bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementary Targeting of Rb Phosphorylation and Growth in Cervical Cancer Cell Cultures and a Xenograft Mouse Model by SHetA2 and Palbociclib
Authors: Kennedy Amy L. , Rai Rajani , Isingizwe Zitha Redempta , Zhao Yan Daniel , Lightfoot Stanley A. , Benbrook Doris M.
Published: May 2020

Cervical cancer is caused by high-risk human papillomavirus (HPV) types and treated with conventional chemotherapy with surgery and/or radiation. HPV E6 and E7 proteins increase phosphorylation of retinoblastoma (Rb) by cyclin D1/cyclin dependent kinase (CDK)4/6 complexes. We hypothesized that cyclin D1 degradation by the SHetA2 drug in combination with palbociclib inhibition of CDK4/6 activity synergistically reduces phosphorylated Rb (phospho-Rb) and inhibits cervical cancer growth. The effects of these drugs, alone, and in combination, were evaluated in SiHa and CaSki HPV-positive and C33A HPV-negative cervical cancer cell lines using cell culture, western blots and ELISA, and in a SiHa xenograft model. Endpoints were compared by isobolograms, ANOVA, and Chi-Square. In all cell lines, combination indexes documented synergistic interaction of SHetA2 and palbociclib in association SHetA2 reduction of cyclin D1 and phospho-Rb, palbociclib reduction of phospho-Rb, and enhanced phospho-Rb reduction upon drug combination. Both drugs significantly reduced phospho-Rb and growth of SiHa xenograft tumors as single agents and acted additively when combined, with no evidence of toxicity. Dilated CD31-negative blood vessels adjacent to, or within, areas of necrosis and apoptosis were observed in all drug-treated tumors. These results justify development of the SHetA2 and palbociclib combination for targeting phospho-Rb in cervical cancer treatment.
Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs
Authors: Marconato Laura , Sabattini Silvia , Marisi Giorgia , Rossi Federica , Leone Vito Ferdinando , Casadei-Gardini Andrea
Published: May 2020

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.
Surface Engineering of WO3/BiVO4 to Boost Solar Water-Splitting
Authors: Cao Yuncheng , Xing Zheng , Wang Bobo , Tang Wei , Wu Rong , Li Jiangyu , Ma Ming
Published: May 2020

Single-phase photoanodes often suffer inferior charge transport, which can be mitigated by constructing efficient heterojunctions. Thus, we have fabricated a fluorine-doped tin oxide (FTO)/WO3/BiVO4 heterojunction using hydrothermal and spin-coating methods. Surface engineering was exploited to further accelerate the reaction kinetics, which was achieved via post-modification with NaOH solution. This treatment alters the surface chemical state of the BiVO4 nanoparticles, leading to enhanced charge transport and surface water oxidation processes. As a result, the optimized sample can produce a photocurrent more than two times that of WO3. The simple post-treatment provides a viable and cost-effective strategy for promoting the photoelectric properties of photoanodes.
Mechanistic Insights into Visible Light-Induced Direct Hydroxylation of Benzene to Phenol with Air and Water over Pt-Modified WO3 Photocatalyst
Authors: Kurikawa Yuya , Togo Masahiro , Murata Michihisa , Matsuda Yasuaki , Sakata Yoshihisa , Kobayashi Hisayoshi , Higashimoto Shinya
Published: May 2020

Activation of C(sp2)-H in aromatic molecules such as benzene is one of the challenging reactions. The tungsten trioxide supported Pt nanoparticles (Pt-WO3) exhibited hydroxylation of benzene in the presence of air and H2O under visible-light (420 < λ < 540 nm) irradiation. The photocatalytic activities (yields and selectivity of phenol) were studied under several experimental conditions. Furthermore, investigations of mechanistic insight into hydroxylation of benzene have been carried out by analyses with apparent quantum yields (AQY), an H218O isotope-labeling experiment, kinetic isotope effects (KIE), electrochemical measurements and density functional theory (DFT) calculations. It was proposed that dissociation of the O–H bond in H2O is the rate-determining step. Furthermore, the substitution of the OH derived from H2O with H abstracted from benzene by photo-formed H2O2 indicated a mechanism involving a push-pull process for the hydroxylation of benzene into phenol.
Lactulose and Melibiose Inhibit α-Synuclein Aggregation and Up-Regulate Autophagy to Reduce Neuronal Vulnerability
Authors: Chen Chiung Mei , Lin Chih-Hsin , Wu Yih-Ru , Yen Chien-Yu , Huang Yu-Ting , Lin Jia-Lan , Lin Chung-Yin , Chen Wan-Ling , Chao Chih-Ying , Lee-Chen Guey-Jen , Su Ming-Tsan , Chang Kuo-Hsuan
Published: May 2020

