bluuebunny/crossref_metadata_2025 huggingface dataset:
Walnut (Juglans regia L.) Volatile Compounds Indicate Kernel and Oil Oxidation
Authors: Grilo Filipa S. , Wang Selina C.
Published: February 2021

Kernel oxidation susceptibility and pellicle darkening are among the biggest concerns regarding walnut quality. Monitoring oxidation is crucial to preserve quality from production to consumption. Chemical oxidation parameters (peroxide value and UV absorbances), fatty acid profile, tocopherols, phenols, and volatiles in ‘Chandler’ and ‘Howard’ kernels were studied at different time points during 28 weeks of storage to evaluate potential oxidation markers. During storage, peroxide value, UV absorbances, and volatiles concentration increased; oxidative stability, phenols, and tocopherols decreased, while fatty acid profile was unaffected. ‘Chandler’ had a lower peroxide value, K232, and K268; and higher kernel and oil oxidative stability compared to ‘Howard’. Phenols and tocopherols decreased 1.2-fold in ‘Chandler’ and 1.3-fold in ‘Howard’. Using multivariate analysis, samples were discriminated in three groups according with their oxidative levels. Increases of volatiles in oil and kernel were associated with higher oxidative levels. Pentanal, 2-methylpropanal, hexanal, (E)-2-pentenal, 3-octanone, octanal, (Z)-2-penten-1-ol, hexanol, (E)-2-octenal, 1-octen-3-ol, benzaldehyde, (E,E)-2,4-nonadienal, and hexanoic acid in kernels were adequate at distinguishing oxidation levels and as oxidative markers in walnuts. Kernel volatiles is a useful measurement for walnut oxidation during storage without any prior fat extraction.
Regulation, Activation and Function of Caspase-11 during Health and Disease
Authors: Agnew Aidan , Nulty Ciara , Creagh Emma M.
Published: February 2021

Caspase-11 is a pro-inflammatory enzyme that is stringently regulated during its expression and activation. As caspase-11 is not constitutively expressed in cells, it requires a priming step for its upregulation, which occurs following the stimulation of pathogen and cytokine receptors. Once expressed, caspase-11 activation is triggered by its interaction with lipopolysaccharide (LPS) from Gram-negative bacteria. Being an initiator caspase, activated caspase-11 functions primarily through its cleavage of key substrates. Gasdermin D (GSDMD) is the primary substrate of caspase-11, and the GSDMD cleavage fragment generated is responsible for the inflammatory form of cell death, pyroptosis, via its formation of pores in the plasma membrane. Thus, caspase-11 functions as an intracellular sensor for LPS and an immune effector. This review provides an overview of caspase-11—describing its structure and the transcriptional mechanisms that govern its expression, in addition to its activation, which is reported to be regulated by factors such as guanylate-binding proteins (GBPs), high mobility group box 1 (HMGB1) protein, and oxidized phospholipids. We also discuss the functional outcomes of caspase-11 activation, which include the non-canonical inflammasome, modulation of actin dynamics, and the initiation of blood coagulation, highlighting the importance of inflammatory caspase-11 during infection and disease.
Inflammation-Related Changes in Mood Disorders and the Immunomodulatory Role of Lithium
Authors: Sakrajda Kosma , Szczepankiewicz Aleksandra
Published: February 2021

Mood disorders are chronic, recurrent diseases characterized by changes in mood and emotions. The most common are major depressive disorder (MDD) and bipolar disorder (BD). Molecular biology studies have indicated an involvement of the immune system in the pathogenesis of mood disorders, and showed their correlation with altered levels of inflammatory markers and energy metabolism. Previous reports, including meta-analyses, also suggested the role of microglia activation in the M1 polarized macrophages, reflecting the pro-inflammatory phenotype. Lithium is an effective mood stabilizer used to treat both manic and depressive episodes in bipolar disorder, and as an augmentation of the antidepressant treatment of depression with a multidimensional mode of action. This review aims to summarize the molecular studies regarding inflammation, microglia activation and energy metabolism changes in mood disorders. We also aimed to outline the impact of lithium on these changes and discuss its immunomodulatory effect in mood disorders.
Tribbles Pseudokinase 2 (TRIB2) Regulates Expression of Binding Partners in Bovine Granulosa Cells
Authors: Warma Aly , Lussier Jacques G. , Ndiaye Kalidou
Published: February 2021

