was determined to be the most significant factor that impacted Ra and Rz. In summary, we found that the tip radius of the TC insert was inversely proportional to the roughness level, indicating that a flatter TC insert cutting end results in a smoother wood surface.
A Critical Study on Stability Measures of Feature Selection with a Novel Extension of Lustgarten Index
Authors: Sen Rikta , Mandal Ashis Kumar , Chakraborty Basabi
Published: September 2021

Stability of feature selection algorithm refers to its robustness to the perturbations of the training set, parameter settings or initialization. A stable feature selection algorithm is crucial for identifying the relevant feature subset of meaningful and interpretable features which is extremely important in the task of knowledge discovery. Though there are many stability measures reported in the literature for evaluating the stability of feature selection, none of them follows all the requisite properties of a stability measure. Among them, the Kuncheva index and its modifications, are widely used in practical problems. In this work, the merits and limitations of the Kuncheva index and its existing modifications (Lustgarten, Wald, nPOG/nPOGR, Nogueira) are studied and analysed with respect to the requisite properties of stability measure. One more limitation of the most recent modified similarity measure, Nogueira’s measure, has been pointed out. Finally, corrections to Lustgarten’s measure have been proposed to define a new modified stability measure that satisfies the desired properties and overcomes the limitations of existing popular similarity based stability measures. The effectiveness of the newly modified Lustgarten’s measure has been evaluated with simple toy experiments.
Influence of Implantation Depth on the Performance of Intracortical Probe Recording Sites
Authors: Usoro Joshua O. , Dogra Komal , Abbott Justin R. , Radhakrishna Rahul , Cogan Stuart F. , Pancrazio Joseph J. , Patnaik Sourav S.
Published: September 2021

Microelectrode arrays (MEAs) enable the recording of electrical activity from cortical neurons which has implications for basic neuroscience and neuroprosthetic applications. The design space for MEA technology is extremely wide where devices may vary with respect to the number of monolithic shanks as well as placement of microelectrode sites. In the present study, we examine the differences in recording ability between two different MEA configurations: single shank (SS) and multi-shank (MS), both of which consist of 16 recording sites implanted in the rat motor cortex. We observed a significant difference in the proportion of active microelectrode sites over the 8-week indwelling period, in which SS devices exhibited a consistent ability to record activity, in contrast to the MS arrays which showed a marked decrease in activity within 2 weeks post-implantation. Furthermore, this difference was revealed to be dependent on the depth at which the microelectrode sites were located and may be mediated by anatomical heterogeneity, as well as the distribution of inhibitory neurons within the cortical layers. Our results indicate that the implantation depth of microelectrodes within the cortex needs to be considered relative to the chronic performance characterization.
Identification of Lactobacillus Strains Capable of Fermenting Fructo-Oligosaccharides and Inulin
Authors: Renye John A. , White Andre K. , Hotchkiss Arland T.
Published: September 2021

Novel probiotic strains that can ferment prebiotics are important for functional foods. The utilization of prebiotics is strain specific, so we screened 86 Lactobacillus strains and compared them to Bifidobacterium breve 2141 for the ability to grow and produce SCFA when 1% inulin or fructo-oligosaccharides (FOS) were provided as the carbon source in batch fermentations. When grown anaerobically at 32 °C, ten Lactobacillus strains grew on both prebiotic substrates (OD600 ≥ 1.2); while Lactobacillus coryniformis subsp. torquens B4390 grew only in the presence of inulin. When the growth temperature was increased to 37 °C to simulate the human body temperature, four of these strains were no longer able to grow on either prebiotic. Additionally, L. casei strains 4646 and B441, and L. helveticus strains B1842 and B1929 did not require anaerobic conditions for growth on both prebiotics. Short-chain fatty acid analysis was performed on cell-free supernatants. The concentration of lactic acid produced by the ten Lactobacillus strains in the presence of prebiotics ranged from 73–205 mM. L. helveticus B1929 produced the highest concentration of acetic acid ~19 mM, while L. paraplantarum B23115 and L. paracasei ssp. paracasei B4564 produced the highest concentrations of propionic (1.8–4.0 mM) and butyric (0.9 and 1.1 mM) acids from prebiotic fermentation. L. mali B4563, L. paraplantarum B23115 and L. paracasei ssp. paracasei B4564 were identified as butyrate producers for the first time. These strains hold potential as synbiotics with FOS or inulin in the development of functional foods, including infant formula.
Microbiome Studies from Saudi Arabia over the Last 10 Years: Achievements, Gaps, and Future Directions
Authors: Alzahrani Khalid J.
Published: September 2021

