bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Energy Retrofit of Heat Exchanger Network Not Containing Utility Path
Authors: Jegla Zdeněk , Freisleben Vít
Published: May 2020

The paper presents a method developed for the energy retrofit of specific Heat Exchanger Networks not containing Utility Paths. This useful and highly practically oriented method involves a systematic approach to obtaining the most efficient minimal modification topology of a Heat Exchanger Network, which brings the greatest benefits in terms of energy savings of the modified process. In principle, it is focused on finding the most suitable location for a new heat exchanger insertion to create the most efficient Utility Path. The next step of the developed retrofit method is the detailed design of the newly integrated heat exchanger using commercial software in combination with several heuristic rules regarding the cost-free investment and maintenance cost minimization of a new heat exchanger and considering heat transfer enhancement within the available exchanger type, space, and fluids pressure drop constraints. The detail design stage of the method also includes observation and reassessment of the performance and operational parameters of the existing heat exchangers. Then, the developed method is applied to the case of the Heat Exchanger Network retrofit in the process of the hydrogenation of oil.
Simulation and Implementation of Predictive Speed Controller and Position Observer for Sensorless Synchronous Reluctance Motors
Authors: Liu Tian-Hua , Ahmad Seerin , Mubarok Muhammad Syahril , Chen Jia-You
Published: May 2020

A position observer and a predictive controller for sensorless synchronous-reluctance-motor (SynRM) drive systems are investigated in this paper. The rotor position observer, based on motor parameters, and stator currents and voltages, was designed and implemented to compute the rotor position. A pole-assignment technique was used to provide similar converging rates of the position observer, even when operated at different speeds. Furthermore, a predictive controller was designed to enhance performance. A digital-signal processor (DSP), TMS-320F-28335, was used as a computation tool. Several simulated results are provided and compared with the measured results. The measured results showed that the implemented predictive controller sensorless SynRM drive system could be adjusted from 30 to 1800 rpm with satisfactory performance, including quicker and better tracking responses, and a lower speed drop than that of a proportional-integral (PI) controller.
Impact of Starch from Cassava Peel on Biogas Produced through the Anaerobic Digestion Process
Authors: Alrefai Alla Mohammed , Alrefai Raid , Benyounis Khaled Younis , Stokes Joseph
Published: May 2020

Cassava is a form of food that is rich in starch abundant in many countries. Several bio-products can be extracted from its starch and used as an alternative for oil-based products. This study primarily aims to investigate the influence of the starch isolated from cassava peel on the quantity and quality of the biogas produced via anaerobic digestion. Beating pre-treatment was applied for the first time to isolate the starch and mechanically pre-treat the substrate. The influence of temperature, volatile solid and sludge quantity investigations were analysed with the aid of Design of Experiments (DOE). An optimisation process was applied in calculating the energy balance at the optimal results and this was needed in evaluating the impact of the starch on the biogas produced. The study revealed that the influence of the starch on the biogas quality is quite low and, as such, negligible. The largest biogas volume as obtained was 3830 cc at 37 °C, 4.2 g-VS and 50% sludge quantity, while at the same time the maximum CH4 g−1-VS was 850 cc g−1-VS at 37 °C, 1.1 g-VS and 50% sludge quantity. The optimal results show the energy gain could be achieved based on the set criteria.
Evaluation of the Instantaneous Power Demand of an Electric Charging Station in an Urban Scenario
Authors: Andrenacci Natascia , Ragona Roberto , Genovese Antonino
Published: May 2020

The existence of an efficient and sufficiently extensive charging infrastructure network appears to be of vital importance for the widespread acceptance of electric mobility by users. The present work aims to develop a tool based on big data analysis that helps to deploy a network of charging stations which can efficiently serve the potential demand, both from the user side, improving the level of service for charging and to cover the territory in a satisfactory way, and from the business side, allowing an analysis of the potential power load. The paper integrates real world traffic data and the results of an experimental campaign on an electric vehicle to evaluate the instantaneous power demand of a fast charging station, based on a procedure for the evaluation and proper time allocation of each charge request.
Multi-Objective Tabu Search for the Location and Sizing of Multiple Types of FACTS and DG in Electrical Networks
Authors: Coronado de Koster Othón Aram , Domínguez-Navarro José Antonio
Published: May 2020

