bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis
Authors: Lo Monaco Melissa , Gervois Pascal , Beaumont Joel , Clegg Peter , Bronckaers Annelies , Vandeweerd Jean-Michel , Lambrichts Ivo
Published: April 2020

Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects.
Male Infertility is a Women’s Health Issue—Research and Clinical Evaluation of Male Infertility Is Needed
Authors: Turner Katerina A. , Rambhatla Amarnath , Schon Samantha , Agarwal Ashok , Krawetz Stephen A. , Dupree James M. , Avidor-Reiss Tomer
Published: April 2020

Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple’s infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm’s internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception.
Darcy-Forchheimer MHD Hybrid Nanofluid Flow and Heat Transfer Analysis over a Porous Stretching Cylinder
Authors: Saeed Anwar , Tassaddiq Asifa , Khan Arshad , Jawad Muhammad , Deebani Wejdan , Shah Zahir , Islam Saeed
Published: April 2020

This research work deals with investigation of the thermal characteristics of the Darcy–Forchheimer hydromagnetic hybrid nanofluid (Al2O3-Cu/H2O) flow through a permeable stretching cylinder. The model equations, which consist of continuity, momentum, and energy equations, are converted to a set of coupled ordinary differential equations through similarity variables transformations and appropriate boundary conditions. Brownian motion and Thermophoresis effects are mainly focused in this work. The impacts of some interesting parameters over velocity, temperature, and concentrations profiles are graphically studied. The present study will be helpful in understanding the thermal characteristics of heat transfer liquids.
Eliminating Nonuniform Smearing and Suppressing the Gibbs Effect on Reconstructed Images
Authors: Sizikov Valery , Dovgan Aleksandra , Lavrov Aleksei
Published: April 2020

In this work, the problem of eliminating a nonuniform rectilinear smearing of an image is considered, using a mathematical- and computer-based approach. An example of such a problem is a picture of several cars, moving with different speeds, taken with a fixed camera. The problem is described by a set of one-dimensional Fredholm integral equations (IEs) of the first kind of convolution type, with a one-dimensional point spread function (PSF) when uniform smearing, and by a set of new one-dimensional IEs of a general type (i.e., not the convolution type), with a two-dimensional PSF when nonuniform smearing. The problem is also described by a two-dimensional IE of the convolution type with a two-dimensional PSF when uniform smearing, and by a new two-dimensional IE of a general type with a four-dimensional PSF when nonuniform smearing. The problem of solving the Fredholm IE of the first kind is ill-posed (i.e., unstable). Therefore, IEs of the convolution type are solved by the Fourier transform (FT) method and Tikhonov’s regularization (TR), and IEs of the general type are solved by the quadrature/cubature and TR methods. Moreover, the magnitude of the image smear, Δ, is determined by the original “spectral method”, which increases the accuracy of image restoration. It is shown that the use of a set of one-dimensional IEs is preferable to one two-dimensional IE in the case of nonuniform smearing. In the inverse problem (i.e., image restoration), the Gibbs effect (the effect of false waves) in the image may occur. This may be an edge or an inner effect. The edge effect is well suppressed by the proposed technique, namely, “diffusing the edges”. The inner effect is difficult to eliminate, but the image smearing itself plays the role of diffusion and suppresses the inner Gibbs effect to a large extent. It is shown (in the presence of impulse noise in an image) that the well-known Tukey median filter can distort the image itself, and the Gonzalez adaptive filter also distorts the image (but to a lesser extent). We propose a modified adaptive filter. A software package was developed in MATLAB and illustrative calculations are performed.
Back-Stress and Its Evolution during Primary Creep in Particle Strengthened Nickel Superalloys
Authors: Sarkar Sanket , Gao Yan , Huang Shenyan , Bhattacharya Saswata , Patil Swapnil , Oruganti Ramkumar
Published: April 2020

According to Eshelby’s theory, inelastically inhomogeneous inclusions in a metallic matrix give rise to a distribution of internal stresses. In the case of particle strengthened materials, such as nickel base superalloys, the presence and evolution of this back-stress leads to various observable effects, such as primary creep, back-flow upon loading, and memory of prior deformation. This article presents the background of the concept of back-stress and how it applies to the scenario of creep. A derivation of an evolution equation for back-stress in the context of primary creep is also presented. The results from neutron diffraction with in-situ creep experiments on directionally solidified nickel superalloys are presented in order to demonstrate the validity of the proposed equation and the corollaries derived therefrom.
Benign Biliary Strictures: A Systematic Review on Endoscopic Treatment Options
Authors: Wong May Y.W. , Saxena Payal , Kaffes Arthur J.
Published: April 2020