In the past ten years, microbiome studies have shown tremendous potentiality for implementation of understanding microbiome structures and functions of various biomes and application of this knowledge for human betterment. Saudi Arabia is full of geographical, ecological, ethnical, and industrial diversities and scientific capacities. Therefore, there is a great potential in Saudi Arabia to conduct and implement microbiome-based research and applications. However, there is no review available on where Saudi Arabia stands with respect to global microbiome research trends. This review highlights the metagenome-assisted microbiome research from Saudi Arabia compared to the global focuses on microbiome research. Further, it also highlights the gaps and areas that should be focused on by Saudi microbiome researchers and the possible initiatives to be taken by Saudi government and universities. This literature review shows that the global trends of microbiome research cover a broad spectrum of human and animal health conditions and diseases, environmental and antimicrobial resistance surveillance, surveillance of food and food processing, production of novel industrial enzymes and bioactive pharmaceutical products, and space applications. However, Saudi microbiome studies are mostly confined to very few aspects of health (human and animal) and environment/ecology in last ten years, without much application. Therefore, Saudi Arabia should focus more on applied microbiome research through government, academic, and industry initiatives and global cooperation to match the global trends.
Bacillus licheniformis and Bacillus subtilis, Probiotics That Induce the Formation of Macrophage Extracellular Traps
Authors: Romo-Barrera Carol M. , Castrillón-Rivera Laura E. , Palma-Ramos Alejandro , Castañeda-Sánchez Jorge I. , Luna-Herrera Julieta
Published: September 2021

Probiotics are considered living microorganisms that help preserve the health of the host who uses them. Bacillus are a genus of Gram-positive bacteria used as probiotics for animal and human consumption. They are currently distributed in various commercial forms. Two of the species used as probiotics are B. licheniformis and B. subtilis. Macrophages are central cells in the immune response, being fundamental in the elimination of microbial pathogens, for which they use various mechanisms, including the formation of extracellular traps (METs). There have been very few studies carried out on the participation of macrophages in response to the interaction of probiotics of the genus Bacillus with the host. In this work, we used macrophages from the J774A mouse cell line.1, and we found that they are susceptible to infection by the two Bacillus species. However, both species were eliminated as the infection progressed. Using confocal microscopy, we identified the formation of METs from the first hours of infection, which were characterized by the presence of myeloperoxidase (MPO) and citrullinated histone (Hit3Cit). Quantitative data on extracellular DNA release were also obtained; release was observed starting in the first hour of infection. The induction of METs by B. licheniformis caused a significant decrease in the colony-forming units (CFU) of Staphylococcus aureus. The induction of METS by bacteria of the Bacillus genus is a mechanism that participates in controlling the probiotic and potentially pathogenic bacteria such as S. aureus. The induction of METs to control pathogens may be a novel mechanism that could explain the beneficial effects of probiotics of the genus Bacillus.
Helicobacter pylori and Respiratory Diseases: 2021 Update
Authors: Durazzo Marilena , Adriani Alessandro , Fagoonee Sharmila , Saracco Giorgio Maria , Pellicano Rinaldo
Published: September 2021

