bluuebunny/crossref_metadata_2025 huggingface dataset:
Розрахунок на температурні впливи монолітного залізобетонного каркасу багатоповерхової будівлі на усіх стадіях зведення та експлуатації
Authors: Gurkivskyi O.B. , Bolotov A.Yu.
Published: May 2020

У багатоповерхових будівлях, побудованих раніше, температурні впливи не мали значного впливу, так як при великій масі зовнішніх і внутрішніх конструкцій і при практично постійних внутрішніх температурах не існувало проблеми різниці подовження елементів. Ситуація значно ускладнюється для сучасних багатоповерхових будівель із статично невизначеними конструкціями значних розмірів. До внутрішніх конструкцій кріпляться конструкції зовнішнього огородження, будівлі мають велику висоту і т.п. В результаті виникає необхідність врахування температурних впливів. При проектуванні будинків треба обов'язково враховувати кліматичні температурні впливи, експлуатаційні теплові впливи, які необхідно нейтралізувати насамперед ізоляцією джерел виділення тепла і прилеглих конструкцій. Різниця температур залежить від функціонального призначення будівлі, його місця розташування, орієнтації по відношенню до країн світу, внутрішнього температурного режиму, поверхні і опорядження огороджувальних та несучих конструкцій. Але найбільш вразливі конструкції при температурному впливі під час зведення будівель. Це обумовлено змінами температури повітря, в яких є цілком закономірні періодичні коливання з річним і добовим періодом. На періодичні коливання накладаються випадкові коливання, пов'язані зі зміною погоди на невеликих відрізках часу (кілька днів). На даний час існує достатня кількість розрахункових інструментів щодо врахування температурного впливу при конструюванні будівель. Основною ж складністю у розрахунках є опис розрахункових ситуацій, що відповідають можливим проявам температурних впливів на усіх стадіях зведення та експлуатації будівель. В статті наведено приклад врахування температурного впливу при розрахунках каркасу будівлі із значними геометричними розмірами як у плані, так і по висоті. Так в рамках розрахунків висотної будівлі в м. Києві нами було проведено розрахунок на температурні впливи під час будівництва, з метою визначення напружено- деформованого стану конструкцій. Розрахунок на температурні впливи було виконано для стадії зведення будівлі (на час перед закриттям опалювального контуру). Дану будівлю рекомендується розділити двома тимчасовими швами. Що в свою чергу дозволило зменшити зусилля у плитах у порівнянні із початковими понад у три рази. При проектуванні та зведенні будівель значних розмірів значний вплив на визначення конструктивних рішень будівлі мають характер та величина температурних впливів. Найбільшими є температурні впливи обумовлені кліматичним, технологічними, експлуатаційними та аварійними факторами. Врахування температурних впливів у розрахунках за допомогою сучасних засобів дозволяє уникати ушкоджень конструкцій на усіх стадіях зведення та експлуатації будівель, визначати технологічні заходи, що дозволяють уникати перевитрат матеріалів, обумовлених необхідністю сприйняття зусиль, які можуть виникати при температурних впливах.
FRONT PAGES
Authors: Table of Contents) (Cover; Editorial Team; from the editor;
Published: May 2020

1. Cover2. Editorial Team3. from the editor4. Table of Contents
Arabidopsis Plants Sense Non-self Peptides to Promote Resistance Against Plectosphaerella cucumerina
Authors: Pastor-Fernández Julia , Gamir Jordi , Pastor Victoria , Sanchez-Bel Paloma , Sanmartín Neus , Cerezo Miguel , Flors Víctor
Published: May 2020

Peptides are important regulators that participate in the modulation of almost every physiological event in plants, including defense. Recently, many of these peptides have been described as defense elicitors, termed phytocytokines, that are released upon pest or pathogen attack, triggering an amplification of plant defenses. However, little is known about peptides sensing and inducing resistance activities in heterologous plants. In the present study, exogenous peptides from solanaceous species, Systemins and HypSys, are sensed and induce resistance to the necrotrophic fungus Plectosphaerella cucumerina in the taxonomically distant species Arabidopsis thaliana. Surprisingly, other peptides from closer taxonomic clades have very little or no effect on plant protection. In vitro bioassays showed that the studied peptides do not have direct antifungal activities, suggesting that they protect the plant through the promotion of the plant immune system. Interestingly, tomato Systemin was able to induce resistance at very low concentrations (0.1 and 1 nM) and displays a maximum threshold being ineffective above at higher concentrations. Here, we show evidence of the possible involvement of the JA-signaling pathway in the Systemin-Induced Resistance (Sys-IR) in Arabidopsis. Additionally, Systemin treated plants display enhanced BAK1 and BIK1 gene expression following infection as well as increased production of ROS after PAMP treatment suggesting that Systemin sensitizes Arabidopsis perception to pathogens and PAMPs.
Exogenous Melatonin Improves Salt Tolerance by Mitigating Osmotic, Ion, and Oxidative Stresses in Maize Seedlings
Authors: Ren Jianhong , Ye Jun , Yin Lina , Li Gouxia , Deng Xiping , Wang Shiwen
Published: May 2020