Parkinson’s disease (PD) is a neurodegenerative disease characterized by selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra (SN) and proteinaceous α-synuclein-positive Lewy bodies and Lewy neuritis. As a chemical chaperone to promote protein stability and an autophagy inducer to clear aggregate-prone proteins, a disaccharide trehalose has been reported to alleviate neurodegeneration in PD cells and mouse models. Its trehalase-indigestible analogs, lactulose and melibiose, also demonstrated potentials to reduce abnormal protein aggregation in spinocerebellar ataxia cell models. In this study, we showed the potential of lactulose and melibiose to inhibit α-synuclein aggregation using biochemical thioflavin T fluorescence, cryogenic transmission electron microscopy (cryo-TEM) and prokaryotic split Venus complementation assays. Lactulose and melibiose further reduced α-synuclein aggregation and associated oxidative stress, as well as protected cells against α-synuclein-induced neurotoxicity by up-regulating autophagy and nuclear factor, erythroid 2 like 2 (NRF2) pathway in DAergic neurons derived from SH-SY5Y cells over-expressing α-synuclein. Our findings strongly indicate the potential of lactulose and melibiose for mitigating PD neurodegeneration, offering new drug candidates for PD treatment.
Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role
Authors: D’Adamo Stefania , Cetrullo Silvia , Panichi Veronica , Mariani Erminia , Flamigni Flavio , Borzì Rosa Maria
Published: May 2020

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.
The Influence of Palmatine Isolated from Berberis sibirica Radix on Pentylenetetrazole-Induced Seizures in Zebrafish
Authors: Gawel Kinga , Kukula-Koch Wirginia , Nieoczym Dorota , Stepnik Katarzyna , van der Ent Wietske , Banono Nancy Saana , Tarabasz Dominik , Turski Waldemar A. , Esguerra Camila V.
Published: May 2020

Palmatine (PALM) and berberine (BERB) are widely identified isoquinoline alkaloids among the representatives of the Berberidaceae botanical family. The antiseizure activity of BERB was shown previously in experimental epilepsy models. We assessed the effect of PALM in a pentylenetetrazole (PTZ)-induced seizure assay in zebrafish, with BERB as an active reference compound. Both alkaloids were isolated from the methanolic root extract of Berberis sibirica by counter-current chromatography, and their ability to cross the blood–brain barrier was determined via quantitative structure–activity relationship assay. PALM exerted antiseizure activity, as confirmed by electroencephalographic analysis, and decreased c-fos and bdnf levels in PTZ-treated larvae. In a behavioral assay, PALM dose-dependently decreased PTZ-induced hyperlocomotion. The combination of PALM and BERB in ED16 doses revealed hyperadditive activity towards PTZ-induced hyperlocomotion. Notably, we have indicated that both alkaloids may exert their anticonvulsant activity through different mechanisms of action. Additionally, the combination of both alkaloids in a 1:2.17 ratio (PALM: BERB) mimicked the activity of the pure extract, which indicates that these two active compounds are responsible for its anticonvulsive activity. In conclusion, our study reveals for the first time the anticonvulsant activity of PALM and suggests the combination of PALM and BERB may have higher therapeutic value than separate usage of these compounds.
The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation
Authors: Amoroso Chiara , Perillo Federica , Strati Francesco , Fantini Massimo , Caprioli Flavio , Facciotti Federica
Published: May 2020

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host−microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.
Exogenous Liposomal Ceramide-C6 Ameliorates Lipidomic Profile, Energy Homeostasis, and Anti-Oxidant Systems in NASH
Authors: Zanieri Francesca , Levi Ana , Montefusco David , Longato Lisa , De Chiara Francesco , Frenguelli Luca , Omenetti Sara , Andreola Fausto , Luong Tu Vinh , Massey Veronica , Caballeria Juan , Fondevila Constantino , Shanmugavelandy Sriram S , Fox Todd , Mazza Giuseppe , Argemi Josepmaria , Bataller Ramon , Cowart Lauren Ashley , Kester Mark , Pinzani Massimo , Rombouts Krista
Published: May 2020

