bluuebunny/crossref_metadata_2025 huggingface dataset:
Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model
Authors: Borg Danielle J. , Faridi Pouya , Giam Kai Lin , Reeves Peta , Fotheringham Amelia K. , McCarthy Domenica A. , Leung Sherman , Ward Micheal S. , Harcourt Brooke E. , Ayala Rochelle , Scheijen Jean L. , Briskey David , Dudek Nadine L. , Schalkwijk Casper G. , Steptoe Raymond , Purcell Anthony W. , Forbes Josephine M.
Published: June 2021

Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50–100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate β-cell effects, NOD-derived MIN6N8 β-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10–12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts β-cell function.
Geometrical Effects on Ultrasonic Al Bump Direct Bonding for Microsystem Integration: Simulation and Experiments
Authors: Lee Jun-Hao , Li Pin-Kuan , Hung Hai-Wen , Chuang Wallace , Schellkes Eckart , Yasuda Kiyokazu , Song Jenn-Ming
Published: June 2021

This study employed finite element analysis to simulate ultrasonic metal bump direct bonding. The stress distribution on bonding interfaces in metal bump arrays made of Al, Cu, and Ni/Pd/Au was simulated by adjusting geometrical parameters of the bumps, including the shape, size, and height; the bonding was performed with ultrasonic vibration with a frequency of 35 kHz under a force of 200 N, temperature of 200 °C, and duration of 5 s. The simulation results revealed that the maximum stress of square bumps was greater than that of round bumps. The maximum stress of little square bumps was at least 15% greater than those of little round bumps and big round bumps. An experimental demonstration was performed in which bumps were created on Si chips through Al sputtering and lithography processes. Subtractive lithography etching was the only effective process for the bonding of bumps, and Ar plasma treatment magnified the joint strength. The actual joint shear strength was positively proportional to the simulated maximum stress. Specifically, the shear strength reached 44.6 MPa in the case of ultrasonic bonding for the little Al square bumps.
Physics-Based TCAD Simulation and Calibration of 600 V GaN/AlGaN/GaN Device Characteristics and Analysis of Interface Traps
Authors: Song Yu-Lin , Reddy Manoj Kumar , Chang Luh-Maan , Sheu Gene
Published: June 2021

This study proposes an analysis of the physics-based TCAD (Technology Computer-Aided Design) simulation procedure for GaN/AlGaN/GaN HEMT (High Electron Mobility Transistor) device structures grown on Si (111) substrate which is calibrated against measurement data. The presence of traps and activation energies in the device structure will impact the performance of a device, the source of traps and position of traps in the device remains as a complex exercise until today. The key parameters for the precise tuning of threshold voltage (Vth) in GaN transistors are the control of the positive fixed charges −5 × 1012 cm−2, donor-like traps −3 × 1013 cm−2 at the nitride/GaN interfaces, the energy of the donor-like traps 1.42 eV below the conduction band and the acceptor traps activation energy in the AlGaN layer and buffer regions with 0.59 eV below the conduction band. Hence in this paper, the sensitivity of the trap mechanisms in GaN/AlGaN/GaN HEMT transistors, understanding the absolute vertical electric field distribution, electron density and the physical characteristics of the device has been investigated and the results are in good agreement with GaN experimental data.
Effect of pH on Effective Slip Length and Surface Charge at Solid–Oil Interfaces of Roughness-Induced Surfaces
Authors: Tian Porui , Li Yifan
Published: June 2021

In the development of micro/nano fluid control systems, fluid resistance has always been one of the key factors restricting its development. According to previous studies, it is found that the boundary slip effect of the solid-liquid interface can effectively reduce the resistance of the microfluid and improve the transport efficiency of the microfluid. The boundary slip length is mainly affected by surface wettability, roughness, and surface charge density. Among them, the influence mechanism of surface charge density on the boundary slip is the most complicated, and there is a lack of relevant research, and further investigation is needed. In this paper, we present research on quantification of effective slip length and surface charge density, where the roughness effect is considered. The electrostatic and hydrodynamic force data obtained from atomic force microscopy (AFM) measurements were fitted and processed for comparative analysis. We obtained the variation of surface charge density and effective slip length when different oleophobic surface samples were immersed in ethylene glycol with different pH values. The effect of pH on the surface charge density and effective slip length was investigated by their variations. The mechanism of the effect of pH on the surface charge density was discussed. The experimental results show that in the ethylene glycol solution, no matter whether the pH value of the solution increases or decreases, the charge density of the surface with the same properties decreases, and the effective boundary slip length also shows a downward trend. In deionized water, the surface charge density and effective boundary slip length decreases with the decrease of PH value.
Cobalt Phthalocyanine-Ionic Liquid Composite Modified Electrodes for the Voltammetric Detection of DNA Hybridization Related to Hepatitis B Virus
Authors: Yaralı Ece , Erdem Arzum
Published: June 2021