Members of the Tribbles (TRIB) family of pseudokinases are critical components of intracellular signal transduction pathways in physiological and pathological processes. TRIBs, including TRIB2, have been previously shown as signaling mediators and scaffolding proteins regulating numerous cellular events such as proliferation, differentiation and cell death through protein stability and activity. However, the signaling network associated with TRIB2 and its binding partners in granulosa cells during ovarian follicular development is not fully defined. We previously reported that TRIB2 is differentially expressed in growing dominant follicles while downregulated in ovulatory follicles following the luteinizing hormone (LH) surge or human chorionic gonadotropin (hCG) injection. In the present study, we used the yeast two-hybrid screening system and in vitro coimmunoprecipitation assays to identify and confirm TRIB2 interactions in granulosa cells (GCs) of dominant ovarian follicles (DFs), which yielded individual candidate binding partners including calmodulin 1 (CALM1), inhibin subunit beta A (INHBA), inositol polyphosphate phosphatase-like 1 (INPPL1), 5′-nucleotidase ecto (NT5E), stearoyl-CoA desaturase (SCD), succinate dehydrogenase complex iron sulfur subunit B (SDHB) and Ras-associated protein 14 (RAB14). Further analyses showed that all TRIB2 binding partners are expressed in GCs of dominant follicles but are differentially regulated throughout the different stages of follicular development. CRISPR/Cas9-driven inhibition along with pQE-driven overexpression of TRIB2 showed that TRIB2 differently regulates expression of binding partners, which reveals the importance of TRIB2 in the control of gene expression linked to various biological processes such as proliferation, differentiation, cell migration, apoptosis, calcium signaling and metabolism. These data provide a larger view of potential TRIB2-regulated signal transduction pathways in GCs and provide strong evidence that TRIB2 may act as a regulator of target genes during ovarian follicular development.
A Mechanistic Model of NMDA and AMPA Receptor-Mediated Synaptic Transmission in Individual Hippocampal CA3-CA1 Synapses: A Computational Multiscale Approach
Authors: Micheli Pietro , Ribeiro Rui , Giorgetti Alejandro
Published: February 2021

Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long-Term Potentiation (LTP) and Long-Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses the ability to easily undergo NMDA-mediated LTP and LTD, which is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results point to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of a few, key, molecular interactions typical of structural biology ones.
The Tumor Microenvironment in Liver Metastases from Colorectal Carcinoma in the Context of the Histologic Growth Patterns
Authors: Garcia-Vicién Gemma , Mezheyeuski Artur , Bañuls María , Ruiz-Roig Núria , Molleví David G.
Published: February 2021

Colorectal carcinoma (CRC) is the third most common cancer. Likewise, it is a disease that has a long survival if it is prematurely detected. However, more than 50% of patients will develop metastases, mainly in the liver (LM-CRC), throughout the evolution of their disease, which accounts for most CRC-related deaths. Treatment it is certainly a controversial issue, since it has not been shown to increase overall survival in the adjuvant setting, although it does improve disease free survival (DFS). Moreover, current chemotherapy combinations are administered based on data extrapolated from primary tumors (PT), not considering that LM-CRC present a very particular tumor microenvironment that can radically condition the effectiveness of treatments designed for a PT. The liver has a particular histology and microenvironment that can determine tumor growth and response to treatments: double blood supply, vascularization through fenestrated sinusoids and the presence of different mesenchymal cell types, among other particularities. Likewise, the liver presents a peculiar immune response against tumor cells, a fact that correlates with the poor response to immunotherapy. All these aspects will be addressed in this review, putting them in the context of the histological growth patterns of LM-CRC, a particular pathologic feature with both prognostic and predictive repercussions.
Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity
Authors: Sávio-Silva Christian , Soinski-Sousa Poliana E. , Simplício-Filho Antônio , Bastos Rosana M. C. , Beyerstedt Stephany , Rangel Érika Bevilaqua
Published: February 2021