In non-alcoholic steatohepatitis (NASH), many lines of investigation have reported a dysregulation in lipid homeostasis, leading to intrahepatic lipid accumulation. Recently, the role of dysfunctional sphingolipid metabolism has also been proposed. Human and animal models of NASH have been associated with elevated levels of long chain ceramides and pro-apoptotic sphingolipid metabolites, implicated in regulating fatty acid oxidation and inflammation. Importantly, inhibition of de novo ceramide biosynthesis or knock-down of ceramide synthases reverse some of the pathology of NASH. In contrast, cell permeable, short chain ceramides have shown anti-inflammatory actions in multiple models of inflammatory disease. Here, we investigated non-apoptotic doses of a liposome containing short chain C6-Ceramide (Lip-C6) administered to human hepatic stellate cells (hHSC), a key effector of hepatic fibrogenesis, and an animal model characterized by inflammation and elevated liver fat content. On the basis of the results from unbiased liver transcriptomic studies from non-alcoholic fatty liver disease patients, we chose to focus on adenosine monophosphate activated kinase (AMPK) and nuclear factor-erythroid 2-related factor (Nrf2) signaling pathways, which showed an abnormal profile. Lip-C6 administration inhibited hHSC proliferation while improving anti-oxidant protection and energy homeostasis, as indicated by upregulation of Nrf2, activation of AMPK and an increase in ATP. To confirm these in vitro data, we investigated the effect of a single tail-vein injection of Lip-C6 in the methionine-choline deficient (MCD) diet mouse model. Lip-C6, but not control liposomes, upregulated phospho-AMPK, without inducing liver toxicity, apoptosis, or exacerbating inflammatory signaling pathways. Alluding to mechanism, mass spectrometry lipidomics showed that Lip-C6-treatment reversed the imbalance in hepatic phosphatidylcholines and diacylglycerides species induced by the MCD-fed diet. These results reveal that short-term Lip-C6 administration reverses energy/metabolic depletion and increases protective anti-oxidant signaling pathways, possibly by restoring homeostatic lipid function in a model of liver inflammation with fat accumulation.
The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice
Authors: Zoicas Iulia , Schumacher Fabian , Kleuser Burkhard , Reichel Martin , Gulbins Erich , Fejtova Anna , Kornhuber Johannes , Rhein Cosima
Published: May 2020

Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tgfb) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tgfb mice than in female Asm-tgfb mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tgfb mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
Glial A2B Adenosine Receptors Modulate Abnormal Tachykininergic Responses and Prevent Enteric Inflammation Associated with High Fat Diet-Induced Obesity
Authors: D’Antongiovanni Vanessa , Benvenuti Laura , Fornai Matteo , Pellegrini Carolina , van den Wijngaard Renè , Cerantola Silvia , Giron Maria Cecilia , Caputi Valentina , Colucci Rocchina , Haskó Gyorgy , Németh Zoltán H. , Blandizzi Corrado , Antonioli Luca
Published: May 2020

The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100β, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1β (IL-1β), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1β, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1β, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.
Blood Eosinophils Subtypes and Their Survivability in Asthma Patients
Authors: Januskevicius Andrius , Jurkeviciute Egle , Janulaityte Ieva , Kalinauskaite-Zukauske Virginija , Miliauskas Skaidrius , Malakauskas Kestutis
Published: May 2020

Eosinophils subtypes as lung-resident (rEOS) and inflammatory (iEOS) eosinophils are different in surface protein expression, functions, response to IL-5 and localization in lungs. rEOS- and iEOS-like eosinophils are found in blood; thus, we aimed to investigate their quantity and survivability in asthma patients. A total of 40 individuals were included: 10 steroid-free non-severe allergic asthma (AA), and 18 severe non-allergic eosinophilic asthma (SNEA) patients, the control group consisted of 12 healthy non-smoking subjects (HS). A bronchial challenge with Dermatophagoides pteronysinnus allergen was performed for AA patients and HS. Blood eosinophils subtyping was completed with magnetic beads’ conjugated antibodies against surface CD62L. Eosinophils adhesion to hTERT airway smooth muscle (ASM) cells was measured by evaluating their peroxidase activity and viability by annexin V and propidium iodide staining. We found that the predominant blood eosinophil subtype in AA patients was iEOS, while rEOS prevailed in SNEA patients (p < 0.05). Moreover, rEOS demonstrated higher adhesion intensity compared with iEOS in all investigated groups. Both eosinophils subtypes of SNEA patients had higher survivability over the AA group. However, iEOS survivability from AA and SNEA groups was higher compared with rEOS under standard conditions, when rEOS survivability increased after their incubation with ASM cells. Bronchial allergen challenge abolished the dominance of blood iEOS in AA patients and prolonged only iEOS survivability. Though the challenge did not affect the adhesion of any eosinophils subtypes, the direct dependence of rEOS and iEOS survivability on their interaction with ASM cells was revealed (p < 0.05). These findings provide the premise for eosinophils subtype-oriented asthma treatment.
A New Pathway Promotes Adaptation of Human Glioblastoma Cells to Glucose Starvation
Authors: Azzalin Alberto , Brambilla Francesca , Arbustini Eloisa , Basello Katia , Speciani Attilio , Mauri Pierluigi , Bezzi Paola , Magrassi Lorenzo
Published: May 2020