Melatonin has been confirmed extensively for the positive effects on increasing plant tolerance to various abiotic stresses. However, the roles of melatonin in mediating different stresses still need to be explored in different plants species and growth periods. To investigate the role of melatonin in mitigating salt stress, maize (Zea mays L.) seedlings growing in hydroponic solution were treated with 100 mM NaCl combined with or without 1 μM melatonin. Melatonin application had no effects on maize growth under normal condition, while it moderately alleviated the NaCl-induced inhibition of plant growth. The leaf area, biomass, and photosynthesis of melatonin-treated plants were higher than that of without melatonin under NaCl treatment. The osmotic potential was lower, and the osmolyte contents (including sucrose and fructose) were higher in melatonin-treated plants. Meanwhile, the decreases in Na+ content and increases in K+/Na+ ratio were found in shoots of melatonin-applied plant under salt stress. Moreover, both enzymatic and nonenzymatic antioxidant activities were significantly increased in leaves with melatonin application under salt treatment. These results clearly indicate that the exogenous melatonin-enhanced salt tolerance under short-term treatment could be ascribed to three aspects, including osmotic adjustment, ion balance, and alleviation of salt-induced oxidative stress.
“They Reckon They’re Man’s Best Friend and I Believe That.” Understanding Relationships with Dogs in Australian Aboriginal Communities to Inform Effective Dog Population Management
Authors: Ma Gemma C , Ford Jason , Lucas Lillian , Norris Jacqueline M , Spencer Jessica , Withers Ann-Margret , Ward Michael P
Published: May 2020

Dogs are important companions to people in many societies; however, dogs can also be associated with risks to public health and safety. Dog population management is therefore an important consideration globally. This study aimed to better understand the role of dogs in Aboriginal communities and the barriers to accessing veterinary services. Semi-structured interviews were conducted with 85 dog owners from nine Aboriginal communities across New South Wales, Australia. Many positive aspects of dog ownership were identified and few negatives. Dogs are considered an important part of family and community life and many dogs are allowed indoors (63.4%), even sharing beds with their owners. Most dogs were kept for companionship (84.7%) and/or as guard dogs (45.9%) and all respondents considered their dog part of their family. However, respondents had low levels of engagement with mainstream veterinary services, and many respondents identified significant barriers to accessing veterinary services, especially cost and transport. This study demonstrates the important and positive role of dogs in Aboriginal families and communities but also highlights a significant veterinary service gap. Our findings demonstrate that different perspectives on the role of dogs necessitates a different, culturally inclusive approach to dog management interventions.
Biomonitoring of Heavy Metal Pollution Using Acanthocephalans Parasite in Ecosystem: An Updated Overview
Authors: Mehana El-Sayed E. , Khafaga Asmaa F. , Elblehi Samar S. , Abd El-Hack Mohamed E. , Naiel Mohammed A.E. , Bin-Jumah May , Othman Sarah I. , Allam Ahmed A.
Published: May 2020

As a result of the global industrial revolution, contamination of the ecosystem by heavy metals has given rise to one of the most important ecological and organismic problems, particularly human, early developmental stages of fish and animal life. The bioaccumulation of heavy metals in fish tissues can be influenced by several factors, including metal concentration, exposure time, method of metal ingestion and environmental conditions, such as water temperature. Upon recognizing the danger of contamination from heavy metals and the effects on the ecosystem that support life on earth, new ways of monitoring and controlling this pollution, besides the practical ones, had to be found. Diverse living organisms, such as insects, fish, planktons, livestock and bacteria can be used as bioindicators for monitoring the health of the natural ecosystem of the environment. Parasites have attracted intense interest from parasitic ecologists, because of the variety of different ways in which they respond to human activity contamination as prospective indices of environmental quality. Previous studies showed that fish intestinal helminths might consider potential bioindicators for heavy metal contamination in aquatic creatures. In particular, cestodes and acanthocephalans have an increased capacity to accumulate heavy metals, where, for example, metal concentrations in acanthocephalans were several thousand times higher than in host tissues. On the other hand, parasitic infestation in fish could induce significant damage to the physiologic and biochemical processes inside the fish body. It may encourage serious impairment to the physiologic and general health status of fish. Thus, this review aimed to highlight the role of heavy metal accumulation, fish histopathological signs and parasitic infestation in monitoring the ecosystem pollutions and their relationship with each other.
Evolution of In Vitro Antimicrobial Susceptibility of Equine Clinical Isolates in France between 2016 and 2019
Authors: Léon Albertine , Castagnet Sophie , Maillard Karine , Paillot Romain , Giard Jean-Christophe
Published: May 2020

The present study described the evolution of antimicrobial resistance in equine pathogens isolated from 2016 to 2019. A collection of 7806 bacterial isolates were analysed for their in vitro antimicrobial susceptibility using the disk diffusion method. The most frequently isolated pathogens were group C Streptococci (27.0%), Escherichia coli (18.0%), Staphylococcus aureus (6.2%), Pseudomonas aeruginosa (3.4%), Klebsiella pneumoniae (2.3%) and Enterobacter spp. (2.1%). The majority of these pathogens were isolated from the genital tract (45.1%, n = 3522). With the implementation of two French national plans (named ECOANTIBIO 1 and 2) in 2012–2016 and 2017–2021, respectively, and a reduction in animal exposure to veterinary antibiotics, our study showed decreases in the resistance of group C Streptococci, Klebsiella pneumoniae and Escherichia coli against five classes, four classes and one class of antimicrobials tested, respectively. However, Staphylococcus aureus, Escherichia coli and Enterobacter spp. presented an increased resistance against all the tested classes, excepted for two fifths of E. coli. Moreover, the percentages of multi-drug resistant strains of Staphylococcus aureus and Enterobacter spp. also increased from 24.5% to 37.4% and from 26.3% to 51.7%, respectively. The data reported here are relevant to equine practitioners and will help to improve knowledge related to antimicrobial resistance in common equine pathogens.
High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation
Authors: Petersen Andreas Munk , Mirsepasi-Lauridsen Hengameh Chloé , Vester-Andersen Marianne K. , Sørensen Nikolaj , Krogfelt Karen Angeliki , Bendtsen Flemming
Published: May 2020