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs’ biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.
Size-Specific Copper Nanoparticle Cytotoxicity Varies between Human Cell Lines
Authors: Na Ina , Kennedy David C.
Published: February 2021

Commercially available copper nanoparticles of three different sizes were tested for cytotoxicity against three human cell lines using four different cytotoxicity assays. This array of data was designed to elucidate trends in particle stability, uptake, and cytotoxicity. The copper nanoparticles are not stable in cell culture media, and rapid changes over the time course of the assays play a critical role in the measured endpoints. Typically, the 40–60 nm particles tested were more cytotoxic than either smaller or larger particles. These particles were also taken up more readily by cells and exhibited different stability dynamics in cell culture media. This provides a good correlation between total cellular uptake of copper and cytotoxicity that may be directly linked to particle stability, though it is unclear why the intermediate-sized particles exhibited these unique properties when compared with both larger and smaller particles.
Treating Prostate Cancer by Antibody–Drug Conjugates
Authors: Rosellini Matteo , Santoni Matteo , Mollica Veronica , Rizzo Alessandro , Cimadamore Alessia , Scarpelli Marina , Storti Nadia , Battelli Nicola , Montironi Rodolfo , Massari Francesco
Published: February 2021

Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP–ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called “antibody–drug conjugates” (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells’ surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.
Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses
Authors: Lee Sung Won , Park Hyun Jung , Jeon Jungmin , Park Yun Hoo , Kim Tae-Cheol , Jeon Sung Ho , Seong Rho Hyun , Van Kaer Luc , Hong Seokmann
Published: February 2021

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.
What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease
Authors: Przybyl Lukasz , Wozna-Wysocka Magdalena , Kozlowska Emilia , Fiszer Agnieszka
Published: February 2021

Among the main challenges in further advancing therapeutic strategies for Huntington’s disease (HD) is the development of biomarkers which must be applied to assess the efficiency of the treatment. HD is a dreadful neurodegenerative disorder which has its source of pathogenesis in the central nervous system (CNS) but is reflected by symptoms in the periphery. Visible symptoms include motor deficits and slight changes in peripheral tissues, which can be used as hallmarks for prognosis of the course of HD, e.g., the onset of the disease symptoms. Knowing how the pathology develops in the context of whole organisms is crucial for the development of therapy which would be the most beneficial for patients, as well as for proposing appropriate biomarkers to monitor disease progression and/or efficiency of treatment. We focus here on molecular peripheral biomarkers which could be used as a measurable outcome of potential therapy. We present and discuss a list of wet biomarkers which have been proposed in recent years to measure pre- and postsymptomatic HD. Interestingly, investigation of peripheral biomarkers in HD can unravel new aspects of the disease pathogenesis. This especially refers to inflammatory proteins or specific immune cells which attract scientific attention in neurodegenerative disorders.
Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome
Authors: Boukens Bastiaan J. , Potse Mark , Coronel Ruben
Published: February 2021

Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.
Predicting Potential SARS-COV-2 Drugs—In Depth Drug Database Screening Using Deep Neural Network Framework SSnet, Classical Virtual Screening and Docking
Authors: Karki Nischal , Verma Niraj , Trozzi Francesco , Tao Peng , Kraka Elfi , Zoltowski Brian
Published: February 2021