Helicobacter pylori (H. pylori) is a Gram-negative bacterium involved in the development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue. Unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency have also been related to H. pylori infection, whereas for other extra-gastric diseases, the debate is still open. In this review, we evaluate and discuss the potential involvement of H. pylori infection in the pathogenesis of several respiratory diseases. A MEDLINE search of all studies published in English from 1965 to 2021 was carried out. Controversial findings have been reported in patients with bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, lung cancer, tuberculosis, cystic fibrosis, and sarcoidosis. Most of the available literature is concerned with case-control studies based on seroprevalence, with a small sample size and low consideration of confounders, which represents a potential issue. So far, there is no clear evidence of a causal association between H. pylori infection and respiratory diseases, and larger studies with appropriate epidemiological design are required.
Seroprevalence Estimates of Latent and Acute Toxoplasma Infections in HIV+ People—Call for Action in Underprivileged Communities
Authors: Rostami Ali , Riahi Seyed Mohammad , Abdollahzadeh Sagha Shayan , Taghipour Ali , Sepidarkish Mahdi , Mohammadnia-Afrouzi Mousa , Ebrahimpour Soheil , Hotez Peter J. , Gamble Ray , Gasser Robin B.
Published: September 2021

We undertook a comprehensive, systematic review of observational studies to estimate respective seroprevalences of latent and acute Toxoplasma gondii infections in HIV+ people at the global, regional and country levels; related seroprevalence to socio-economic variables and CD4+ cell counts; and assessed temporal changes in prevalence and risk factors for this group. We systematically searched international databases for seroepidemiological surveys between 1 January 1980 and 31 July 2020. We used a random effects model to calculate pooled seroprevalences with 95% confidence intervals (CI), and estimated the numbers of HIV+ people inferred to harbour latent and acute T. gondii infections (LT or AT). We grouped seroprevalence data according to the geographic regions defined by the World Health Organization (WHO) and conducted subgroup and meta-regression analyses of the data. Of a total of 4024 studies identified, 150 and 65 of them met the inclusion criteria for LT and AT in HIV+ people, respectively. The overall, pooled seroprevalences of LT and AT were 37.4% (95% CI, 33.4–41.4) and 1.3% (95% CI, 0.9–1.8%), equating to ~14.2 and 0.5 million HIV+ people, respectively. Most HIV+ people with T. gondii infections originated from Africa, and the highest seroprevalences were in low-income countries with low human development indices. Significant risk factors for toxoplasmosis in HIV+ patients included the consumption of raw/undercooked meat, frequent contact with soil, a low CD4+ T lymphocyte number (<200 cells per μL) and age. Overall, the finding of high seroprevalences of particularly latent T. gondii infection in HIV+ people in underprivileged regions of the world, such as parts of Africa, calls for preventative action. Programs that include routine serological monitoring, counselling, care, animal control and/or prophylactic treatment measures are needed to prevent severe toxoplasmosis from developing in people living with HIV infection. Our study highlights the potential importance of parasite chemoprophylaxis in resource-poor settings, particularly in low-income countries.
Comparison of Two Cutibacterium acnes Biofilm Models
Authors: Varin-Simon Jennifer , Lamret Fabien , Colin Marius , Gangloff Sophie C. , Mongaret Céline , Reffuveille Fany
Published: September 2021

The study of biofilms in vitro is complex and often limited by technical problems due to simplified models. Here, we compared C. acnes biofilm formation, from species involved in bone and prosthesis infection, in a static model with a dynamic model. Using similar parameters, the percentage of live bacteria within the biofilm was higher in dynamic than in static approach. In both models, bacterial internalization in osteoblast-like cells, playing the role of stress factor, affected this proportion but in opposite ways: increase of live bacteria proportion in the static model (×2.04 ± 0.53) and of dead bacteria proportion (×3.5 ± 1.03) in the dynamic model. This work highlights the huge importance in the selection of a relevant biofilm model in accordance with the environmental or clinical context to effectively improve the understanding of biofilms and the development of better antibiofilm strategies.
Editorial for Special Issue “Archaeological Ceramic Diagenesis”
Authors: Golitko Mark
Published: September 2021

