bluuebunny/crossref_metadata_2025 huggingface dataset:
The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon
Authors: Manneck David , Manz Gisela , Braun Hannah-Sophie , Rosendahl Julia , Stumpff Friederike
Published: May 2021

A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·L−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·L−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl− or 25 HCO3− reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3−. The removal of 120 Cl− had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO3− via apical CFTR and basolateral Na+-HCO3− cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1.
High Flexibility of RNaseH2 Catalytic Activity with Respect to Non-Canonical DNA Structures
Authors: Dede Maria , Napolitano Silvia , Melati Anna , Pirota Valentina , Maga Giovanni , Crespan Emmanuele
Published: May 2021

Ribonucleotides misincorporated in the human genome are the most abundant DNA lesions. The 2′-hydroxyl group makes them prone to spontaneous hydrolysis, potentially resulting in strand breaks. Moreover, their presence may decrease the rate of DNA replication causing replicative fork stalling and collapse. Ribonucleotide removal is initiated by Ribonuclease H2 (RNase H2), the key player in Ribonucleotide Excision Repair (RER). Its absence leads to embryonic lethality in mice, while mutations decreasing its activity cause Aicardi–Goutières syndrome. DNA geometry can be altered by DNA lesions or by peculiar sequences forming secondary structures, like G-quadruplex (G4) and trinucleotide repeats (TNR) hairpins, which significantly differ from canonical B-form. Ribonucleotides pairing to lesioned nucleotides, or incorporated within non-B DNA structures could avoid RNase H2 recognition, potentially contributing to genome instability. In this work, we investigate the ability of RNase H2 to process misincorporated ribonucleotides in a panel of DNA substrates showing different geometrical features. RNase H2 proved to be a flexible enzyme, recognizing as a substrate the majority of the constructs we generated. However, some geometrical features and non-canonical DNA structures severely impaired its activity, suggesting a relevant role of misincorporated ribonucleotides in the physiological instability of specific DNA sequences.
EnvIRONmental Aspects in Myelodysplastic Syndrome
Authors: Petzer Verena , Theurl Igor , Weiss Günter , Wolf Dominik
Published: May 2021

Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (TET2), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.
Adenosine Signaling in Mast Cells and Allergic Diseases
Authors: Garcia-Garcia Lucia , Olle Laia , Martin Margarita , Roca-Ferrer Jordi , Muñoz-Cano Rosa
Published: May 2021

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.
An Improved Vector System for Homogeneous and Stable Gene Regulation
Authors: Michalec-Wawiórka Barbara , Czapiński Jakub , Filipek Kamil , Rulak Patrycja , Czerwonka Arkadiusz , Tchórzewski Marek , Rivero-Müller Adolfo
Published: May 2021

Precise analysis of the genetic expression and functioning of proteins requires experimental approaches that, among others, enable tight control of gene expression at the transcriptional level. Doxycycline-induced Tet-On/Tet-Off expression systems provide such an opportunity, and are frequently used to regulate the activity of genes in eukaryotic cells. Since its development, the Tet-system has evolved tight gene control in mammalian cells; however, some challenges are still unaddressed. In the current set up, the establishment of the standard Tet-based system in target cells is time-consuming and laborious and has been shown to be inefficient, especially in a long-term perspective. In this work, we present an optimized inducible expression system, which enables rapid generation of doxycycline-responsive cells according to a one- or two-step protocol. The reported modifications of the Tet-On system expand the toolbox for regulated mammalian gene expression and provide high, stable, and homogenous expression of the Tet-On3G transactivator, which is of fundamental importance in the regulation of transgenes.
The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer
Authors: Pedersen Stine F. , Flinck Mette , Pardo Luis A.
Published: May 2021

Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and mitochondrial phenotype undergo pervasive changes during cancer development, and both play key roles in driving the malignancy. However, the link between these events has been largely ignored. This review comprehensively summarizes and critically discusses the role of the reciprocal relationship between ion transport and mitochondria in crucial cellular functions, including metabolism, signaling, and cell fate decisions. We focus on Ca2+, H+, and K+, which play essential and highly interconnected roles in mitochondrial function and are profoundly dysregulated in cancer. We describe the transport and roles of these ions in normal mitochondria, summarize the changes occurring during cancer development, and discuss how they might impact tumorigenesis.
A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial–Mesenchymal Transition
Authors: Lin Feng-Yen , Lin Yi-Wen , Shih Chun-Ming , Lin Shing-Jong , Tung Yu-Tang , Li Chi-Yuan , Chen Yung-Hsiang , Lin Cheng-Yen , Tsai Yi-Ting , Huang Chun-Yao
Published: May 2021

Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. We previously identified an index for the prediction of HDL functionality, relative HDL (rHDL) index, and preliminarily explored that dysfunctional HDL (rHDL index value > 2) failed to rescue the damage to endothelial progenitor cells (EPCs). To confirm the effectiveness of the rHDL index for predicting HDL functions, here we evaluated the effects of HDL from patients with different rHDL index values on the endothelial–mesenchymal transition (EndoMT) of EPCs. We also analyzed the lipid species in HDL with different rHDL index values and investigated the structural differences that affect HDL functions. The results indicate that HDL from healthy adults and subjects with an rHDL index value < 2 protected transforming growth factor (TGF)-β1-stimulated EndoMT by modulating Smad2/3 and Snail activation. HDL from subjects with an rHDL index value > 2 failed to restore the functionality of TGF-β1-treated EPCs. Lipidomic analysis demonstrated that HDL with different rHDL index values may differ in the composition of triglycerides, phosphatidylcholine, and phosphatidylinositol. In conclusion, we confirmed the applicability of the rHDL index value to predict HDL function and found structural differences that may affect the function of HDL, which warrants further in-depth studies.
Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
Authors: Bak Andrzej
Published: May 2021

A key question confronting computational chemists concerns the preferable ligand geometry that fits complementarily into the receptor pocket. Typically, the postulated ‘bioactive’ 3D ligand conformation is constructed as a ‘sophisticated guess’ (unnecessarily geometry-optimized) mirroring the pharmacophore hypothesis—sometimes based on an erroneous prerequisite. Hence, 4D-QSAR scheme and its ‘dialects’ have been practically implemented as higher level of model abstraction that allows the examination of the multiple molecular conformation, orientation and protonation representation, respectively. Nearly a quarter of a century has passed since the eminent work of Hopfinger appeared on the stage; therefore the natural question occurs whether 4D-QSAR approach is still appealing to the scientific community? With no intention to be comprehensive, a review of the current state of art in the field of receptor-independent (RI) and receptor-dependent (RD) 4D-QSAR methodology is provided with a brief examination of the ‘mainstream’ algorithms. In fact, a myriad of 4D-QSAR methods have been implemented and applied practically for a diverse range of molecules. It seems that, 4D-QSAR approach has been experiencing a promising renaissance of interests that might be fuelled by the rising power of the graphics processing unit (GPU) clusters applied to full-atom MD-based simulations of the protein-ligand complexes.
Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/β-Catenin Signaling Inhibition
Authors: Abd El-Fadeal Noha M. , Nafie Mohamed S. , K. El-kherbetawy Mohammed , El-mistekawy Amr , Mohammad Hala M. F. , Elbahaie Alaaeldeen M. , Hashish Abdullah A. , Alomar Suliman Y. , Aloyouni Sheka Yagub , El-dosoky Mohamed , Morsy Khaled M. , Zaitone Sawsan A.
Published: May 2021

In colon cancer, wingless (Wnt)/β-catenin signaling is frequently upregulated; however, the creation of a molecular therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/β-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) versus normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and β-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 µM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 µM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/β-catenin/glycogen synthase kinase-3β (GSK-3β) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/β-catenin/GSK-3β signaling.
Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition
Authors: Helmi Summer A. , Rohani Leili , Zaher Ahmed R. , El Hawary Youssry M. , Rancourt Derrick E.
Published: May 2021

