bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose-Oxygen Biofuel Cell with Biotic and Abiotic Catalysts: Experimental Research and Mathematical Modeling
Authors: Vasilenko Violetta , Arkadeva Irina , Bogdanovskaya Vera , Sudarev George , Kalenov Sergei , Vocciante Marco , Koltsova Eleonora
Published: October 2020

The demand for alternative sources of clean, sustainable, and renewable energy has been a focus of research around the world for the past few decades. Microbial/enzymatic biofuel cells are one of the popular technologies for generating electricity from organic substrates. Currently, one of the promising fuel options is based on glucose due to its multiple advantages: high energy intensity, environmental friendliness, low cost, etc. The effectiveness of biofuel cells is largely determined by the activity of biocatalytic systems applied to accelerate electrode reactions. For this work with aerobic granular sludge as a basis, a nitrogen-fixing community of microorganisms has been selected. The microorganisms were immobilized on a carbon material (graphite foam, carbon nanotubes). The bioanode was developed from a selected biological material. A membraneless biofuel cell glucose/oxygen, with abiotic metal catalysts and biocatalysts based on a microorganism community and enzymes, has been developed. Using methods of laboratory electrochemical studies and mathematical modeling, the physicochemical phenomena and processes occurring in the cell has been studied. The mathematical model includes equations for the kinetics of electrochemical reactions and the growth of microbiological population, the material balance of the components, and charge balance. The results of calculations of the distribution of component concentrations over the thickness of the active layer and over time are presented. The data obtained from the model calculations correspond to the experimental ones. Optimization for fuel concentration has been carried out.
Optimal ESS Scheduling for Peak Shaving of Building Energy Using Accuracy-Enhanced Load Forecast
Authors: Hwang Jin Sol , Rosyiana Fitri Ismi , Kim Jung-Su , Song Hwachang
Published: October 2020

This paper proposes an optimal Energy Storage System (ESS) scheduling algorithm Building Energy Management System (BEMS). In particular, the focus is placed on how to reduce the peak load using ESS and load forecast. To this end, first, an existing deep learning-based load forecast method is applied to a real building energy prediction and it is shown that the deep learning-based method leads to an accuracy-enhanced load forecast. Second, an optimization problem is formulated in order to devise an ESS scheduling. In the optimization problem, the objective function and constraints are defined such that the peak load is reduced; the cost for electricity is minimized; and the ESS’s lifetime is elongated considering the accuracy-enhanced load forecast, real-time electricity price, and the state-of-charge of the ESS. For the purpose of demonstrating the effectiveness of the proposed ESS scheduling method, it is implemented using a real building load power and temperature data. The simulation results show that the proposed method can reduce the peak load and results in smooth charging and discharging, which is important for the ESS lifetime.
Multiple Ecological Drivers Determining Vegetation Attributes across Scales in a Mountainous Dry Valley, Southwest China
Authors: Yang Jie , El-Kassaby Yousry A. , Guan Wenbin
Published: October 2020

Identifying the ecological processes determining spatial variation in community composition and structure is a central issue in arid areas, especially in the face of climate change. This study aims to estimate how environmental and spatial processes jointly determine vegetation attributes across scales in the Min dry valley, one of the dry valleys in Hengduan Mountainous region suffering severe ecological degradation. A total of 48 plots along slope transects were investigated at three sites along the dry valley, with vegetation and environmental information gathered. Distance-based Moran’s eigenvector maps (dbMEM) was used to extract local spatial variables, while geographic coordinates were used as regional spatial variables. We used redundancy analysis (RDA) and variation partitioning to detect the relative importance of environmental and spatial processes in influencing community composition and vegetation structure (including biomass, coverage, height, density, α and β diversity), and to identify the most determinant environmental variables at different spatial scales. Results showed that both environmental and spatial processes accounted for significant and comparable variations in both vegetation composition and structure. Local spatial variables provided significant and comparable contribution as regional spatial variables to vegetation composition, while provided more contribution than regional spatial variables to vegetation structure. Topography had an overriding effect relative to soil on both vegetation composition and structure. Multi-scale analyses showed elevation was the most important variable (associated with soil moisture and nutrient) at the regional scale; while microtopography, especially slope aspect and shape, dominated at the local scale. We also demonstrated how vegetation composition and structure varied along environmental gradients. The study revealed the overriding role of topography in determining vegetation attributes in this mountainous dry valley, highlighting the advantage of multi-scale spatial analysis for better understanding spatial variation in vegetation pattern and with their important implications for biodiversity conservation and ecological management in the arid mountain areas.
Browser Forensic Investigations of WhatsApp Web Utilizing IndexedDB Persistent Storage
Authors: Paligu Furkan , Varol Cihan
Published: October 2020