In their seminal publication on neutron activation analysis of archaeological ceramics, Sayre, Dodson, and Burr Thompson [...]
Biodepression of Copper-Activated Pyrite with Acidithiobacillus ferrooxidans in Flotation with Fresh and Seawater
Authors: San Martín Francisca , Valles Ignacio , Kracht Willy , Vargas Tomás , Aguilar Claudio
Published: September 2021

Acidithiobacillus ferrooxidans has been shown to be a good depressant of pyrite in freshwater and seawater flotation. However, the effect of these bacteria over copper-activated pyrite has not been studied. At the industrial scale, the activation of pyrite with copper is a common process that occurs because Cu2+ ions, released from other minerals, react with pyrite. This is a problem because Cu2+ ions facilitate the reaction of pyrite with the xanthate collectors, becoming hydrophobic and reaching the froth. In this study, microflotation experiments in a Hallimond tube were conducted to evaluate the depressant effect of A. ferrooxidans over non-activated and Cu-activated pyrite in freshwater and seawater flotation. The experiments were carried out at pH 4, 6, 8, 10 and 12 and pyrite was mixed with CuSO4 at 2.5×10−5 and 5×10−5 M in order to activate its surface. Considering the results obtained in the microflotation tests, it is possible to conclude that Acidithiobacillus ferrooxidans is able to depress non-activated and Cu-activated pyrite at the entire pH range studied (4–12) in freshwater. On the other hand, the use of bacteria in flotation with seawater proved to be effective to depress non-activated and Cu-activated pyrite at pH 8 and 10 with better results achieved at pH 10. At this pH, the non-activated pyrite recovery dropped from 96% to 15%, and the recovery of Cu-activated pyrite dropped from 95% to 32% when the activation was carried out at 2.5×10−5 M, and from 87% to 50% when the activation was conducted at 5×10−5 M of CuSO4. The XPS analysis showed that chalcopyrite and copper (II) hydroxide were formed on the pyrite surface when it is contacted with CuSO4.
Microscopic Diffusion Characteristics of Linear Alkylbenzene Sulfonates on the Surface of Anthracite: The Influence of Different Attachment Sites of Benzene Ring in the Backbone
Authors: Chen Xuanlai , Yan Guochao , Yang Xianglin , Xu Guang , Wei Shuai
Published: September 2021

In order to explore the effect of the attachment site of the benzene ring in the backbone of the surfactant on its diffusion characteristics on the surface of anthracite, the molecular dynamics simulation method was used, and the four isomers (m-C16, m = 2,4,6,8; m represents the attachment site of the benzene ring in the backbone) of sodium hexadecyl benzene sulfonate (SHS) were selected. Binary models of surfactant/anthracite, surfactant/graphene modified by oxygen-containing functional groups, and a ternary model of water/surfactant/anthracite were constructed. By analyzing a series of properties such as interaction energy, contact surface area, relative concentration distribution, radial distribution function, hydrophobic tail chain order parameter, etc., it is concluded that the adsorption strength of 4-C16 on the surface of anthracite is the highest; the reason is that 4-C16 has the highest degree of aggregation near the oxygen-containing functional groups on the surface of anthracite. Further investigations find that 4-C16 can be densely covered on the ketone group, and the longer branch chain of 4-C16 has the highest degree of order in the Z-axis direction.
Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length
Authors: Xu Simeng , Cao Yufang , Luo Yu , Xiao Di , Wang Wei , Wang Zhiren , Yang Xiaoping
Published: September 2021