Adaptation of glioblastoma to caloric restriction induces compensatory changes in tumor metabolism that are incompletely known. Here we show that in human glioblastoma cells maintained in exhausted medium, SHC adaptor protein 3 (SHC3) increases due to down-regulation of SHC3 protein degradation. This effect is reversed by glucose addition and is not present in normal astrocytes. Increased SHC3 levels are associated to increased glucose uptake mediated by changes in membrane trafficking of glucose transporters of the solute carrier 2A superfamily (GLUT/SLC2A). We found that the effects on vesicle trafficking are mediated by SHC3 interactions with adaptor protein complex 1 and 2 (AP), BMP-2-inducible protein kinase and a fraction of poly ADP-ribose polymerase 1 (PARP1) associated to vesicles containing GLUT/SLC2As. In glioblastoma cells, PARP1 inhibitor veliparib mimics glucose starvation in enhancing glucose uptake. Furthermore, cytosol extracted from glioblastoma cells inhibits PARP1 enzymatic activity in vitro while immunodepletion of SHC3 from the cytosol significantly relieves this inhibition. The identification of a new pathway controlling glucose uptake in high grade gliomas represents an opportunity for repositioning existing drugs and designing new ones.
Pragmatic Markers in the Management of Asthma: A Real-World-Based Approach
Authors: Ciprandi Giorgio , Marseglia Gian Luigi , Ricciardolo Fabio Luigi Massimo , Tosca Maria Angela
Published: May 2020

Bronchial hyperreactivity, reversible airflow limitation and chronic airway inflammation characterize asthma pathophysiology. Personalized medicine, i.e., a tailored management approach, is appropriate for asthma management and is based on the identification of peculiar phenotypes and endotypes. Biomarkers are necessary for defining phenotypes and endotypes. Several biomarkers have been described in asthma, but most of them are experimental and/or not commonly available. The current paper will, therefore, present pragmatic biomarkers useful for asthma management that are available in daily clinical practice. In this regard, eosinophil assessment and serum allergen-specific IgE assay are the most reliable biomarkers. Lung function, mainly concerning forced expiratory flow at 25-755 of vital capacity (FEF25-75), and nasal cytology may be envisaged as ancillary biomarkers in asthma management. In conclusion, biomarkers have clinical relevance in asthma concerning both the endotype definition and the personalization of the therapy.
Fabrication of Composite Ultrafiltration Membrane by Coating Urea Formaldehyde Resin on Filter Paper
Authors: Lu Hailong , Zhang Lili , Shi Yong , Ma Jinxia , Zhou Xiaofan
Published: May 2020

Urea-formaldehyde resin (UFR), a thermosetting resin, is used to prepare ultrafiltration membranes because of its excellent mechanical properties and filtration performance. Herein, a porous ultrafiltration membrane is prepared by coating a mixture of UFR and carboxymethylcellulose (CMC) on the surface of filter paper via a facile acid-curing treatment method. CMC is used as a thickening agent, and hydrochloric acid is used as a curing agent to accelerate composite membrane formation. The mesoporous UFR is embedded in the large pores of the paper matrix by coating treatment, and the presence of CMC can decrease the flowability of the resin. The effects of UFR concentration, CMC dosage, and hydrochloric acid concentration on the performance of the composite ultrafiltration membrane are studied. The ultrafiltration membrane demonstrates a rejection rate of 85% and a pure water flux of 850 L/(m2·h) with the optimized resin concentration, CMC dosage, hydrochloric acid concentration, and coating amount at 30%, 20% (resin dry), 12%, and 250 g/m2, respectively.
Composite of PLA Nanofiber and Hexadecyl Trimethyl-Ammonium Chloride-Modified Montmorillonite Clay: Fabrication and Morphology
Authors: Mushtaq Muhammad , Wasim Muhammad , Naeem Muhammad , Khan Muhammad , Yue Sun , Saba Hina , Hussain Tanveer , Siddiqui Muhammad , Farooq Amjad , Wei Qufu
Published: May 2020