Digital Evidence is becoming an indispensable factor in most legal cases. However, technological advancements that lead to artifact complexity, are forcing investigators to create sophisticated connections between the findings and the suspects for admissibility of evidence in court. This paper scrutinizes whether IndexedDB, an emerging browser technology, can be a source of digital evidence to provide additional and correlating support for traditional investigation methods. It particularly focuses on the artifacts of the worldwide popular application, WhatsApp. A single case pretest–posttest quasi experiment is applied with WhatsApp Messenger and Web Application to populate and investigate artifacts in IndexedDB storage of Google Chrome. The findings are characterized and presented with their potential to be utilized in forensic investigation verifications. The storage locations of the artifacts are laid out and operations of extraction, conversion and presentation are systematized. Additionally, a proof of concept tool is developed for demonstration. The results show that WhatsApp Web IndexedDB storage can be employed for time frame analysis, demonstrating its value in evidence verification.
Multi-Morbidity and Polypharmacy in Older People: Challenges and Opportunities for Clinical Practice
Authors: Aggarwal Pritti , Woolford Stephen J. , Patel Harnish P.
Published: October 2020

Multi-morbidity and polypharmacy are common in older people and pose a challenge for health and social care systems, especially in the context of global population ageing. They are complex and interrelated concepts in the care of older people that require early detection and patient-centred shared decision making underpinned by multi-disciplinary team-led comprehensive geriatric assessment (CGA) across all health and social care settings. Personalised care plans need to remain responsive and adaptable to the needs and wishes of the patient, enabling the individual to maintain their independence. In this review, we aim to give an up-to-date account of the recognition and management of multi-morbidity and polypharmacy in the older person.
The “Irish” Female Servant in Valerie Martin’s Mary Reilly and Elaine Bergstrom’s Blood to Blood
Authors: Downey Dara
Published: October 2020

This article examines two neo-Victorian novels by American writers—Valerie Martin’s Mary Reilly (1990) and Elaine Bergstrom’s Blood to Blood (2000)—which “write back” to Robert Louis Stevenson’s Strange Case of Dr Jekyll and Mr Hyde (1886) and Bram Stoker’s Dracula (1897), respectively. Both novels ostensibly critique the socio-cultural inequalities of Victorian London, particularly for women, immigrants, and the working class, and the gender and class politics and structures of the original texts. However, as this article demonstrates, the presence of invented Irish female servants as key figures in these “re-visionary” narratives also undermines some aspects of this critique. Despite acting as gothic heroines, figures who traditionally uncover patriarchal abuses, these servant characters also facilitate their employers’ lives and negotiations of the supernatural (with varying degrees of success), while also themselves becoming associated with gothic monstrosity, via their extended associations with Irish-Catholic violence and barbarity on both sides of the Atlantic. This article therefore argues that Irish servant figures in neo-Victorian texts by American writers function as complex signifiers of pastness and barbarity, but also of assimilation and progressive modernization. Indeed, the more “Irish” the servant, the better equipped she will be to help her employer navigate the world of the supernatural.
Fast Response to Superspreading: Uncertainty and Complexity in the Context of COVID-19
Authors: Zenk Lukas , Steiner Gerald , Pina e Cunha Miguel , Laubichler Manfred D. , Bertau Martin , Kainz Martin J. , Jäger Carlo , Schernhammer Eva S.
Published: October 2020