Flexible AC transmission systems and distributed generation units in power systems provide several benefits such as voltage stability, power loss minimization, thermal limits enhancement, or enables power system management close to the limit operation points; and by extension, economic benefits such as power fuel cost and power loss cost minimization. This work presents a multi-objective optimization algorithm to determine the location and size of hybrid solutions based on a combination of Flexible AC transmission systems devices and distributed generation. Further, the work expands the types of FACTS usually considered. The problem is solved by means of a Tabu search algorithm with good results when tested in a network of 300 nodes.
Feasibility Study of a Centralised Electrically Driven Air Source Heat Pump Water Heater to Face Energy Poverty in Block Dwellings in Madrid (Spain)
Authors: Barrella Roberto , Priego Irene , Linares José Ignacio , Arenas Eva , Romero José Carlos , Centeno Efraim
Published: May 2020

Energy poverty can be defined as the inability to pay the bills that are required for maintaining the comfort conditions (usually in winter) in dwellings. The use of energy efficient systems is one way forward to mitigate this problem, with one option being the electrically driven air source heat pump water heater. This paper assesses the performance of a centralised heat pump (200 kW of heating capacity) to meet the space heating demand of block dwellings in Madrid (tier four out of five in winter severity in Spain). Two models have been developed to obtain the following variables: the hourly thermal energy demand and the off-design heat pump performance. The proposed heat pump is driven by a motor with variable rotational speed to modulate the heating capacity in an efficient way. A back-up system is also considered to meet the peak demand. A levelised cost of heating of 92.22 €/MWh is obtained for a middle-level energy efficiency in housing (class E, close to D). Moreover, the following energy-environmental parameters have been achieved: more than 74% share of renewable energy in primary energy and 131.7 g CO2 avoided per kWh met. A reduction of 60% in the heating cost per dwelling is obtained if an energy retrofit is carried out, improving the energy performance class from E to C. These results prove that the proposed technology is among the most promising measures for addressing energy poverty in vulnerable households.
An Efficient Analytical Approach for the Solution of Certain Fractional-Order Dynamical Systems
Authors: Qin Ya , Khan Adnan , Ali Izaz , Al Qurashi Maysaa , Khan Hassan , Shah Rasool , Baleanu Dumitru
Published: May 2020

Mostly, it is very difficult to obtained the exact solution of fractional-order partial differential equations. However, semi-analytical or numerical methods are considered to be an alternative to handle the solutions of such complicated problems. To extend this idea, we used semi-analytical procedures which are mixtures of Laplace transform, Shehu transform and Homotopy perturbation techniques to solve certain systems with Caputo derivative differential equations. The effectiveness of the present technique is justified by taking some examples. The graphical representation of the obtained results have confirmed the significant association between the actual and derived solutions. It is also shown that the suggested method provides a higher rate of convergence with a very small number of calculations. The problems with derivatives of fractional-order are also solved by using the present method. The convergence behavior of the fractional-order solutions to an integer-order solution is observed. The convergence phenomena described a very broad concept of the physical problems. Due to simple and useful implementation, the current methods can be used to solve problems containing the derivative of a fractional-order.
Three-Dimensional Convective Planforms for Inclined Darcy-Bénard Convection
Authors: Rees D. Andrew S. , Barletta Antonio
Published: May 2020

We investigate the onset of convection in an inclined Darcy-Bénard layer. When such a layer is unbounded in the spanwise direction it is generally known that longitudinal rolls comprise the most unstable planform. On the other hand, when a layer has a sufficiently small spanwise width, then transverse rolls form the most unstable planform. However, the layer remains stable to transverse roll disturbances when the inclination is above roughly 31 degrees from the horizontal. This paper considers the transition between these two extreme cases where the spanwise width takes moderate values and where rectangular cells are considered. It is found that the most unstable planform is quite strongly sensitive to the magnitude of the spanwise width and that there are large regions of parameter space within which three-dimensional convection patterns have the smallest critical Darcy-Rayleigh number.
Temporal Patterns in Performance of the 30 s Chair-Stand Test Evince Differences in Physical and Mental Characteristics among Community-Dwelling Older Adults in Japan
Authors: Goda Akio , Murata Shin , Nakano Hideki , Matsuda Hina , Yokoe Kana , Mitsumoto Hodaka , Shiraiwa Kayoko , Abiko Teppei , Horie Jun
Published: May 2020