Severe Acute Respiratory Syndrome Corona Virus 2 has altered life on a global scale. A concerted effort from research labs around the world resulted in the identification of potential pharmaceutical treatments for CoVID-19 using existing drugs, as well as the discovery of multiple vaccines. During an urgent crisis, rapidly identifying potential new treatments requires global and cross-discipline cooperation, together with an enhanced open-access research model to distribute new ideas and leads. Herein, we introduce an application of a deep neural network based drug screening method, validating it using a docking algorithm on approved drugs for drug repurposing efforts, and extending the screen to a large library of 750,000 compounds for de novo drug discovery effort. The results of large library screens are incorporated into an open-access web interface to allow researchers from diverse fields to target molecules of interest. Our combined approach allows for both the identification of existing drugs that may be able to be repurposed and de novo design of ACE2-regulatory compounds. Through these efforts we demonstrate the utility of a new machine learning algorithm for drug discovery, SSnet, that can function as a tool to triage large molecular libraries to identify classes of molecules with possible efficacy.
Correction: Braun, T., et al. Expanding the Genetic Code for Site-Directed Spin-Labeling. Int. J. Mol. Sci. 2019, 20, 373
Authors: Braun Theresa , Drescher Malte , Summerer Daniel
Published: February 2021

The authors wish to make the following two corrections to this paper [...]
Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells
Authors: Chyau Charng-Cherng , Wu Huei-Lin , Peng Chiung-Chi , Huang Shiau-Huei , Chen Chin-Chu , Chen Cheng-Hsu , Peng Robert Y.
Published: February 2021

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.
Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model
Authors: Butovich Igor A. , Wilkerson Amber , Yuksel Seher
Published: February 2021

Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.
Clinical Outcomes of Radical Surgery and Antimicrobial Agents in Vascular Pythiosis: A Multicenter Prospective Study
Authors: Torvorapanit Pattama , Chuleerarux Nipat , Plongla Rongpong , Worasilchai Navaporn , Manothummetha Kasama , Thongkam Achitpol , Langsiri Nattapong , Diewsurin Jaruwan , Kongsakpaisan Prasopchai , Bansong Ratiporn , Susaengrat Nuttapon , Wattanasoontornsakul Watchara , Chindamporn Ariya , Permpalung Nitipong
Published: February 2021

Vascular pythiosis is a rare, neglected, life-threatening disease with mortality of 100% in patients with incomplete surgical resection or patients with persistently elevated serum β-d-glucan (BDG). The study was conducted to understand the clinical outcomes of new treatment protocols and potential use of erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) as alternative monitoring tools, given recent favorable minimum inhibitory concentrations (MICs) of antibacterial agents and prohibitive cost of serum BDG in Thailand. A prospective cohort study of patients with vascular pythiosis was conducted between February 2019 and August 2020. After diagnosis, patients were followed at 0.5, 1, 1.5, 3, and 6 months. Descriptive statistics, Spearman’s correlation coefficient, and general linear model for longitudinal data were used. Amongst the cohort of ten vascular pythiosis patients, four had residual disease after surgery. Among four with residual disease, one developed disseminated disease and died, one developed relapse disease requiring surgery, and two were successfully managed with antimicrobial agents. The spearman’s correlation coefficients between BDG and ESR, and between BDG and CRP in patients without relapse or disseminated disease were 0.65 and 0.60, respectively. Tetracyclines and macrolides had most favorable minimum inhibitory concentrations and synergistic effects were observed in combinations of these two antibiotic classes. Adjunctive use of azithromycin and doxycycline preliminarily improved survival in vascular pythiosis patients with residual disease. Further studies are needed to understand the trends of ESR and CRP in this population.
Urban Development and Sustainable Mobility: A Spatial Analysis in the Buenos Aires Metropolitan Area
Authors: Mendiola Lorea , González Pilar
Published: February 2021