Although the first coronavirus disease 2019 (COVID-19) wave has peaked with the second wave underway, the world is still struggling to manage potential systemic risks and unpredictability of the pandemic. A particular challenge is the “superspreading” of the virus, which starts abruptly, is difficult to predict, and can quickly escalate into medical and socio-economic emergencies that contribute to long-lasting crises challenging our current ways of life. In these uncertain times, organizations and societies worldwide are faced with the need to develop appropriate strategies and intervention portfolios that require fast understanding of the complex interdependencies in our world and rapid, flexible action to contain the spread of the virus as quickly as possible, thus preventing further disastrous consequences of the pandemic. We integrate perspectives from systems sciences, epidemiology, biology, social networks, and organizational research in the context of the superspreading phenomenon to understand the complex system of COVID-19 pandemic and develop suggestions for interventions aimed at rapid responses.
Chronic Severe Sleep Problems among Non-Nordic Immigrants. Data from a Population Postal Survey in Mid-Sweden
Authors: Löfvander Monica , Beckman Linda , von Kobyletzki Laura
Published: October 2020

Sweden has a large population of both recent and established immigrants with high prevalence of risk factors for ill health. Here, we aimed to explore the prevalence of chronic severe sleep problems (CSSP) among non-Nordic-born persons, and to evaluate the risk for CSSP when fully adjusted for covariates. Our additional hypothesis was that lengthier time since immigration would reduce the risk for CSSP. We used data from a large-population postal survey covering life and health issues among inhabitants in mid-Sweden. Relationship between different countries of birth and CSSP was assessed in logistic analyses for more severe and longstanding pain, sex, employment, mental disability, gastrointestinal problems, and length of stay (short, middle time, and up to ten years of stay). Persons of non-Nordic birth reported significantly more often CSSP, regardless of short or long-term stay. Our findings indicate that non-Nordic birth, regardless of residence time and covariates, was an independent and significant predictor for CSSP. The findings may contribute to increasing awareness in healthcare personnel to recognize chronic sleep problems among immigrant patients. Thus, our study might contribute to developing strategies to enhance health for minorities.
Exploring the Psychological Effects of Optimism on Life Satisfaction in Students: The Mediating Role of Goal Orientations
Authors: Usán Supervía Pablo , Salavera Bordás Carlos , Murillo Lorente Víctor
Published: October 2020

Subjective wellbeing is a current issue today. Various variables affect subjective wellbeing during adolescence: a crucial stage in the life of the individual. This study focuses on analysing the relationship between academic goal orientation, optimism and life satisfaction in adolescent students, as well as the possible mediating role of the goal orientation (task and ego) in the relationship between optimism and life satisfaction in adolescents. Methods: The sample comprises 1602 students (male N = 871; 54.36% and female N = 731; 45.63%) from nine secondary schools. The instruments used were the Life Orientation Test Revised (LOT-R), the Perception of Success Questionnaire (POSQ) and the Satisfaction With Life Scale (SWLS) questionnaire. Results: The results of the study reveal significant correlations between optimism-related variables, goal orientation and life satisfaction. In addition, goal orientation was found to have a positive mediating role on optimism and life satisfaction. Conclusion: The study shows the importance of promoting adaptive behaviours in goal orientation in adolescents, leading to optimal levels on variables such as optimism and life satisfaction, which in turn improve the individual’s psychological development and academic performance.
Racial Disparities in Hypertension Prevalence within US Gentrifying Neighborhoods
Authors: Smith Genee S. , McCleary Rachael R. , Thorpe Roland J.
Published: October 2020