Studies involving the 30 s chair-stand test (CS-30) have shown that subjects’ movements can vary during the test, and that these variations may follow several patterns. The present study aimed to define these different patterns and their respective incidences among a population of community-dwelling older adults in Japan. We also investigated, among the patterns identified, potential associations with physical and mental characteristics. The study population comprised 202 community-dwelling older adults. Subjects were classified into four groups based on how their CS-30 performance (defined through sit–stand–sit cycle count) changed over three successive 10 s segments: “steady-goers,” “fluctuators,” “decelerators,” and “accelerators.” Several other measures were also evaluated, including sit-up count, knee-extension strength, toe-grip strength, and Mini-Mental State Examination score. We found that steady-goers and decelerators comprised 70% of the sample. Fluctuators and steady-goers showed comparable physical function. Decelerators exhibited significant correlations between CS-30 score (total cycles) and tasks involving persistence and repetitive actions (p < 0.05). In addition, accelerators showed significantly stronger knee extension than steady-goers (p < 0.01). Differences in temporal patterns of CS-30 performance corresponded to differences in certain dimensions of physical and mental function. Our findings may be useful for planning and evaluating intervention programs aimed at long-term-care prevention among community-dwelling older adults.
Constructing Geospatial Concept Graphs from Tagged Images for Geo-Aware Fine-Grained Image Recognition
Authors: Nitta Naoko , Nakamura Kazuaki , Babaguchi Noboru
Published: May 2020

While visual appearances play a main role in recognizing the concepts captured in images, additional information can provide complementary information for fine-grained image recognition, where concepts with similar visual appearances such as species of birds need to be distinguished. Especially for recognizing geospatial concepts, which are observed only at specific places, geographical locations of the images can improve the recognition accuracy. However, such geo-aware fine-grained image recognition requires prior information about the visual and geospatial features of each concept or the training data composed of high-quality images for each concept associated with correct geographical locations. By using a large number of images photographed in various places and described with textual tags which can be collected from image sharing services such as Flickr, this paper proposes a method for constructing a geospatial concept graph which contains the necessary prior information for realizing the geo-aware fine-grained image recognition, such as a set of visually recognizable fine-grained geospatial concepts, their visual and geospatial features, and the coarse-grained representative visual concepts whose visual features can be transferred to several fine-grained geospatial concepts. Leveraging the information from the images captured by many people can automatically extract diverse types of geospatial concepts with proper features for realizing efficient and effective geo-aware fine-grained image recognition.
Geovisualization and Geographical Analysis for Fire Prevention
Authors: Guldåker Nicklas
Published: May 2020

Swedish emergency services still have relatively limited resources and time for proactive fire prevention. As a result of this, there is an extensive need for strategic working methods and knowledge to take advantage of spatial analyses. In addition, decision-making based on visualizations and analyses of their own collected data has the potential to increase the validity of strategic decisions. The objective of this paper is to critically examine how some different geovisualization techniques—point data, kernel density and choropleth mapping—actively can complement each other and be applied in fire preventive work. The results show that each technique itself has limitations, but that, in combination, they increase the scope for interpretation and the possibilities of targeting different forms of preventive measures. The investigated geovisualization techniques facilitate various forms of fire prevention such as identifying which areas to prioritize for outreach, home visits, identification and targeting of different risk groups and customized information campaigns about certain types of fires in risk-prone areas. Furthermore, fairly simple mapping techniques can be utilized directly to evaluate incident reports and increase the quality of geocoded fire incidents. The study also shows how some of these techniques can be applied when analyzing residential fire incidents and their relation to underlying structural and socio-economic factors as well as spatio-temporal dimensions of fire incident data. The spatial analyses and supporting maps can help find and predict risk areas for residential fires or be used directly to formulate hypotheses on fire patterns. The generic functionality of the visualization methods makes them also useful for visual analysis of other types of incidents, such as reported crimes and accidents. Finally, the results are applicable to a work process adapted to the Swedish legislation on confidential data.
Association between P2X7 Polymorphisms and Post-Transplant Outcomes in Allogeneic Haematopoietic Stem Cell Transplantation
Authors: Koldej Rachel M , Perera Travis , Collins Jenny , Ritchie David S
Published: May 2020