This study provides empirical evidence on the links between urban development factors and the use of specific modes of transport in commuting in the Buenos Aires metropolitan area. The case study is of interest because quantitative research on developing countries is scarce and their rapid urban growth and high rates of inequality may generate different results compared to the US or Europe. This relationship was assessed on locality level using regression methods. Spatial econometric techniques were applied to avoid unreliable inferences generated by spatial dependence and to detect the existence of externalities. Furthermore, we include in the model the socio-economic profile of each locality identified using cluster analysis. The findings reveal that population density affects motorised transport, that diversity is relevant for public transport and non-motorised trips, and urban design characteristics affect all modes of transport. Spatial dependence is detected for motorised transport, which may imply the existence of externalities, suggesting the need for coordinated decision-making processes on a metropolitan level. Finally, modal split depends on the socio-economic profile of a locality, which may influence the response to public transport policies. To sum up, these results may be useful when it comes to helping policymakers design integrated public policies on urban and transport planning.
Designing the Adaptive Landscape: Leapfrogging Stacked Vulnerabilities
Authors: Roggema Rob , Tillie Nico , Hollanders Matthijs
Published: February 2021

In the Anthropocene, climate impacts are expected to fundamentally change the way we live in, and plan and design for, our cities and landscapes. Long-term change and uncertainty require a long view, while current planning approaches and policy making are mostly short-term oriented and are therefore not well suited to respond adequately. The path-dependency it implies causes an irresolvable dilemma between short-term effect and long-term necessities. The objective of the research is to investigate an alternative planning and design approach which is able to overcome the current constraints and take a holistic long-term perspective. Therefore, the methods used in the study underpin a creative process of future visioning through backcasting and finding a dynamic equilibrium in the past as a primer for long-term climate adaptation. This way, the individual vulnerabilities of current sectoral policies can be leapfrogged and integrated into one intervention. This design-led method is applied to the northern landscape of the Groningen region in The Netherlands. This intervention is positioned as a re-dynamization of the landscape by re-establishing the exchange between the land and the sea. The findings in the study show that a long-term perspective on the future of the regional landscape increases climate adaptation and enriches the opportunities for viable agriculture, increased biodiversity, and a raised land that is not only protected against possible storm surges, but benefits from the sediments the sea brings. The economic analysis shows that a new perspective for farming within saline conditions is profitable on a fraction of the land, the biodiversity can be enriched by more than 75%, and the ground level of the landscape can be raised by one meter or more in the next 50–100 years. Moreover, the study shows how a long-term perspective can be implemented in logic stages that comply with the natural step-changes occurring in climate change.
Whither Magnetic Hyperthermia? A Tentative Roadmap
Authors: Rubia-Rodríguez Irene , Santana-Otero Antonio , Spassov Simo , Tombácz Etelka , Johansson Christer , De La Presa Patricia , Teran Francisco J. , Morales María del Puerto , Veintemillas-Verdaguer Sabino , Thanh Nguyen T. K. , Besenhard Maximilian O. , Wilhelm Claire , Gazeau Florence , Harmer Quentin , Mayes Eric , Manshian Bella B. , Soenen Stefaan J. , Gu Yuanyu , Millán Ángel , Efthimiadou Eleni K. , Gaudet Jeff , Goodwill Patrick , Mansfield James , Steinhoff Uwe , Wells James , Wiekhorst Frank , Ortega Daniel
Published: February 2021

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.
Physico-Chemical Investigation of Endodontic Sealers Exposed to Simulated Intracanal Heat Application: Hydraulic Calcium Silicate-Based Sealers
Authors: Donnermeyer David , Ibing Magdalena , Bürklein Sebastian , Weber Iris , Reitze Maximilian P. , Schäfer Edgar
Published: February 2021