Racial disparities in hypertension remain a persistent public health concern in the US. While several studies report Black–White differences in the health impacts of gentrification, little is known concerning the impact of living in a gentrifying neighborhood on hypertension disparities. Data from the American Community Survey were used to identify gentrifying neighborhoods across the US from 2006 to 2017. Health and demographic data were obtained for non-Hispanic Black and White respondents of the 2014 Medical Expenditure Panel Survey (MEPS) residing in gentrifying neighborhoods. Modified Poisson models were used to determine whether there is a difference in the prevalence of hypertension of individuals by their race/ethnicity for those that live in gentrifying neighborhoods across the US. When compared to Whites living within gentrifying neighborhoods, Blacks living within gentrifying neighborhoods had a similar prevalence of hypertension. The non-existence of Black–White hypertension disparities within US gentrifying neighborhoods underscores the impact of neighborhood environment on race differences in hypertension.
Fisher’s Linear Discriminant Function Analysis and its Potential Utility as a Tool for the Assessment of Health-and-Wellness Programs in Indigenous Communities
Authors: Liberda Eric N. , Zuk Aleksandra M. , Martin Ian D. , Tsuji Leonard J. S.
Published: October 2020

Diabetes mellitus is a growing public health problem affecting persons in both developed and developing nations. The prevalence of type 2 diabetes mellitus (T2DM) is reported to be several times higher among Indigenous populations compared to their non-Indigenous counterparts. Discriminant function analysis (DFA) is a potential tool that can be used to quantitatively evaluate the effectiveness of Indigenous health-and-wellness programs (e.g., on-the-land programs, T2DM interventions), by creating a type of pre-and-post-program scoring system. As the communities of the Eeyou Istchee territory, subarctic Quebec, Canada, have varying degrees of isolation, we derived a DFA tool for point-of-contact evaluations to aid in monitoring and assessment of health-and-wellness programs in rural and remote locations. We developed several DFA models to discriminate between those with and without T2DM status using age, fasting blood glucose, body mass index, waist girth, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, and total cholesterol in participants from the Eeyou Istchee. The models showed a ~97% specificity (i.e., true positives for non-T2DM) in classification. This study highlights how varying risk factor models can be used to discriminate those without T2DM with high specificity among James Bay Cree communities in Canada.
Validation of a Cell-Based Assay for Detection of Active Shiga Toxins Produced by Escherichia coli in Water
Authors: Hughes Anna C. , Patfield Stephanie , Rasooly Reuven , He Xiaohua
Published: October 2020

Shiga toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases, including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Almost 5% of STEC infections result from waterborne exposures, yet there is no test listed in the EPA’s current Selected Analytical Methods for the detection of active Shiga toxins (Stxs) in water. In this study, a HeLa cell-based assay is validated for the detection of metabolically active Stxs produced by STEC in water, including tap, bottled, and pond water. Active Stxs are detected even when the number of Stx-producing bacteria is less than 0.4 CFU/mL and the assay performance is not affected by background flora or chlorine in the water. This assay is not only as simple and affordable as cell-free assays but also detects active holotoxins without the use of live animals. In addition, the assay is designed for use in multi-well formats, making it ideal for high-throughput screening of water samples and therefore useful for environmental public health surveillance programs to reduce human risk of infection with STEC.
Firefighter Overexertion: A Continuing Problem Found in an Analysis of Non-Fatal Injury Among Career Firefighters
Authors: B. Le Aurora , McNulty Lily A. , Dyal Mari-Amanda , DeJoy David M. , Smith Todd D.
Published: October 2020

Traditionally, safety-related research on firefighting has focused on fires and fireground smoke as the primary source of non-fatal firefighter injury. However, recent research has found that overexertion and musculoskeletal disorders may be the primary source of firefighter injury. This study aimed to provide an update on injury occurrence among career firefighters. Injury data were collected over a two-year period from two large metropolitan fire departments in the U.S. Injury data were categorized based on the Bureau of Labor Statistics’ Occupational Injury and Illness Classification System. Cross-tabulations and Chi-square tests were used to determine the primary causes of injury, as well as the injury region. Between the two fire departments, there were 914 firefighters included in the analysis. The median age was 40.7 years old with those aged 40–49 as the largest age group for injury cases (38.3%). The most frequently reported cause of injury was ‘overexertion and bodily reaction’ (n = 494; 54.1%). The most reported injury region was in ‘multiple body parts’ (n = 331; 36.3%). To prevent subsequent musculoskeletal disorders that may arise due to overexertion, initiatives that promote enhanced fitness and ergonomics based on an analysis of the physical demands of firefighting are suggested.
Life Cycle Sustainability Performance Assessment Method for Comparison of Civil Engineering Works Design Concepts: Case Study of a Bridge
Authors: Ek Kristine , Mathern Alexandre , Rempling Rasmus , Brinkhoff Petra , Karlsson Mats , Norin Malin
Published: October 2020