Benign biliary strictures can be difficult to manage. Untreated biliary strictures can lead to complications, such as chronic cholestasis, jaundice, recurrent sepsis, and secondary biliary cirrhosis, which can have severe ramifications. The management landscape is constantly evolving, with the development of modifiable self-expandable metal stents and biodegradable stents. This review critically appraises current endoscopic treatment strategies, in particular focusing on the shortfalls, such as stent migration and stricture recurrence. It also proposes a treatment algorithm based on aetiologias and the location of the strictures.
Statistical Inference of the Half-Logistic Inverse Rayleigh Distribution
Authors: Almarashi Abdullah M. , Badr Majdah M. , Elgarhy Mohammed , Jamal Farrukh , Chesneau Christophe
Published: April 2020

The inverse Rayleigh distribution finds applications in many lifetime studies, but has not enough overall flexibility to model lifetime phenomena where moderately right-skewed or near symmetrical data are observed. This paper proposes a solution by introducing a new two-parameter extension of this distribution through the use of the half-logistic transformation. The first contribution is theoretical: we provide a comprehensive account of its mathematical properties, specifically stochastic ordering results, a general linear representation for the exponentiated probability density function, raw/inverted moments, incomplete moments, skewness, kurtosis, and entropy measures. Evidences show that the related model can accommodate the treatment of lifetime data with different right-skewed features, so far beyond the possibility of the former inverse Rayleigh model. We illustrate this aspect by exploring the statistical inference of the new model. Five classical different methods for the estimation of the model parameters are employed, with a simulation study comparing the numerical behavior of the different estimates. The estimation of entropy measures is also discussed numerically. Finally, two practical data sets are used as application to attest of the usefulness of the new model, with favorable goodness-of-fit results in comparison to three recent extended inverse Rayleigh models.
Pushed Out for Missing School: The Role of Social Disparities and School Truancy in Dropping Out
Authors: Mireles-Rios Rebeca , Rios Victor M. , Reyes Augustina
Published: April 2020

Research: The goal of this study is to understand the experiences of Black and Latino former high school students who dropped out, or were pushed out, of a large urban school district in Southern California. Specifically, this paper examines the barriers students faced that contributed to them leaving high school and their journey afterward. Thirty-nine former high school students who “dropped out”, or were pushed out of school, 61.5% males (n = 24) and 38.5% females (n = 15), were interviewed. Findings: The findings indicate the use of punitive truancy control for dealing with health and psychological needs of students, transportation issues, personnel–student relationships, and standardized testing. Examining the experiences of students who have been pushed out of school can help educators and policy makers address some of the inequities within schools. Results: We argue that pushout prevention can be developed by changing truancy and other discipline policies in schools. Implications from this study help us understand how we can better support students before they are pushed out.
Conditioning of Spent Electrolyte Surrogate LiCl-KCl-CsCl Using Magnesium Potassium Phosphate Compound
Authors: Kulikova Svetlana A. , Belova Kseniya Yu. , Tyupina Ekaterina A. , Vinokurov Sergey E.
Published: April 2020

The current work was aimed at developing a new conditioning method of spent electrolyte-radioactive waste (RW) generated during the pyrochemical reprocessing of mixed nitride uranium-plutonium spent nuclear fuel. Magnesium potassium phosphate (MPP) compound samples were synthesized under solidification of the electrolyte surrogate solution in a LiCl-KCl-CsCl system. The phase composition and structure of obtained compounds were studied by XRD and SEM-EDS methods. It was found that the compounds possessed a high compressive strength of 17–26 MPa. Hydrolytic stability of the compounds was evaluated in accordance with the long semi-dynamic test GOST R 52126-2003 and with the static PCT test. The 137Cs content in the leached solutions was determined by gamma-ray spectrometry, and other compound components were determined by ICP–AES and ICP–MS methods. The differential leaching rate of Cs at 25 °C from monolithic samples on the 91st day of samples contact with water was 5–11 × 10−5 g/(cm2·day) (GOST R 52126-2003), and was 4–29 × 10−7 g/(cm2∙day) on the 7th day at 90 °C from crushed samples (PCT). The thermal stability of the compound at 180 °C and 450 °C was shown. The characteristics of the obtained MPP compound correspond to the current regulatory requirements for materials for RW conditioning.
Energy Monitoring in a Heating and Cooling System in a Building Based on the Example of the Turówka Hotel
Authors: Borowski Marek , Mazur Piotr , Kleszcz Sławosz , Zwolińska Klaudia
Published: April 2020