Our research aim is to develop a new composite material via electrospinning and dip coating methodology. Among bioabsorbable polymers, Polylactic acid (PLA) is viewed as a suitable base material for biomedical usages such as drug delivery and wound dressing. Additionally, these bioabsorbable materials can be used for filtration applications in terms of antibacterial activity the integration of hexadecyl trimethyl ammonium chloride-modified montmorillonite (CTAC-MMT) into PLA fibers would improve mechanical and absorption properties of the PLA fibers. This research aimed to investigated a new method of combining electrospun PLA with dip coating of CTAC-MMT solution. Precisely, electrospun PLA nanofibers were treated with methanol and dipped in a CTAC-MMT suspension. The resultant layer composite of PLA nanofibers and CTAC-MMT was then characterized by elemental analysis. For material characterization and morphological structure analysis, we performed FTIR, SEM-EDS, XPS, DSC, and X-ray diffraction. Through mechanical testing and contact angle measurements, it was found that CTAC-MMT shows a slight improvement in mechanical and absorption properties. Results of characterization techniques have shown that CTAC-MMT can be used as a good filler for composites processed through the dip-coating method. Moreover, results also showed that the diameter of microfibers is affected by concentrations of PLA.
The Maximum Common Subgraph Problem: A Parallel and Multi-Engine Approach
Authors: Quer Stefano , Marcelli Andrea , Squillero Giovanni
Published: May 2020

The maximum common subgraph of two graphs is the largest possible common subgraph, i.e., the common subgraph with as many vertices as possible. Even if this problem is very challenging, as it has been long proven NP-hard, its countless practical applications still motivates searching for exact solutions. This work discusses the possibility to extend an existing, very effective branch-and-bound procedure on parallel multi-core and many-core architectures. We analyze a parallel multi-core implementation that exploits a divide-and-conquer approach based on a thread pool, which does not deteriorate the original algorithmic efficiency and it minimizes data structure repetitions. We also extend the original algorithm to parallel many-core GPU architectures adopting the CUDA programming framework, and we show how to handle the heavily workload-unbalance and the massive data dependency. Then, we suggest new heuristics to reorder the adjacency matrix, to deal with “dead-ends”, and to randomize the search with automatic restarts. These heuristics can achieve significant speed-ups on specific instances, even if they may not be competitive with the original strategy on average. Finally, we propose a portfolio approach, which integrates all the different local search algorithms as component tools; such portfolio, rather than choosing the best tool for a given instance up-front, takes the decision on-line. The proposed approach drastically limits memory bandwidth constraints and avoids other typical portfolio fragility as CPU and GPU versions often show a complementary efficiency and run on separated platforms. Experimental results support the claims and motivate further research to better exploit GPUs in embedded task-intensive and multi-engine parallel applications.
Investigation of Total Phenolic Content and Antioxidant Activities of Spruce Bark Extracts Isolated by Deep Eutectic Solvents
Authors: Jablonsky Michal , Majova Veronika , Strizincova Petra , Sima Jozef , Jablonsky Jozef
Published: May 2020

Extracts from spruce bark obtained using different deep eutectic solvents were screened for their total phenolic content (TPC) and antioxidant activities. Water containing choline chloride-based deep eutectic solvents (DESs) with lactic acid and 1,3-propanediol, 1,3-butanediol, 1,4-butanediol, and 1,5-pentanediol, with different molar ratios, were used as extractants. Basic characteristics of the DESs (density, viscosity, conductivity, and refractive index) were determined. All the DESs used behave as Newtonian liquids. The extractions were performed for 2 h at 60 °C under continuous stirring. TPC was determined spectrophotometrically, using the Folin-Ciocalteu reagent, and expressed as gallic acid equivalent (GAE). The antioxidant activity was determined spectrophotometrically by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The TPC varied from 233.6 to 596.2 mg GAE/100 g dry bark; radical scavenging activity (RSA) ranged between 81.4% and 95%. This study demonstrated that deep eutectic solvents are suitable solvents for extracting phenolic compounds from spruce bark.
Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab
Authors: Shimizu Takuto , Miyake Makito , Hori Shunta , Ichikawa Kazuki , Omori Chihiro , Iemura Yusuke , Owari Takuya , Itami Yoshitaka , Nakai Yasushi , Anai Satoshi , Tomioka Atsushi , Tanaka Nobumichi , Fujimoto Kiyohide
Published: May 2020