Bone healing is a complex, well-organized process. Multiple factors regulate this process, including growth factors, hormones, cytokines, mechanical stimulation, and aging. One of the most important signaling pathways that affect bone healing is the Notch signaling pathway. It has a significant role in controlling the differentiation of bone mesenchymal stem cells and forming new bone. Interventions to enhance the healing of critical-sized bone defects are of great importance, and stem cell transplantations are eminent candidates for treating such defects. Understanding how Notch signaling impacts pluripotent stem cell differentiation can significantly enhance osteogenesis and improve the overall healing process upon transplantation. In Rancourt’s lab, mouse embryonic stem cells (ESC) have been successfully differentiated to the osteogenic cell lineage. This study investigates the role of Notch signaling inhibition in the osteogenic differentiation of mouse embryonic and induced pluripotent stem cells (iPS). Our data showed that Notch inhibition greatly enhanced the differentiation of both mouse embryonic and induced pluripotent stem cells.
Innovative Strategies to Facilitate Patient-Centered Research in Multiple Chronic Conditions
Authors: Garg Tullika , Polenick Courtney A. , Schoenborn Nancy , Jih Jane , Hajduk Alexandra , Wei Melissa Y. , Hughes Jaime
Published: May 2021

Multiple chronic conditions (MCC) are one of today’s most pressing healthcare concerns, affecting 25% of all Americans and 75% of older Americans. Clinical care for individuals with MCC is often complex, condition-centric, and poorly coordinated across multiple specialties and healthcare services. There is an urgent need for innovative patient-centered research and intervention development to address the unique needs of the growing population of individuals with MCC. In this commentary, we describe innovative methods and strategies to conduct patient-centered MCC research guided by the goals and objectives in the Department of Health and Human Services MCC Strategic Framework. We describe methods to (1) increase the external validity of trials for individuals with MCC; (2) study MCC epidemiology; (3) engage clinicians, communities, and patients into MCC research; and (4) address health equity to eliminate disparities.
Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study
Authors: Abuzakouk Mohamed , Saleh Khaled , Algora Manuel , Nusair Ahmad , Alameri Jawahir , Alshehhi Fatema , Alkhaja Sara , Badr Mohamed , Abdallah Khaled , De Oliveira Bruno , Nadeem Ashraf , Varghese Yeldho , Munde Dnyaseshwar , Salam Shameen , Abduljawad Baraa , Elkambergy Hussam , Wahla Ali , Taha Ahmed , Dibu Jamil , Bayrlee Ahmed , Hamed Fadi , AbdelWareth Laila , Rahman Nadeem , Guzman Jorge , Mallat Jihad
Published: May 2021

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.
Detection of Renal Injury Following Primary Coronary Intervention among ST-Segment Elevation Myocardial Infarction Patients: Doubling the Incidence Using Neutrophil Gelatinase-Associated Lipocalin as a Renal Biomarker
Authors: Lupu Lior , Rozenfeld Keren-Lee , Zahler David , Morgan Samuel , Merdler Ilan , Shtark Moshe , Goldiner Ilana , Banai Shmuel , Shacham Yacov
Published: May 2021

Background: A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer “subclinical AKI”. We investigated the incidence and possible implications of “subclinical AKI”, compared to no and clinical AKI among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI). Methods: We included 223 patients with STEMI treated with PCI. Neutrophil gelatinase-associated lipocalin (NGAL) was used as a marker of renal tubular damage in the absence of functional AKI, with NGAL levels ≥100 ng/mL suggesting subclinical AKI. Patients were assessed for the occurrence of in-hospital adverse outcomes. Results: Of the study patients, 45 (25%) had subclinical AKI. These patients were more likely to have left ventricular ejection fraction ≤45% (33% vs. 23%. p = 0.01), in-hospital adverse outcomes (73% vs. 48%; p = 0.005), and a combination of the two. The multivariate regression model demonstrated that subclinical AKI was independently associated with in-hospital adverse outcomes (OR 3.71, 95% CI 1.30–10.62, p = 0.02). Conclusions: Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI.
What Is New with Total Pancreatectomy and Autologous Islet Cell Transplantation? Review of Current Progress in the Field
Authors: Baldwin Xavier L. , Williams Brittney M. , Schrope Beth , Desai Chirag S.
Published: May 2021