The energy consumption of buildings is very important for both economic and environmental reasons. Newly built buildings are characterized by higher insulation and airtightness of the building envelope, and are additionally equipped with technologies that minimize energy consumption in order to meet legal requirements. In existing buildings, the modernization process should be properly planned, taking into account available technologies and implementation possibilities. Hotel buildings are characterized by a large variability of energy demand, both on a daily and a yearly basis. Monitoring systems, therefore, provide the necessary information needed for proper energy management in the building. This article presents an energy analysis of the Turówka hotel located in Wieliczka (southern Poland). The historical hotel facility is being modernized as part of the project to adapt the building to the requirements of a sustainable building. The modernization proposal includes a trigeneration system with a multifunctional reverse regenerator and control module using neural algorithms. The main purpose is to improve the energy efficiency of the building and adapt it to the requirements of low-energy buildings. The implementation of a monitoring system enables energy consumption to be reduced and improves the energy performance of the building, especially through using energy management systems and control modules. The proposed retrofit solution considers the high energy consumption, structure of the energy demand, and limits of retrofit intervention on façades.
Development and Verification of an Aero-Hydro-Servo-Elastic Coupled Model of Dynamics for FOWT, Based on the MoWiT Library
Authors: Leimeister Mareike , Kolios Athanasios , Collu Maurizio
Published: April 2020

The complexity of floating offshore wind turbine (FOWT) systems, with their coupled motions, aero-hydro-servo-elastic dynamics, as well as non-linear system behavior and components, makes modeling and simulation indispensable. To ensure the correct implementation of the multi-physics, the engineering models and codes have to be verified and, subsequently, validated for proving the realistic representation of the real system behavior. Within the IEA (International Energy Agency) Wind Task 23 Subtask 2 offshore code-to-code comparisons have been performed. Based on these studies, using the OC3 phase IV spar-buoy FOWT system, the Modelica for Wind Turbines (MoWiT) library, developed at Fraunhofer IWES, is verified. MoWiT is capable of fully-coupled aero-hydro-servo-elastic simulations of wind turbine systems, onshore, offshore bottom-fixed, or even offshore floating. The hierarchical programing and multibody approach in the object-oriented and equation-based modeling language Modelica have the advantage (over some other simulation tools) of component-based modeling and, hence, easily modifying the implemented system model. The code-to-code comparisons with the results from the OC3 studies show, apart from expected differences due to required assumptions in consequence of missing data and incomplete information, good agreement and, consequently, substantiate the capability of MoWiT for fully-coupled aero-hydro-servo-elastic simulations of FOWT systems.
Carbon Storage in Old-Growth Homestead Windbreaks of Small Islands in Okinawa: Toward the Sustainable Management and Conservation
Authors: Chen Bixia , Wang Yi-Chung
Published: April 2020

Research Highlights: This study contributes to the improvement of the understanding of ecosystem functions of trees growing outside the forest, by quantifying the carbon sequestration function of a homestead windbreak, for example, a linear forest belt planted bordering a farmhouse in small islands. Background and objectives: Carbon storage in small-scale stands of forests have been less studied compared to that in large-scale forests. The aims of the present study were to clarify the ecological functions of carbon storage and the economic value of homestead windbreaks to propose effective conservation strategies for old-growth homestead windbreaks in the face of climate change. Materials and Methods: On the small islands of Okinawa Prefecture, the dominant tree species used for the homestead windbreaks is fukugi (Garcinia subelliptica Merr.). We collected data on the diameter at breast height (DBH) and the height of 23,518 fukugi trees in 10 villages from 2009 to 2018. Results: The total amount of carbon stored in the remnant fukugi homestead trees of the 10 surveyed hamlets was 6089 t-CO2. The amount is equivalent to the carbon amount that is stored in a 40-year-old Japanese cedar (Cryptomeria japonica) forest, a representative tree species in Japan, of 20.9 ha area. Furthermore, the estimated economic value of the homestead trees was equivalent to USD 235,433, in terms of the plantation and management costs of 40-year-old Japanese cedar forests. This study revealed that homestead trees planted in an orderly line usually have a high density; hence, they have a high potential for biomass accumulation, carbon sequestration, and climate change mitigation. Moreover, homestead trees could contribute to a reduction in carbon diffusion, by cooling the house and reducing potential energy consumption. The findings related to homestead trees are consistent with those of other types of trees outside forests or small patches of trees: not adding to future land use competition and highly effective at carbon sequestration. Conclusions: The finding related to the carbon storage of homestead trees will provide basic information, as well as a new perspective on future local conservation and its contribution to climate change mitigation. This study suggests the necessity of the existing trees being properly managed, recruiting trees to be planted to replace old-growth trees, and replanting trees near newly established houses or old homesteads where trees have been cut.
Blockchain Behavioral Traffic Model as a Tool to Influence Service IT Security
Authors: Elagin Vasiliy , Spirkina Anastasia , Levakov Andrei , Belozertsev Ilya
Published: April 2020

The present article describes the behavioral model of blockchain services; their reliability is confirmed on the basis of experimental data. The authors identify the main technical characteristics and features associated with data transmission through the network. The authors determine the network scheme, working with blockchain transactions and the dependence of network characteristics on application parameters. They analyze the application of this model for the detection of the blockchain service and the possibility of the existing security mechanisms of this technology being evaded. Furthermore, the article offers recommendations for hiding the blockchain traffic profile to significantly complicate its identification in the data network.
Improving Recommendation Accuracy Using Social Network of Owners in Social Internet of Vehicles
Authors: Zia Kashif , Shafi Muhammad , Farooq Umar
Published: April 2020