In this study, cobalt phthalocyanine (CoPc) and ionic liquid (IL) modified pencil graphite electrodes (PGEs) were designed and implemented to detect sequence-selective DNA hybridization related to the Hepatitis B virus (HBV). The surface characterization of CoPc-IL-PGEs was investigated by scanning electron microscopy (SEM), and the electrochemical behavior of electrodes were studied by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. The voltammetric detection of hybridization was investigated by evaluating the guanine oxidation signal, measured by differential pulse voltammetry (DPV) technique. The implementation of our biosensor to serum samples was also examined using fetal bovine serum (FBS). The detection limit was established as 0.19 µg/mL in phosphate buffer solution (PBS) (pH 7.40) and 2.48 µg/mL in FBS medium. The selectivity of our assay regarding HBV DNA hybridization in FBS medium was tested in the presence of other DNA sequences. With this aim, the hybridization of DNA probe with non-complementary (NC) or mismatched DNA sequence (MM), or in the presence of mixture samples containing DNA target NC (1:1) or DNA target MM (1:1), was studied based on the changes in guanine signal.
Large-Area and Ultrathin MEMS Mirror Using Silicon Micro Rim
Authors: Ahn Myeong-Su , Jeon Jaehun , Jang Kyung-Won , Jeong Ki-Hun
Published: June 2021

A large-area and ultrathin MEMS (microelectromechanical system) mirror can provide efficient light-coupling, a large scanning area, and high energy efficiency for actuation. However, the ultrathin mirror is significantly vulnerable to diverse film deformation due to residual thin film stresses, so that high flatness of the mirror is hardly achieved. Here, we report a MEMS mirror of large-area and ultrathin membrane with high flatness by using the silicon rim microstructure (SRM). The ultrathin MEMS mirror with SRM (SRM-mirror) consists of aluminum (Al) deposited silicon nitride membrane, bimorph actuator, and the SRM. The SRM is simply fabricated underneath the silicon nitride membrane, and thus effectively inhibits the tensile stress relaxation of the membrane. As a result, the membrane has high flatness of 10.6 m−1 film curvature at minimum without any deformation. The electrothermal actuation of the SRM-mirror shows large tilting angles from 15° to −45° depending on the applied DC voltage of 0~4 VDC, preserving high flatness of the tilting membrane. This stable and statically actuated SRM-mirror spurs diverse micro-optic applications such as optical sensing, beam alignment, or optical switching.
An Investigation of the Cutting Strategy for the Machining of Polar Microstructures Used in Ultra-Precision Machining Optical Precision Measurement
Authors: Zhao Chen-Yang , Cheung Chi Fai , Fu Wen-Peng
Published: June 2021

In this paper, an investigation of cutting strategy is presented for the optimization of machining parameters in the ultra-precision machining of polar microstructures, which are used for optical precision measurement. The critical machining parameters affecting the surface generation and surface quality in the machining of polar microstructures are studied. Hence, the critical ranges of machining parameters have been determined through a series of cutting simulations, as well as cutting experiments. First of all, the influence of field of view (FOV) is investigated. After that, theoretical modeling of polar microstructures is built to generate the simulated surface topography of polar microstructures. A feature point detection algorithm is built for image processing of polar microstructures. Hence, an experimental investigation of the influence of cutting tool geometry, depth of cut, and groove spacing of polar microstructures was conducted. There are transition points from which the patterns of surface generation of polar microstructures vary with the machining parameters. The optimization of machining parameters and determination of the optimized cutting strategy are undertaken in the ultra-precision machining of polar microstructures.
Multi-Vortex Regulation for Efficient Fluid and Particle Manipulation in Ultra-Low Aspect Ratio Curved Microchannels
Authors: Shen Shaofei , Wang Xin , Niu Yanbing
Published: June 2021