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.
Chemical and Biological Characterization of Particulate Matter (PM 2.5) and Volatile Organic Compounds Collected at Different Sites in the Los Angeles Basin
Authors: Cho Arthur K. , Shinkai Yasuhiro , Schmitz Debra A. , Di Stefano Emma , Eiguren-Fernandez Arantza , Guarieiro Aline Lefol Nani , Salinas Erika M. , Froines John R. , Melega William P.
Published: May 2020

Background: Most studies on air pollution (AP) exposure have focused on adverse health effects of particulate matter (PM). Less well-studied are the actions of volatile organic compounds (VOCs) not retained in PM collections. These studies quantified chemical and biological properties of both PM2.5 and VOCs. Methods: Samples were collected near the Port of Los Angeles (Long Beach, LB), railroads (Commerce, CM), and a pollution-trapping topography-site (San Bernardino, SB). Quantitative assays were conducted: (1) chemical—prooxidant and electrophile content, (2) biological—tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) expression (3), VOC modulation of PM effects and (4), activation of the antioxidant response element (ARE) using murine RAW 264.7 macrophages. Results: SB site samples were the most potent in the chemical and biological assays, followed by a CM railroad site. Only PM2.5 exhibited significant proinflammatory responses. VOCs were more potent than PM2.5 in generating anti-inflammatory responses; further, VOC pretreatment reduced PM-associated TNF-α expression. VOCs significantly increased ARE activation compared to their corresponding PM2.5 which remained at background levels. Conclusion: Ambient VOCs are major contributors to adaptive responses that can modulate PM effects, in vitro, and, as such, need to be included in comprehensive assessments of AP.
Far Off-Resonance Laser Frequency Stabilization Technology
Authors: Liu Chang , Yue Ziqian , Xu Zitong , Ding Ming , Zhai Yueyang
Published: May 2020

In atomic physics experiments, a frequency-stabilized or ‘locked’ laser source is commonly required. Many established techniques are available for locking close to an atomic resonance. However, in many instances, such as atomic magnetometer and magic wavelength optical lattices in ultra-cold atoms, it is desirable to lock the frequency of the laser far away from the resonance. This review presents several far off-resonance laser frequency stabilization methods, by which the frequency of the probe beam can be locked on the detuning as far as several tens of gigahertz (GHz) away from atomic resonance line, and discusses existing challenges and possible future directions in this field.
Fatigue Evaluation of Steel Bridge Details Integrating Multi-Scale Dynamic Analysis of Coupled Train-Track-Bridge System and Fracture Mechanics
Authors: Li Huile , Wu Gang
Published: May 2020

Increased running speed and axle weight in the transportation network lead to significant dynamic interactions between the vehicles and bridges. It is essential to capture these interactions in fatigue analysis of steel bridges. This paper presents a framework for fatigue evaluation of critical steel bridge details through multi-scale dynamic analysis of the train-track-bridge system and linear elastic fracture mechanics. The multi-scale coupled dynamic analysis allows accurate and efficient computation of fatigue stresses produced by the moving trains in structural details based on a vehicle-bridge analysis model composed of a 3D vehicle model, multi-scale bridge finite element model including the track system, and a wheel–rail interaction model. Field data from an existing steel-truss railway bridge are used to validate the multi-scale analysis method. Enhanced fatigue evaluation of the bridge detail is performed using the computed fatigue load effects and linear elastic fracture mechanics. The effects of the track irregularity and operating train speed on fatigue crack propagation life are investigated. The presented framework is general and can be applied to other types of steel bridges such as the steel-box girder bridge with orthotropic decks.
Method of Multi-Angle Transmission Radiowave Tomography of Dielectric Objects
Authors: Sukhanov Dmitry , Zavyalova Kseniya
Published: May 2020

A method for solving the inverse problem for reconstructing the spatial distribution of dielectric permittivity from the results of multi-angle transmission broadband radiosounding is proposed. The method is based on inverse wave propagation. The average refractive index of the medium along the wave trajectory is calculated by comparing the results of the calculation of the time delay of the inverse signal in the entire sounding region and the forward propagation time in a homogeneous medium. This method takes into account diffraction effects in solving a direct problem, which allows one to obtain a resolution in the order of a wavelength. The combination of time delays obtained at different probing angles allows the restoration of the distribution of the refractive index in the medium. The paper presents the results of the numerical simulation of this method. The novelty of the proposed approach compared to the conventional back-projection algorithm is that ray approximation is not applied. Instead of the absorption coefficient (used in X-ray tomography), a time delay is considered, which is restored in the entire probed region. The developed method can be widely used in radiowave tomography or microwave tomography for remote non-destructive testing, diagnostics for the internal structures of inhomogeneous media and the restoration of the shapes of opaque objects based on multisensor sensing.
Software for Estimation of Stochastic Model Parameters for a Compacting Reservoir
Authors: Witkowski Wojciech T. , Hejmanowski Ryszard
Published: May 2020