Allogeneic stem cell transplantation (alloSCT) is a highly effective treatment method for haematologic malignancies. However, infection of acute organ dysfunction and graft versus host disease (GVHD) impact negatively on patient outcomes. Pre-transplant conditioning regimes are associated with high levels of immunogenic cell death and the release of extracellular ATP, which binds to the P2X7 receptor. It has been proposed that signaling through the P2X7 receptor may lead to activation of downstream effectors that influence alloSCT outcome. In this study, we examined the effect of gain-of-function (GOF) or loss-of-function (LOF) P2X7 Single Nucleotide Polymorphisms (SNP) in 453 paired alloSCT donors and recipients and correlated their presence or absence to the major post-transplant outcomes of acute GVHD, relapse free survival and overall survival. The allelic frequency of P2X7 SNP in recipients and donors was not different from those SNP for which there is published population data. The LOF SNP Glu496Ala was overrepresented in recipients who did not develop severe acute GVHD and was associated with improved overall survival in rare homozygous recipients, whereas the LOF SNP Ile568Asn was more common in patients with grade 1–4 GVHD but lost statistical association in patients with grade 2–4 aGVHD, and was associated with reduced overall survival in heterozygotes due to an excess of infection-related deaths. The GOF variant haplotype (homozygous Gln460Arg-Ala348Thr) had no impact on post-alloSCT outcomes. Overall, our data indicate that allelic variations in recipients or donors occurs at the same frequency as the general population and may have a minor, but clinically nominal, impact on post-alloSCT outcomes.
Increase in the Number of Bone Marrow Osteoclast Precursors at Different Skeletal Sites, Particularly in Long Bone and Jaw Marrow in Mice Lacking IL-1RA
Authors: Ascone Giuliana , Cao Yixuan , Jansen Ineke D.C. , Di Ceglie Irene , van den Bosch Martijn H.J. , Blom Arjen B. , van Lent Peter L.E.M. , Everts Vincent , de Vries Teun J.
Published: May 2020

Recently, it was shown that interleukin-1β (IL-1β) has diverse stimulatory effects on different murine long bone marrow osteoclast precursors (OCPs) in vitro. In this study, interleukin-1 receptor antagonist deficient (Il1rn−/−) and wild-type (WT) mice were compared to investigate the effects of enhanced IL-1 signaling on the composition of OCPs in long bone, calvaria, vertebra, and jaw. Bone marrow cells were isolated from these sites and the percentage of early blast (CD31hi Ly-6C−), myeloid blast (CD31+ Ly-6C+), and monocyte (CD31− Ly-6Chi) OCPs was assessed by flow cytometry. At the time-point of cell isolation, Il1rn−/− mice showed no inflammation or bone destruction yet as determined by histology and microcomputed tomography. However, Il1rn−/− mice had an approximately two-fold higher percentage of OCPs in long bone and jaw marrow compared to WT. Conversely, vertebrae and calvaria marrow contained a similar composition of OCPs in both strains. Bone marrow cells were cultured with macrophage colony stimulating factor (M-CSF) and receptor of NfκB ligand (RANKL) on bone slices to assess osteoclastogenesis and on calcium phosphate-coated plates to analyze mineral dissolution. Deletion of Il1rn increased osteoclastogenesis from long bone, calvaria, and jaw marrows, and all Il1rn−/− cultures showed increased mineral dissolution compared to WT. However, osteoclast markers increased exclusively in Il1rn−/− osteoclasts from long bone and jaw. Collectively, these findings indicate that a lack of IL-1RA increases the numbers of OCPs in vivo, particularly in long bone and jaw, where rheumatoid arthritis and periodontitis develop. Thus, increased bone loss at these sites may be triggered by a larger pool of OCPs due to the disruption of IL-1 inhibitors.
Aptamer Cocktail to Detect Multiple Species of Mycoplasma in Cell Culture
Authors: Wan Quanyuan , Liu Xiaohui , Zeng Zihua , Chen Zhenghu , Liu Yanting , Zu Youli
Published: May 2020

Mycoplasma contamination of cell line cultures is a common, yet often undetected problem in research laboratories. Many of the existing techniques to detect mycoplasma contamination of cultured cells are time-consuming, expensive, and have significant drawbacks. Here, we describe a mycoplasma detection system that is useful for detecting multiple species of mycoplasma in infected cell lines. The system contains three dye-labeled detection aptamers that can specifically bind to mycoplasma-infected cells and a dye-labeled control aptamer that minimally binds to cells. With this system, mycoplasma-contaminated cells can be detected within 30 min by using a flow cytometer, fluorescence microscope, or microplate reader. Further, this system may be used to detect mycoplasma-contaminated culture medium. This study presents an novel mycoplasma detection model that is simple, rapid, inexpensive, and sensitive.
Metabolomic Fingerprinting of Potato Cultivars Differing in Susceptibility to Spongospora subterranea f. sp. subterranea Root Infection
Authors: Lekota Moleboheng , Modisane Kehumile J. , Apostolides Zeno , van der Waals Jacquie E.
Published: May 2020