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.
Clustering and Kernel Density Estimation for Assessment of Measurable Residual Disease by Flow Cytometry
Authors: Jacqmin Hugues , Chatelain Bernard , Louveaux Quentin , Jacqmin Philippe , Dogné Jean-Michel , Graux Carlos , Mullier François
Published: May 2020

Standardization, data mining techniques, and comparison to normality are changing the landscape of multiparameter flow cytometry in clinical hematology. On the basis of these principles, a strategy was developed for measurable residual disease (MRD) assessment. Herein, suspicious cell clusters are first identified at diagnosis using a clustering algorithm. Subsequently, automated multidimensional spaces, named “Clouds”, are created around these clusters on the basis of density calculations. This step identifies the immunophenotypic pattern of the suspicious cell clusters. Thereafter, using reference samples, the “Abnormality Ratio” (AR) of each Cloud is calculated, and major malignant Clouds are retained, known as “Leukemic Clouds” (L-Clouds). In follow-up samples, MRD is identified when more cells fall into a patient’s L-Cloud compared to reference samples (AR concept). This workflow was applied on simulated data and real-life leukemia flow cytometry data. On simulated data, strong patient-dependent positive correlation (R2 = 1) was observed between the AR and spiked-in leukemia cells. On real patient data, AR kinetics was in line with the clinical evolution for five out of six patients. In conclusion, we present a convenient flow cytometry data analysis approach for the follow-up of hematological malignancies. Further evaluation and validation on more patient samples and different flow cytometry panels is required before implementation in clinical practice.
Order Indices and Entanglement Production in Quantum Systems
Authors: Yukalov Vyacheslav I.
Published: May 2020

The review is devoted to two important quantities characterizing many-body systems, order indices and the measure of entanglement production. Order indices describe the type of order distinguishing statistical systems. Contrary to the order parameters characterizing systems in the thermodynamic limit and describing long-range order, the order indices are applicable to finite systems and classify all types of orders, including long-range, mid-range, and short-range orders. The measure of entanglement production quantifies the amount of entanglement produced in a many-partite system by a quantum operation. Despite that the notions of order indices and entanglement production seem to be quite different, there is an intimate relation between them, which is emphasized in the review.
Finding Efficient and Lower Capacitance Paths for the Transfer of Energy in a Digital Microgrid
Authors: Jiang Zhengqi , Rojas-Cessa Roberto
Published: May 2020

In a digital microgrid (DMG), different from an analogous microgrid, energy is transmitted in well-defined amounts and in a store-and-forward fashion. Nodes of a DMG network, or energy packet switches (EPSs), use supercapacitors as temporary energy storage units to control the amount of energy supplied to a load. An EPS aggregates energy coming from different inputs or sources and forwards it to other EPSs or to a load. Rather than referring to electrical power, we measure the delivery of it as energy. An EPS is built with many supercapacitors to be able to provide significant amounts of energy to one or multiple loads. An EPS dedicates a configurable number of supercapacitors to an energy flow. In this paper, we find the conditions to achieve the smallest energy loss in the supply of energy from energy sources to loads in a DMG and propose a routing algorithm to find a path with small capacitance in a DMG network built with store-and-forward energy nodes. In addition, because an EPS has a finite amount of capacitance, the number of flows that the DMG can sustain may be limited. Exacerbating this problem, the passive transfer of energy between energy units may suffer losses as a result of the capacitance used and energy transmitted between supercapacitors. Therefore, the path between a source and a load has to be carefully selected. To solve this problem, our proposed routing algorithm finds the smallest capacitance paths to enable the scalability of the DMG. We analyze a path of supercapacitor-based networks and underscore the conditions to achieve minimal energy losses, to minimize the path capacitance, and to balance these two conflicting objectives. We analyze these approaches and show numerical examples on a small power network. Results show that total energy loss in this DMG is path independent as this loss depends on only the voltage of the capacitors at Node 1; the node connected to the source. In addition, results show that by adopting the proposed algorithm, the scalability of the DMG can be increased by finding the smallest capacitance paths to transfer energy between the sources and the loads. We show how store-and-forward transfer works on an actual DMG testbed with two EPSs and two loads.
Methodology for Asynchronous Motor Impedance Measurement by Using Higher Order Harmonics
Authors: Dambrauskas Karolis , Vanagas Jonas , Bugenis Saulius , Zimnickas Tomas , Kalvaitis Artūras
Published: May 2020