Inertial microfluidics enables fluid and particle manipulation for biomedical and clinical applications. Herein, we developed a simple semicircular microchannel with an ultra-low aspect ratio to interrogate the unique formations of the helical vortex and Dean vortex by introducing order micro-obstacles. The purposeful and powerful regulation of dimensional confinement in the microchannel achieved significantly improved fluid mixing effects and fluid and particle manipulation in a high-throughput, highly efficient and easy-to-use way. Together, the results offer insights into the geometry-induced multi-vortex mechanism, which may contribute to simple, passive, continuous operations for biochemical and clinical applications, such as the detection and isolation of circulating tumor cells for cancer diagnostics.
Soft, Conductive, Brain-Like, Coatings at Tips of Microelectrodes Improve Electrical Stability under Chronic, In Vivo Conditions
Authors: Sridharan Arati , Muthuswamy Jit
Published: June 2021

Several recent studies have reported improved histological and electrophysiological outcomes with soft neural interfaces that have elastic moduli ranging from 10 s of kPa to hundreds of MPa. However, many of these soft interfaces use custom fabrication processes. We test the hypothesis that a readily adoptable fabrication process for only coating the tips of microelectrodes with soft brain-like (elastic modulus of ~5 kPa) material improves the long-term electrical performance of neural interfaces. Conventional tungsten microelectrodes (n = 9 with soft coatings and n = 6 uncoated controls) and Pt/Ir microelectrodes (n = 16 with soft coatings) were implanted in six animals for durations ranging from 5 weeks to over 1 year in a subset of rats. Electrochemical impedance spectroscopy was used to assess the quality of the brain tissue–electrode interface under chronic conditions. Neural recordings were assessed for unit activity and signal quality. Electrodes with soft, silicone coatings showed relatively stable electrical impedance characteristics over 6 weeks to >1 year compared to the uncoated control electrodes. Single unit activity recorded by coated electrodes showed larger peak-to-peak amplitudes and increased number of detectable neurons compared to uncoated controls over 6–7 weeks. We demonstrate the feasibility of using a readily translatable process to create brain-like soft interfaces that can potentially overcome variable performance associated with chronic rigid neural interfaces.
Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review
Authors: Zhao Qianbin , Cole Tim , Zhang Yuxin , Tang Shi-Yang
Published: June 2021

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.
Probiotics for the Management of Sepsis: Advances in Animal Models and Intensive Care Unit Environments
Authors: dos Santos Vinicios R. , de Carvalho Gabriela O. , Silva José Bruno N. F.
Published: June 2021

Sepsis frequently leads to multiple organ failure and is a major cause of morbidity and mortality in critically ill patients. Although intensive care protocols and antibiotic therapy have improved sepsis treatment, specific management is lacking with respect to efficient protection from tissue damage and long-term outcomes. Probiotics are live microbes that modulate the immune system and inflammation and colonize the gut. In this narrative review, we have traced the evolution of the administration of probiotics in an animal model of sepsis and treatment alternatives in the intensive care unit setting. First, probiotics are categorized by species before describing their modulation of the microbiota, repair of tissue-specific damage, immune response, and molecular pathways to prevent complications. The impact on therapy for infant and adult patients is also addressed. Finally, we have emphasized the challenges and gaps in current studies as well as future perspectives for further investigation. The present review can open up avenues for new strategies that employ promising probiotic strains for the treatment of sepsis and discusses their ability to prevent disease-associated long-term complications.
Novel Protozoans in Austria Revealed through the Use of Dogs as Sentinels for Ticks and Tick-Borne Pathogens
Authors: Wijnveld Michiel , Schötta Anna-Margarita , Stelzer Theresa , Duscher Georg , Leschnik Michael , Stockinger Hannes , Lindgren Per-Eric , Stanek Gerold
Published: June 2021