Standardized and transparent life cycle sustainability performance assessment methods are essential for improving the sustainability of civil engineering works. The purpose of this paper is to demonstrate the potential of using a life cycle sustainability assessment method in a road bridge case study. The method is in line with requirements of relevant standards, uses life cycle assessment, life cycle costs and incomes, and environmental externalities, and applies normalization and weighting of indicators. The case study involves a short-span bridge in a design-build infrastructure project, which was selected for its generality. Two bridge design concepts are assessed and compared: a concrete slab frame bridge and a soil-steel composite bridge. Data available in the contractor’s tender phase are used. The two primary aims of this study are (1) to analyse the practical application potential of the method in carrying out transparent sustainability assessments of design concepts in the early planning and design stages, and (2) to examine the results obtained in the case study to identify indicators in different life cycle stages and elements of the civil engineering works project with the largest impacts on sustainability. The results show that the method facilitates comparisons of the life cycle sustainability performance of design concepts at the indicator and construction element levels, enabling better-informed and more impartial design decisions to be made.
Loneliness and Social Engagement in Older Adults Based in Lombardy during the COVID-19 Lockdown: The Long-Term Effects of a Course on Social Networking Sites Use
Authors: Rolandi Elena , Vaccaro Roberta , Abbondanza Simona , Casanova Georgia , Pettinato Laura , Colombo Mauro , Guaita Antonio
Published: October 2020

Older adults are less familiar with communication technology, which became essential to maintain social contacts during the COVID-19 lockdown. The present study aimed at exploring how older adults, previously trained for Social Networking Sites (SNSs) use, experienced the lockdown period. In the first two weeks of May 2020, telephone surveys were conducted with individuals aged 81–85 years and resident in Abbiategrasso (Milan), who previously participated in a study aimed at evaluating the impact of SNSs use on loneliness in old age (ClinicalTrials.gov, NCT04242628). We collected information on SNSs use, self-perceived loneliness, and social engagement with family and friends. Interviewed participants were stratified as trained (N = 60) and untrained (N = 70) for SNSs use, based on their attendance to group courses held the previous year as part of the main experimental study. The groups were comparable for sociodemographics and clinical features. Participants trained for SNSs use reported significantly higher usage of SNSs and reduced feeling of being left out. Compared to pre-lockdown levels, individuals trained for SNSs use showed a lighter reduction in social contacts. These findings support the utility of training older adults for SNSs use in order to improve their social inclusion, even in extreme conditions of self-isolation and perceived vulnerability.
Exploring Similarities and Differences of Non-European Migrants among Forensic Patients with Schizophrenia
Authors: Huber David A. , Lau Steffen , Sonnweber Martina , Günther Moritz P. , Kirchebner Johannes
Published: October 2020

Migrants diagnosed with schizophrenia are overrepresented in forensic-psychiatric clinics. A comprehensive characterization of this offender subgroup remains to be conducted. The present exploratory study aims at closing this research gap. In a sample of 370 inpatients with schizophrenia spectrum disorders who were detained in a Swiss forensic-psychiatric clinic, 653 different variables were analyzed to identify possible differences between native Europeans and non-European migrants. The exploratory data analysis was conducted by means of supervised machine learning. In order to minimize the multiple testing problem, the detected group differences were cross-validated by applying six different machine learning algorithms on the data set. Subsequently, the variables identified as most influential were used for machine learning algorithm building and evaluation. The combination of two childhood-related factors and three therapy-related factors allowed to differentiate native Europeans and non-European migrants with an accuracy of 74.5% and a predictive power of AUC = 0.75 (area under the curve). The AUC could not be enhanced by any of the investigated criminal history factors or psychiatric history factors. Overall, it was found that the migrant subgroup was quite similar to the rest of offender patients with schizophrenia, which may help to reduce the stigmatization of migrants in forensic-psychiatric clinics. Some of the predictor variables identified may serve as starting points for studies aimed at developing crime prevention approaches in the community setting and risk management strategies tailored to subgroups of offenders with schizophrenia.
Population, Income, and Farmland Pricing in an Open Economy
Authors: Dong Huijian , Guo Xiaomin
Published: October 2020