The latest manifestation of “all connected world" is the Internet of Things (IoT), and Internet of Vehicles (IoV) is one of the key examples of IoT these days. In Social IoV (SIoV), each vehicle is treated as a social object where it establishes and manages its own Social Network (SN). Incidentally, most of the SIoV research in the literature is related to proximity-based connectivity and interactions. In this paper, we bring people in the loop by incorporating their SNs. While emphasizing a recommendation scenario, in which vehicles may require recommendations from SNs of their owners (in addition to their own SIoV), we proposed an agent-based model of information sharing (for context-based recommendations) on a hypothetical population of smart vehicles. Some important hypotheses were tested using a realistic simulation setting. The simulation results reveal that a recommendation using weak ties is more valuable than a recommendation using strong ties in pure SIoV. The simulation results also demonstrate that recommendations using the most-connected person in the social network are not more valuable than recommendation using a random person in the social network. The model presented in this paper can be used to design a multi-scale recommendation system, which uses SIoV and a typical SN in combination.
Molecular Mechanisms, Diagnostic Aspects and Therapeutic Opportunities of Micro Ribonucleic Acids in Atrial Fibrillation
Authors: Böhm Allan , Vachalcova Marianna , Snopek Peter , Bacharova Ljuba , Komarova Dominika , Hatala Robert
Published: April 2020

Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules responsible for regulation of gene expression. They are involved in many pathophysiological processes of a wide spectrum of diseases. Recent studies showed their involvement in atrial fibrillation. They seem to become potential screening biomarkers for atrial fibrillation and even treatment targets for this arrhythmia. The aim of this review article was to summarize the latest knowledge about miRNA and their molecular relation to the pathophysiology, diagnosis and treatment of atrial fibrillation.
A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization
Authors: Grant Benjamin M. M. , Enomoto Masahiro , Ikura Mitsuhiko , Marshall Christopher B.
Published: April 2020

Calmodulin (CaM) is a Ca2+-sensor that regulates a wide variety of target proteins, many of which interact through short basic helical motifs bearing two hydrophobic ‘anchor’ residues. CaM comprises two globular lobes, each containing a pair of EF-hand Ca2+-binding motifs that form a Ca2+-induced hydrophobic pocket that binds an anchor residue. A central flexible linker allows CaM to accommodate diverse targets. Several reported CaM interactors lack these anchors but contain Lys/Arg-rich polybasic sequences adjacent to a lipidated N- or C-terminus. Ca2+-CaM binds the myristoylated N-terminus of CAP23/NAP22 with intimate interactions between the lipid and a surface comprised of the hydrophobic pockets of both lobes, while the basic residues make electrostatic interactions with the negatively charged surface of CaM. Ca2+-CaM binds farnesylcysteine, derived from the farnesylated polybasic C-terminus of KRAS4b, with the lipid inserted into the C-terminal lobe hydrophobic pocket. CaM sequestration of the KRAS4b farnesyl moiety disrupts KRAS4b membrane association and downstream signaling. Phosphorylation of basic regions of N-/C-terminal lipidated CaM targets can reduce affinity for both CaM and the membrane. Since both N-terminal myristoylated and C-terminal prenylated proteins use a Singly Lipidated Polybasic Terminus (SLIPT) for CaM binding, we propose these polybasic lipopeptide elements comprise a non-canonical CaM-binding motif.
Mark4 Inhibited the Browning of White Adipose Tissue by Promoting Adipocytes Autophagy in Mice
Authors: Yang Kun , Cai Jiarui , Pan Miao , Sun Qian , Sun Chao
Published: April 2020

Autophagy can remove excess or dysfunctional proteins and organelles to maintain cellular homeostasis. Browning of white adipose tissue increases the energy expenditure. Microtubules affinity regulated kinase 4 (Mark4) can regulate a variety of physiological processes. According to previous studies, we speculated that Mark4-autophagy-browning of white adipose tissue had certain linkages. Here, we established two autophagy models through serum starvation and rapamycin treatment and detected that the overexpression of Mark4 increased the expression of autophagy-related factors Beclin1, ATG7, and significantly decreased the autophagy substrate P62. Further tests showed that the overexpression of Mark4 promoted the conversion of autophagy marker protein LC3A to LC3B-II by activating the AMP-activated protein kinase (AMPK) pathway and inhibition of the AKT/mTOR signaling. Moreover, Mark4 decreased the expression of thermogenesis genes via promoting autophagy. These results indicated that Mark4 inhibited the browning of white adipose tissue via promoting autophagy.
In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP
Authors: Eckert Priska , Knickmeyer Max D. , Heermann Stephan
Published: April 2020

Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed “pioneer cells.” Based on morphology, localization, and downregulation of the neuroretinal (NR) precursor marker rx2, these cells could be considered as retinal pigment epithelial (RPE) progenitors. Notably, pioneer cells regain rx2 expression and integrate into the NR after fusion, indicating that they do not belong to the pool of RPE progenitors, supported by the lack of RPE marker expression in pioneer cells. They establish the first cellular contact between the margins in the proximal fissure region and separate the hyaloid artery and vein. After initiation, the fusion site is progressing distally, increasing the distance between the hyaloid artery and vein. A timed BMP (Bone Morphogenetic Protein) induction, resulting in coloboma, did not alter the morphology of the fissure margins, but it did affect the expression of NR and RPE markers within the margins. In addition, it resulted in a persisting basal lamina and persisting remnants of periocular mesenchyme and hyaloid vasculature within the fissure, supporting the necessity of BMP antagonism within the fissure margins. The hampered fissure fusion had severe effects on the vasculature of the eye.
Ileal Transcriptome Profiles of Japanese Quail Divergent in Phosphorus Utilization
Authors: Oster Michael , Reyer Henry , Trakooljul Nares , Weber Frank M. , Xi Lu , Muráni Eduard , Ponsuksili Siriluck , Rodehutscord Markus , Bennewitz Jörn , Wimmers Klaus
Published: April 2020

Phosphorus (P) is an essential component for all living beings. Low P diets prompt phenotypic and molecular adaptations to maintain P homeostasis and increase P utilization (PU). Knowledge of the molecular mechanisms of PU is needed to enable targeted approaches to improve PU efficiency and thus lower P excretion in animal husbandry. In a previous population study, Japanese quail were subjected to a low P diet lacking mineral P and exogenous phytase. Individual PU was determined based on total P intake and excretion. A subset of 20 extreme siblings discordant for PU was selected to retrieve gene expression patterns of ileum (n = 10 per PU group). Sequencing reads have been successfully mapped to the current Coturnix japonica reference genome with an average mapping rate of 86%. In total, 640 genes were found to be differentially abundant between the low and high PU groups (false discovery rate ≤ 0.05). Transcriptional patterns suggest a link between improved PU and mitochondrial energy metabolism, accelerated cell proliferation of enterocytes, and gut integrity. In assessing indicators of the efficient use of macro- and micronutrients, further research on turnover and proliferation rates of intestinal cells could provide an approach to improve P efficiency in poultry species.
Chromatin, Epigenetics and Plant Physiology
Authors: Fojtová Miloslava , Fajkus Jiří
Published: April 2020

The ever-increasing interest in epigenetics comes from the fact that in the diverse life situations of organisms, e [...]
Cost Effective Use of a Thiosulfinate-Enriched Allium sativum Extract in Combination with Chemotherapy in Colon Cancer
Authors: Perez-Ortiz Jose Manuel , Galan-Moya Eva Maria , de la Cruz-Morcillo Miguel Angel , Rodriguez Juan Francisco , Gracia Ignacio , Garcia Maria Teresa , Redondo-Calvo Francisco Javier
Published: April 2020

In this work, we sought to investigate the effects of a thiosulfinate-enriched garlic extract, co-administered with 5-fluorouracil (5-FU) or oxaliplatin chemotherapy, on the viability of colon cancer cells (Caco-2 and HT-29). We also addressed the economic feasibility of a new combined treatment of this thiosulfinate-enriched garlic extract, with oxaliplatin that could reduce the dosage and costs of a monotherapy. The thiosulfinate-enriched garlic extract not only enhanced the impact of 5-FU and oxaliplatin (500 µM) in decreasing Caco-2 and HT-29 viability, but also showed a higher effect than standard 5-FU and oxaliplatin chemotherapy as anti-cancer agents. These results provided evidences for the combination of lyophilized garlic extract and 5-FU or oxaliplatin as a novel chemotherapy regimen in colon cancer cells that may also reduce the clinical therapy costs.
Mitochondrial Protection by PARP Inhibition
Authors: Gallyas Jr Ferenc , Sumegi Balazs
Published: April 2020

Inhibitors of the nuclear DNA damage sensor and signalling enzyme poly(ADP-ribose) polymerase (PARP) have recently been introduced in the therapy of cancers deficient in double-strand DNA break repair systems, and ongoing clinical trials aim to extend their use from other forms of cancer non-responsive to conventional treatments. Additionally, PARP inhibitors were suggested to be repurposed for oxidative stress-associated non-oncological diseases resulting in a devastating outcome, or requiring acute treatment. Their well-documented mitochondria- and cytoprotective effects form the basis of PARP inhibitors’ therapeutic use for non-oncological diseases, yet can limit their efficacy in the treatment of cancers. A better understanding of the processes involved in their protective effects may improve the PARP inhibitors’ therapeutic potential in the non-oncological indications. To this end, we endeavoured to summarise the basic features regarding mitochondrial structure and function, review the major PARP activation-induced cellular processes leading to mitochondrial damage, and discuss the role of PARP inhibition-mediated mitochondrial protection in several oxidative stress-associated diseases.
Tamsulosin Associated with Interstitial Lung Damage in CYP2D6 Variant Alleles Carriers
Authors: Jessurun Naomi T. , Wijnen Petal A. , Bast Aalt , van Puijenbroek Eugène P. , Bekers Otto , Drent Marjolein
Published: April 2020