Patients with chronic pancreatitis have benefited from total pancreatectomy and autologous islet cell transplantation (TPAIT) since the 1970s. Over the past few decades, improvements have been made in surgical technique and perioperative management that have led to improved success of islet cell function, insulin independence and patient survival. This article focuses on recent updates and advances for the TPAIT procedure that continue to expand and innovate the impact on patients with debilitating disease.
Opioid Prescriptions in Chronic Pain Rehabilitation. A Prospective Study on the Prevalence and Association between Individual Patient Characteristics and Opioids
Authors: Svanberg Mikael , Stålnacke Britt-Marie , Quinn Patrick D. , Boersma Katja
Published: May 2021

While against recommendations, long-term opioid therapy (LTOT) for chronic pain is common. This study aimed to describe the prevalence of opioid prescriptions and to study the association of patient characteristics (demographics, pain characteristics, anxiety, depressive symptoms and pain coping) with future LTOT. The sample included N = 1334 chronic musculoskeletal pain patients, aged 18–65, who were assessed for Interdisciplinary Multimodal Pain Rehabilitation (IMMR) in Swedish specialist rehabilitation. Prescriptions were tracked across a two-year target period after assessment. In total, 9100 opioid prescriptions were prescribed to 55% of the sample (Mmedian = 6, IQR = 14). Prediction of LTOT was analyzed separately for those who did (24%) and did not (76%) receive IMMR. The odds of receiving opioids was similar for these subsamples, after controlling for differences in baseline characteristics. In both samples, there were significant associations between patient characteristics and future opioid prescriptions. Dysfunctional pain coping was a unique predictor of LTOT in those who received IMMR while pain intensity and depressive symptoms were unique predictors in those who did not receive IMMR. The results underscore that opioid treatment is common among patients in chronic pain rehabilitation and relates to pain and psychological factors. Understanding in detail why these factors relate to opioid prescription patterns is an important future study area as it is a prerequisite for better management and fundamental for preventing overuse.
Should We Stop Collecting the Preoperative Autologous Blood before Bone Marrow Harvest?
Authors: Lysák Daniel , Hejretová Lenka , Hrabětová Marcela , Jindra Pavel
Published: May 2021

Preoperative autologous blood donation (PAD) in bone marrow (BM) donors is performed to meet potential post-harvest transfusion needs and to avoid the risk of allogeneic transfusions. We reviewed retrospectively bone marrow harvests in 216 healthy donors during a ten-year period to determine the use of autologous blood. All donors except four had undergone PAD. The initial hemoglobin level of 153 g/L (male donors) and 135 g/L (female donors), respectively, decreased by about 8 g/L after preoperative blood donation and by 23 g/L after bone marrow harvest (medians). Autologous blood was administered to 70% of donors, 30% of the units remained unused. The evaluation of the risk of reaching transfusion threshold (<115 g/L males, <105 g/L females) revealed that donors with initial hemoglobin above 145 g/L and those weighing above 75 kg have minimal risk of requiring blood substitution (about 10%). A larger volume of bone marrow was obtained from male compared to female donors (1300 vs. 1100 mL) because of their higher body weight, which resulted in a higher number of procured nucleated cells (362 vs. 307 × 106/kg TNC, ns). The donor-recipient weight difference predicted the probability of sufficient collection. Only 1.5% of donors weighing ≥ 20 kg more than recipients failed to reach ≥3 × 108/kg TNC recipient. Our findings affirm previous data that PAD is unnecessary for healthy marrow donors and may be indicated individually after considering the pre-collection hemoglobin level, donor and recipient weight, and expected blood loss. Reasonable substitution cut-offs have to be set together with clinical symptom evaluation. The effective use of PAD also requires an adequate time interval between PAD and BM harvest.
Remote Density Measurements of Molten Salts via Neutron Radiography
Authors: Long Alexander M. , Parker S. Scott , Carver D. Travis , Jackson J. Matt , Monreal Marisa J. , Newmark Darcy A. , Vogel Sven C.
Published: May 2021