Farmland valuation models usually incorporate local purchasing power as one of the pricing factors. A plausible rationale is that a larger population and higher income per capita imply increasing demand for agricultural products and farmland. In this paper, we study the relationship between the agricultural land prices, the regional population, and income per capita in an open economy setting in nominal and real variable terms using data from 1929 to 2018 at the state level. We show that in most areas of the United States, agricultural land prices are less affected by the state population or personal income. The valuation of agricultural land should not factor in the local purchasing power factors, with a few exceptions.
Cyclic Peptide-Based Biologics Regulating HGF-MET
Authors: Sato Hiroki , Imamura Ryu , Suga Hiroaki , Matsumoto Kunio , Sakai Katsuya
Published: October 2020

Using a random non-standard peptide integrated discovery system, we obtained cyclic peptides that bind to hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor. (MET) HGF-inhibitory peptide-8 (HiP-8) selectively bound to two-chain active HGF, but not to single-chain precursor HGF. HGF showed a dynamic change in its molecular shape in atomic force microscopy, but HiP-8 inhibited dynamic change in the molecular shape into a static status. The inhibition of the molecular dynamics of HGF by HiP-8 was associated with the loss of the ability to bind MET. HiP-8 could selectively detect active HGF in cancer tissues, and active HGF probed by HiP-8 showed co-localization with activated MET. Using HiP-8, cancer tissues with active HGF could be detected by positron emission tomography. HiP-8 seems to be applicable for the diagnosis and treatment of cancers. In contrast, based on the receptor dimerization as an essential process for activation, the cross-linking of the cyclic peptides that bind to the extracellular region of MET successfully generated an artificial ligand to MET. The synthetic MET agonists activated MET and exhibited biological activities which were indistinguishable from the effects of HGF. MET agonists composed of cyclic peptides can be manufactured by chemical synthesis but not recombinant protein expression, and thus are expected to be new biologics that are applicable to therapeutics and regenerative medicine.
Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology
Authors: Zubor Pavol , Wang Yun , Liskova Alena , Samec Marek , Koklesova Lenka , Dankova Zuzana , Dørum Anne , Kajo Karol , Dvorska Dana , Lucansky Vincent , Malicherova Bibiana , Kasubova Ivana , Bujnak Jan , Mlyncek Milos , Dussan Carlos Alberto , Kubatka Peter , Büsselberg Dietrich , Golubnitschaja Olga
Published: October 2020

Vulvar cancer (VC) is a specific form of malignancy accounting for 5–6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as “plasma medicine” and “plasma oncology”. This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered.
No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice
Authors: Misof Barbara M. , Blouin Stéphane , Hofstaetter Jochen G. , Roschger Paul , Zwerina Jochen , Erben Reinhold G.
Published: October 2020

Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (−9.5%, p < 0.05 after two months and −10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.
Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton’s Tyrosine Kinase
Authors: Lee Eun , Cho Hyewon , Lee Da Kyung , Ha JuHyun , Choi Byeong Jo , Jeong Ji Hye , Ryu Jae-Ha , Kang Jong Soon , Jeon Raok
Published: October 2020