The paper presents a computer program called SubCom v1.0 for determining mathematical model parameters of compaction layers in areas of oil, gas or groundwater extraction. A stochastic model based on the influence function was used to model compaction and subsidence. Estimation of the model parameters was based on solving the inverse problem. Two model parameters were determined: the compaction coefficient Cm of reservoir rocks, and the parameter tgβ, which indirectly describes the mechanical properties of the overburden. The calculations were performed on leveling measurements of land subsidence, as well as on the geometry of the compaction layer and pressure changes in aquifers. The estimation of model parameters allows the prediction of surface deformations due to planned fluid extraction. An algorithm with a graphical user interface was implemented in the Scilab environment. The use of SubCom v1.0 is presented using the case of an underground hard coal mine. Water drainage from rock mass accompanying coal extraction resulted in compaction of the aquifer, which in turn led to additional surface subsidence. As a result, a subsidence trough occurred with a maximum subsidence of 0.56 m.
Using Early Data to Estimate the Actual Infection Fatality Ratio from COVID-19 in France
Authors: Roques Lionel , Klein Etienne K , Papaïx Julien , Sar Antoine , Soubeyrand Samuel
Published: May 2020

The number of screening tests carried out in France and the methodology used to target the patients tested do not allow for a direct computation of the actual number of cases and the infection fatality ratio (IFR). The main objective of this work is to estimate the actual number of people infected with COVID-19 and to deduce the IFR during the observation window in France. We develop a ‘mechanistic-statistical’ approach coupling a SIR epidemiological model describing the unobserved epidemiological dynamics, a probabilistic model describing the data acquisition process and a statistical inference method. The actual number of infected cases in France is probably higher than the observations: we find here a factor ×8 (95%-CI: 5–12) which leads to an IFR in France of 0.5% (95%-CI: 0.3–0.8) based on hospital death counting data. Adjusting for the number of deaths in nursing homes, we obtain an IFR of 0.8% (95%-CI: 0.45–1.25). This IFR is consistent with previous findings in China (0.66%) and in the UK (0.9%) and lower than the value previously computed on the Diamond Princess cruse ship data (1.3%).
Assessment of the Pharmacological Properties and Phytochemical Profile of Bruguiera gymnorhiza (L.) Lam Using In Vitro Studies, In Silico Docking, and Multivariate Analysis
Authors: Bibi Sadeer Nabeelah , Sinan Kouadio Ibrahime , Cziáky Zoltán , Jekő József , Zengin Gokhan , Jeewon Rajesh , Abdallah Hassan H. , Rengasamy Kannan R. R. , Fawzi Mahomoodally Mohamad
Published: May 2020

Bruguiera gymnorhiza (L.) Lam. is claimed to effectively manage a number of ailments including diabetes and associated complications. Nonetheless, no attempt has been made to delineate its pharmacological propensities and phytochemical profile. This study was designed to appraise the antioxidant and enzymatic inhibitory properties relevant to the management of diabetes mellitus, obesity, and neurodegenerative and skin disorders. A combination of colorimetric assays and ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) were applied for the phytochemical screening of leaf, root, twig, and fruit extracts (methanol and ethyl acetate). In vitro antioxidant evaluations were via radical scavenging abilities (DPPH, ABTS), reducing potential (FRAP, CUPRAC), chelating power, and total antioxidant capacity (phosphomolybdenum). Seven key metabolic enzymes (α-amylase, α-glucosidase, tyrosinase, elastase, lipase, AChE, and BChE) were targeted to determine the inhibitory effects. Multivariate and in silico docking analysis were performed on collected data. Methanolic fruit extract yielded the highest total phenolic, tannin, and triterpenoid contents (174.18 ± 4.27 mg GAE/g, 176.24 ± 3.10 mg CE/g, 63.11 ± 3.27 mg OAE/g, respectively); significantly depressed tyrosinase, elastase, and α-amylase activities (155.35 ± 0.29 mg KAE/g, 4.56 ± 0.10 mg CAE/g, 1.00 ± 0.05 mmol ACAE/g, accordingly); and harboured the most potent antioxidant capacities with DPPH, CUPRAC, FRAP (492.62 ± 5.31, 961.46 ± 11.18, 552.49 ± 8.71 mg TE/g, respectively), and phosphomolybdenum (4.17 ± 0.31 mmol TE/g) assays. Multivariate analysis suggested that the type of solvents used influenced the biological activities more compared to plant parts. Docking analysis showed that azelaic acid binds with tyrosinase by Van der Waals and conventional hydrogen bonds. We anticipate that the present study may establish baseline data on this halophyte that could open new avenues for the development of biomedicine.
D-Loop Mutation G42A/G46A Decreases Actin Dynamics
Authors: Matsuzaki Mizuki , Fujiwara Ikuko , Kashima Sae , Matsumoto Tomoharu , Oda Toshiro , Hayashi Masahito , Maeda Kayo , Takiguchi Kingo , Maéda Yuichiro , Narita Akihiro
Published: May 2020