With an increased interest in the use of molten salts in both nuclear and non-nuclear systems, measuring important thermophysical properties of specific salt mixtures becomes critical in understanding salt performance and behavior. One of the more basic and significant thermophysical properties of a given salt system is density as a function of temperature. With this in mind, this work aims to present and layout a novel approach to measuring densities of molten salt systems using neutron radiography. This work was performed on Flight Path 5 at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. In order to benchmark this initial work, three salt mixtures were measured, NaCl, LiCl (58.2 mol%) + KCl (41.8 mol%), and MgCl2 (32 mol%) + KCl (68 mol%). Resulting densities as a function of temperature for each sample from this work were then compared to previous works employing traditional techniques. Results from this work match well with previous literature values for all salt mixtures measured, establishing that neutron radiography is a viable technique to measure density as a function of temperature in molten salt systems. Finally, advantages of using neutron radiography over other methods are discussed and future work in improving this technique is covered.
Nonlinear Wave Evolution in Interaction with Currents and Viscoleastic Muds
Authors: Sharifineyestani Elham , Tahvildari Navid
Published: May 2021

A numerical model is extended to investigate the nonlinear dynamics of surface wave propagation over mud in the presence of currents. A phase-resolving frequency-domain model for wave-current interaction is improved to account for wave modulations due to viscoelastic mud of arbitrary thickness. The model compares well with published laboratory data and performs slightly better than the model with viscous mud-induced wave damping mechanism. Monochromatic and random wave simulations are conducted to examine the combined effect of currents, mud-induced wave dissipation and modulation, and nonlinear wave-wave interactions on surface wave spectra. Results indicate that current effects on wave damping over viscoelastic mud is not as straightforward as that over viscous mud. For example, while opposing currents consistently increase damping of random waves over viscous mud, they can decrease damping over viscoelastic mud due to high variations in frequency-dependent damping stemming from mud’s elasticity. It is shown that a model that assumes the mud layer to be thin for simplification can overestimate wave damping over thick mud layers.
CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection
Authors: Tran Vuvi G. , Nguyen Na N. Z. , Kwon Byungsuk
Published: May 2021

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9−/− mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9−/− mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.
Benchmarking—A Way of Finding Risk Factors in Business Performance
Authors: Horváthová Jarmila , Mokrišová Martina , Vrábliková Mária
Published: May 2021

The purpose of this study was to emphasize that the Data Envelopment Analysis (DEA) method is an important benchmarking tool which provides necessary information for improving business performance. To fulfil the abovementioned goal, we used a sample of 48 Slovak companies involved in the field of heat supply. As their position in the economic and social environment of the country is essential, considerable attention should be paid to improving their performance. In addition to the DEA method, we applied the Best Value Method (BVM). We found that DEA is a highly important benchmarking tool, as it provides benchmarks for units that have problems with performance and helps us to reveal risk performance factors. The DEA method also allows us to determine target values of indicators. The originality of this paper is in its comparison of the results of the BVM and the DEA methods.
The Application of Genetic Algorithm in Land Use Optimization Research: A Review
Authors: Ding Xiaoe , Zheng Minrui , Zheng Xinqi
Published: May 2021