The aim of this study was to gain information about the effect of thermal treatment of calcium silicate-based sealers. BioRoot RCS (BR), Total Fill BC Sealer (TFBC), and Total Fill BC Sealer HiFlow (TFHF) were exposed to thermal treatment at 37 °C, 47 °C, 57 °C, 67 °C, 77 °C, 87 °C and 97 °C for 30 s. Heat treatment at 97 °C was performed for 60 and 180 s to simulate inappropriate application of warm obturation techniques. Thereafter, specimens were cooled to 37 °C and physical properties (setting time/flow/film thickness according to ISO 6876) were evaluated. Chemical properties (Fourier-transform infrared spectroscopy) were assessed after incubation of the specimens in an incubator at 37 °C and 100% humidity for 8 weeks. Statistical analysis of physical properties was performed using the Kruskal-Wallis-Test (P = 0.05). The setting time, flow, and film thickness of TFBC and TFHF were not relevantly influenced by thermal treatment. Setting time of BR decreased slightly when temperature of heat application increased from 37 °C to 77 °C (P < 0.05). Further heat treatment of BR above 77 °C led to an immediate setting. FT-IR spectroscopy did not reveal any chemical changes for either sealers. Thermal treatment did not lead to any substantial chemical changes at all temperature levels, while physical properties of BR were compromised by heating. TFBC and TFHF can be considered suitable for warm obturation techniques.
Glass Transition Behavior of Wet Polymers
Authors: Li Hai , Xiao Rui
Published: February 2021

We have performed a systematical investigation on the glass transition behavior of amorphous polymers with different solvent concentrations. Acrylate-based amorphous polymers are synthesized and treated by isopropyl alcohol to obtain specimens with a homogenous solvent distribution. The small strain dynamic mechanical tests are then performed to obtain the glass transition behaviors. The results show that the wet polymers even with a solvent concentration of more than 60 wt.% still exhibit a glass transition behavior, with the glass transition region shifting to lower temperatures with increasing solvent concentrations. A master curve of modulus as a function of frequency can be constructed for all the polymer–solvent systems via the time–temperature superposition principle. The relaxation time and the breadth of the relaxation spectrum are then obtained through fitting the master curve using a fractional Zener model. The results indicate that the breadth of the relaxation spectrum has been greatly expanded in the presence of solvents, which has been rarely reported in the literature. Thus, this work can potentially advance the fundamental understanding of the effects of solvent on the glass transition behaviors of amorphous polymers.
The Plastic Deformation Mechanisms of hcp Single Crystals with Different Orientations: Molecular Dynamics Simulations
Authors: Ma Zhi-Chao , Tang Xiao-Zhi , Mao Yong , Guo Ya-Fang
Published: February 2021

The deformation mechanisms of Mg, Zr, and Ti single crystals with different orientations are systematically studied by using molecular dynamics simulations. The affecting factors for the plasticity of hexagonal close-packed (hcp) metals are investigated. The results show that the basal  dislocation, prismatic  dislocation, and pyramidal  dislocation are activated in Mg, Zr, and Ti single crystals. The prior slip system is determined by the combined effect of the Schmid factor and the critical resolved shear stresses (CRSS). Twinning plays a crucial role during plastic deformation since basal and prismatic slips are limited. The 101¯2 twinning is popularly observed in Mg, Zr, and Ti due to its low CRSS. The 101¯1 twin appears in Mg and Ti, but not in Zr because of the high CRSS. The stress-induced hcp-fcc phase transformation occurs in Ti, which is achieved by successive glide of Shockley partial dislocations on basal planes. More types of plastic deformation mechanisms (including the cross-slip, double twins, and hcp-fcc phase transformation) are activated in Ti than in Mg and Zr. Multiple deformation mechanisms coordinate with each other, resulting in the higher strength and good ductility of Ti. The simulation results agree well with the related experimental observation.
Experimental Studies on Fretting Wear Behavior of PVDF Piezoelectric Thin Films
Authors: Shu Yuanjie , Ke Liaoliang , Su Jie , Shen Fei
Published: February 2021