Drugs are serious but underestimated causative agents of interstitial lung disease (ILD). Both cytotoxic and immune mechanisms may be involved in drug-induced ILD (DI-ILD). We aimed to investigate whether polymorphisms of relevant CYP enzymes involved in the metabolization of tamsulosin might explain the pathologic mechanism of the DI-ILD in the cases with suspected tamsulosin DI-ILD. We collected 22 tamsulosin-associated DI-ILD cases at two ILD Expertise Centers in the Netherlands between 2009 and 2020. CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 single nucleotide polymorphisms were genotyped and compared with a control group of 78 healthy Caucasian male volunteers. Nine cases were phenotyped as CYP2D6 poor metabolizers and 13 as CYP2D6 intermediate metabolizers. The phenotypes of the cases differed significantly from those of the healthy controls, with more poor metabolizers. After withdrawal of tamsulosin, the pulmonary condition of three cases had improved, six patients had stabilized, and one patient stabilized after reducing the tamsulosin dose. The described 22 cases suggest that an association between the presence of CYP2D6 allelic variants and tamsulosin-associated ILD is highly likely. These cases highlight the importance of both clinical and genetic risk stratification aimed to achieve a more accurate prevention of DI-ILD in the future and enhance the quality of life of patients.
Heterogeneity of Stemlike Circulating Tumor Cells in Invasive Breast Cancer
Authors: Savelieva Olga E. , Tashireva Liubov A. , Kaigorodova Evgeniya V. , Buzenkova Angelina V. , Mukhamedzhanov Rustam Kh. , Grigoryeva Evgeniya S. , Zavyalova Marina V. , Tarabanovskaya Natalia A. , Cherdyntseva Nadezhda V. , Perelmuter Vladimir M.
Published: April 2020

The presence of stem and epithelial–mesenchymal-transition (EMT) features in circulating tumor cells (CTCs) determines their invasiveness, adaptability to the microenvironment, and resistance to proapoptotic signals and chemotherapy. It also allows them to fulfil the role of metastatic “seeds”. We evaluated the heterogeneity of stem CTCs by their CD44, ALDH1, and CD133 expression depending on N-cadherin expression in breast-cancer patients. A total of 38 female patients were selected for this study. CTC phenotypes were determined by flow cytometry before any type of treatment. Multiplex immunofluorescence was used for the evaluation of tumor-cell heterogeneity in primary lesions. In patients who had CD44-CD24- CTCs, a subset of cells with the expression of other stem-cell markers (CD133 and ALDH1) were detected. Expression of CD133 and/or ALDH1 may be associated with expression of N-cadherin: all populations of N-cadherin+ CTCs demonstrate stem features; in the absence of N-cadherin expression, true nonstem (CD44-CD24-CD133-ALDH1-) cells are found. The heterogeneity of stem marker expression in CTCs was observed regardless of N-cadherin expression. In our study, stromal cell-derived factor-1 (SDF-1) receptor expression in CTCs did not depend on stemlike traits, but was instead associated with N-cadherin expression. Subpopulations of tumor cells, detected both in tumors and blood, were identified. Breast cancer was characterized by pronounced interpersonal and intrapersonal heterogeneity of CTCs by the presence and combination of various stem features and N-cadherin expression. To complete the characterization of stemlike features of CTCs, we suggest the simultaneous use of the three stem markers.
Iterative Truncated Unscented Particle Filter
Authors: Wang Yanbo , Wang Fasheng , He Jianjun , Sun Fuming
Published: April 2020

The particle filter method is a basic tool for inference on nonlinear partially observed Markov process models. Recently, it has been applied to solve constrained nonlinear filtering problems. Incorporating constraints could improve the state estimation performance compared to unconstrained state estimation. This paper introduces an iterative truncated unscented particle filter, which provides a state estimation method with inequality constraints. In this method, the proposal distribution is generated by an iterative unscented Kalman filter that is supplemented with a designed truncation method to satisfy the constraints. The detailed iterative unscented Kalman filter and truncation method is provided and incorporated into the particle filter framework. Experimental results show that the proposed algorithm is superior to other similar algorithms.
Using UPLC–MS/MS to Evaluate the Dissemination of Pyriproxyfen by Aedes Mosquitoes to Combat Cryptic Larval Habitats after Source Reduction in Kaohsiung in Southern Taiwan
Authors: Chen Ying-An , Lai Yi-Ting , Wu Kuo-Chih , Yen Tsai-Ying , Chen Chia-Yang , Tsai Kun-Hsien
Published: April 2020