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton’s tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481. In this article, we have described the structure–activity relationships (SARs) leading to a novel series of potent and selective piperazine and tetrahydroisoquinoline linked 5-phenoxy-2-aminopyridine irreversible inhibitors of BTK. Compound 18g showed good potency and selectivity, and its biological activity was evaluated in hematological tumor cell lines. The in vivo efficacy of 18g was also tested in a Raji xenograft mouse model, and it significantly reduced tumor size, with 46.8% inhibition compared with vehicle. Therefore, we have presented the novel, potent, and selective irreversible inhibitor 18g as a type II BTK inhibitor.
Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake
Authors: Sabourian Parinaz , Yazdani Ghazaleh , Ashraf Seyed Sajad , Frounchi Masoud , Mashayekhan Shohreh , Kiani Sahar , Kakkar Ashok
Published: October 2020

Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle–cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure–property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake.
Photobiomodulation of the Visual System and Human Health
Authors: Buch John , Hammond Billy
Published: October 2020

Humans express an expansive and detailed response to wavelength differences within the electromagnetic (EM) spectrum. This is most clearly manifest, and most studied, with respect to a relatively small range of electromagnetic radiation that includes the visible wavelengths with abutting ultraviolet and infrared, and mostly with respect to the visual system. Many aspects of our biology, however, respond to wavelength differences over a wide range of the EM spectrum. Further, humans are now exposed to a variety of modern lighting situations that has, effectively, increased our exposure to wavelengths that were once likely minimal (e.g., “blue” light from devices at night). This paper reviews some of those biological effects with a focus on visual function and to a lesser extent, other body systems.
Co-Culture of Primary Human Coronary Artery and Internal Thoracic Artery Endothelial Cells Results in Mutually Beneficial Paracrine Interactions
Authors: Shishkova Daria , Markova Victoria , Sinitsky Maxim , Tsepokina Anna , Frolov Alexey , Zagorodnikov Nikita , Bogdanov Leo , Kutikhin Anton
Published: October 2020

Although saphenous veins (SVs) are commonly used as conduits for coronary artery bypass grafting (CABG), internal thoracic artery (ITA) grafts have significantly higher long-term patency. As SVs and ITA endothelial cells (ECs) have a considerable level of heterogeneity, we suggested that synergistic paracrine interactions between CA and ITA ECs (HCAECs and HITAECs, respectively) may explain the increased resistance of ITA grafts and adjacent CAs to atherosclerosis and restenosis. In this study, we measured the gene and protein expression of the molecules responsible for endothelial homeostasis, pro-inflammatory response, and endothelial-to-mesenchymal transition in HCAECs co-cultured with either HITAECs or SV ECs (HSaVECs) for an ascending duration. Upon the co-culture, HCAECs and HITAECs showed augmented expression of endothelial nitric oxide synthase (eNOS) and reduced expression of endothelial-to-mesenchymal transition transcription factors Snail and Slug when compared to the HCAEC–HSaVEC model. HCAECs co-cultured with HITAECs demonstrated an upregulation of HES1, a master regulator of arterial specification, of which the expression was also exclusively induced in HSaVECs co-cultured with HCAECs, suggestive of their arterialisation. In addition, co-culture of HCAECs and HITAECs promoted the release of pro-angiogenic molecules. To conclude, co-culture of HCAECs and HITAECs results in reciprocal and beneficial paracrine interactions that might contribute to the better performance of ITA grafts upon CABG.
Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation
Authors: Hwang Soonjae , Yi Hye Chin , Hwang Samnoh , Jo Minjeong , Rhee Ki-Jong
Published: October 2020

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic Bacteroides fragilis (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the Bacteroides fragilis toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.
Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease
Authors: Gracia Pablo , Camino José D. , Volpicelli-Daley Laura , Cremades Nunilo
Published: October 2020

α-Synuclein amyloid aggregation is a defining molecular feature of Parkinson’s disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer’s disease. The process of α-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of α-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of α-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct α-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases.
Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells
Authors: Oh Jung Hwan , Karadeniz Fatih , Seo Youngwan , Kong Chang-Suk
Published: October 2020

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.
Effect of the Cationic Head Group on Cationic Surfactant-Based Surfactant Mediated Gelation (SMG)
Authors: Aramaki Kenji , Takimoto Eriko , Yamaguchi Takumi
Published: October 2020