Land use optimization (LUO) first considers which types of land use should exist in a certain area, and secondly, how to allocate these land use types to specific land grid units. As an intelligent global optimization search algorithm, the Genetic Algorithm (GA) has been widely used in this field. However, there are no comprehensive reviews concerning the development process for the application of the Genetic Algorithm in land use optimization (GA-LUO). This article used a bibliometric analysis method to explore current state and development trends for GA-LUO from 1154 relevant documents published over the past 25 years from Web of Science. We also displayed a visualization network from the aspects of core authors, research institutions, and highly cited literature. The results show the following: (1) The countries that published the most articles are the United States and China, and the Chinese Academy of Sciences is the research institution that publishes the most articles. (2) The top 10 cited articles focused on describing how to build GA models for multi-objective LUO. (3) According to the number of keywords that appear for the first time in each time period, we divided the process of GA-LUO into four stages: the presentation and improvement of methods stage (1995–2004), the optimization stage (2005–2008), the hybrid application of multiple models stage (2009–2016), and the introduction of the latest method stage (after 2017). Furthermore, future research trends are mainly manifested in integrating together algorithms with GA and deepening existing research results. This review could help researchers know this research domain well and provide effective solutions for land use problems to ensure the sustainable use of land resources.
Just Mothering: Amy Coney Barrett and the Racial Politics of American Motherhood
Authors: Williams H. Howell
Published: May 2021

Justice Amy Coney Barrett’s nomination and confirmation featured frequent references to her role as a mother. This article situates these references within the trajectory of American political development to demonstrate how motherhood operates as a mechanism for enforcing a white-centered racial order. Through a close analysis of both the history of politicized motherhood as well as Barrett’s nomination and confirmation hearings, I make a series of claims about motherhood and contemporary conservatism. First, conservatives stress the virtuousness of motherhood through a division between public and private spheres that valorizes the middle-class white mother. Second, conservatives emphasize certain mothering practices associated with the middle-class white family. Third, conservatives leverage an epistemological claim about the universality of mothering experiences to universalize white motherhood. Finally, this universalism obscures how motherhood operates as a site in which power distinguishes between good and bad mothers and allocates resources accordingly. By attending to what I call the “republican motherhood script” operating in contemporary conservatism, I argue that motherhood is an ideological apparatus for enforcing a racial order premised on white protectionism.
Saudi Procurement System and Regulations: Overview of Local and International Administrative Contracts
Authors: Alanzi Awad Ali
Published: May 2021

This research investigated the Saudi procurement system and regulations in the context of local and international administrative contracts. Mainly, Saudi Government Tenders and Procurement Law was investigated in more detail to understand basic rules and regulations of the bidding, selection process, and penalties in case of delay in the administrative contract process. Moreover, a matter of direct purchase was also investigated to understand the circumstances and conditions of a direct purchase. In addition, the international administrative contract was discussed to comprehend the nature and regulations of such contracts. A matter of arbitration was also investigated to know the arbitrator’s role and powers in case of a dispute in contracting and performing international administrative contracts outside the country. The arguments against arbitration were also deliberated to recognize the limitations of arbitration in the presence of local and foreign legislations. Overall, Saudi Government Tenders and Procurement Law is well-versed and organized in displaying all-important jurisdictions and matters regarding administrative contracts and the procurement system.
Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications
Authors: Giorgetti Arianna , Pascali Jennifer , Fais Paolo , Pelletti Guido , Gabbin Andrea , Franchetti Giorgia , Cecchetto Giovanni , Viel Guido
Published: May 2021

Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.
Formulation to Calculate Isothermal, Non-Newtonian Elastohydrodynamic Lubrication Problems Using a Pressure Gradient Coordinate System and Its Verification by an Experimental Grease
Authors: Kakoi Kunihiko
Published: May 2021