The policy regarding mosquito control strategies in Taiwan is based on integrated vector management (IVM). The major approach is source reduction via collaboration by both residents and governments. However, small and cryptic habitats of dengue vectors are hard to find and eliminate in urban communities. Therefore, this study evaluated a complementary approach that targeted cryptic habitats by utilizing mosquitoes themselves as vehicles to transfer an insect growth regulator, pyriproxyfen (PPF), to their breeding sites; the amount of PPF in breeding water was determined with ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS). A bioassay conducted by introducing ten late-instar larvae into PPF solution was performed to assess emergence inhibition (EI). PPF was found at 0.56 ± 0.04 ng in 25 mL of water by dissemination via ten Aedes aegypti mosquitoes exposed to 0.01% PPF, leading to 100% EI. After the community-level source reduction, a field trial in Kaohsiung in Southern Taiwan showed that 30.8–31.5% of cryptic ovitraps reached EI ≥ 50% one month after spraying 0.01% PPF in microhabitats favored by mosquitoes. IVM in parallel with residual spraying of PPF on resting surfaces of mosquitoes could serve as a simple and complementary approach to reduce cryptic larval sources in urban communities in Southern Taiwan.
Global Bank Capital and Liquidity after 30 Years of Basel Accords
Authors: Benink Harald
Published: April 2020

In this paper we analyze the effectiveness of more than 30 years of efforts by international banking supervisors, working together in the Basel Committee on Banking Supervision, to harmonize capital and liquidity standards for internationally active banks. Notwithstanding the great efforts and progress made by international banking supervisors since the financial crisis of 2007–2009, two important issues require further attention. First, although bank capital ratios have been raised significantly since the recent financial crisis, they are still at historically low levels. In a world in which global debt ratios have risen even further during the past decade, this is a worrying signal of fragility in the global financial system. Second, bank liquidity requirements may have become too complex and could also have unintented and unpredictable interaction effects with bank capital requirements.
Influence of Firing Temperature on the Physical, Thermal and Microstructural Properties of Kankara Kaolin Clay: A Preliminary Investigation
Authors: Abubakar Muazu , Muthuraja Ayyankalai , Rajak Dipen Kumar , Ahmad Norhayati , Pruncu Catalin I. , Lamberti Luciano , Kumar Ashwini
Published: April 2020

In this study, natural deposits of Kankara kaolin clay were collected and investigated in order to determine physical, microstructural, thermal, and firing properties and assess clay’s suitability as starting material for various ceramic applications. Chemical analysis of the clay was performed using XRF. Mineralogical analysis and thermal analysis of the clay were conducted using XRD and thermogravimetric thermal analysis (TGA)/differential thermal analysis (DTA), respectively. In order to assess its ceramic behavior, the clay was fired at 900–1200 °C. Maturation characteristics of fired ceramics were assessed by measuring bulk density, apparent porosity, and shrinkage. It was found that main oxides in the clay are alumina, silica, and potassium oxide, while other oxides are present in trace quantities. Kaolinite, quartz, and illite are the phases found from the XRD results, while mullite ceramic phase formed at firing temperature above 1100 °C. Maturation tests showed that ceramic properties such as bulk density and shrinkage increase with temperature, while apparent porosity decreases with temperature. The results presented in this study prove that the clay is an appropriate material for producing traditional ceramics.
Stability of a Petroleum-Like Hydrocarbon Mixture at Thermobaric Conditions That Correspond to Depths of 50 km
Authors: Serovaiskii Aleksandr , Dubrovinky Leonid , Kutcherov Vladimir
Published: April 2020

The commercial discovery of giant crude oil deposits at depths deeper than 10 km in various petroleum basins worldwide casts doubt on the validity of the theoretical calculations that have determined that the main zone of petroleum formation is at depths of 6–8 km (the ‘oil window’). However, the behavior of complex hydrocarbon systems at thermobaric conditions, which correspond to depths below 6–8 km, is poorly known. We experimentally investigated the thermal stability of a complex hydrocarbon system at the pressure-temperature conditions of Earth’s lower crust by means of Raman and Mössbauer spectroscopies. Our results demonstrated the chemical stability of the complex hydrocarbon system at thermobaric conditions corresponding to depths of 50 km, including the redox stability of the hydrocarbon system in a highly oxidative environment. The results of these experiments allowed us to revise the depth range in which petroleum deposits could occur.
Hypolipidemic Effects of β-Glucans, Mannans, and Fucoidans: Mechanism of Action and Their Prospects for Clinical Application
Authors: Korolenko Tatiana A. , Bgatova Nataliya P. , Ovsyukova Marina V. , Shintyapina Alexandra , Vetvicka Vaclav
Published: April 2020