Among the known biguanide drugs, proguanil has the best antiproliferative activity. In contrast, newly synthesized biguanide derivatives containing fluorine atoms have excellent biological activity, among which trifluoromethoxy compounds show the strongest ability. Preliminary work in our laboratory exhibited that n-heptyl containing proguanil derivatives on one alkyl chain side have better biological activity than those with a shorter carbon chain. However, the relationship between the length of the carbon chain and the activity of the compounds is unknown. In this study, we synthesized 10 new trifluoromethoxy-containing proguanil derivatives with various carbon chain lengths. The phenyl side is fixed as the trifluoromethoxy group with change of carbon chain length in alkyl chain side. It was found that the anti-cancer abilities of 5C–8C with n-pentyl to n-octyl groups was significantly better than that of proguanil in the five human cancer cell lines. The colony formation assay demonstrated that 6C–8C at 0.5 to 1.0 μM significantly inhibited the colony formation of human cancer cell lines, much stronger than that of proguanil. Pharmacologically, 8C activates AMPK, leading to inactivation of the mTOR/p70S6K/4EBP1 pathway. Thus, these novel compounds have a great potential for developing new anti-cancer candidates.
Density of Deep Eutectic Solvents: The Path Forward Cheminformatics-Driven Reliable Predictions for Mixtures
Authors: Halder Amit Kumar , Haghbakhsh Reza , Voroshylova Iuliia V. , Duarte Ana Rita C. , Cordeiro M. Natalia D. S.
Published: September 2021

Deep eutectic solvents (DES) are often regarded as greener sustainable alternative solvents and are currently employed in many industrial applications on a large scale. Bearing in mind the industrial importance of DES—and because the vast majority of DES has yet to be synthesized—the development of cheminformatic models and tools efficiently profiling their density becomes essential. In this work, after rigorous validation, quantitative structure-property relationship (QSPR) models were proposed for use in estimating the density of a wide variety of DES. These models were based on a modelling dataset previously employed for constructing thermodynamic models for the same endpoint. The best QSPR models were robust and sound, performing well on an external validation set (set up with recently reported experimental density data of DES). Furthermore, the results revealed structural features that could play crucial roles in ruling DES density. Then, intelligent consensus prediction was employed to develop a consensus model with improved predictive accuracy. All models were derived using publicly available tools to facilitate easy reproducibility of the proposed methodology. Future work may involve setting up reliable, interpretable cheminformatic models for other thermodynamic properties of DES and guiding the design of these solvents for applications.
The Design, Synthesis, and Biological Activities of Pyrrole-Based Carboxamides: The Novel Tubulin Inhibitors Targeting the Colchicine-Binding Site
Authors: Boichuk Sergei , Galembikova Aigul , Syuzov Kirill , Dunaev Pavel , Bikinieva Firuza , Aukhadieva Aida , Zykova Svetlana , Igidov Nazim , Gankova Ksenia , Novikova Maria , Kopnin Pavel
Published: September 2021

Microtubule targeting agents (MTAs) that interfere with the dynamic state of the mitotic spindle are well-known and effective chemotherapeutic agents. These agents interrupt the microtubule network via polymerization or depolymerization, halting the cell cycle progression and leading to apoptosis. We report two novel pyrrole-based carboxamides (CAs) (CA-61 and -84) as the compounds exhibiting potent anti-cancer properties against a broad spectrum of epithelial cancer cell lines, including breast, lung, and prostate cancer. The anti-cancer activity of CAs is due to their ability to interfere with the microtubules network and inhibit tubulin polymerization. Molecular docking demonstrated an efficient binding between these ligands and the colchicine-binding site on the tubulin. CA-61 formed two hydrogen bond interactions with THR 179 (B) and THR 353 (B), whereas two hydrogen bonds with LYS 254 (B) and 1 with ASN 101 (A) were identified for CA-84. The binding energy for CA-84 and CA-61 was −9.910 kcal/mol and −9.390 kcal/mol. A tubulin polymerization assay revealed a strong inhibition of tubulin polymerization induced by CA-61 and -84. The immunofluorescence data revealed the disruption of the tubulin assembly in CA-treated cancer cells. As an outcome of the tubulin inhibition, these compounds halted the cell cycle progression in the G2/M phase, leading to the accumulation of the mitotic cells, and further induced apoptosis. Lastly, the in vivo study indicated that CAs significantly inhibited the HCC1806 breast cancer xenograft tumor growth in a nude mouse model. Collectively, we identified the novel CAs as potent MTAs, inhibiting tubulin polymerization via binding to the colchicine-binding site, disrupting the microtubule network, and exhibiting potent pro-apoptotic activities against the epithelial cancer cell lines both in vitro and in vivo.
Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Torello Cristiane Okuda , Alvarez Marisa Claudia , Olalla Saad Sara T.
Published: September 2021