Depolymerization and polymerization of the actin filament are indispensable in eukaryotes. The DNase I binding loop (D-loop), which forms part of the interface between the subunits in the actin filament, is an intrinsically disordered loop with a large degree of conformational freedom. Introduction of the double mutation G42A/G46A to the D-loop of the beta cytoskeletal mammalian actin restricted D-loop conformational freedom, whereas changes to the critical concentration were not large, and no major structural changes were observed. Polymerization and depolymerization rates at both ends of the filament were reduced, and cofilin binding was inhibited by the double mutation. These results indicate that the two glycines at the tip of the D-loop are important for actin dynamics, most likely by contributing to the large degree of conformational freedom.
Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson’s Disease
Authors: Hribar Casey A. , Cobbold Peter H. , Church Frank C.
Published: May 2020

While we are still learning more about COVID-19, caused by the novel SARS-CoV-2 virus, finding alternative and already available methods to reduce the risk and severity of the disease is paramount. One such option is vitamin D, in the form of vitamin D3 (cholecalciferol) supplementation, due to its potential antiviral properties. It has become apparent that older individuals have a greater risk of developing severe COVID-19, and compared to younger adults, the elderly have lower levels of vitamin D due to a variety of biological and behavioral factors. Older adults are also more likely to be diagnosed with Parkinson’s disease (PD), with advanced age being the single greatest risk factor. In addition to its immune-system-modulating effects, it has been suggested that vitamin D supplementation plays a role in slowing PD progression and improving PD-related quality of life. We completed a review of the literature to determine the relationship between vitamin D, PD, and COVID-19. We concluded that the daily supplementation of 2000–5000 IU/day of vitamin D3 in older adults with PD has the potential to slow the progression of PD while also potentially offering additional protection against COVID-19.
Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives
Authors: Wołącewicz Mikołaj , Hrynkiewicz Rafał , Grywalska Ewelina , Suchojad Tomasz , Leksowski Tomasz , Roliński Jacek , Niedźwiedzka-Rystwej Paulina
Published: May 2020

Bladder cancer is one of the most significant genitourinary cancer, causing high morbidity and mortality in a great number of patients. Over the years, various treatment methods for this type of cancer have been developed. The most common is the highly efficient method using Bacillus Calmette-Guerin, giving a successful effect in a high percentage of patients. However, due to the genetic instability of bladder cancer, together with individual needs of patients, the search for different therapy methods is ongoing. Immune checkpoints are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Among those checkpoints, the PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death protein ligand 1) inhibitors aim at blocking those molecules, which results in T cell activation, and in bladder cancer the use of Atezolizumab, Avelumab, Durvalumab, Nivolumab, and Pembrolizumab has been described. The inhibition of another pivotal immune checkpoint, CTLA-4 (cytotoxic T cell antigen), may result in the mobilization of the immune system against bladder cancer and, among anti-CTLA-4 antibodies, the use of Ipilimumab and Tremelimumab has been discussed. Moreover, several different approaches to successful bladder cancer treatment exists, such as the use of ganciclovir and mTOR (mammalian target of rapamycin) kinase inhibitors, IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). The use of gene therapies and the disruption of different signaling pathways are currently being investigated. Research suggests that the combination of several methods increases treatment efficiency and the positive outcome in individual.
Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma
Authors: Song Yeonhwa , Kim Sanghwa , Lee Hyeryon , No Joo Hwan , Ryu Hyung Chul , Kim Jason , Lim Jee Woong , Kim Moonhee , Choi Inhee , Seo Haeng Ran
Published: May 2020

Hepatocellular carcinoma (HCC) is a highly malignant human cancer that has increasing mortality rates worldwide. Because CD133+ cells control tumor maintenance and progression, compounds that target CD133+ cancer cells could be effective in combating HCC. We found that the administration of chromenopyrimidinone (CPO) significantly decreased spheroid formation and the number of CD133+ cells in mixed HCC cell populations. CPO not only significantly inhibited cell proliferation in HCC cells exhibiting different CD133 expression levels, but also effectively induced apoptosis and increased the expression of LC3-II in HCC cells. CPO also exhibits in vivo therapeutic efficiency in HCC. Specifically, CPO suppressed the expression of CD133 by altering the subcellular localization of CD133 from the membrane to lysosomes in CD133+ HCC cells. Moreover, CPO treatment induced point mutations in the ADRB1, APOB, EGR2, and UBE2C genes and inhibited the expression of these proteins in HCC and the expression of UBE2C is particularly controlled by CD133 expression among those four proteins in HCC. Our results suggested that CPO may suppress stemness and malignancies in vivo and in vitro by decreasing CD133 and UBE2C expression in CD133+ HCC. Our study provides evidence that CPO could act as a novel therapeutic agent for the effective treatment of CD133+ HCC.
The Role of Support Hydrophobicity in the Selective Hydrogenation of Enones and Unsaturated Sulfones over Cu/SiO2 Catalysts
Authors: Cavuoto Denise , Zaccheria Federica , Marelli Marcello , Evangelisti Claudio , Piccolo Oreste , Ravasio Nicoletta
Published: May 2020