We previously isolated and cultivated the novel Rickettsia raoultii strain Jongejan. This prompted us to ask whether this strain is unique or more widely present in Austria. To assess this issue, we retrospectively screened ticks collected from dogs in 2008. Of these collected ticks, we randomly selected 75 (47 females and 28 males) Dermacentor reticulatus, 44 (21 females, 7 males, and 16 nymphs) Haemaphysalis concinna, and 55 (52 females and 3 males) ticks of the Ixodes ricinus complex. Subsequently, these ticks were individually screened for the presence of tick-borne pathogens using the reverse line blot hybridization assay. In our current study, we detected DNA from the following microbes in D. reticulatus: Anaplasma phagocytophilum, Borrelia lusitaniae, Borrelia spielmanii, Borrelia valaisiana, and R. raoultii, all of which were R. raoultii strain Jongejan. In H. concinna, we found DNA of a Babesia sp., Rickettsia helvetica, and an organism closely related to Theileria capreoli. Lastly, I. ricinus was positive for Anaplasma phagocytophilum, Borrelia afzelii, Borrelia burgdorferi sensu stricto, Borrelia garinii/Borrelia bavariensis, B. lusitaniae, B. spielmanii, B. valaisiana, Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, Rickettsia monacensis, and Theileria (Babesia) microti DNA. The detection of DNA of the Babesia sp. and an organism closely related to Theileria capreoli, both found in H. concinna ticks, is novel for Austria.
Corynebacterium glutamicum Regulation beyond Transcription: Organizing Principles and Reconstruction of an Extended Regulatory Network Incorporating Regulations Mediated by Small RNA and Protein–Protein Interactions
Authors: Escorcia-Rodríguez Juan M. , Tauch Andreas , Freyre-González Julio A.
Published: June 2021

Corynebacterium glutamicum is a Gram-positive bacterium found in soil where the condition changes demand plasticity of the regulatory machinery. The study of such machinery at the global scale has been challenged by the lack of data integration. Here, we report three regulatory network models for C. glutamicum: strong (3040 interactions) constructed solely with regulations previously supported by directed experiments; all evidence (4665 interactions) containing the strong network, regulations previously supported by nondirected experiments, and protein–protein interactions with a direct effect on gene transcription; sRNA (5222 interactions) containing the all evidence network and sRNA-mediated regulations. Compared to the previous version (2018), the strong and all evidence networks increased by 75 and 1225 interactions, respectively. We analyzed the system-level components of the three networks to identify how they differ and compared their structures against those for the networks of more than 40 species. The inclusion of the sRNA-mediated regulations changed the proportions of the system-level components and increased the number of modules but decreased their size. The C. glutamicum regulatory structure contrasted with other bacterial regulatory networks. Finally, we used the strong networks of three model organisms to provide insights and future directions of the C.glutamicum regulatory network characterization.
Optimizing Antimicrobial Drug Dosing in Critically Ill Patients
Authors: Póvoa Pedro , Moniz Patrícia , Pereira João Gonçalves , Coelho Luís
Published: June 2021

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients.
Monitoring of Flotation Systems by Use of Multivariate Froth Image Analysis
Authors: Aldrich Chris , Liu Xiu
Published: June 2021

Froth image analysis has been considered widely in the identification of operational regimes in flotation circuits, the characterisation of froths in terms of bubble size distributions, froth stability and local froth velocity patterns, or as a basis for the development of inferential online sensors for chemical species in the froth. Relatively few studies have considered flotation froth image analysis in unsupervised process monitoring applications. In this study, it is shown that froth image analysis can be combined with traditional multivariate statistical process monitoring methods for reliable monitoring of industrial platinum metal group flotation plants. This can be accomplished with well-established methods of multivariate image analysis, such as the Haralick feature set derived from grey level co-occurrence matrices and local binary patterns that were considered in this investigation.
Bond Properties of NHL-Based Mortars with Viscosity-Modifying Water-Retentive Admixtures
Authors: Žižlavský Tomáš , Bayer Patrik , Vyšvařil Martin
Published: June 2021

This article studies the influence of biopolymeric viscosity-modifying admixtures with water-retentive function on the physico-mechanical properties of natural hydraulic lime-based mortars and their adherence to the traditional fired-clay brick substrate. The use of admixtures increases the water/binder ratio, which in turn leads to a decrease in the strength of the mortars. The viscosity-modifying function improves the adhesive strength between mortar and pre-wetter brick by increasing the binder paste viscosity, while the water-retentive function along with increased water content may lead to a decrease in adhesive strength. On the contrary, water retention and increased water content are beneficial on a dry surface, while paste viscosity plays only a minor role. When subjected to temperature-varying cycles, the mortars are more prone to in-mortar failure during the pull-off test. The air-entraining function of some admixtures improves the frost resistance of the mortars; however, it would negatively affect the adhesive strength by incorporating pores into the contact zone between the mortar and brick substrate. This study showed that the use of some of the studied admixtures may improve the adhesion of mortar to the brick substrate.
The Pb-Zn (Ba) Nonsulfide Mineralizations at Bou Caïd (Ouarsenis, Algeria): Mineralogy, Isotope Geochemistry, and Genetic Inferences
Authors: Louha Hassina , Balassone Giuseppina , Boutaleb Abdelhak , Boni Maria , Joachimski Michael M. , Mondillo Nicola
Published: June 2021