Plants defend themselves from pathogens by producing bioactive defense chemicals. The biochemical mechanisms relating to quantitative resistance of potato to root infection by Spongospora subterranea f. sp. subterranea (Sss) are, however, not understood, and are not efficiently utilized in potato breeding programs. Untargeted metabolomics using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to elucidate the biochemical mechanisms of susceptibility to Sss root infection. Potato roots and root exudate metabolic profiles of five tolerant cultivars were compared with those of five susceptible cultivars, following Sss inoculation, to identify tolerance-related metabolites. Comparison of the relative metabolite abundance of tolerant versus susceptible cultivars revealed contrasting responses to Sss infection. Metabolites belonging to amino acids, organic acids, fatty acids, phenolics, and sugars, as well as well-known cell wall thickening compounds were putatively identified and were especially abundant in the tolerant cultivars relative to the susceptible cultivars. Metabolites known to activate plant secondary defense metabolism were significantly increased in the tolerant cultivars compared to susceptible cultivars following Sss inoculation. Root-exuded compounds belonging to the chemical class of phenolics were also found in abundance in the tolerant cultivars compared to susceptible cultivars. This study illustrated that Sss infection of potato roots leads to differential expression of metabolites in tolerant and susceptible potato cultivars.
The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis
Authors: Hutchings Greg , Janowicz Krzysztof , Moncrieff Lisa , Dompe Claudia , Strauss Ewa , Kocherova Ievgeniia , Nawrocki Mariusz J. , Kruszyna Łukasz , Wąsiatycz Grzegorz , Antosik Paweł , Shibli Jamil A. , Mozdziak Paul , Perek Bartłomiej , Krasiński Zbigniew , Kempisty Bartosz , Nowicki Michał
Published: May 2020

Neovascularization and angiogenesis are vital processes in the repair of damaged tissue, creating new blood vessel networks and increasing oxygen and nutrient supply for regeneration. The importance of Adipose-derived Mesenchymal Stem Cells (ASCs) contained in the adipose tissue surrounding blood vessel networks to these processes remains unknown and the exact mechanisms responsible for directing adipogenic cell fate remain to be discovered. As adipose tissue contains a heterogenous population of partially differentiated cells of adipocyte lineage; tissue repair, angiogenesis and neovascularization may be closely linked to the function of ASCs in a complex relationship. This review aims to investigate the link between ASCs and angiogenesis/neovascularization, with references to current studies. The molecular mechanisms of these processes, as well as ASC differentiation and proliferation are described in detail. ASCs may differentiate into endothelial cells during neovascularization; however, recent clinical trials have suggested that ASCs may also stimulate angiogenesis and neovascularization indirectly through the release of paracrine factors.
New Data on Spermatogenic Cyst Formation and Cellular Composition of the Testis in a Marine Gastropod, Littorina saxatilis
Authors: Demin Sergei Iu. , Bogolyubov Dmitry S. , Granovitch Andrey I. , Mikhailova Natalia A.
Published: May 2020

Knowledge of the testis structure is important for gastropod taxonomy and phylogeny, particularly for the comparative analysis of sympatric Littorina species. Observing fresh tissue and squashing fixed tissue with gradually increasing pressure, we have recently described a peculiar type of cystic spermatogenesis, rare in mollusks. It has not been documented in most mollusks until now. The testis of adult males consists of numerous lobules filled with multicellular cysts containing germline cells at different stages of differentiation. Each cyst is formed by one cyst cell of somatic origin. Here, we provide evidence for the existence of two ways of cyst formation in Littorina saxatilis. One of them begins with a goniablast cyst formation; it somewhat resembles cyst formation in Drosophila testes. The second way begins with capture of a free spermatogonium by the polyploid cyst cell which is capable to move along the gonad tissues. This way of cyst formation has not been described previously. Our data expand the understanding of the diversity of spermatogenesis types in invertebrates.
Cognitive Deficits in Myopathies
Authors: Peristeri Eleni , Aloizou Athina-Maria , Keramida Paraskevi , Tsouris Zisis , Siokas Vasileios , Mentis Alexios-Fotios A. , Dardiotis Efthimios
Published: May 2020

Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred.
Liver Fibrosis and Inflammation under the Control of ERK2
Authors: Jeng Kuo-Shyang , Lu Ssu-Jung , Wang Chih-Hsuan , Chang Chiung-Fang
Published: May 2020

Chronic liver injury could lead the formation of liver fibrosis, eventually some would develop to hepatocellular carcinoma (HCC), one of the leading malignancies worldwide. The aim of the study is to dissect the role of extracellular signal-regulated kinase 2 (ERK2) signaling in liver fibrosis and inflammation. The choline-deficient, ethionine-supplemented (CDE) diet could lead to fatty livers and generate oval cells, activate hepatocyte stellate cell (HSC) and recruit immune cells as the liver fibrosis model mice. WT and ERK2 deficient (ERK2−/−) mice were compared in terms of liver weight/body weight, liver function, liver fibrosis markers and the differential gene expression in hepatotoxicity. ERK2−/− mice display the less degree of liver fibrosis when compared to WT mice. The protein level of alpha smooth muscle (α-SMA) was reduced and several hepatocellular carcinoma-related genes such as MMP9, FoxM1 were down-regulated. In addition, the cell proliferation and the percentages of activated T cells were reduced in ERK2−/− mice upon liver injury. Therefore, ERK2 plays an important role in regulating liver cirrhosis and inflammation.
Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis
Authors: Bartoletti Michele , Pelizzari Giacomo , Gerratana Lorenzo , Bortot Lucia , Lombardi Davide , Nicoloso Milena , Scalone Simona , Giorda Giorgio , Baldassarre Gustavo , Sorio Roberto , Puglisi Fabio
Published: May 2020

Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status. Methods: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt). Results: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54–0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36–0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63–1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively). Conclusions: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.
Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson’s Disease
Authors: Chen Yong-Ren , Lai Pei-Lun , Chien Yueh , Lee Po-Hui , Lai Ying-Hsiu , Ma Hsin-I , Shiau Chia-Yang , Wang Kuo-Chuan
Published: May 2020

Parkinson’s disease (PD) is a long-term degenerative disease of the central nervous system (CNS) that primarily affects the motor system. So far there is no effective treatment for PD, only some drugs, surgery, and comprehensive treatment can alleviate the symptoms of PD. Stem cells derived from human exfoliated deciduous teeth (SHED), mesenchymal stem cells derived from dental pulp, may have promising potential in regenerative medicine. In this study, we examine the therapeutic effect of SHED-derived conditioned medium (SHED-CM) in a rotenone-induced PD rat model. Intravenous administration of SHED-CM generated by standardized procedures significantly improved the PD symptoms accompanied with increased tyrosine hydroxylase amounts in the striatum, and decreased α-synuclein levels in both the nigra and striatum, from rotenone-treated rats. In addition, this SHED-CM treatment decreased both Iba-1 and CD4 levels in these brain areas. Gene ontology analysis indicated that the biological process of genes affected by SHED-CM was primarily implicated in neurodevelopment and nerve regeneration. The major constituents of SHED-CM included insulin-like growth factor binding protein-6 (IGFBP-6), tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-1, and transforming growth factor β1 (TGF-β1). RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) revealed that these factors may ameliorate PD symptoms through modulating the cholinergic synapses, calcium signaling pathways, serotoninergic synapses, and axon guidance. In conclusion, our data indicate that SHED-CM contains active constituents that may have promising efficacy to alleviate PD.
Impact of a Histone Deacetylase Inhibitor—Trichostatin A on Neurogenesis after Hypoxia-Ischemia in Immature Rats
Authors: Zalewska Teresa , Jaworska Joanna , Sypecka Joanna , Ziemka-Nalecz Malgorzata
Published: May 2020

Hypoxia-ischemia (HI) in the neonatal brain frequently results in neurologic impairments, including cognitive disability. Unfortunately, there are currently no known treatment options to minimize ischemia-induced neural damage. We previously showed the neuroprotective/neurogenic potential of a histone deacetylase inhibitor (HDACi), sodium butyrate (SB), in a neonatal HI rat pup model. The aim of the present study was to examine the capacity of another HDACi—Trichostatin A (TSA)—to stimulate neurogenesis in the subgranular zone of the hippocampus. We also assessed some of the cellular/molecular processes that could be involved in the action of TSA, including the expression of neurotrophic factors (glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF)) as well as the TrkB receptor and its downstream signalling substrate— cAMP response element-binding protein (CREB). Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by hypoxia for 1 h. TSA was administered directly after the insult (0.2 mg/kg body weight). The study demonstrated that treatment with TSA restored the reduced by hypoxia-ischemia number of immature neurons (neuroblasts, BrdU/DCX-positive) as well as the number of oligodendrocyte progenitors (BrdU/NG2+) in the dentate gyrus of the ipsilateral damaged hemisphere. However, new generated cells did not develop the more mature phenotypes. Moreover, the administration of TSA stimulated the expression of BDNF and increased the activation of the TrkB receptor. These results suggest that BDNF-TrkB signalling pathways may contribute to the effects of TSA after neonatal hypoxic-ischemic injury.
Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
Authors: Orienti Isabella , Gentilomi Giovanna Angela , Farruggia Giovanna
Published: May 2020