The substitution of complex hydrides and Ni- and noble metal-based catalysts in the synthesis of pharma and fragrance products is a relevant topic in the green chemistry scenario. Here, we report that non-toxic, non-noble metal-based Cu/SiO2 catalysts are effective and very selective in the hydrogenation of α,β-unsaturated ketones, esters and sulfones under very mild conditions. Vanillyl acetone can be obtained in quantitative yield in 1 h at 90 °C and 1 bar of H2. High dispersion of the metallic phase and support wettability play a significant role in determining catalytic performance.
Three-Dimensional Mesoporous Ni-CeO2 Catalysts with Ni Embedded in the Pore Walls for CO2 Methanation
Authors: Wang Luhui , Hu Junang , Liu Hui , Wei Qinhong , Gong Dandan , Mo Liuye , Tao Hengcong , Zhang Chengyang
Published: May 2020

Mesoporous Ni-based catalysts with Ni confined in nanochannels are widely used in CO2 methanation. However, when Ni loadings are high, the nanochannels are easily blocked by nickel particles, which reduces the catalytic performance. In this work, three-dimensional mesoporous Ni-CeO2-CSC catalysts with high Ni loadings (20−80 wt %) were prepared using a colloidal solution combustion method, and characterized by nitrogen adsorption–desorption, X-ray diffraction (XRD), transmission electron microscopy (TEM) and H2 temperature programmed reduction (H2-TPR). Among the catalysts with different Ni loadings, the 50% Ni-CeO2-CSC with 50 wt % Ni loading exhibited the best catalytic performance in CO2 methanation. Furthermore, the 50% Ni-CeO2-CSC catalyst was stable for 50 h at 300° and 350 °C in CO2 methanation. The characterization results illustrate that the 50% Ni-CeO2-CSC catalyst has Ni particles smaller than 5 nm embedded in the pore walls, and the Ni particles interact with CeO2. On the contrary, the 50% Ni-CeO2-CP catalyst, prepared using the traditional coprecipitation method, is less active and selective for CO2 methanation due to the larger size of the Ni and CeO2 particles. The special three-dimensional mesoporous embedded structure in the 50% Ni-CeO2-CSC can provide more metal–oxide interface and stabilize small Ni particles in pore walls, which makes the catalyst more active and stable in CO2 methanation.
Epigenetic Regulation of Neuregulin-1 Tunes White Adipose Stem Cell Differentiation
Authors: Cordero Alyssa D. , Callihan Evan C. , Said Rana , Alowais Yasir , Paffhausen Emily S. , Bracht John R.
Published: May 2020

Expansion of subcutaneous adipose tissue by differentiation of new adipocytes has been linked to improvements in metabolic health. However, an expandability limit has been observed wherein new adipocytes cannot be produced, the existing adipocytes become enlarged (hypertrophic) and lipids spill over into ectopic sites. Inappropriate ectopic storage of these surplus lipids in liver, muscle, and visceral depots has been linked with metabolic dysfunction. Here we show that Neuregulin-1 (NRG1) serves as a regulator of adipogenic differentiation in subcutaneous primary human stem cells. We further demonstrate that DNA methylation modulates NRG1 expression in these cells, and a 3-day exposure of stem cells to a recombinant NRG1 peptide fragment is sufficient to reprogram adipogenic cellular differentiation to higher levels. These results define a novel molecular adipogenic rheostat with potential implications for the expansion of adipose tissue in vivo.
Managing the Oocyte Meiotic Arrest—Lessons from Frogs and Jellyfish
Authors: Jessus Catherine , Munro Catriona , Houliston Evelyn
Published: May 2020

During oocyte development, meiosis arrests in prophase of the first division for a remarkably prolonged period firstly during oocyte growth, and then when awaiting the appropriate hormonal signals for egg release. This prophase arrest is finally unlocked when locally produced maturation initiation hormones (MIHs) trigger entry into M-phase. Here, we assess the current knowledge of the successive cellular and molecular mechanisms responsible for keeping meiotic progression on hold. We focus on two model organisms, the amphibian Xenopus laevis, and the hydrozoan jellyfish Clytia hemisphaerica. Conserved mechanisms govern the initial meiotic programme of the oocyte prior to oocyte growth and also, much later, the onset of mitotic divisions, via activation of two key kinase systems: Cdk1-Cyclin B/Gwl (MPF) for M-phase activation and Mos-MAPkinase to orchestrate polar body formation and cytostatic (CSF) arrest. In contrast, maintenance of the prophase state of the fully-grown oocyte is assured by highly specific mechanisms, reflecting enormous variation between species in MIHs, MIH receptors and their immediate downstream signalling response. Convergence of multiple signalling pathway components to promote MPF activation in some oocytes, including Xenopus, is likely a heritage of the complex evolutionary history of spawning regulation, but also helps ensure a robust and reliable mechanism for gamete production.
Targeting Cellular Metabolism in Acute Myeloid Leukemia and the Role of Patient Heterogeneity
Authors: Grønningsæter Ida Sofie , Reikvam Håkon , Aasebø Elise , Bartaula-Brevik Sushma , Tvedt Tor Henrik , Bruserud Øystein , Hatfield Kimberley Joanne
Published: May 2020