The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of polysaccharides. There are several validated agents altering lipid levels which reduce the risk of atherosclerotic cardiovascular events. Nonetheless, for many people, the risk of such an event remains unacceptably high despite treatment with these agents. This situation has prompted the search for new therapies to reduce the residual cardiovascular risk. The lipid-lowering effect of β-glucans consumed with food was demonstrated in patients with atherosclerosis. The mechanism of the protective effect of β-glucans is poorly studied. The effects of β-glucans are mediated by Toll-like receptors, by dectin-1, and possibly by other receptors. Nevertheless, the mechanism of the protective action of β-glucan in lipemic mice has been studied insufficiently. This review will present up-to-date information regarding experimental hypolipidemic polysaccharide compounds that hold promise for medicine. Phagocyte-specific chitotriosidase in humans contributes to innate immune responses against chitin-containing fungi. This enzyme has been first described in patients with Gaucher disease and serves as an important diagnostic biomarker. It has been reported that, in mice, chitin particles of certain size are recognized by macrophages through Toll-like receptors, dectin-1, and to a lesser extent through mannose receptor.
Targeted Isolation of Antioxidant Constituents from Plantago asiatica L. and In Vitro Activity Assay
Authors: Dong Yuanyang , Hou Qihang , Sun Meng , Sun Jingjing , Zhang Bingkun
Published: April 2020

Plantago asiatica L. is widely distributed in Eastern Asia and a commonly used drug in China, Korea, and Japan for diuretic and antiphlogistic purposes. In this experiment, the present study was performed to isolate antioxidant molecules based on the DPPH scavenging activity assay and discover the bioactive compounds which contributed to performing the function of Plantago asiatica L. Each faction was chosen for further isolation guided by DPPH scavenging activity assay. Afterwards, two potential bioactive molecules, aesculetin and apigenin, were isolated for in vitro antioxidant activity in cells. Hydrogen-peroxide-induced oxidative stress led to decreased cell viability, impaired intercellular junction, and damage to the cell membrane and DNA. Furthermore, aesculetin ameliorated decreased cell viability induced by hydrogen peroxide via upregulation of antioxidant related genes, and apigenin also protected against H2O2 mainly by improving the glutathione (GSH) antioxidant system, such as increasing the activity of glutathione peroxidase (GPX), glutathione reductase (GR), and the ration of GSH/glutathione disulfide (GSSG). Above all, these findings suggest that aesculetin and apigenin may be bioactive compounds for antioxidant function in Plantago asiatica L.
Essential Oil Phytocomplex Activity, a Review with a Focus on Multivariate Analysis for a Network Pharmacology-Informed Phytogenomic Approach
Authors: Buriani Alessandro , Fortinguerra Stefano , Sorrenti Vincenzo , Caudullo Giada , Carrara Maria
Published: April 2020

Thanks to omic disciplines and a systems biology approach, the study of essential oils and phytocomplexes has been lately rolling on a faster track. While metabolomic fingerprinting can provide an effective strategy to characterize essential oil contents, network pharmacology is revealing itself as an adequate, holistic platform to study the collective effects of herbal products and their multi-component and multi-target mediated mechanisms. Multivariate analysis can be applied to analyze the effects of essential oils, possibly overcoming the reductionist limits of bioactivity-guided fractionation and purification of single components. Thanks to the fast evolution of bioinformatics and database availability, disease-target networks relevant to a growing number of phytocomplexes are being developed. With the same potential actionability of pharmacogenomic data, phytogenomics could be performed based on relevant disease-target networks to inform and personalize phytocomplex therapeutic application.
Quantum-Mechanical Assessment of the Energetics of Silver Decahedron Nanoparticles
Authors: Polsterová Svatava , Friák Martin , Všianská Monika , Šob Mojmír
Published: April 2020

We present a quantum-mechanical study of silver decahedral nanoclusters and nanoparticles containing from 1 to 181 atoms in their static atomic configurations corresponding to the minimum of the ab initio computed total energies. Our thermodynamic analysis compares T = 0 K excess energies (without any excitations) obtained from a phenomenological approach, which mostly uses bulk-related properties, with excess energies from ab initio calculations of actual nanoclusters/nanoparticles. The phenomenological thermodynamic modeling employs (i) the bulk reference energy, (ii) surface energies obtained for infinite planar (bulk-related) surfaces and (iii) the bulk atomic volume. We show that it can predict the excess energy (per atom) of nanoclusters/nanoparticles containing as few as 7 atoms with the error lower than 3%. The only information related to the nanoclusters/nanoparticles of interest, which enters the phenomenological modeling, is the number of atoms in the nanocluster/nanoparticle, the shape and the crystallographic orientation(s) of facets. The agreement between both approaches is conditioned by computing the bulk-related properties with the same computational parameters as in the case of the nanoclusters/nanoparticles but, importantly, the phenomenological approach is much less computationally demanding. Our work thus indicates that it is possible to substantially reduce computational demands when computing excess energies of nanoclusters and nanoparticles by ab initio methods.