Flavonoids are ubiquitous groups of polyphenolic compounds present in most natural products and plants. These substances have been shown to have promising chemopreventive and chemotherapeutic properties with multiple target interactions and multiple pathway regulations against various human cancers. Polyphenolic flavonoid compounds can block the initiation or reverse the promotion stage of multistep carcinogenesis. Quercetin is one of the most abundant flavonoids found in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) therapy remains a challenge for hematologists worldwide, and the outcomes for patients with both disorders continue to be poor. This scenario indicates the increasing demand for innovative drugs and rational combinative therapies. Herein, we discuss the multitarget effects of the flavonoid quercetin, a naturally occurring flavonol, on AML and MDS.
A Path Integral Molecular Dynamics Simulation of a Harpoon-Type Redox Reaction in a Helium Nanodroplet
Authors: Castillo-García Alvaro , Hauser Andreas W. , de Lara-Castells María Pilar , Villarreal Pablo
Published: September 2021

We present path integral molecular dynamics (PIMD) calculations of an electron transfer from a heliophobic Cs2 dimer in its (3Σu) state, located on the surface of a He droplet, to a heliophilic, fully immersed C60 molecule. Supported by electron ionization mass spectroscopy measurements (Renzler et al., J. Chem. Phys.2016, 145, 181101), this spatially quenched reaction was characterized as a harpoon-type or long-range electron transfer in a previous high-level ab initio study (de Lara-Castells et al., J. Phys. Chem. Lett.2017, 8, 4284). To go beyond the static approach, classical and quantum PIMD simulations are performed at 2 K, slightly below the critical temperature for helium superfluidity (2.172 K). Calculations are executed in the NVT ensemble as well as the NVE ensemble to provide insights into real-time dynamics. A droplet size of 2090 atoms is assumed to study the impact of spatial hindrance on reactivity. By changing the number of beads in the PIMD simulations, the impact of quantization can be studied in greater detail and without an implicit assumption of superfluidity. We find that the reaction probability increases with higher levels of quantization. Our findings confirm earlier, static predictions of a rotational motion of the Cs2 dimer upon reacting with the fullerene, involving a substantial displacement of helium. However, it also raises the new question of whether the interacting species are driven out-of-equilibrium after impurity uptake, since reactivity is strongly quenched if a full thermal equilibration is assumed. More generally, our work points towards a novel mechanism for long-range electron transfer through an interplay between nuclear quantum delocalization within the confining medium and delocalized electronic dispersion forces acting on the two reactants.
NMF-Based Approach for Missing Values Imputation of Mass Spectrometry Metabolomics Data
Authors: Xu Jingjing , Wang Yuanshan , Xu Xiangnan , Cheng Kian-Kai , Raftery Daniel , Dong Jiyang
Published: September 2021

In mass spectrometry (MS)-based metabolomics, missing values (NAs) may be due to different causes, including sample heterogeneity, ion suppression, spectral overlap, inappropriate data processing, and instrumental errors. Although a number of methodologies have been applied to handle NAs, NA imputation remains a challenging problem. Here, we propose a non-negative matrix factorization (NMF)-based method for NA imputation in MS-based metabolomics data, which makes use of both global and local information of the data. The proposed method was compared with three commonly used methods: k-nearest neighbors (kNN), random forest (RF), and outlier-robust (ORI) missing values imputation. These methods were evaluated from the perspectives of accuracy of imputation, retrieval of data structures, and rank of imputation superiority. The experimental results showed that the NMF-based method is well-adapted to various cases of data missingness and the presence of outliers in MS-based metabolic profiles. It outperformed kNN and ORI and showed results comparable with the RF method. Furthermore, the NMF method is more robust and less susceptible to outliers as compared with the RF method. The proposed NMF-based scheme may serve as an alternative NA imputation method which may facilitate biological interpretations of metabolomics data.
Understanding the Adsorption of Peptides and Proteins onto PEGylated Gold Nanoparticles
Authors: Perera Yasiru Randika , Xu Joanna Xiuzhu , Amarasekara Dhanush L. , Hughes Alex C. , Abbood Ibraheem , Fitzkee Nicholas C.
Published: September 2021