This paper discusses an in-depth experimental study on the fretting wear behavior of PVDF (polyvinylidene fluoride) piezoelectric thin film against a Si3N4 ceramic sphere under air conditions. A fretting wear device with a ball-on-plate contact configuration was applied. The changes of displacement amplitude, normal force, and applied voltage were taken into account. The friction logs were used to determine the contact state of the PVDF thin film during the fretting test. The 3D topography instrument and scanning electron microscope (SEM) were used to measure the details of the surface morphology and wear volume. The test results of PVDF thin films under different normal force, displacement amplitude, and applied voltage are summarized through the collection and analysis of experimental data. It is shown that the creep and plastic deformation lead to obvious winkles at the contact surface, which may decrease the specific wear rate of PVDF thin films.
A Collision Avoidance Strategy for Redundant Manipulators in Dynamically Variable Environments: On-Line Perturbations of Off-Line Generated Trajectories
Authors: Scoccia Cecilia , Palmieri Giacomo , Palpacelli Matteo Claudio , Callegari Massimo
Published: February 2021

In this work, a comprehensive control strategy for obstacle avoidance in redundant manipulation is presented, consisting of a combination of off-line path planning algorithms with on-line motion control. Path planning allows the avoidance of fixed obstacles detected before the start of the robot’s motion; it is based on the potential fields method combined with a smoothing process realized by means of interpolation with Bezier curves. The on-line motion control is designed to compensate for the motion of the obstacles and to avoid collisions along the kinematic chain of the manipulator; it is realized by means of a velocity control law based on the null space method for redundancy control. A new term is introduced in the control law to take into account the speed of the obstacles as well as their position. Simulations on a simplified planar case are presented to assess the validity of the algorithms and to estimate the computational effort in order to verify the transferability of our approach to a real system.
Non-Parametric Generalized Additive Models as a Tool for Evaluating Policy Interventions
Authors: Pinilla Jaime , Negrín Miguel
Published: February 2021

The interrupted time series analysis is a quasi-experimental design used to evaluate the effectiveness of an intervention. Segmented linear regression models have been the most used models to carry out this analysis. However, they assume a linear trend that may not be appropriate in many situations. In this paper, we show how generalized additive models (GAMs), a non-parametric regression-based method, can be useful to accommodate nonlinear trends. An analysis with simulated data is carried out to assess the performance of both models. Data were simulated from linear and non-linear (quadratic and cubic) functions. The results of this analysis show how GAMs improve on segmented linear regression models when the trend is non-linear, but they also show a good performance when the trend is linear. A real-life application where the impact of the 2012 Spanish cost-sharing reforms on pharmaceutical prescription is also analyzed. Seasonality and an indicator variable for the stockpiling effect are included as explanatory variables. The segmented linear regression model shows good fit of the data. However, the GAM concludes that the hypothesis of linear trend is rejected. The estimated level shift is similar for both models but the cumulative absolute effect on the number of prescriptions is lower in GAM.
A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis
Authors: Park Jeongho , Kim Hyun-Ouk , Park Kwang-Hyun , Wie Myung-Bok , Choi Sun-Eun , Yun Jang-Hyuk
Published: February 2021

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.
Sliding Water Droplet on Oil Impregnated Surface and Dust Particle Mitigation
Authors: Bahatab Saeed , Yilbas Bekir Sami , Abubakar Abba Abdulhamid , Hassan Ghassan , Mohammed Anwaruddin Siddiqui , Al-Qahtani Hussain , Sahin Ahmet Z. , Al-Sharafi Abdullah
Published: February 2021