The ore deposits of Bou Caïd (Ouarsenis, Algeria) occur in Jurassic and Cretaceous sedimentary rocks. The barite and Pb-Zn (Fe, Cu, and F) ore deposits of Bou Caïd belong to vein- and karst-type. The mineralization is represented in the whole area by a mixture of barite (currently still exploited) and nonsulfides consisting of hemimorphite, smithsonite, cerussite, hydrozincite, and Fe-oxy-hydroxides, with remnants of galena and sphalerite in variable proportions. Mineralogical and geochemical analyses were carried out on the Bou Caïd nonsulfides. Several samples representing nonsulfide mineralization (Grand Pic and at Srâa Abdelkader) were subjected to a multidisciplinary analytical approach, using optical microscopy (OM), powder X-ray diffraction (PXRD), Scanning Electron Microscopy with Energy Dispersive Spectrometry (SEM-EDS). Nonsulfide mineralization consists of a mixture of hemimorphite, hydrozincite, smithsonite, cerussite, and Fe-oxy-hydroxides, often with zebra-like textures. In the proposed paragenetic scheme, covellite and chalcocite are followed by cerussite, jarosite, smithsonite, and hydrozincite. Then, hemimorphite crystallizes, accompanied by mimetite, traces of malachite and clay minerals (also Zn-bearing), precipitate. Fe-(Mn)-oxy-hydroxides can form during various phases of the supergene stage. Small amounts of late barite can be related to partial remobilization and occur as reprecipitation products. Stable isotope analyses were performed on the calcites and metal carbonates of the supergene ores. Carbon and oxygen isotope values of smithsonite and hydrozincite were comparable to published supergene Zn carbonate data. The isotope values of the Bou Caïd calcites fell both into the hydrothermal carbonate and in the supergene fields.
Partial Least Squares Regression of Oil Sands Processing Variables within Discrete Event Simulation Digital Twin
Authors: Wilson Ryan , Mercier Patrick H. J. , Patarachao Bussaraporn , Navarra Alessandro
Published: June 2021

Oil remains a major contributor to global primary energy supply and is, thus, fundamental to the continued functioning of modern society and related industries. Conventional oil and gas reserves are finite and are being depleted at a relatively rapid pace. With alternative fuels and technologies still unable to fill the gap, research and development of unconventional petroleum resources have accelerated markedly in the past 20 years. With some of the largest bitumen deposits in the world, Canada has an active oil mining and refining industry. Bitumen deposits, also called oil sands, are formed in complex geological environments and subject to a host of syn- and post-depositional processes. As a result, some ores are heterogeneous, at both individual reservoir and regional scales, which poses significant problems in terms of extractive processing. Moreover, with increased environmental awareness and enhanced governmental regulations and industry best practices, it is critical for oil sands producers to improve process efficiencies across the spectrum. Discrete event simulation (DES) is a computational paradigm to develop dynamic digital twins, including the interactions of critical variables and processes. In the case of mining systems, the digital twin includes aspects of geological uncertainty. The resulting simulations include alternate operational modes that are characterized by separate operational policies and tactics. The current DES framework has been customized to integrate predictive modelling data, generated via partial least squares (PLS) regression, in order to evaluate system-wide response to geological uncertainty. Sample computations that are based on data from Canada’s oil sands are presented, showing the framework to be a powerful tool to assess and attenuate operational risk factors in the extractive processing of bitumen deposits. Specifically, this work addresses blending control strategies prior to bitumen extraction and provides a pathway to incorporate geological variation into decision-making processes throughout the value chain.
Non-Dilatant Brittle Deformation and Strength Reduction of Olivine Gabbro due to Hydration
Authors: Akamatsu Yuya , Nagase Kumpei , Katayama Ikuo
Published: June 2021