At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.
Empowering Shotgun Mass Spectrometry with 2DE: A HepG2 Study
Authors: Kiseleva Olga , Zgoda Victor , Naryzhny Stanislav , Poverennaya Ekaterina
Published: May 2020

One of the major goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to catalog and annotate a myriad of heterogeneous proteoforms, produced by ca. 20 thousand genes. To achieve a detailed and personalized understanding into proteomes, we suggest using a customized RNA-seq library of potential proteoforms, which includes aberrant variants specific to certain biological samples. Two-dimensional electrophoresis coupled with high-performance liquid chromatography allowed us to downgrade the difficulty of biological mixing following shotgun mass spectrometry. To benchmark the proposed pipeline, we examined heterogeneity of the HepG2 hepatoblastoma cell line proteome. Data are available via ProteomeXchange with identifier PXD018450.
Steroids and TRP Channels: A Close Relationship
Authors: Méndez-Reséndiz Karina Angélica , Enciso-Pablo Óscar , González-Ramírez Ricardo , Juárez-Contreras Rebeca , Rosenbaum Tamara , Morales-Lázaro Sara Luz
Published: May 2020

Transient receptor potential (TRP) channels are remarkable transmembrane protein complexes that are essential for the physiology of the tissues in which they are expressed. They function as non-selective cation channels allowing for the signal transduction of several chemical, physical and thermal stimuli and modifying cell function. These channels play pivotal roles in the nervous and reproductive systems, kidney, pancreas, lung, bone, intestine, among others. TRP channels are finely modulated by different mechanisms: regulation of their function and/or by control of their expression or cellular/subcellular localization. These mechanisms are subject to being affected by several endogenously-produced compounds, some of which are of a lipidic nature such as steroids. Fascinatingly, steroids and TRP channels closely interplay to modulate several physiological events. Certain TRP channels are affected by the typical genomic long-term effects of steroids but others are also targets for non-genomic actions of some steroids that act as direct ligands of these receptors, as will be reviewed here.
Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways
Authors: Tang Jia Xin , Thompson Kyle , Taylor Robert W. , Oláhová Monika
Published: May 2020

The assembly of mitochondrial oxidative phosphorylation (OXPHOS) complexes is an intricate process, which—given their dual-genetic control—requires tight co-regulation of two evolutionarily distinct gene expression machineries. Moreover, fine-tuning protein synthesis to the nascent assembly of OXPHOS complexes requires regulatory mechanisms such as translational plasticity and translational activators that can coordinate mitochondrial translation with the import of nuclear-encoded mitochondrial proteins. The intricacy of OXPHOS complex biogenesis is further evidenced by the requirement of many tightly orchestrated steps and ancillary factors. Early-stage ancillary chaperones have essential roles in coordinating OXPHOS assembly, whilst late-stage assembly factors—also known as the LYRM (leucine–tyrosine–arginine motif) proteins—together with the mitochondrial acyl carrier protein (ACP)—regulate the incorporation and activation of late-incorporating OXPHOS subunits and/or co-factors. In this review, we describe recent discoveries providing insights into the mechanisms required for optimal OXPHOS biogenesis, including the coordination of mitochondrial gene expression with the availability of nuclear-encoded factors entering via mitochondrial protein import systems.
Reference Ranges of 8-Isoprostane Concentrations in Exhaled Breath Condensate (EBC): A Systematic Review and Meta-Analysis
Authors: Shoman Yara , Wild Pascal , Hemmendinger Maud , Graille Melanie , Sauvain Jean-Jacques , B. Hopf Nancy , Guseva Canu Irina
Published: May 2020

Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation.
1,4-Disubstituted 1H-1,2,3-Triazoles for Renal Diseases: Studies of Viability, Anti-Inflammatory, and Antioxidant Activities
Authors: Cheng Ching-Yi , Haque Ashanul , Hsieh Ming-Fa , Imran Hassan Syed , Faizi Md. Serajul Haque , Dege Necmi , Khan Muhammad S.
Published: May 2020

Inflammation is a hallmark of many metabolic diseases. We previously showed that ferrocene-appended 1H-1,2,3-triazole hybrids inhibit nitric oxide (NO) production in in vitro models of lipopolysaccharide-induced inflammation in the BV-2 cell. In the present study, we explored the viability, anti-inflammatory, and antioxidant potential of ferrocene-1H-1,2,3-triazole hybrids using biochemical assays in rat mesangial cells (RMCs). We found that, among all the ferrocene-1H-1,2,3-triazole hybrids, X2–X4 exhibited an antioxidant effect on mitochondrial free radicals. Among all the studied compounds, X4 demonstrated the best anti-inflammatory effect on RMCs. These results were supplemented by in silico studies including molecular docking with human cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) enzymes as well as absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Besides, two new crystal structures of the compounds have also been reported. In addition, combining the results from the inducible nitric oxide synthase (iNOS), cPLA2, COX-2, and matrix metalloproteinase-9 (MMP-9) enzymatic activity analysis and NO production also confirmed this argument. Overall, the results of this study will be a valuable addition to the growing body of work on biological activities of triazole-based compounds.
CSI NGS Portal: An Online Platform for Automated NGS Data Analysis and Sharing
Authors: An Omer , Tan Kar-Tong , Li Ying , Li Jia , Wu Chan-Shuo , Zhang Bin , Chen Leilei , Yang Henry
Published: May 2020

Next-generation sequencing (NGS) has been a widely-used technology in biomedical research for understanding the role of molecular genetics of cells in health and disease. A variety of computational tools have been developed to analyse the vastly growing NGS data, which often require bioinformatics skills, tedious work and a significant amount of time. To facilitate data processing steps minding the gap between biologists and bioinformaticians, we developed CSI NGS Portal, an online platform which gathers established bioinformatics pipelines to provide fully automated NGS data analysis and sharing in a user-friendly website. The portal currently provides 16 standard pipelines for analysing data from DNA, RNA, smallRNA, ChIP, RIP, 4C, SHAPE, circRNA, eCLIP, Bisulfite and scRNA sequencing, and is flexible to expand with new pipelines. The users can upload raw data in FASTQ format and submit jobs in a few clicks, and the results will be self-accessible via the portal to view/download/share in real-time. The output can be readily used as the final report or as input for other tools depending on the pipeline. Overall, CSI NGS Portal helps researchers rapidly analyse their NGS data and share results with colleagues without the aid of a bioinformatician. The portal is freely available at: https://csibioinfo.nus.edu.sg/csingsportal.
An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases
Authors: Qasim Syed Saad B. , Al-Otaibi Dalal , Al-Jasser Reham , Gul Sarhang S. , Zafar Muhammad Sohail
Published: May 2020

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.
Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β Activity in Colorectal Cancer Cell Lines
Authors: Saieva Laura , Barreca Maria Magdalena , Zichittella Chiara , Prado Maria Giulia , Tripodi Marco , Alessandro Riccardo , Conigliaro Alice
Published: May 2020

The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibition, in hypoxic cells, hampered β-catenin nuclear localization and its transcriptional activity, while lncH19 silencing did not induce the same effects. Interestingly, our data revealed that miRNA inhibition in hypoxic cells restored the activity of Glycogen Synthase Kinase 3β (GSK-3β) reducing the amount of P-Ser9 kinase, thus unveiling a role of the miR-675-5p in controlling GSK-3β activity. Bioinformatics analyses highlighted the serine/threonine-protein phosphatases PPP2CA, responsible for GSK-3β activation, among the miR-675-5p targets, thus indicating the molecular mediator through which miR-675-5p may control β-catenin nuclear localization. In conclusion, here we demonstrated that the inhibition of the hypoxia-induced non-coding RNA miR-675-5p hampered the nuclear localization of β-catenin by regulating GSK-3β activity, thus proposing the miR-675-5p as a new therapeutic target for the treatment of colorectal cancer.
Phenotypic and Functional Diversity of Mast Cells
Authors: Tanaka Satoshi
Published: May 2020

Mast cells, which originate from hematopoietic stem cells, are distributed in nearly all vascularized tissues [...]