Acute myeloid leukemia (AML) is an aggressive blood cancer resulting in accumulation of immature, dysfunctional blood cells in the bone marrow. Changes in cell metabolism are features of many cancers, including AML and this may be exploited as a therapeutic target. In this study we investigated the in vitro antileukemic effects of seven metabolic inhibitors that target different metabolic pathways. The metabolic inhibitors were tested on AML cells derived from 81 patients using proliferation and viability assays; we also compared global gene expression and proteomic profiles for various patient subsets. Metformin, 2DG, 6AN, BPTES and ST1326 had strong antiproliferative and proapoptotic effects for most patients, whereas lonidamine and AZD3965 had an effect only for a minority. Antiproliferative effects on AML cells were additive when combined with the chemotherapeutic agent AraC. Using unsupervised hierarchical clustering, we identified a strong antiproliferative effect on AML cells after treatment with metabolic inhibitors for a subset of 29 patients. Gene expression and proteomic studies suggested that this subset was characterized by altered metabolic and transcriptional regulation. In addition, the Bcl-2 inhibitor venetoclax, in combination with 2DG or 6AN, increased the antiproliferative effects of these metabolic inhibitors on AML cells. Therapeutic targeting of cellular metabolism may have potential in AML, but the optimal strategy will likely differ between patients.
Cell-Free Circulating Mitochondrial DNA: A Potential Blood-Based Marker for Atrial Fibrillation
Authors: Wiersma Marit , van Marion Denise M.S. , Bouman Emma J. , Li Jin , Zhang Deli , Ramos Kennedy S. , Lanters Eva A.H. , de Groot Natasja M.S. , Brundel Bianca J.J.M.
Published: May 2020

Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated with serious complications, such as stroke and heart failure. Early recognition of AF, essential to prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction to drive experimental and human AF, we evaluated whether cell-free circulating mitochondrial DNA (cfc-mtDNA) represents a potential serum marker. Therefore, the levels of two mtDNA genes, COX3 and ND1, were measured in 84 control patients (C), 59 patients undergoing cardiac surgery without a history of AF (SR), 100 paroxysmal (PAF), 116 persistent (PeAF), and 20 longstanding-persistent (LS-PeAF) AF patients undergoing either cardiac surgery or AF treatment (electrical cardioversion or pulmonary vein isolation). Cfc-mtDNA levels were significantly increased in PAF patients undergoing AF treatment, especially in males and patients with AF recurrence after AF treatment. In PeAF and LS-PeAF, cfc-mtDNA levels gradually decreased. Importantly, cfc-mtDNA in serum may originate from cardiomyocytes, as in vitro tachypaced cardiomyocytes release mtDNA in the medium. The findings suggest that cfc-mtDNA is associated with AF stage, especially in males, and with patients at risk for AF recurrence after treatment.
Role of Endoplasmic Reticulum Stress Sensor IRE1α in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation
Authors: Riaz Thoufiqul Alam , Junjappa Raghu Patil , Handigund Mallikarjun , Ferdous Jannatul , Kim Hyung-Ryong , Chae Han-Jung
Published: May 2020

Inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) is the most prominent and evolutionarily conserved unfolded protein response (UPR) signal transducer during endoplasmic reticulum functional upset (ER stress). A IRE1α signal pathway arbitrates yin and yang of cellular fate in objectionable conditions. It plays several roles in fundamental cellular physiology as well as in several pathological conditions such as diabetes, obesity, inflammation, cancer, neurodegeneration, and in many other diseases. Thus, further understanding of its molecular structure and mechanism of action during different cell insults helps in designing and developing better therapeutic strategies for the above-mentioned chronic diseases. In this review, recent insights into structure and mechanism of activation of IRE1α along with its complex regulating network were discussed in relation to their basic cellular physiological function. Addressing different binding partners that can modulate IRE1α function, UPRosome triggers different downstream pathways depending on the cellular backdrop. Furthermore, IRE1α are in normal cell activities outside the dominion of ER stress and activities under the weather of inflammation, diabetes, and obesity-related metaflammation. Thus, IRE1 as an ER stress sensor needs to be understood from a wider perspective for comprehensive functional meaning, which facilitates us with assembling future needs and therapeutic benefits.
The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in Human Cancer Cells
Authors: Cal Magdalena , Matyjaszczyk Irwin , Litwin Ireneusz , Augustyniak Daria , Ogórek Rafał , Ko Young , Ułaszewski Stanisław
Published: May 2020

3-bromopyruvate (3-BP) is a small molecule with anticancer and antimicrobial activities. 3-BP is taken up selectively by cancer cells’ mono-carboxylate transporters (MCTs), which are highly overexpressed by many cancers. When 3-BP enters cancer cells it inactivates several glycolytic and mitochondrial enzymes, leading to ATP depletion and the generation of reactive oxygen species. While mechanisms of 3-BP uptake and its influence on cell metabolism are well understood, the impact of 3-BP at certain concentrations on DNA integrity has never been investigated in detail. Here we have collected several lines of evidence suggesting that 3-BP induces DNA damage probably as a result of ROS generation, in both yeast and human cancer cells, when its concentration is sufficiently low and most cells are still viable. We also demonstrate that in yeast 3-BP treatment leads to generation of DNA double-strand breaks only in S-phase of the cell cycle, possibly as a result of oxidative DNA damage. This leads to DNA damage, checkpoint activation and focal accumulation of the DNA response proteins. Interestingly, in human cancer cells exposure to 3-BP also induces DNA breaks that trigger H2A.X phosphorylation. Our current data shed new light on the mechanisms by which a sufficiently low concentration of 3-BP can induce cytotoxicity at the DNA level, a finding that might be important for the future design of anticancer therapies.
Deciphering the Enigma of the Histone H2A.Z-1/H2A.Z-2 Isoforms: Novel Insights and Remaining Questions
Authors: Cheema Manjinder S. , Good Katrina V. , Kim Bohyun , Soufari Heddy , O’Sullivan Connor , Freeman Melissa E. , Stefanelli Gilda , Casas Ciro Rivera , Zengeler Kristine E. , Kennedy Andrew J. , Eirin Lopez Jose Maria , Howard Perry L. , Zovkic Iva B. , Shabanowitz Jeffrey , Dryhurst Deanna D. , Hunt Donald F. , Mackereth Cameron D. , Ausió Juan
Published: May 2020