To investigate the influence of hydration on brittle deformation of oceanic crustal rocks, we conducted triaxial deformation experiments on gabbroic rocks with various degrees of hydration at a confining pressure of 20 MPa and room temperature, measuring elastic wave velocity. Hydrated olivine gabbros reached a maximum differential stress of 225–350 MPa, which was considerably less than those recorded for gabbros (~450 MPa), but comparable to those for serpentinized ultramafic rocks (250–300 MPa). Elastic wave velocities of hydrated olivine gabbros did not show a marked decrease even prior to failure. This indicated that the deformation of hydrated olivine gabbro is not associated with the opening of the stress-induced cracks that are responsible for dilatancy. Microstructural observations of the samples recovered after deformation showed crack damage to be highly localized to fault zones with no trace of stress-induced crack opening, consistent with the absence of dilatancy. These data suggest that strain localization of hydrated olivine gabbro can be caused by the development of shear cracks in hydrous minerals such as serpentine and chlorite, even when they are present in only small amounts. Our results suggest that the brittle behavior of the oceanic crust may considerably change due to limited hydration.
Respirable Coal Mine Dust: A Review of Respiratory Deposition, Regulations, and Characterization
Authors: Shekarian Younes , Rahimi Elham , Rezaee Mohammad , Su Wei-Chung , Roghanchi Pedram
Published: June 2021

In the late 1990s, despite years of efforts to understand and reduce coal worker’s pneumoconiosis (CWP) prevalence from more than 30% in 1970 to less than 4.2%, the level of occurrence among the US coal miners increased unexpectedly. The recent resurgence of lung diseases has raised concerns in the scientific and regulatory communities. In 2014, the United States Mine Safety and Health Administration (MSHA) issued a new dust rule changing the respirable coal mine dust (RCMD) exposure limits, measurement technology, and sampling protocol. The analysis for probable causes for the substantial increase in the CWP incidence rate is rather complicated. This paper aims to conduct a review of RCMD respiratory deposition, health effects, monitoring, regulations, and particle characteristics. The primary sources of RCMD along with the health risks from potential exposure are highlighted, and the current RCMD exposure regulations of the major coal producer countries are compared. A summary of RCMD characterization studies from 1972 to the present is provided. A review of the literature revealed that numerous factors, including geological and mining parameters, advancements in mining practices, particle characteristics, and monitoring approaches are considered to contribute to the recent resurgence of RCMD lung diseases. However, the root causes of the problem are still unknown. The effectiveness of the new dust rules in the United States will probably take years to be correctly assessed. Therefore, future research is needed to understand the relationship between RCMD particle characteristics and lung deposition, and the efficacy of current monitoring practices to measure the true dose of RCMD exposure.
Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review
Authors: Khazeei Tabari Mohammad Amin , Iranpanah Amin , Bahramsoltani Roodabeh , Rahimi Roja
Published: June 2021

A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.
Antimicrobial Compounds Isolated from Endolichenic Fungi: A Review
Authors: Wethalawe A. Nethma , Alwis Y. Vindula , Udukala Dinusha N. , Paranagama Priyani A.
Published: June 2021

A lichen is a symbiotic relationship between a fungus and a photosynthetic organism, which is algae or cyanobacteria. Endolichenic fungi are a group of microfungi that resides asymptomatically within the thalli of lichens. Endolichenic fungi can be recognized as luxuriant metabolic artists that produce propitious bioactive secondary metabolites. More than any other time, there is a worldwide search for new antibiotics due to the alarming increase in microbial resistance against the currently available therapeutics. Even though a few antimicrobial compounds have been isolated from endolichenic fungi, most of them have moderate activities, implying the need for further structural optimizations. Recognizing this timely need and the significance of endolichenic fungi as a promising source of antimicrobial compounds, the activity, sources and the structures of 31 antibacterial compounds, 58 antifungal compounds, two antiviral compounds and one antiplasmodial (antimalarial) compound are summarized in this review. In addition, an overview of the common scaffolds and structural features leading to the corresponding antimicrobial properties is provided as an aid for future studies. The current challenges and major drawbacks of research related to endolichenic fungi and the remedies for them have been suggested.
Green Tea and Its Relation to Human Gut Microbiome
Authors: Pérez-Burillo Sergio , Navajas-Porras Beatriz , López-Maldonado Alicia , Hinojosa-Nogueira Daniel , Pastoriza Silvia , Rufián-Henares José Ángel
Published: June 2021