Polyethylene glycol (PEG) surface conjugations are widely employed to render passivating properties to nanoparticles in biological applications. The benefits of surface passivation by PEG are reduced protein adsorption, diminished non-specific interactions, and improvement in pharmacokinetics. However, the limitations of PEG passivation remain an active area of research, and recent examples from the literature demonstrate how PEG passivation can fail. Here, we study the adsorption amount of biomolecules to PEGylated gold nanoparticles (AuNPs), focusing on how different protein properties influence binding. The AuNPs are PEGylated with three different sizes of conjugated PEG chains, and we examine interactions with proteins of different sizes, charges, and surface cysteine content. The experiments are carried out in vitro at physiologically relevant timescales to obtain the adsorption amounts and rates of each biomolecule on AuNP-PEGs of varying compositions. Our findings are relevant in understanding how protein size and the surface cysteine content affect binding, and our work reveals that cysteine residues can dramatically increase adsorption rates on PEGylated AuNPs. Moreover, shorter chain PEG molecules passivate the AuNP surface more effectively against all protein types.
Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson’s Disease
Authors: Altwal Feras , Padovan-Neto Fernando E. , Ritger Alexandra , Steiner Heinz , West Anthony R.
Published: September 2021

L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr1A antagonist WAY-100635, demonstrating a critical role for 5-HTr1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.
Simultaneous Analysis of Fenpropimorph and Fenpropimorph Acid in Six Different Livestock Products Using a Single-Sample Preparation Method Followed by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Kim Seon Wook , Lim Da Jung , Kim In Seon
Published: September 2021

Pesticides in livestock products must be measured to ensure food safety. We developed a single-sample preparation method followed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) for simultaneous determination of fenpropimorph and fenpropimorph acid in six different livestock products. The extraction method was a modification of the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and was validated according to the CODEX guidelines. The matrix-matched calibration curves for fenpropimorph and fenpropimorph acid exhibited good linearity, with coefficients of determination (R2 values) higher than 0.998. The limit of detection (LOD) and the limit of quantitation (LOQ) were 1.25 and 5.0 µg kg−1, respectively. The average recovery values ranged from 61.5% to 97.1% for samples fortified to the LOQ, 2 × LOQ, and 10 × LOQ. The method fully complied with the CODEX guidelines and was successfully applied to real samples obtained from domestic markets.
Time Evolution of Microbial Composition and Metabolic Profile for Biogenic Amines and Free Amino Acids in a Model Cucumber Fermentation System Brined with 0.5% to 5.0% Sodium Chloride
Authors: Świder Olga , Wójcicki Michał , Bujak Marzena , Juszczuk-Kubiak Edyta , Szczepańska Magdalena , Roszko Marek Ł.
Published: September 2021