The surfactant-mediated gelation (SMG) method allows us to formulate hydrogels using a water-insoluble organogelator. In this study, we formulated hydrogels using three cationic surfactants, hexadecyltrimethylammonium bromide (CTAB), hexadecyltrimethylammonium chloride (CTAC), and hexadecylpyridinium chloride (CPC)] and an organogelator (12-hydroxyoctadecanoic acid (12-HOA), and studied their structures and mechanical properties. A fiber-like structure similar to that found in the 12-HOA-based organogels was observed by optical microscopy. Small- and wide-angle X-ray scattering profiles showed Bragg peaks derived from the long- and short-spacing of the crystalline structures in the gel fibers and a correlation peak from the surfactant micelles in the small-angle region. Furthermore, the formation of micelles in the hydrogels was confirmed by UV-vis spectroscopic measurements of the gel samples in the presence of Rhodamine 6G. We concluded that the hydrogels prepared by the SMG method in the present systems are orthogonal molecular assembled systems in which two different molecular assembled structures coexist. Among the three surfactant systems, the CTAB system presented the lowest critical gelation concentration and highest sol-gel transition temperature and viscoelasticity. These differences in gel fiber formation and gel properties were discussed from the viewpoint of the degree of solubilization of the gelator molecules in micelles coexisting with gel fibers and diffusion of the gelator molecules in the gel formation process.
Advanced Numerical Method for Determining the Wetted Area of Container Ships for Increased Estimation Accuracy of Copper Biocide Emissions
Authors: Ivče Renato , Bakota Mario , Kos Serdjo , Brčić David
Published: October 2020

Research into the consequences of the accumulation of copper biocides in the marine environment has intensified since the ban on the use of organotin tributyltin (TBT) and the introduction of copper-based compounds in antifouling (AF) coatings. The specific emission of copper biocides and the surface of the wetted area of a vessel are the key parameters for the estimation of biocide emission. The estimated values of specific emissions of copper biocides should be taken with caution and their limitations and suitability for various surfaces and types of vessel should be known. Baseline limitations are also present in determining vessels’ wetted area. The available models do not provide realistic values, allowing multiple deviations. The proposed method of determining the wetted area considering container vessels and the specifics of their forms results in a set of hydrostatic diagrams that enable much more accurate estimation. The use of Automatic Identification System (AIS) is also proposed in terms of independent collection of required calculation parameters, enabling a full assessment of the total emission of copper biocides from container ships in the observed area.
How Important Are Resistance, Dispersal Ability, Population Density and Mortality in Temporally Dynamic Simulations of Population Connectivity? A Case Study of Tigers in Southeast Asia
Authors: Ash Eric , Cushman Samuel A. , Macdonald David W. , Redford Tim , Kaszta Żaneta
Published: October 2020

Development of landscape connectivity and spatial population models is challenging, given the uncertainty of parameters and the sensitivity of models to factors and their interactions over time. Using spatially and temporally explicit simulations, we evaluate the sensitivity of population distribution, abundance and connectivity of tigers in Southeast Asia to variations of resistance surface, dispersal ability, population density and mortality. Utilizing a temporally dynamic cumulative resistant kernel approach, we tested (1) effects and interactions of parameters on predicted population size, distribution and connectivity, and (2) displacement and divergence in scenarios across timesteps. We evaluated the effect of varying levels of factors on simulated population, cumulative resistance kernel extent, and kernel sum across nine timesteps, producing 24,300 simulations. We demonstrate that predicted population, range shifts, and landscape connectivity are highly sensitive to parameter values with significant interactions and relative strength of effects varying by timestep. Dispersal ability, mortality risk and their interaction dominated predictions. Further, population density had intermediate effects, landscape resistance had relatively low impacts, and mitigation of linear barriers (highways) via lowered resistance had little relative effect. Results are relevant to regional, long-term tiger population management, providing insight into potential population growth and range expansion across a landscape of global conservation priority.