Green tea can influence the gut microbiota by either stimulating the growth of specific species or by hindering the development of detrimental ones. At the same time, gut bacteria can metabolize green tea compounds and produce smaller bioactive molecules. Accordingly, green tea benefits could be due to beneficial bacteria or to microbial bioactive metabolites. Therefore, the gut microbiota is likely to act as middle man for, at least, some of the green tea benefits on health. Many health promoting effects of green tea seems to be related to the inter-relation between green tea and gut microbiota. Green tea has proven to be able to correct the microbial dysbiosis that appears during several conditions such as obesity or cancer. On the other hand, tea compounds influence the growth of bacterial species involved in inflammatory processes such as the release of LPS or the modulation of IL production; thus, influencing the development of different chronic diseases. There are many studies trying to link either green tea or green tea phenolic compounds to health benefits via gut microbiota. In this review, we tried to summarize the most recent research in the area.
The Effect of Soil Moisture on the Ability to Detect TNT Pairs from the Sand Layer in Order to Prevent Environmental Pollution and Groundwater
Authors: Pawłowski Wojciech , Karpińska Monika
Published: June 2021

The aim of the study was to investigate the influence of sand bed moisture on TNT transport from under the sand layer. The MO-2M explosive vapor detector was used, the detection mechanism of which is based on the FAIMS method. In addition, it was determined after what time the detector alarm appears, signaling the presence of TNT vapors, and how it affects the thickness of the sand layer. The performed work allowed us to assess the suitability and possibly adapt the MO-2M detector to detect non-metal mines, which will help develop new application possibilities for this device. These tests can also be used to eliminate environmental contamination resulting from the deposition of explosives in the ground and the migration of harmful compounds to groundwater.
Solvatochromic Study of Two Carbanion Monosubstituted 4-Tolyl-1,2,4-triazol-1-ium Phenacylids in Binary Hydroxyl Solvent Mixtures
Authors: Dorohoi Dana Ortansa , Dimitriu Dan-Gheorghe , Dulcescu-Oprea Mihaela Maria , Morosanu Ana Cezarina , Puica-Melniciuc Nicoleta , Ardelean Elena , Gritco-Todirascu Antonina , Cheptea Corina
Published: June 2021

Two 4-tolyl-1,2,4-triazol-1-ium methylids, namely 4-tolyl-1,2,4-triazol-1-ium-phenacylid and 4-tolyl-1,2,4-triazol-1-ium-4′-nitro-phenacylid, are studied from solvatochromic point of view in binary solvent mixtures of water with ethanol and water with methanol. The contributions (expressed in percent) of the universal and specific interactions are separated from the spectral shifts recorded in the visible range for each composition of the binary solvent mixture. The essential role of the orientation and induction interactions in the studied solutions was demonstrated. Based on the statistic cell model of the binary solvent mixture solutions, the difference between the formation energies of ylid-water and ylid-alcohol complexes is estimated. The composition of the ylid’s first solvation shell was also established using the model of the binary solvent mixture solutions. The results obtained from the statistical cell model were compared with those obtained by using the Suppan’s model, resulting a good agreement.
Comprehensive Assessment of Flow and Other Analytical Methods Dedicated to the Determination of Zinc in Water
Authors: Kościelniak Paweł , Nowak Paweł Mateusz , Kozak Joanna , Wieczorek Marcin
Published: June 2021

An original strategy to evaluate analytical procedures is proposed and applied to verify if the flow-based methods, generally favorable in terms of green chemistry, are competitive when their evaluation also relies on other criteria. To this end, eight methods for the determination of zinc in waters, including four flow-based ones, were compared and the Red–Green–Blue (RGB) model was exploited. This model takes into account several features related to the general quality of an analytical method, namely, its analytical efficiency, compliance with the green analytical chemistry, as well as practical and economic usefulness. Amongst the investigated methods, the best was the flow-based spectrofluorimetric one, and a negative example was that one involving a flow module, ICP ionization and MS detection, which was very good in analytical terms, but worse in relation to other aspects, which significantly limits its overall potential. Good assessments were also noted for non-flow electrochemical methods, which attract attention with a high degree of balance of features and, therefore, high versatility. The original attempt to confront several worldwide accepted analytical strategies, although to some extent subjective and with limitations, provides interesting information and indications, establishing a novel direction towards the development and evaluation of analytical methods.
Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway
Authors: Wang Yiou , Zhang Bingxue , Huang Yibing , Yao Wenjun , Tao Fei , Chen Yuxin
Published: June 2021