The control methods of asynchronous motors have changed during past decades. In the past, asynchronous motors were connected to grid directly. Later, thyristors as switching element-based frequency converters for asynchronous motors have appeared. Today, asynchronous motors are controlled with variable speed drives that are frequency converters consisting of IGBT power modules as switching elements that form the output voltage for asynchronous motors. Because of IGBT’s high switching speed of around few kilohertz, higher order harmonics appear in the output voltage. Their influence was not analyzed in the past as the methodology of asynchronous motor winding resistance measurement was under development. In this article, a new methodology of motor resistance measurement for mass production is introduced. The resistance—compared to higher order harmonics values between the windings of benchmark and tested motors—gives an ability to faster and more accurately determine a motor’s characteristics and losses induced by higher order harmonics that appear when a motor is powered by a variable speed drive. Motor winding’s inductance dependency on the current of magnetic biasing and the higher frequency of voltage is analyzed in this article. In addition, the simulation model of resistance to higher order harmonics of motor measurement is introduced and analyzed in this article.
Vehicular Emission: Estimate of Air Pollutants to Guide Local Political Choices. A Case Study
Authors: Mazza Sergio , Aiello Donatella , Macario Anastasia , De Luca Pierantonio
Published: May 2020

The aim of this case study was to show how, with the use of software, is it possible to carry out a preventive screening of vehicular emissions. Moreover, thanks to this preliminary analysis, some areas that are potentially polluted can be identified in advance and suitable samplings on small-scale on them would help to verify the effectiveness of policies that can be adopted for the reduction of pollution. To this end, this paper reports a case study on vehicle traffic pollution in Calabria, a region in the south of Italy. We used the methodology called Corinair (Coordination Information AIR), developed by the EEA (European Environment Agency) and uses the software Copert4 (Computer Program to calculate Emission from Road Traffic). The total emissions per area were analyzed and the emissions for particular pollutants per unit area (km²) and per citizen were considered. The obsolete vehicles determined a substantial impact on the local atmospheric pollution. It was demonstrated how it is possible to substantially reduce the pollution of an area by adopting policies that encourage, for example, through tax concessions, the replacement of old cars of private citizens.
Harnessing the Residual Nutrients in Anaerobic Digestate for Ethanol Fermentation and Digestate Remediation Using Saccharomyces cerevisiae
Authors: Ujor Victor Chinomso , Okonkwo Christopher Chukwudi , Rush Brennen Bradley , McCrea Grace Ellen , Ezeji Thaddeus Chukwuemeka
Published: May 2020

This study evaluated the feasibility of concomitant nutrient removal, cleaner water recovery, and improved ethanol production via glucose fermentation in the liquid fraction of anaerobic digestate (ADE) by Saccharomyces cerevisiae. The 25%, 50%, and 100% (v/v) ADE supported the growth of S. cerevisiae, glucose utilization (~100 g/L) and ethanol production (up to 50.4 ± 6.4 g/L). After a 144 h fermentation in the 50% ADE, the concentrations of ammonia, total nitrogen, phosphate, and total phosphorus decreased 1000-, 104.43-, 1.94-, and 2.20-fold, respectively. Notably, only 0.40 ± 0.61 mg/L ammonia was detected in the 50% ADE post-fermentation. Similarly, the concentrations of aluminum, copper, magnesium, manganese, molybdenum, potassium, sodium, iron, sulfur, zinc, chloride, and sulfate decreased significantly in the ADE. Further analysis suggests that the nitrogen (ammonia and protein), phosphate, and the metal contents of the digestate work in tandem to promote growth and ethanol production. Among these, ammonia and protein appear to exert considerable effects on S. cerevisiae. These results represent a significant first step towards repurposing ADE as a resource in bio-production of fuels and chemicals, whilst generating effluent that is economically treatable by conventional wastewater treatment technologies.
Multi-Blockchain Structure for a Crowdsensing-Based Smart Parking System
Authors: Kim Mihui , Kim Youngmin
Published: May 2020

As a representative example for the construction of a smart city, a smart parking system has been developed in past research and implemented through IoT and cloud technologies. However, the initial installation cost of IoT sensor devices is preventing the spread of this technology, and thus as an alternative, a crowdsensing-based system, operating through data from publicly owned mobile devices, has been proposed. In this paper, we propose a multi-blockchain structure (i.e., constructed with public chain and private chain) in a crowdsensing-based smart parking system. In this structure, many sensing data contributors participate through the opened public blockchain, to transparently provide sensing information and to claim corresponding rewards. The private blockchain provides an environment for sharing the collected information among service providers in real time and for providing parking information to users. The bridge node performs an information relay role between the two blockchains. Performance analysis and security analysis on the implemented proposed system show the feasibility of our proposed system.
Electrical Conductivity of Field-Structured Emulsions
Authors: Zakinyan Arthur R. , Kulgina Ludmila M. , Zakinyan Anastasia A. , Turkin Sergey D.
Published: May 2020