Salt concentrations in brine and temperature are the major environmental factors that affect activity of microorganisms and, thus may affect formation of biogenic amines (BAs) during the fermentation process. A model system to ferment cucumbers with low salt (0.5%, 1.5% or 5.0% NaCl) at two temperatures (11 or 23 °C) was used to study the ability of indigenous microbiota to produce biogenic amines and metabolize amino acid precursors. Colony counts for presumptive Enterococcus and Enterobacteriaceae increased by 4 and up to 2 log of CFU∙mL−1, respectively, and remained viable for more than 10 days. 16S rRNA sequencing showed that Lactobacillus and Enterobacter were dominant in fermented cucumbers with 0.5% and 1.5% salt concentrations after storage. The initial content of BAs in raw material of 25.44 ± 4.03 mg∙kg−1 fluctuated throughout experiment, but after 6 months there were no significant differences between tested variants. The most abundant BA was putrescine, that reached a maximum concentration of 158.02 ± 25.11 mg∙kg−1. The Biogenic Amines Index (BAI) calculated for all samples was significantly below that needed to induce undesirable effects upon consumption. The highest value was calculated for the 23 °C/5.0% NaCl brine variant after 192 h of fermentation (223.93 ± 54.40). Results presented in this work indicate that possibilities to control spontaneous fermentation by changing salt concentration and temperature to inhibit the formation of BAs are very limited.
Natural Polyphenols as Immunomodulators to Rescue Immune Response Homeostasis: Quercetin as a Research Model against Severe COVID-19
Authors: Bernini Roberta , Velotti Francesca
Published: September 2021

The COVID-19 pandemic is caused by SARS-CoV-2 and is leading to the worst health crisis of this century. It emerged in China during late 2019 and rapidly spread all over the world, producing a broad spectrum of clinical disease severity, ranging from asymptomatic infection to death (4.3 million victims so far). Consequently, the scientific research is devoted to investigating the mechanisms of COVID-19 pathogenesis to both identify specific therapeutic drugs and develop vaccines. Although immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, new understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection, which are mainly focused on the dysregulated inflammatory response in severe COVID-19. Polyphenols are naturally occurring products with immunomodulatory activity, playing a relevant role in reducing inflammation and preventing the onset of serious chronic diseases. Mainly based on data collected before the appearance of SARS-CoV-2, polyphenols have been recently suggested as promising agents to fight COVID-19, and some clinical trials have already been approved with polyphenols to treat COVID-19. The aim of this review is to analyze and discuss the in vitro and in vivo research on the immunomodulatory activity of quercetin as a research model of polyphenols, focusing on research that addresses issues related to the dysregulated immune response in severe COVID-19. From this analysis, it emerges that although encouraging data are present, they are still insufficient to recommend polyphenols as potential immunomodulatory agents against COVID-19.
C,C- and C,N-Chelated Organocopper Compounds
Authors: Liu Liang , Chen Hui , Yang Zhenqiang , Wei Junnian , Xi Zhenfeng
Published: September 2021

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds could advance the rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize unstable organocopper compounds. Bidentate ligands can chelate to the same copper atom via η2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via η1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via μ2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure–reactivity relationships.
Study of the Seasonal Variations of the Fatty Acid Profiles of Selected Macroalgae
Authors: Pereira Tatiana , Horta André , Barroso Sónia , Mendes Susana , Gil Maria M.
Published: September 2021

Due to the high consumption of fat-rich processed foods, efforts are being done to reduce their saturated fat (SFA) contents and replace it with polyunsaturated fatty acids (PUFA), creating a necessity to find alternative PUFA sources. Macroalgae, being a promising natural source of healthy food, may be such an alternative. The fatty acid (FA) profile of Fucus spiralis, Bifurcaria bifurcata, Ulva lactuca, and Saccorhiza polyschides were determined through direct transesterification and their seasonal variation was studied. F. spiralis showed the highest FA content overall, B. bifurcata presented the higher PUFA amounts, and U. lactuca and S. polyschides the higher SFA. The production of FA was shown to be influenced by the seasons. Spring and summer seemed to induce the FA production in F. spiralis and B. bifurcata while in U. lactuca the same was verified in winter. U. lactuca presented a ω6/ω3 ratio between 0.59 and 1.38 while B. bifurcata presented a ratio around 1.31. The study on the seasonal variations of the macroalgal FA profile can be helpful to understand the best season to yield FA of interest, such as ALA, EPA, and DHA. It may also provide valuable information on the best culturing conditions for the production of desired FAs.