Self-cleaning of surfaces becomes challenging for energy harvesting devices because of the requirements of high optical transmittance of device surfaces. Surface texturing towards hydrophobizing can improve the self-cleaning ability of surfaces, yet lowers the optical transmittance. Introducing optical matching fluid, such as silicon oil, over the hydrophobized surface improves the optical transmittance. However, self-cleaning ability, such as dust mitigation, of the oil-impregnated hydrophobic surfaces needs to be investigated. Hence, solution crystallization of the polycarbonate surface towards creating hydrophobic texture is considered and silicon oil impregnation of the crystallized surface is explored for improved optical transmittance and self-cleaning ability. The condition for silicon oil spreading over the solution treated surface is assessed and silicon oil and water infusions on the dust particles are evaluated. The movement of the water droplet over the silicon oil-impregnated sample is examined utilizing the high-speed facility and the tracker program. The effect of oil film thickness and the tilting angle of the surface on the sliding droplet velocity is estimated for two droplet volumes. The mechanism for the dust particle mitigation from the oil film surface by the sliding water droplet is analyzed. The findings reveal that silicon oil impregnation of the crystallized sample surface improves the optical transmittance significantly. The sliding velocity of the water droplet over the thick film (~700 µm) remains higher than that of the small thickness oil film (~50 µm), which is attributed to the large interfacial resistance created between the moving droplet and the oil on the crystallized surface. The environmental dust particles can be mitigated from the oil film surface by the sliding water droplet. The droplet fluid infusion over the dust particle enables to reorient the particle inside the droplet fluid. As the dust particle settles at the trailing edge of the droplet, the sliding velocity decays on the oil-impregnated sample.
Impact of Lignocellulose Pretreatment By-Products on S. cerevisiae Strain Ethanol Red Metabolism during Aerobic and An-aerobic Growth
Authors: Kłosowski Grzegorz , Mikulski Dawid
Published: February 2021

Understanding the specific response of yeast cells to environmental stress factors is the starting point for selecting the conditions of adaptive culture in order to obtain a yeast line with increased resistance to a given stress factor. The aim of the study was to evaluate the specific cellular response of Saccharomyces cerevisiae strain Ethanol Red to stress caused by toxic by-products generated during the pretreatment of lignocellulose, such as levulinic acid, 5-hydroxymethylfurfural, furfural, ferulic acid, syringaldehyde and vanillin. The presence of 5-hydroxymethylfurfural at the highest analyzed concentration (5704.8 ± 249.3 mg/L) under aerobic conditions induced the overproduction of ergosterol and trehalose. On the other hand, under anaerobic conditions (during the alcoholic fermentation), a decrease in the biosynthesis of these environmental stress indicators was observed. The tested yeast strain was able to completely metabolize 5-hydroxymethylfurfural, furfural, syringaldehyde and vanillin, both under aerobic and anaerobic conditions. Yeast cells reacted to the presence of furan aldehydes by overproducing Hsp60 involved in the control of intracellular protein folding. The results may be helpful in optimizing the process parameters of second-generation ethanol production, in order to reduce the formation and toxic effects of fermentation inhibitors.
The Mechanism of Honey in Reversing Metabolic Syndrome
Authors: Hashim Khairun-Nisa , Chin Kok-Yong , Ahmad Fairus
Published: February 2021

Metabolic syndrome is a constellation of five risk factors comprising central obesity, hyperglycaemia, dyslipidaemia, and hypertension, which predispose a person to cardiometabolic diseases. Many studies reported the beneficial effects of honey in reversing metabolic syndrome through its antiobesity, hypoglycaemic, hypolipidaemic, and hypotensive actions. This review aims to provide an overview of the mechanism of honey in reversing metabolic syndrome. The therapeutic effects of honey largely depend on the antioxidant and anti-inflammatory properties of its polyphenol and flavonoid contents. Polyphenols, such as caffeic acid, p-coumaric acid, and gallic acid, are some of the phenolic acids known to have antiobesity and antihyperlipidaemic properties. They could inhibit the gene expression of sterol regulatory element-binding transcription factor 1 and its target lipogenic enzyme, fatty acid synthase (FAS). Meanwhile, caffeic acid and quercetin in honey are also known to reduce body weight and fat mass. In addition, fructooligosaccharides in honey are also known to alter lipid metabolism by reducing FAS activity. The fructose and phenolic acids might contribute to the hypoglycaemic properties of honey through the phosphatidylinositol 3-kinase/protein kinase B insulin signalling pathway. Honey can increase the expression of Akt and decrease the expression of nuclear factor-kappa B. Quercetin, a component of honey, can improve vasodilation by enhancing nitric oxide production via endothelial nitric oxide synthase and stimulate calcium-activated potassium channels. In conclusion, honey can be used as a functional food or adjuvant therapy to prevent and manage metabolic syndrome.