The structure formation influence on various macroscopic properties of fluid–fluid disperse systems is poorly investigated. The present work deals with the experimental study of the charge transfer in emulsions whose dispersed phase droplets are arranged into chainlike structures under the action of an external force field. The emulsions studied are the fluid system in which water droplets are dispersed in a hydrocarbon-based magnetic fluid. Under the effect of an external uniform magnetic field, anisotropic aggregates form from the emulsion dispersed phase drops. The low-frequency electrical conductivity of emulsions has been measured. It is demonstrated that the emulsions’ conductivity grows several times under the effect of magnetic field parallel to the measuring electrical field. The anisotropic character of the emulsion electrical conductivity in the presence of magnetic field has been demonstrated. It is revealed that the maximal response of conductivity on the magnetic field action takes place at the dispersed phase volume fraction of about 20%. The dynamics of the conductivity variation is analyzed in dependence on the magnetic field strength and the dispersed phase volume fraction. The obtained results may be of interest in the development of potential applications of disperse systems with magnetic-field-controllable properties.
Social Cues and the Online Purchase Intentions of Organic Wine
Authors: Sohn Stefanie , Seegebarth Barbara , Kissling Martin , Sippel Tabea
Published: May 2020

This study investigates how online store atmospherics (i.e., social cues) affect consumer purchase intentions of organic wine. A between-subject experiment with a quantitative survey conducted among German consumers reveals that the mere presence of social cues (i.e., a chat box) on a wine sellers’ online platform positively affects the intention to purchase organic wine from this online store because social cues elicit perceptions of social presence that translate into trust in the online store and brand trust. The latter promotes purchase intentions. Internal (i.e., familiarity with organic wine purchases) and situational (i.e., goal-directedness of shopping) factors do not moderate the effects of social cues.
Characteristics, Occurrence, Detection and Detoxification of Aflatoxins in Foods and Feeds
Authors: Nazhand Amirhossein , Durazzo Alessandra , Lucarini Massimo , Souto Eliana B. , Santini Antonello
Published: May 2020

Mycotoxin contamination continues to be a food safety concern globally, with the most toxic being aflatoxins. On-farm aflatoxins, during food transit or storage, directly or indirectly result in the contamination of foods, which affects the liver, immune system and reproduction after infiltration into human beings and animals. There are numerous reports on aflatoxins focusing on achieving appropriate methods for quantification, precise detection and control in order to ensure consumer safety. In 2012, the International Agency for Research on Cancer (IARC) classified aflatoxins B1, B2, G1, G2, M1 and M2 as group 1 carcinogenic substances, which are a global human health concern. Consequently, this review article addresses aflatoxin chemical properties and biosynthetic processes; aflatoxin contamination in foods and feeds; health effects in human beings and animals due to aflatoxin exposure, as well as aflatoxin detection and detoxification methods.
Coumarins in Food and Methods of Their Determination
Authors: Lončar Mirjana , Jakovljević Martina , Šubarić Drago , Pavlić Martina , Buzjak Služek Vlatka , Cindrić Ines , Molnar Maja
Published: May 2020

Coumarin is a natural product with aromatic and fragrant characteristics, widespread in the entire plant kingdom. It is found in different plant sources such as vegetables, spices, fruits, and medicinal plants including all parts of the plants—fruits, roots, stems and leaves. Coumarin is found in high concentrations in certain types of cinnamon, which is one of the most frequent sources for human exposure to this substance. However, human exposure to coumarin has not been strictly determined, since there are no systematic measurements of consumption of cinnamon-containing foods. The addition of pure coumarin to foods is not allowed, since large amounts of coumarin can be hepatotoxic. However, according to the new European aroma law, coumarin may be present in foods only naturally or as a flavoring obtained from natural raw materials (as is the case with cinnamon). In this paper, the overview of the current European regulations on coumarin levels in food is presented, along with the most common coumarin food sources, with a special emphasis on cinnamon-containing food. Human exposure to coumarins in food is also reviewed, as well as the methods for determination and separation of coumarin and its derivatives in food.