This paper presents a formulation of point contact elastohydrodynamic lubrication analysis for an isothermal, non-Newtonian flow. A coordinate system of the pressure gradient was employed herein. A Couette flow and a Poiseuille flow were considered along the directions of the zero and non-zero pressure gradients, respectively. The Poiseuille flow velocity was assumed to be represented by a 4th-order polynomial of z along the film thickness direction. The Couette flow velocity was assumed to be represented by a linear function of z. Subsequently, the modified Reynolds equation, which contains an equivalent viscosity, was obtained. Using Bauer’s rheological model, the formulation presented in this study was applied to a grease that has been previously experimented upon. The results of previous studies were compared with those of the present study and a reasonable agreement was noted. The distribution of the equivalent viscosity showed a notable difference from that of Newtonian flow. The formulation can be incorporated easily to the usual elastohydrodynamic lubrication calculation procedure for Newtonian flow. The method can be easily applied to other non-Newtonian rheological models. The equivalent viscosity can be calculated using the one-parameter Newton-Raphson’s method; as a result, the calculation can be performed within a reasonable time.
Novel Cold Crucible Ultrasonic Atomization Powder Production Method for 3D Printing
Authors: Żrodowski Łukasz , Wróblewski Rafał , Choma Tomasz , Morończyk Bartosz , Ostrysz Mateusz , Leonowicz Marcin , Łacisz Wojciech , Błyskun Piotr , Wróbel Jan S. , Cieślak Grzegorz , Wysocki Bartłomiej , Żrodowski Cezary , Pomian Karolina
Published: May 2021

A new powder production method has been developed to speed up the search for novel alloys for additive manufacturing. The technique involves an ultrasonically agitated cold crucible installed at the top of a 20 kHz ultrasonic sonotrode. The material is melted with an electric arc and undergoes pulverization with standing wave vibrations. Several different alloys in various forms, including noble and metallic glass alloys, were chosen to test the process. The atomized particles showed exceptional sphericity, while powder output suitable for additive manufacturing reached up to 60%. The AMZ4 metallic glass powder remained amorphous below the 50 μm fraction, while tungsten addition led to crystallization in each fraction. Minor contamination and high Mn and Zn evaporation, especially in the finest particles, was observed in atomized powders. The innovative ultrasonic atomization method appears as a promising tool for material scientists to develop powders with tailored chemical composition, size and structure.
Application of Selective Induction Heating for Improvement of Mechanical Properties of Elastic Hinges
Authors: Muszyński Paweł , Poszwa Przemysław , Gessner Andrzej , Mrozek Krzysztof
Published: May 2021

Injection molding is a polymer processing technology used for manufacturing parts with elastic hinges. Elastic hinges are widely used in FMCG (Fast Moving Consumer Goods) packaging (e.g., bottle closures of shampoos, sauces) and in the electrical engineering industry. Elastic hinge is a thin film that connect two regions of the injection molded part, where significant shear rates are present, which can lead to the degradation of polymers and the decrease in mechanical properties. Selective induction heating is the method that improves the flow of the polymer melt through thin regions by the local increase in mold temperature. In this study, selective induction heating was used to improve mechanical properties of elastic hinges by the reduction of material degradation due to high shear rates. To verify the change of shear rates, selective induction heating simulation and injection molding simulations were performed. The linear relation between mold temperature and maximum shear rate in the cross-section was identified and the mechanical tests showed significant differences in hinge stiffness, tensile strength and elongation at break.
An Experimental Study of Possible Post-War Ferronickel Slag Waste Disposal in Szklary (Lower Silesian, Poland) as Partial Aggregate Substitute in Concrete: Characterization of Physical, Mechanical, and Thermal Properties
Authors: Małek Marcin , Jackowski Mateusz , Łasica Waldemar , Dydek Kamil , Boczkowska Anna
Published: May 2021