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.
Wheat Bran Modifications for Enhanced Nutrition and Functionality in Selected Food Products
Authors: Onipe Oluwatoyin O. , Ramashia Shonisani E. , Jideani Afam I. O.
Published: June 2021

The established use of wheat bran (WB) as a food ingredient is related to the nutritional components locked in its dietary fibre. Concurrently, the technological impairment it poses has impeded its use in product formulations. For over two decades, several modifications have been investigated to combat this problem. Ninety-three (93) studies (review and original research) published in English between January 1997 and April 2021 reporting WB modifications for improved nutritional, structural, and functional properties and prospective utilisation in food formulations were included in this paper. The modification methods include mechanical (milling), bioprocessing (enzymatic hydrolysis and fermentation with yeasts and bacteria), and thermal (dry heat, extrusion, autoclaving), treatments. This review condenses the current knowledge on the single and combined impact of various WB pre-treatments on its antioxidant profile, fibre solubilisation, hydration properties, microstructure, chemical properties, and technological properties. The use of modified WB in gluten-free, baked, and other food products was reviewed and possible gaps for future research are proposed. The application of modified WB will have broader application prospects in food formulations.
Size Effect of Graphene Quantum Dots on Photoluminescence
Authors: Liu Ziyi , Li Fei , Luo Yi , Li Ming , Hu Guanghui , Pu Xianjuan , Tang Tao , Wen Jianfeng , Li Xinyu , Li Weitao
Published: June 2021

High-photoluminescence (PL) graphene quantum dots (GQDs) were synthesized by a simple one-pot hydrothermal process, then separated by dialysis bags of different molecular weights. Four separated GQDs of varying sizes were obtained and displayed different PL intensities. With the decreasing size of separated GQDs, the intensity of the emission peak becomes much stronger. Finally, the GQDs of the smallest size revealed the most energetic PL intensity in four separated GQDs. The PL energy of all the separated GQDs shifted slightly, supported by density functional theory calculations.
Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity
Authors: Abdel-Rahman Adel A.-H. , Shaban Amira K. F. , Nassar Ibrahim F. , EL-Kady Dina S. , Ismail Nasser S. M. , Mahmoud Samy F. , Awad Hanem M. , El-Sayed Wael A.
Published: June 2021

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.
Aroma-Active Compounds in Robusta Coffee Pulp Puree—Evaluation of Physicochemical and Sensory Properties
Authors: Buck Nina , Wohlt Daria , Winter Anne Ruth , Ortner Eva
Published: June 2021

Wet coffee processing generates a large amount of coffee pulp waste that is mostly disposed of in the processing units. To reduce this waste and the associated environmental burden, an alternative strategy would be to exploit the coffee pulp to produce a durable and stable consumable product. Accordingly, a puree produced from Robusta coffee pulp was investigated in relation to its physicochemical and sensory properties. After thermal and chemical stabilization, the obtained puree (pH 3.6) was found to exhibit a multimodal particle size distribution, shear-thinning behavior, and lower discoloration, as well as an antioxidant capacity of 87.9 µmolTE/gDM. The flavor of the puree was examined by sensory evaluation and the corresponding analyses of aroma-active volatile compounds, as determined using aroma extract dilution analyses (AEDA) and gas chromatography-mass spectrometry/olfactometry (GC-MS/O). The puree was characterized by dominant fruity (4.4), floral (3.4), citrusy (3.3) and hay-like (3.3) odor impressions. The aroma-active compounds were predominantly aldehydes, acids, and lactones, whereby (E)-β-damascenone, geraniol, 4-methylphenol, 3-hydroxy-4,5-dimethylfuran-2(5H)-one, and 4-hydroxy-3-methoxybenzaldehyde exhibited the highest flavor dilution (FD) factor (1024), thereby indicating their high impact on the overall aroma of the puree. This study demonstrates an approach to stabilize coffee pulp to produce a sweet, fruity puree with comparable physical properties to other fruit purees and that can be used as a new and versatile flavoring ingredient for various food applications.