The replication independent (RI) histone H2A.Z is one of the more extensively studied variant members of the core histone H2A family, which consists of many replication dependent (RD) members. The protein has been shown to be indispensable for survival, and involved in multiple roles from DNA damage to chromosome segregation, replication, and transcription. However, its functional involvement in gene expression is controversial. Moreover, the variant in several groups of metazoan organisms consists of two main isoforms (H2A.Z-1 and H2A.Z-2) that differ in a few (3–6) amino acids. They comprise the main topic of this review, starting from the events that led to their identification, what is currently known about them, followed by further experimental, structural, and functional insight into their roles. Despite their structural differences, a direct correlation to their functional variability remains enigmatic. As all of this is being elucidated, it appears that a strong functional involvement of isoform variability may be connected to development.
The β-carboline Harmine Induces Actin Dynamic Remodeling and Abrogates the Malignant Phenotype in Tumorigenic Cells
Authors: Le Moigne Ronan , Subra Frédéric , Karam Manale , Auclair Christian
Published: May 2020

Numerous studies have shown that alteration of actin remodeling plays a pivotal role in the regulation of morphologic and phenotypic changes leading to malignancy. In the present study, we searched for drugs that can regulate actin polymerization and reverse the malignant phenotype in cancer cells. We developed a cell-free high-throughput screening assay for the identification of compounds that induce the actin polymerization in vitro, by fluorescence anisotropy. Then, the potential of the hit compound to restore the actin cytoskeleton and reverse the malignant phenotype was checked in EWS-Fli1-transformed fibroblasts and in B16-F10 melanoma cells. A β-carboline extracted from Peganum harmala (i.e., harmine) is identified as a stimulator of actin polymerization through a mechanism independent of actin binding and requiring intracellular factors involved in a process that regulates actin kinetics. Treatment of malignant cells with non-cytotoxic concentrations of harmine induces the recovery of a non-malignant cell morphology accompanied by reorganization of the actin cytoskeleton, rescued cell–cell adhesion, inhibition of cell motility and loss of anchorage-independent growth. In conclusion, harmine induces the reversion of the malignant phenotype by a process involving the modulation of actin dynamics and is a potential anti-tumor agent acting principally through a non-cytotoxic process.
Polyethylene Glycol Pulsed Electrodeposition for the Development of Antifouling Coatings on Titanium
Authors: Buxadera-Palomero Judit , Albó Kim , Gil Francisco Javier , Mas-Moruno Carlos , Rodríguez Daniel
Published: May 2020

Titanium dental implants are widely used for the replacement of damaged teeth. However, bacterial infections at the interface between soft tissues and the implant can impair the functionality of the device and lead to failure. In this work, the preparation of an antifouling coating of polyethylene glycol (PEG) on titanium by pulsed electrodeposition was investigated in order to reduce Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) adhesion while maintaining human fibroblast adhesion. Different pulsed conditions were prepared and characterized by contact angle, Focused Ion Beam (FIB), Fourier Transformed Infrared Spectroscopy in the Attenuated Total Reflectance mode (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS). XPS tested fibronectin adsorption. S. aureus, E. coli and human fibroblast adhesion was tested in vitro in both mono and co-culture settings. Physicochemical characterization proved useful for confirming the presence of PEG and evaluating the efficiency of the coating methods. Fibronectin adsorption decreased for all of the conditions, but an adsorption of 20% when compared to titanium was maintained, which supported fibroblast adhesion on the surfaces. In contrast, S. aureus and E. coli attachment on coated surfaces decreased up to 90% vs. control titanium. Co-culture studies with the two bacterial strains and human fibroblasts showed the efficacy of the coatings to allow for eukaryotic cell adhesion, even in the presence of pre-adhered bacteria.
On Detecting Relay Attacks on RFID Systems Using Qubits
Authors: Abidin Aysajan
Published: May 2020

As RFID technology is being widely used in access control systems to identify and track both objects and people, relay attacks on RFID systems continue to pose serious threats to security. To mitigate relay attacks, distance bounding protocols can be used. Until recently, all distance bounding protocols were based on classical cryptography and communication techniques. In this paper, we take a closer look at a recently proposed protocol by Jannati and Ardeshir-Larijani [Quantum Information Processing 2016, 18] to detect relay attacks using qubits. We first observe that the protocol has a weakness which allows an adversary to mount a successful attack on the protocol. We then propose a countermeasure to restore security and compare the fixed protocol with the state of the art.