Aggregates derived from waste, due to the growing awareness of global warming, are more and more often used in the concrete production process. This way, their disposal not only reduces the pollution of the Earth but also lowers the consumption of natural aggregates, which are limited. One of the new “eco” aggregates may be a ferronickel slag waste (FNSW), which was generated in post-war metallurgical processes and stored in Szklary (Lower Silesian, Poland). In order to determine the possibility of using ferronickel slag waste aggregate (FNSWA) in the concrete production process, new concrete mixtures were designed and tested. Physical properties (cone slump, air content, pH, and density), mechanical properties (compressive strength, flexural strength, and tensile strength), and thermal properties (thermal conductivity) were assessed for all new laboratory recipes. Moreover, the modulus of elasticity and Poisson’s ratio were determined. This study includes five different contents of FNSWA in the amount of 5%, 10%, 15%, 20%, and 25% of the mass of natural aggregate as its partial substitute. The final results were compared to the base sample (BS) containing 100% natural aggregate, which was granite.
Critical Dynamics of Defects and Mechanisms of Damage-Failure Transitions in Fatigue
Authors: Naimark Oleg , Oborin Vladimir , Bannikov Mikhail , Ledon Dmitry
Published: May 2021

An experimental methodology was developed for estimating a very high cycle fatigue (VHCF) life of the aluminum alloy AMG-6 subjected to preliminary deformation. The analysis of fatigue damage staging is based on the measurement of elastic modulus decrement according to “in situ” data of nonlinear dynamics of free-end specimen vibrations at the VHCF test. The correlation of fatigue damage staging and fracture surface morphology was studied to establish the scaling properties and kinetic equations for damage localization, “fish-eye” nucleation, and transition to the Paris crack kinetics. These equations, based on empirical parameters related to the structure of the material, allows us to estimate the number of cycles for the nucleation and advance of fatigue crack.
Generalization Process by Second Grade Students
Authors: Torres María D. , Moreno Antonio , Cañadas María C.
Published: May 2021

This study is part of a broader study on algebraic reasoning in elementary education. The research objective of the present survey, namely to describe generalization among second grade (7- to 8-year-old) students, was pursued through semi-structured interviews with six children in connection with a contextualized generalization task involving the function y = x + 3. Particular attention was paid to the structures recognized and the type of generalization expressed by these students as they reasoned. In all six, we observed three phases of inductive reasoning: (a) abductive, (b) inductive and (c) generalization. The students correctly recognized the structure at least once during the interview and expressed generalization in three ways.
More Effective Results for Testing Oscillation of Non-Canonical Neutral Delay Differential Equations
Authors: Ramos Higinio , Moaaz Osama , Muhib Ali , Awrejcewicz Jan
Published: May 2021

In this work, we address an interesting problem in studying the oscillatory behavior of solutions of fourth-order neutral delay differential equations with a non-canonical operator. We obtained new criteria that improve upon previous results in the literature, concerning more than one aspect. Some examples are presented to illustrate the importance of the new results.
A Wavelet-Based Method for the Impact of Social Media on the Economic Situation: The Saudi Arabia 2030-Vision Case
Authors: Balalaa Majed S. , Ben Mabrouk Anouar , Abdessalem Habiba
Published: May 2021

In the present paper, a wavelet method is proposed to study the impact of electronic media on economic situation. More precisely, wavelet techniques are applied versus classical methods to analyze economic indices in the market. The technique consists firstly of filtering the data from unprecise circumstances (noise) to construct next a wavelet denoised contingency table. Next, a thresholding procedure is applied to such a table to extract the essential information porters. The resulting table subject finally to correspondence analysis before and after thresholding. As a case of study, the KSA 2030-vision is considered in the empirical part based on electronic and social media. Effects of the electronic media texts about the trading 2030 vision on the Saudi and global economy has been studied. Recall that the Saudi market is the most important representative market in the GCC continent. It has both regional and worldwide influence on economies and besides, it is characterized by many political, economic and financial movements such as the worldwide economic NEOM project. The findings provided in the present paper may be applied to predict the future situation of markets in GCC region and may constitute therefore a guide for investors to decide about investing or not in these markets.
Polyamine Homeostasis in Development and Disease
Authors: Nakanishi Shima , Cleveland John L.
Published: May 2021

Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.